Incidence, predictors and 6-month overall outcome of acute kidney injury in Chinese patients receiving PD-1 inhibitors.

Aim: To explore the incidence, risk factors and overall outcome of the first episode of immune checkpoint inhibitor-related acute kidney injury (ICI-AKI) in Chinese patients receiving PD-1 inhibitors. Methods: Data for patients receiving PD-1 inhibitors at Jiangsu Province Hospital between December 2017 and January 2020 were retrospectively reviewed. Results: A total of 5.6% of 551 patients receiving PD-1 inhibitors developed ICI-AKI. Concomitant use of NSAIDs, ICI cycles and extrarenal immune-related adverse events may be independently associated with ICI-AKI. ICI-AKI may not be a risk factor for increased mortality or worse progression-free survival. Conclusions: ICI-AKI is relatively rare and its occurrence may not affect the overall 6-month outcome of patients receiving PD-1 inhibitors. Further studies are needed to verify these findings.

Immune checkpoint inhibitors (ICIs) have been more and more commonly used in patients with cancer. Therefore, it is important to understand the immune-related adverse events (irAEs), including immune-related renal adverse events, caused by ICIs. In this article, the authors explore the incidence, clinical features, risk factors and overall outcome of immune checkpoint inhibitor related-acute kidney injury (ICI-AKI) in Chinese patients treated with PD-1 inhibitors for the first time. Among 551 patients treated with PD-1 inhibitors, 65 patients experienced AKI and 31 patients experienced ICI-AKI. Patients with ICI-AKI may be more likely to receive nonsteroidal anti-inflammatory drugs, to receive PD-1 inhibitors for longer cycles or to experience extrarenal immune-related adverse events prior to or concomitant with ICI-AKI. The occurrence of ICI-AKI may not affect the survival time or disease progression of patients with cancer.

Association of Serum Sclerostin Level, Coronary Artery Calcification, and Patient Outcomes in Maintenance Dialysis Patients.

OBJECTIVE: The objective of this study is to investigate the association between the serum sclerostin, the coronary artery calcification (CAC), and patient outcomes in maintenance dialysis patients. METHODS: We performed a prospective cohort study of 65 maintenance dialysis patients in 2014, including 39 patients on peritoneal dialysis and 26 on hemodialysis, and followed up for 5 years. Parameters of mineral metabolism including bone-specific alkaline phosphatase, fibroblast growth factor 23, sclerostin, and other biochemical factors were determined at the baseline. Meanwhile, the CAC score was analyzed by cardiac computed tomography. RESULTS: Serum sclerostin in hemodialysis patients was significantly higher than that in peritoneal dialysis patients (632.35 ± 369.18 vs. 228.85 ± 188.92, p < 0.001). The patients with CAC were older, receiving hemodialysis, lower Kt/V, and had longer dialysis vintage, as well as higher levels of serum 25-(OH)-vit D and sclerostin. In multivariate logistic regression analysis, older age and lower Kt/V were risk factors for CAC. The area under the receiver operating characteristic curves for prediction of CAC by sclerostin was 0.74 (95% confidence interval 0.605-0.878, p = 0.03), and the cutoff value of sclerostin is 217.55 pg/mL with the sensitivity 0.829 and specificity 0.619. After 5 years of follow-up, 51 patients survived. The patients in the survival group had significantly lower age, sclerostin levels, and low CAC scores than the nonsurvival group. Old age (≥60 years, p < 0.001) and high CAC score (≥50 Agatston unit, p = 0.031) were significant risk factors for the patient survival. CONCLUSIONS: Sclerostin is significantly elevated in dialysis patients with CAC. But sclerostin is not a risk factor for CAC. After 5 years of follow-up, patients in the survival group are younger and have lower sclerostin levels and CAC scores. But sclerostin levels are not independent risk factors for high mortality in dialysis patients.

Ratio of Overhydration and Extracellular Water Versus Ratio of Extracellular Water and Body Cell Mass in the Assessment of Fluid Status in Patients With Acute Kidney Injury Requiring Kidney Replacement Therapy: A Cohort Study.

OBJECTIVES: The aim of this study is to analyze the association between the ratio of overhydration and extracellular water (OH/ECW) and the ratio of extracellular water and body cell mass (ECW/BCM) measured by bioelectrical impedance and outcomes of patients with acute kidney injury (AKI) requiring kidney replacement therapy (KRT). METHODS: Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed using a body composition monitor before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors mainly included OH/ECW and ECW/BCM. The association between all-cause mortality and predictors were analyzed using Cox regression. RESULTS: A total of 152 patients were included in this study with a median follow-up of 39 (interquartile range 8-742) days. The 28-day mortality, 90-day mortality, and 1-year mortality were 46.7%, 54.6%, and 60.5%, respectively. A high ratio of OH/ECW (adjusted hazard ratio per standard deviation, 1.45; 95% confidence interval = 1.15-1.82, P = .002) and a high ratio of ECW/BCM (adjusted hazard ratio per standard deviation, 1.33, 95% confidence interval = 1.07-1.64, P = .009) before KRT were associated with all-cause mortality during follow-up. Higher ECW/BCM rather than OH/ECW at 7th day was associated with poorer outcomes. Furthermore, a reduction of OH/ECW with an increase of ECW/BCM had higher 1-year mortality as compared to others (85.7% vs. 51.2%, P = .004) in patients who survived 7 days after KRT initiation. CONCLUSIONS: ECW/BCM performed better than OH/ECW in assessment of fluid status in AKI patients requiring KRT. This study suggested that a simple reduction of OH/ECW without decreasing ECW/BCM may not improve outcomes.

Clinicopathological characteristics and outcome predictors of anti-glomerular basement membrane glomerulonephritis.

OBJECTIVE: To explore the clinicopathological features of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (anti-GBM-GN) and the prognostic values of clinical and laboratory indicators at diagnosis on renal and patient survival. METHODS: A total of 76 patients (34 males and 42 females) with anti-GBM-GN who were hospitalized in the First Affiliated Hospital of Nanjing Medical University between January 2010 and June 2021 were included in this study. The baseline clinical features, histopathological data from renal biopsies, and predictors of renal and patient survival were retrospectively analyzed. RESULTS: Among the 76 patients, the median serum creatinine at diagnosis was 618.0 (350.98, 888.25) µmol/L and the median estimated glomerular filtration rate (eGFR) was 6.62 (4.39, 14.41) mL/min. Of these 76 patients, 55 (72.4%) received initial kidney replacement therapy (KRT) and 39 (51.3%) received plasma exchange or double-filtered plasmapheresis (DFPP). During a median follow-up duration of 28.5 (6.0, 71.8) months, 53 (69.7%) patients progressed to kidney failure with replacement therapy (KFRT) and received maintenance dialysis. Initial KRT (HR = 3.48, 95% CI = 1.22-9.97, p = 0.020) was a significant risk factor for renal survival. During the follow-up, 49 (64.5%) of 76 patients survived. Age (≥60 years, HR = 4.13, 95% CI = 1.65-10.38, p = 0.003) and initial KRT (HR = 2.87, 95% CI = 1.01-8.14, p = 0.047) were predictive of patient survival. CONCLUSIONS: Among patients with anti-GBM-GN, initial KRT at presentation was predictive of KFRT while older age and initial KRT were associated with higher all-cause mortality.

Body Composition Analysis as a Predictor of Prognosis for Patients With Acute Kidney Injury Requiring Kidney Replacement Therapy.

OBJECTIVES: The aim of this study is to investigate the association between body composition, measured by bioelectrical impedance analysis, and outcomes in patients with acute kidney injury (AKI) receiving kidney replacement therapy (KRT). METHODS: Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed by body composition analysis before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors included lean tissue index (LTI), fat tissue index, and body cell mass index (BCMI). The association between all-cause mortality and predictors was analyzed using Cox regression. RESULTS: A total of 152 patients were included in this study, with a 28-day mortality of 46.7% and 1-year mortality of 60.5%. LTI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.66, P < .001) and BCMI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.67, P < .001) on day 7 after initiation of KRT, rather than before KRT, were associated with mortality during follow-up. LTI and BCMI before KRT were associated with 28-day mortality rather than 1-year mortality. CONCLUSIONS: LTI and BCMI before KRT were associated with short-term prognosis, and those on day 7 after KRT initiation were associated with intermediate mortality in patients with AKI requiring KRT.

Ultrafast Growth of Large Area Graphene on Si Wafer by a Single Pulse Current.

Graphene has many excellent optical, electrical and mechanical properties due to its unique two-dimensional structure. High-efficiency preparation of large area graphene film is the key to achieve its industrial applications. In this paper, an ultrafast quenching method was firstly carried out to flow a single pulse current through the surface of a Si wafer with a size of 10 mm × 10 mm for growing fully covered graphene film. The wafer surface was firstly coated with a 5-nm-thick carbon layer and then a 25-nm-thick nickel layer by magnetron sputtering. The optimum quenching conditions are a pulse current of 10 A and a pulse width of 2 s. The thus-prepared few-layered graphene film was proved to cover the substrate fully, showing a high conductivity. Our method is simple and highly efficient and does not need any high-power equipment. It is not limited by the size of the heating facility due to its self-heating feature, providing the potential to scale up the size of the substrates easily. Furthermore, this method can be applied to a variety of dielectric substrates, such as glass and quartz.

Risk factors affecting renal function and survival of patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis
.

OBJECTIVE: To determine the prognostic values of clinical and laboratory features at the time of presentation on renal function and survival of patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. (MPO-ANCA GN). MATERIALS AND METHODS: A total of 119 patients (52 males and 67 females) with MPO-ANCA GN and hospitalized at the First Affiliated Hospital of Nanjing Medical University from January 2010 to April 2018 were enrolled. The baseline clinical characteristics, renal biopsy pathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed. RESULTS: Among these 119 patients, the median serum creatinine at diagnosis was 354.30 (range, 216.10 - 637.30) mmol/L and the median estimated glomerular filtration rate (eGFR) was 14.78 (range, 7.23 - 29.21) mL/min. In total, 58 (48.7%) patients received initial renal replacement therapy (RRT). During a median follow-up duration of 32 (range, 3 - 113) months, 57 (47.9%) patients progressed to end-stage renal disease (ESRD). Initial renal function status (i.e., initial RRT, serum creatinine, and eGFR) (p < 0.001) and hemoglobin level (p = 0.027) were significant risk factors for renal survival. During the follow-up, 69 (57.6%) of 119 patients survived. Age (p = 0.009) and urine red blood cell count (p = 0.012) were predictive of patient survival. CONCLUSION: Among patients with MPO-ANCA GN, poor renal function and lower hemoglobin level were predictive of ESRD, while older age and higher urinary red blood cell count were associated with a higher risk for all-cause mortality.

One Second Formation of Large Area Graphene on a Conical Tip Surface via Direct Transformation of Surface Carbide.

Graphene functionalized nanotips are expected to possess promising potential for various applications based on the outstanding electrical and mechanical properties of graphene. However, current methods, usually requiring a high growth temperature and identical crystal surface to match graphene lattice, are suitable for graphene formation on a flat surface. It remains a big challenge to grow graphene on a nanosized convex surface and fabricate functionalized nanotips with high quality graphene at the apex. In this work, a novel ultrafast annealing method is developed for growing large area graphene on Ni nanotips within 1-2 s. Few layered or multiple layered graphene is presented on the apex or sidewall of the conical tip surface. Direct experimental evidences support that thus-produced graphene is formed via the direct conversion of nickel carbide at the outer surface under the instantaneous high temperature, which is different from the conventional segregation mechanism. This newly developed ultrafast method provides a new route to produce graphene efficiently and economically, promising for both convex surfaces and flat substrates. Moreover, the graphene functionalized nanotips exhibit a great potential for nanoelectrical measurements and conductive scanning probe microscopy (SPM) applications.

Parathyroidectomy Increases Heart Rate Variability and Leptin Levels in Patients with Stage 5 Chronic Kidney Disease.

BACKGROUND: In chronic kidney disease (CKD) patients, decreased heart rate variability (HRV) reflects impaired cardiac automatic nervous function and high risk of cardiovascular disease (CVD). Lower HRV in patients with severe secondary hyperparathyroidism (SHPT), a clinical manifestation of CKD-mineral and bone disorder (CKD-MBD), could be reversed by parathyroidectomy (PTX). It has been proved that leptin interacts with the autonomic nervous function. However, the associations between leptin and HRV in CKD patients and their longitudinal changes in SHPT patients after PTX are still unknown. METHODS: This was a cross-sectional study including 141 stage 5 CKD patients, and a prospective study in 36 severe SHPT patients with PTX. HRV was measured by Holter and serum leptin was measured by ELISA. Serum leptin levels were adjusted for body mass index (BMI) and transformed using natural logarithm (lnleptin/BMI). RESULTS: With a gradient of lnleptin/BMI across quartiles from Q1 to Q4 in CKD patients, HRV indices showed no differences among quartiles. Patients in Q1 group had higher mean 24 h heart rates, and lower ln(very low frequency) (lnVLF) than other quartiles, although there were no statistically significant difference. In multivariate stepwise regression, serum leptin/BMI was an independent predictor for low frequency/high frequency. HRV indices and lnleptin/BMI levels were increased in severe SHPT patients after PTX. Compared to other quartiles, SHPT patients in Q1 group had larger improvement of lnVLF after PTX. CONCLUSION: Circulating leptin levels may be a novel treatment target to reduce CVD risk in advanced CKD-MBD patients.

Prognostic factors in continuous hemofiltration therapy for patients with cardiorenal syndrome.

AIMS: The aims of this study were to investigate the efficacy and identify the prognostic factors of continuous hemofiltration in patients with cardiorenal syndrome (CRS) and, finally, to optimally select patients who could benefit more from this therapy. METHODS: A total of 59 patients with CRS type 1 or type 2 treated with continuous hemofiltration were enrolled. We collected their clinical data and divided them into 2 groups according to their survival or death during hospitalization to conduct a retrospective analysis on factors affecting mortality. RESULTS: The following items were significantly different between the survival (n = 30) and death (n = 29) groups: serum creatinine, serum total bilirubin, direct bilirubin, white blood cells, hemoglobin, hematocrit, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, systolic blood pressure and mean arterial pressure before hemofiltration, and average dehydration volume during the hemofiltration process. Leukocytosis was a risk factor for death (OR 1.242, 95% CI 1.242-1.480), and elevated sCr was not a key negative factor in the prognosis of CRS (OR 0.994, 95% CI 0.989-1.000). CONCLUSIONS: Cardiac function before hemofiltration and the amount of dehydration during the hemofiltration process both affected the prognosis. Infection and fluid overload condition at the beginning of hemofiltration were independently associated with mortality during hospitalization.

Ferroptosis: New Strategies and Ideas for the Treatment of Pancreatic Ductal Adenocarcinoma.

Pancreatic cancer is a malignancy that affects the digestive tract and has a low 5-year survival rate of lower than 15%. Owing to its genetic mutation and metabolic complexity, pancreatic cancer is difficult to treat with surgical resection, radiotherapy, and chemotherapy. The predominant modality of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), primarily attributed to mutations in KRAS gene. Ferroptosis, an iron-mediated reactive oxygen species (ROS)-elevated nonapoptotic cell death caused by lipid peroxidation, is distinct from any other known type of cell death. Ferroptosis is closely related to the occurrence and progression of different types of cancers, including PDAC. Previous research has demonstrated that ferroptosis not only triggers cell death in PDAC and hampers tumor growth but also enhances the effectiveness of antitumor medications. In our review, we mainly focus on the core mechanism of ferroptosis, reveal its interrelationship with PDAC, and illustrate the progress of ferroptosis in different treatment methods of PDAC.

Clinical characteristics and outcome of double-seropositive patients with anti-glomerular basement membrane antibodies and anti-neutrophil cytoplasmic antibodies.

OBJECTIVE: To explore the clinical characteristics of double-seropositive patients (DPPs) with anti-glomerular basement membrane (Anti-GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA). METHODS: We collected patients with both ANCA and anti-GBM positive glomerulonephritis who were hospitalized in the Department of Nephrology at the First Affiliated Hospital of Nanjing Medical University from January 2010 to August 2022. Retrospective analysis of the baseline clinical characteristics of patients and follow-up to explore relevant factors affecting renal and patient survival. RESULTS: A total of 386 patients, including 69 ANCA negative anti-GBM glomerulonephritis patients, 296 anti-GBM negative ANCA associated vasculitis (AAV) patients, and 21 DPPs were enrolled in this study. Among the 21 DPPs aged 68.0 years (59.5, 74.0), there were 11 males and 10 females. The median serum creatinine at diagnosis was 629.0 (343.85, 788.75) µmol/L, and the median eGFR (CKD-EPI) was 7.58 (4.74, 13.77) mL/min. Fifteen cases (71.4 %) underwent initial RRT. After a follow-up of 40.0 (11.0, 73.0) months, 13 out of 21 DPPs (61.9 %) received maintenance RRT, while 49 out of 69 (71.0 %) ANCA negative anti-GBM-GN patients and 124 out of 296 (41.9 %) anti-GBM negative AAV patients received maintenance RRT (P < 0.001). Kaplan-Meier survival analysis showed that DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients (P = 0.001). Among the 21 patients with DPPs, renal survival was significantly better in patients with better initial renal function, including those who did not receive initial RRT (P = 0.003), with lower serum creatinine levels (Cr < 629.0 µmol/L, P = 0.004) and higher eGFR levels (eGFR ≥ 7.60 ml/min, P = 0.005) than those with poor initial renal function. At the end of follow-up, 14 out of 21 DPPs (66.7 %) survived. Survival analysis showed no significant difference among patients in DPPs group, ANCA negative anti-GBM-GN group, and anti-GBM negative AAV group. CONCLUSIONS: DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients. In DPPs, the poor renal function at diagnosis might be a risk factor associated with poor renal survival.

Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis. A large number of patients with PDAC develop metastases before they are diagnosed with metastatic pancreatic cancer (mPDAC). For mPDAC, FOLFIRINOX or gemcitabine plus nab-paclitaxel are the current first-line treatments. It is important to note, however, that many patients will fail chemotherapy because of drug resistance. ​Heterogeneous tumors and complex tumor microenvironments are key factors. As a result, clinical researchers are exploring a variety of alternative treatment modalities. Current understanding of the molecular signature and immune landscape of PDAC has motivated the emergence of different targeted and immune-based therapeutic approaches, some of which have shown promising results. The purpose of this review is to discuss the new targets and new drugs for mPDAC in terms of specific pathogenic factors such as metabolic vulnerability, DNA damage repair system, tumor microenvironment and immune system, in order to identify potential vulnerabilities in mPDAC patients and hopefully improve the prognosis of mPDAC patients.

Research progress and applications of epigenetic biomarkers in cancer.

Epigenetic changes are heritable changes in gene expression without changes in the nucleotide sequence of genes. Epigenetic changes play an important role in the development of cancer and in the process of malignancy metastasis. Previous studies have shown that abnormal epigenetic changes can be used as biomarkers for disease status and disease prediction. The reversibility and controllability of epigenetic modification changes also provide new strategies for early disease prevention and treatment. In addition, corresponding drug development has also reached the clinical stage. In this paper, we will discuss the recent progress and application status of tumor epigenetic biomarkers from three perspectives: DNA methylation, non-coding RNA, and histone modification, in order to provide new opportunities for additional tumor research and applications.

Acute kidney injury in advanced lung cancer patients treated with PD-1 inhibitors: a single center observational study.

PURPOSE: Immune checkpoint inhibitor (ICI) therapy is now the stand of care for lung cancer. Due to the low incidence, the study of acute kidney injury (AKI) in lung cancer patients treated with ICIs was hardly reported. We focused on the incidence, characteristics, risk factors, and mortality of AKI in advanced lung cancer patients receiving PD-1 inhibitors. METHODS: We reviewed advanced lung cancer patients receiving PD-1 inhibitors between January 2018 to August 2020 at Jiangsu Province Hospital. Patients were followed up for 6 months. We used the logistic regression model to evaluate risk factors for AKI, and Kaplan-Meier method to assess the association between AKI and mortality. RESULTS: A total of 305 advanced lung cancer patients treated with PD-1 inhibitors. The median age was 64 years and 80.6% of patients were male. The incidence of AKI was 10.2%, and the incidence of ICI-AKI was 4.6%. Multivariate analysis showed that concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR 2.509; 95% CI 1.053-5.974) and renin-angiotensin-aldosterone system (RAAS) inhibitors (OR 2.656; 95% CI 1.091-6.466) were risk factors for AKI. In addition, concomitant use of NSAIDs (OR 5.170; 95% CI 1.087-24.595) and RAAS inhibitors (OR 5.921; 95% CI 1.871-18.737), and the occurrence of extra-renal immune-related adverse events (OR 4.726; 95% CI 1.462-15.280) were significantly associated with ICI-AKI. ICI-AKI was not associated with mortality while severe AKI was associated with higher risk of mortality. CONCLUSION: AKI is common in advanced lung cancer patients treated with PD-1 inhibitors. The characteristics and risk factors of ICI-AKI were similar to those previously reported in other solid organ malignancies treated with ICIs. Severe AKI may indicate higher mortality.

Ecological drivers of macroinvertebrate metacommunity assembly in a subtropical river basin in the Yangtze River Delta, China.

Identifying the underlying ecological drivers of macroinvertebrate community assembly is fundamental to metacommunity ecology. Comparably, determining the influence of different drivers on beta diversity patterns can provide insight into processes governing community organization. Exploring the ecological drivers of metacommunity and beta diversity are major avenues to improve bioassessment, restoration, and river management, which are still poorly explored in China, especially in subtropical highly developed river networks. To address this gap, we use a dataset (macroinvertebrate communities and environmental variables) collected from the Yangtze River Delta, China to test the above ideas. We used the K-means clustering method to divide 405 river sites into three anthropogenic impacted groups, nearly pristine sites, moderately impacted sites, and heavily impacted sites, and subsequently used partial Mantel tests to investigate how species sorting and dispersal shaped the metacommunity that varied with the levels of anthropogenic impacts and to explore the responses of different components of beta diversity to environmental and spatial distances among sites for each group. Our results revealed that both species sorting and dispersal shape communities, but the importance of species sorting and dispersal varied with the levels of anthropogenic impacts. Nearly pristine sites were mostly shaped only by species sorting, while heavily impacted sites were shaped by dispersal. We also found that turnover was by far the dominant component of beta diversity across all levels of impact. Therefore, we encourage that environmental variables and spatial processes should be considered in bioassessment approaches. In addition, it is essential to focus on maintaining habitat heterogeneity and identifying and protecting regional species pools that could improve local biodiversity through dispersal for ecosystem management of the Yangtze River Delta of China.

Ultrafast Growth of Highly Conductive Graphene Films by a Single Subsecond Pulse of Microwave.

Currently, graphene films are expected to achieve real applications in various fields. However, the conventional synthesis methods still have intrinsic limitations, especially not being applicable on a surface with high curvature. Herein, an ultrafast synthesis method was developed for graphene and turbostratic graphite growth by a single subsecond pulse of microwaves generated by a household magnetron. We succeeded in growing high-quality around 10-layered turbostratic graphite in 0.16 s directly on the surface of an atomic force microscope probe and maintaining a tip curvature radius of less than 30 nm. The thus-produced probes showed high conductivity and tip durability. Moreover, turbostratic graphite film was also demonstrated to grow on the surface of dielectric Si flat substrates in a full coverage. Graphene can also grow on metallic Ni tips by this method. Our microwave ultrafast method can be used to grow high-quality graphene in a facile, efficient, and economical way.

Effectiveness and safety of Belimumab combined with standard therapy in severe active lupus nephritis requiring kidney replacement therapy: A case report and literature review.

Lupus Nephritis (LN) is the most common manifestation of severe organ damage for systemic lupus erythematosus (SLE) patients. Severe active LN could result in acute kidney injury (AKI), which could even require Kidney Replacement Therapy (KRT). Therefore, there needs to be a more proactive and safe induction therapy to quickly and effectively control renal immune inflammation, maintain kidney function or reverse kidney damage. While multiple clinical studies have proven the efficacy and safety of Belimumab in treating SLE and LN, these studies have not included cases of severe LN requiring KRT. We observed the effectiveness and safety of Belimumab in treating four severe active LN patients undergoing KRT. With Belimumab administered at a dosage of 10mg/kg, all four patients were able to discontinue KRT with no adverse events (AEs) to date ultimately. These cases provided an excellent basis for the application of Belimumab combined with standard therapy to LN patients with a medium to severe kidney injury.

A novel long-term intravenous combined with local treatment with human amnion-derived mesenchymal stem cells for a multidisciplinary rescued uremic calciphylaxis patient and the underlying mechanism.

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis, with high mortality and no proven therapy. Here, we reported a severe uremic calciphylaxis patient with progressive skin ischemia, large areas of painful malodorous ulcers, and mummified legs. Because of the worsening symptoms and signs refractory to conventional therapies, treatment with human amnion-derived mesenchymal stem cells (hAMSCs) was approved. Preclinical release inspections of hAMSCs, efficacy, and safety assessment, including cytokine secretory ability, immunocompetence, tumorigenicity, and genetics analysis in vitro, were introduced. We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats, abnormal immune response tests in C57BL/6 mice, and tumorigenicity tests in neonatal Balbc-nu nude mice. After the preclinical research, the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers. When followed up to 15 months, the blood-based markers of bone and mineral metabolism improved, with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells. Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis, and 20 months later, the re-epithelialization restored the integrity of the damaged site. No infusion or local treatment-related adverse events occurred. Thus, this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, anti-inflammatory and immune modulation, multidifferentiation, re-epithelialization, and restoration of integrity.

Comparative Risk of Renal Adverse Events in Patients Receiving Immune Checkpoint Inhibitors: A Bayesian Network Meta-Analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICI-based regimens, especially ICI combination therapy. METHODS: We carried out a network meta-analysis of randomized controlled trials (RCTs) to compare the risk of RAEs between ICI-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types. RESULTS: Ninety-five eligible RCTs involving 40,552 participants were included. The overall incidence of RAEs, grade 3-5 RAEs, acute kidney injury (AKI), and grade 3-5 AKI was 4.3%, 1.2%, 1.3%, and 0.8%, respectively. Both ICI-based treatment regimens and traditional cancer therapy showed significantly higher risk of RAEs and AKI than the placebo. Among ICI monotherapy, anti-PD-1 (RR: 0.51, 95%CI: 0.29-0.91) was significantly safer than anti-CTLA-4 in terms of RAEs. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR: 0.33, 95%CI: 0.14-0.77), anti-PD-L1 (RR: 0.38, 95%CI:0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR: 0.32, 95%CI: 0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICI monotherapy and traditional cancer therapy, except that targeted therapy seemed the least toxic therapy in terms of the incidence of AKI. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1 (RR: 1.61, 95%CI: 1.02-2.56). The difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICI plus chemotherapy showed increased risk of both RAEs and AKI compared with ICI monotherapy, chemotherapy, and targeted therapy. The overall results remained robust in the meta-regression and sensitivity analyses. CONCLUSIONS: Among ICI monotherapy, anti-CTLA-4 appeared to be associated with increased toxicity, especially in terms of grade 3-5 RAEs. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1. However, the difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICIs plus chemotherapy seemed to be the most toxic treatment regimen in terms of RAEs, AKI, and grade 3-5 AKI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42020197039.