To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection. This multicenter cross-sectional parallel control study was conducted in 11 children's hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman's rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection. A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum (0.970.01). The linear regression equation was PCT=0.135+0.929×PCT. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods (0.51-0.92, all 0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 μg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 μg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 μg/L, respectively. There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.

: Transpulmonary biomarkers may provide insight into pulmonary hypertension (PH) pathophysiology, but require cardiac catheterization. We investigated whether the peripheral arterial-venous ratio (PR) could substitute for the transpulmonary ratio (TPR). Blood from the pulmonary artery (PA), pulmonary arterial wedge (PAW), peripheral venous, and peripheral arterial positions was analysed for ET-1, NT-pro-BNP and cAMP levels in subjects with no PH ( = 18) and PH due to left heart disease (PH-LHD), which included combined pre- and post-capillary PH (Cpc-PH;  = 7) and isolated post-capillary PH (Ipc-PH;  = 9). Bland-Altman comparisons were made between peripheral venous and PA samples and between peripheral arterial and PAW samples. TPR was defined as [PAW]/[PA]. For ET-1, Bland-Altman analysis indicated negative bias (-24%) in peripheral arterial compared to PAW concentration and positive bias (23%) in peripheral venous compared to PA concentration. There was <10% absolute bias for NT-pro-BNP and cAMP. For ET-1, there was no difference in PR between Cpc-PH and Ipc-PH (0.87 ± 0.4 0.94 ± 0.6,  = 0.8), whereas there was a difference in TPR (2.2 ± 1.1 1.1 ± 0.2,  < 0.05). In PH-LHD, peripheral samples may be inadequate surrogates for transpulmonary samples, particularly when measuring mediators with prominent pulmonary secretion or clearance, such as ET-1.

OBJECTIVE:To assess the safety and efficacy of glucocorticoids (GCs), immunosuppressive agents (IM) and rituximab (RTX), alone or in combination, for the treatment of IgG4-RD. METHODS:Relevant articles published were searched in the databases with relevant key words. Network meta-analysis was conducted, with various outcomes including relapse rate, remission rate and adverse events. Data were calculated with odds ratio (ORs) and 95% CI. P-score was used to rank the treatments. RESULTS:A total of 15 studies involving 1169 patients were included. Network meta-analysis indicated that RTX maintenance therapy had the lowest relapse rate of all treatments (OR = 0.10, 95% CI [0.01, 1.63]), whereas GCs + IM was associated with a lower relapse rate compared with GCs alone (OR = 0.39, 95% CI [0.20, 0.80]). Further, patients treated with GCs + IM had a higher remission rate than those given GCs (OR= 3.36, 95% CI [1.44, 7.83]), IM (OR= 55.31, 95% CI [13.73, 222.73]) monotherapies or RTX induction therapy only (OR= 7.38, 95% CI [1.56, 34.94]). The rate of adverse events was comparable among the different treatment groups. CONCLUSION:Treatment of IgG4-RD patients with GCs and IM was associated with higher remission rates and lower relapse rates, as well as comparable safety profiles compared with GC, IM and RTX induction therapy. RTX maintenance therapy had a larger reduction in the relapse rate compared with GC and IM. The current evidence should be carefully scrutinized as the included studies were observational in design. Larger randomized controlled trials are needed to confirm.

Immunoglobulin A nephropathy (IgAN) is a common autoimmune glomerulonephritis that can result in end-stage renal disease (ESRD). Whether immunosuppressants are superior or equivalent to supportive care is still controversial. A network meta-analysis was conducted to compare the efficacy and safety of immunosuppressive treatment for IgAN. Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and EMBASE were searched on December 30, 2018. We used a random-effects model with a Bayesian approach to appraise both renal outcomes and serious adverse effects. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated to present the relative effects. The ranking probabilities were calculated by the surface under the cumulative ranking curve (SUCRA). In total, 24 RCTs comprising 6 interventions were analyzed. Steroids significantly delayed the progression of renal deterioration with acceptable serious adverse effects, compared with supportive care (RR = 0.28, 95% CI = 0.13-0.51, SUCRA = 48.7%). AZA combined with steroids might be an alternative immunosuppressive therapy. Tacrolimus might decrease the proteinuria level (RR = 3.1, 95% CI = 1.2-9.4, SUCRA = 66.5%) but cannot improve renal function, and the side effects of tacrolimus should not be neglected. MMF and CYC showed no superiority in the treatment of IgAN. In summary, steroids might be recommended as the first-line immunosuppressive therapy for IgAN.

The efficacy and safety of immunosuppressive monotherapy agents were evaluated for immunoglobulin A nephropathy (IgAN) using a network meta-analysis approach. Randomized controlled trials (RCTs) published prior to October 1, 2019, using immunosuppressive agents for treating IgAN, were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science databases. Relative risks (RRs) or standard mean differences with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes were clinical remission, end-stage renal disease (ESRD), and serious adverse events (SAEs). The secondary outcomes were urinary protein excretion and serum creatinine. Twenty-five RCTs with 2,005 participants were deemed eligible. Six medications were evaluated: corticosteroids, mycophenolate mofetil (MMF), tacrolimus (TAC), cyclosporine, leflunomide, and hydroxychloroquine (HCQ). Steroids (RR 1.50, 95% CI 1.17-1.93), MMF (RR 2.05, 95% CI 1.15-3.65), TAC (RR 3.67, 95% CI 1.06-12.63), and HCQ (RR 3.25, 95% CI 1.05-10.09) significantly improved clinical remission rates compared to supportive care alone. Only steroids reduced the risk of ESRD (RR 0.35, 95% CI 0.12-0.98); however, there were significantly more SAEs than in the control group (RR 2.90, 95% CI 1.37-6.13). No significantly different effects in serum creatinine levels were found among the therapies. MMF showed no significant improvement in remission when excluding studies with a follow-up of fewer than 2 years in the sensitivity analysis (RR 1.41, 95% CI 0.40-4.92). The effect of TAC in the decrease of proteinuria was reversed after discontinuing medication for 3 months; the long-term effects of HCQ could not be evaluated due to the short follow-up duration. Corticosteroids might induce remission and increase renal survival in IgAN; however, adverse reactions should be taken into consideration. MMF, TAC, and HCQ might improve the remission of proteinuria when treating IgAN, but showed no superiority compared to steroids, and the long-term effects require further study.

BACKGROUND:Idiopathic membranous nephropathy (IMN) is the most common pathological type of adult nephrotic syndrome. However, the treatments for IMN patients had not been compared from the perspectives of therapeutic effect and pharmacoeconomics. Therefore, a network meta-analysis and a cost-effectiveness analysis were conducted to find the optimum treatment for IMN patients. METHODS:Randomized controlled trials (RCTs) which compared the treatments including cyclophosphamide (CTX), mycophenolate mofetil (MMF), cyclosporine (CsA), tacrolimus (TAC), leflunomide (LEF), chlorambucil (CLB) and rituximab (RTX) for patients with IMN were reviewed. The complete and partial remission rates were extracted and then compared by network meta-analysis. The surface under the cumulative ranking area (SUCRA) was calculated to rank the remission rate for all treatments. Then, the cost-effectiveness analysis was performed to compared the incremental cost-effectiveness ratio (ICER) of different treatments. RESULTS:A total of 75 articles with 4806 participants were included according to the inclusion and exclusion criteria. Compared with the glucocorticoids (GC) group, CTX + GC (95%RR 1.02,1.76), CsA + GC (95%RR 1.11,2.13) and TAC + GC (95%RR 1.44,2.59) were associated with a significantly higher rate of complete remission. TAC + GC were most likely to be ranked the best (SUCRA of 92.1%). From the perspective of the cost-effectiveness analysis in China, the ICER of LEF + GC to CTX + GC was $30616.336 per unit utility, and that of TAC + GC to CTX + GC was $670475.210 per unit utility. And the ICER of CTX + GC to LEF + GC in the UK was $-65680.879 per unit utility. CONCLUSIONS:CTX + GC was the cheapest treatment with obvious curative effect in China, while LEF + GC was a cost-effective alternative to CTX + GC. The remission rate of TAC + GC was highest despite the high single-dose cost.