Efficacy and safety of belimumab in systemic lupus erythematosus patients with severe lupus nephritis requiring renal replacement therapy.

BACKGROUND: Systemic lupus erythematosus is a chronic inflammatory autoimmune disease that has various manifestations. Lupus nephritis is a common and severe presentation, which results in increased morbidity and mortality. Belimumab added on standard therapy has been proved to induce disease remission and improve renal parameters. However, the use of belimumab has not been explored in patients requiring dialysis treatment. METHODS: Seven patients diagnosed as SLE with renal involvement requiring dialysis, who received belimumab in addition to steroids or immunosuppressants were identified. Clinical and biological data were extracted from medical records and laboratory databases. Ten mg/kg belimumab was applied on day 1, 15, 29, and every 28 days thereafter for a total of 8 dose. Renal parameters including urine output and serum creatinine level, immunologic index including anti-ds-DNA antibody titer and complement level, and disease activity were documented to reveal the response to belimumab. RESULTS: After belimumab therapy, all the 7 patients receiving dialysis therapy showed immunologic improvement. Disease activity significantly declined from 16.5 to 5.33 using SLEDAI-2K score. Apart from patient 7 on maintenance dialysis, 5 of 6 patients had increased urine output and were out of dialysis treatment. Patient 5 and 6 showed significant decrease in serum creatinine level. Only one pulmonary infection was documented. CONCLUSIONS: Belimumab added to steroids or immunosuppressive agents was able to improve renal and immunologic parameters and decrease disease activity of SLE patients receiving dialysis treatment. The safety issue is promising with no severe adverse effect recorded. Further large, controlled, randomized clinical trials are required to confirm the results.

Extended infusion of rituximab combined with steroids is effective in inducing remission and reducing relapse in adult minimal change disease.

BACKGROUND: Minimal change disease is a common cause of nephrotic syndrome in adults. Higher relapse rate put patients at risk of steroids toxicity due to long-term exposure. Rituximab has been suggested to maintain long time remission and withdraw steroids and other immunosuppressants with fewer adverse events. However, optimal dose and dosing interval have not been explored. METHODS: Twenty-five patients were enrolled from 2017-10 to 2020-03 in Nanfang Hospital in China. Clinical and biological data were extracted from medical records and laboratory databases. Therapy composed of 375mg/m2 rituximab once three weeks for 3 dose and corticosteroid was applied. Complete remission was defined as reduction of proteinuria to 0.3g/d. Remission rate, relapse rate, steroids used before and after rituximab therapy and adverse effects were documented at a mean time of 14.71 months. RESULTS: Twenty-two patients achieved complete remission for an average of 3.26 months and only 3 patients experienced one relapse respectively during the follow-up period. The mean remission maintenance time was 11.6 months, and was 5 months after steroids withdrawal. Steroids dose at last follow-up was 6.09mg/d, which was significantly reduced compared to 28.15mg/d before rituximab. Relapse rate before and after rituximab was 1.43 and 0.1, respectively. Only four minor adverse events were recorded. CONCLUSIONS: Therapy consisted of 375mg/m2 rituximab once three weeks for 3 dose combined with corticosteroid is effective in inducing remission in adult patients with minimal change disease. Both of the relapse rate and dose of steroids used are significantly decreased with fewer side effects.

Yes associated protein 1 promotes resistance to 5-fluorouracil in gastric cancer by regulating GLUT3-dependent glycometabolism reprogramming of tumor-associated macrophages.

The antimetabolite 5-fluorouracil (5-FU) is a widely used chemotherapy regimen for the treatment of gastric cancer (GC). However, resistance to 5-FU remains a major drawback in the clinical use. The treatments of anti-tumor chemo-agents recruit tumor associated macrophages (TAMs) which are highly implicated in the chemoresistance development, but the underlying molecular mechanism is unclear. Here, we demonstrate that YAP1 is overexpressed in resistant GC tissues compared to sensitive GC tissues. Further, IL-3 secreted by YAP1-overexpressed GC could skew macrophage polarization to M2-like phenotype and inducing GLUT3-depended glycolysis program. Meanwhile, polarized M2 macrophages enhance 5-FU resistance in tumor cells by secreting CCL8 and activating phosphorylation of JAK1/STAT3 signaling pathway.

Proton pump inhibitors and the risk of hospital-acquired acute kidney injury in children.

BACKGROUND: To evaluate the association between use of proton pump inhibitor (PPI) and the risk of hospital-acquired acute kidney injury (HA-AKI) in hospitalized children. METHODS: We conducted a multicenter retrospective cohort study in hospitalized children aged 1 month to 18 years from 25 tertiary hospitals across China from 2013 to 2015. Patient-level data were obtained from the electronic hospitalization databases. AKI was defined and staged using the serum creatinine (SCr) data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Among 42,232 children analyzed, 11,496 (27.2%) used PPI, 1,760 (4.2%) used histamine 2 receptor antagonist (H2RA), and 3,514 (8.3%) had HA-AKI during hospitalization. Over 85% of PPIs were prescribed for prophylaxis of gastro-duodenal lesions in children. The use of PPI was associated with a significantly increased risk of HA-AKI compared with both non-users [odds ratio (OR), 1.37; 95% confidence interval (CI), 1.23-1.53)] and H2RA users (OR, 1.24; 95% CI, 1.01-1.52). The associations were consistent across children of different age range, gender, subtypes of PPIs and methods of administration. A larger effect was observed in children with chronic kidney disease (OR, 3.37; 95% CI, 2.46-4.62) and those needed intensive care (OR, 1.54; 95% CI, 1.33-1.78). The risk of HA-AKI was increased even within the recommended dosage range of PPI. CONCLUSIONS: PPIs were widely used and associated with an increased risk of HA-AKI in hospitalized children in China.

Epidemiology of acute kidney injury in hospitalized pregnant women in China.

BACKGROUND: Epidemiologic data of acute kidney injury (AKI) during pregnancy is lacking in China. This study aims to determine the effect of pregnancy on the risk of AKI among hospitalized women of childbearing age, and to describe the incidence, risk factors and outcomes of AKI in hospitalized pregnant women in China. METHODS: We previously conducted a nationwide, multi-centered cohort of hospitalized patients from 25 hospitals in China during 1/1/2013 to 31/12/2015. Women of childbearing age (14-50 year) who had at least two serum creatinine tests within any 7-day window were selected as analysis set. Patient-level data were obtained from the electronic hospitalization information system and laboratory databases. AKI events were identified according to the creatinine criteria of Kidney Disease Improving Global Outcomes. RESULTS: Among 110,873 women of childbearing age, pregnant women (n = 10,920) had a 51% higher risk of AKI than non-pregnant women (n = 99,953). Community acquired and hospital acquired AKI occurred in 3.6% (n = 393) and 3.7% (n = 402) of the pregnant women, respectively, giving rise to an overall AKI incidence of 7.3%. While, hospital coding would have identified less than 5% of AKI episodes. The top three risk factors of AKI during pregnancy, ranked in order of decreasing population attributable fractions were pregnancy-induced hypertension syndrome (21.1%), acute fatty liver (13.5%), and chronic kidney disease (6.2%). CONCLUSION: AKI in pregnancy is associated with increased maternal mortality rate, longer length of stay and higher daily cost. AKI is a common and severe complication during pregnancy in China.

Influence of Uniaxial Stress on the Shear-Wave Spectrum Propagating in Steel Members.

Structural health monitoring technologies have provided extensive methods to sense the stress of steel structures. However, monitored stress is a relative value rather than an absolute value in the structure's current state. Among all the stress measurement methods, ultrasonic methods have shown great promise. The shear-wave amplitude spectrum and phase spectrum contain stress information along the propagation path. In this study, the influence of uniaxial stress on the amplitude and phase spectra of a shear wave propagating in steel members was investigated. Furthermore, the shear-wave amplitude spectrum and phase spectrum were compared in terms of characteristic frequency (CF) collection, parametric calibration, and absolute stress measurement principles. Specifically, the theoretical expressions of the shear-wave amplitude and phase spectra were derived. Three steel members were used to investigate the effect of the uniaxial stress on the shear-wave amplitude and phase spectra. CFs were extracted and used to calibrate the parameters in the stress measurement formula. A linear relationship was established between the inverse of the CF and its corresponding stress value. The test results show that both the shear-wave amplitude and phase spectra can be used to evaluate uniaxial stress in structural steel members.

Epidemiology and outcomes of acute kidney injury in hospitalized cancer patients in China.

Acute kidney injury (AKI) is a common complication in cancer patients, but the data are lacking in Asian countries. We aimed to assed the epidemiology, correlated risk factors and outcomes of AKI in cancer patients from China. We conducted a nationwide cohort study of cancer patients who were admitted to 25 general and children hospitals across China from January 1, 2013 to December 31, 2015. We obtained patient-level data from the electronic hospitalization information system and laboratory databases of all inpatients who had at least two serum creatinine tests within any 7-day window during their first 30 days of hospitalization. AKI was defined and staged according to Kidney Disease Improving Global Outcomes criteria. Incidence rate and risk factor profiles for AKI were examined. Outcomes of interest included in-hospital mortality, length of stay and daily costs. A total of 136,756 adult cancer patients were assessed in our study. The overall incidence of AKI was 7.5%, of which 1.6% were community acquired and 5.9% hospital acquired. The top three cancer types with high incidence of AKI were bladder cancer, leukemia, and lymphoma. Risk factors for community-acquired and hospital-acquired AKI were similar, including age, increased baseline serum creatinine, shock and urinary tract obstruction. In-hospital death occurred in 12.0% with AKI vs. 0.9% cancer patients without AKI. After adjustment for confounders, the severe AKI was associated with higher risk of in-hospital death, prolonged length of stay and higher daily costs. Clinicians should increase their awareness of AKI in hospitalized cancer patients.

The Spectrum of Biopsy-Proven Glomerular Diseases among Children in China: A National, Cross-Sectional Survey.

BACKGROUND AND OBJECTIVES: High-quality epidemiologic data on the spectrum of biopsy-proven glomerular diseases among children are limited. This study aimed to determine the profile of and temporal change in biopsy-proven pediatric glomerular diseases in China. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We previously conducted a nationwide kidney biopsy survey including 71,151 patients over an 11-year period from January 2004 to December 2014. A total of 7962 children younger than 18 years old from 115 hospitals across China with biopsy-proven glomerular diseases were included in this study. The demographic and clinical variables were extracted from referral records and pathology reports. The composition of pediatric glomerular diseases and clinicopathologic correlations in different sexes, age groups, and regions were assessed. The changing patterns of common glomerulopathies over the study period were examined. RESULTS: Nephrotic syndrome (50%) was the most frequent indication for kidney biopsy in children. Minimal change disease was the most common primary glomerular disease (29%) followed by IgA nephropathy (17%). Henoch-Schonlein purpura nephritis (13%) and lupus nephritis (9%) were the most common secondary glomerular diseases. The proportion of minimal change disease was significant higher in boys (38%) than in girls (13%), whereas lupus nephritis was more prevalent in girls (20%) than in boys (3%). Purpura nephritis (23%) was the major pathologic pattern in younger children (0-12 years old), whereas minimal change disease (33%) was the most common glomerulopathy in adolescents (13-18 years old). The clinicopathologic correlations were slightly different between sexes and age groups. We observed increases in the proportions of minimal change disease, purpura nephritis, and membranous nephropathy over the study period that were contemporaneous with a fall in the proportion of FSGS. CONCLUSIONS: The spectrum of glomerular diseases among children varied across sexes, age groups, and regions and changed substantially from 2004 to 2014 in China.

The modern spectrum of biopsy-proven renal disease in Chinese diabetic patients-a retrospective descriptive study.

BACKGROUND: Renal biopsies performed in diabetic patients are increasing and becoming more complex. Comprehensive data on modern spectrum of biopsy-proven renal disease in Chinese diabetic patients are lacking. METHODS: In a nationwide renal biopsy survey including 71,151 native biopsies from 2004 to 2014, diabetic patients were identified according to the clinical diagnosis from referral records. The clinical data were extracted from referral records and pathological reports. RESULTS: A total of 1,604 diabetic patients, including 61 patients with T1DM, were analyzed in this study. The median age is 51.39 ± 11.37 years. Male patients accounted for 58% of the population. We found that only 44.7% of diabetic patients had the isolated pathological diagnosis of diabetic nephropathy (DN), while 49.1% had non-diabetic renal disease (NDRD) alone, and 6.2% had NDRD superimposed on DN. Nephrotic syndrome (n = 824, 51.4%) was the most common clinical indication for renal biopsy. Among 887 patients with NDRD, membranous nephropathy (n = 357) was the leading diagnosis, followed by IgA nephropathy (n = 179). Hypertensive renal disease (n = 32), tubulointerstitial nephropathy (n = 27) and acute tubular necrosis (n = 16) accounted for 3.5%, 2.9%, 1.7% of the NDRD cases respectively. Nearly a half (49.2%) of patients with T1DM had NDRD. DISCUSSION: Over 55% diabetic patients with kidney disease were diagnosed as non-diabetic renal disease, among which MN and IgAN were the most common two pathological types.