Intraperitoneal vancomycin plus levofloxacin for the treatment of peritoneal dialysis-related peritonitis in patients with no response to cefazolin plus ceftazidime.

INTRODUCTION: Peritoneal dialysis-related peritonitis (PDRP) should be treated as soon as possible by an empirical regimen without waiting for effluent bacterial culture results. We retrospectively investigated patients treated with vancomycin plus levofloxacin as a treatment regimen if there was no response to cefazolin plus ceftazidime. MATERIALS AND METHODS: We collected records of adult patients with PDRP from January 1, 2013, to November 30, 2020. The characteristics of episodes of PDRP with no response to cefazolin plus ceftazidime treated by intraperitoneal (IP) injection of vancomycin plus levofloxacin were analyzed. RESULTS: 118 episodes of PDRP were recorded, among which 115 episodes were treated with IP antibiotics. 93 episodes were treated with cefazolin plus ceftazidime. In 38 episodes, treatment was switched to IP injection of vancomycin plus levofloxacin if there was no response to cefazolin plus ceftazidime. 26/38 (68.4%) episodes were cured by vancomycin plus levofloxacin. Fever, diabetes, fasting glucose, a decrease in effluent leukocytes on day 3 and day 5, and Charlson Comorbidity Index (CCI) scores were significantly different between uncured and cured episodes. No variable was associated with treatment failure after multiple logistic regression. Fever, diabetes, a decrease in effluent leukocytes on day 3, and CCI score were associated with treatment failure after univariable logistic regression. CONCLUSION: Vancomycin plus levofloxacin may be effective if patients are not responsive to cefazolin plus ceftazidime.

The effectiveness and safety of corticosteroid therapy for IgA nephropathy with crescents: a prospective, randomized, controlled study.

BACKGROUND: Pozzi protocol (methylprednisolone intravenous infusion in 1st-3rd-5th months and oral steroid for 6 months) has been thought to be the classic therapy for IgA nephropathy (IgAN) patients with proteinuria> 1.0 g/24 h. There is no consensus on the treatments for IgAN with active pathological changes, especially for IgAN patients with crescents proportion < 50%. This study aimed to evaluate the effectiveness and safety of the treatment protocol of methylprednisolone intravenous infusion at the 1st-2nd-3rd months for IgAN patients with crescents. METHODS: In this prospective, randomized, controlled, non-blind study, 68 IgAN patients with crescents proportion < 50% were divided into the 1-2-3 group receiving 0.25 g/d methylprednisolone intravenously for 3 consecutive days in the 1st-2nd-3rd months, and oral prednisone 0.5 mg/kg/d on consecutive days for 6 months and the 1-3-5 group with the same intravenous methylprednisolone treatment in the 1st-3rd-5th months, and the same oral prednisone. The primary outcome measure was remission of proteinuria (complete or partial); while the secondary outcome measures were deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine levels, or a 25% decline from baseline eGFR levels). RESULTS: There was no significant difference in incidence of crescents (median 14.66% vs. 11.45%, p = 0.143) between the 1-2-3 and 1-3-5 groups. From month 1 to month 6, there was a decreasing trend in the levels of urine protein and serum creatinine and an increasing trend in eGFR in both groups. The mean period of remission in the 1-2-3 group seemed shorter. Overall, there were 55 (80.89%) patients meeting remission. The rates of remission in the 1-2-3 group and 1-3-5 group were 85.3 and 76.47%, respectively (P = 0.644). The 1-2-3 group had lower creatinine and higher eGFR than the 1-3-5 group, but the difference was not significant. The complication rate was 11.11 and 15.79% in the two groups, respectively. There was no significant difference in the complications between groups. CONCLUSIONS: Both the 1st-3rd-5th and 1st-2nd-3rd protocols can effectively alleviate proteinuria and protect renal function in IgAN patients with crescents but the 1st-2nd-3rd protocol seemed to have better effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02160132 , Registered June 10, 2014.

Platelet-to-lymphocyte ratio and the first occurrence of peritonitis in peritoneal dialysis patients.

BACKGROUND: Platelet-to-lymphocyte ratio (PLR) has been used as a potential biomarker of inflammation-related diseases, but its role in the peritoneal dialysis-related peritonitis (PDRP) is still uncertain. This study was aimed to investigate the association between PLR and the new-onset PDRP in peritoneal dialysis (PD) patients. METHODS: In this multicenter retrospective study, 1378 PD Chinese PD patients were recruited from four centers, who were divided into the high PLR group (HPG) and the low PLR group (LPG) according to the cutoff value of PLR. The correlation between PLR and the new-onset PDRP was assessed using the Cox regression model analysis. RESULTS: During follow-up, 121 new-onset PDRP events were recorded. Kaplan-Meier survival curve showed a higher risk of new-onset PDRP in the HPG (log-rank test, P < 0.001). After adjusting for confounding factors, the Cox regression model showed the risk of new-onset PDRP was higher in the HPG than that in the LPG (HR 1.689, 95%CI 1.096-2.602, P = 0.017). Competitive risk model analysis showed that significant differences still existed between the two PLR groups in the presence of other competitive events (P < 0.001). CONCLUSION: PLR is independently associated with the new-onset PDRP in PD patients.

Retracted Association of STAT4 gene polymorphism with systemic lupus erythematosus / lupus nephritis risk.

OBJECTIVE: The association of STAT4 gene polymorphism with systemic lupus erythematosus (SLE) / lupus nephritis (LN) results from the published studies is still conflicting. This meta-analysis was performed to evaluate the relationship between STAT4 rs7574865, rs16833431, rs11889341, rs8179673, rs10168266, rs7582694, rs3821236, rs7601754 gene polymorphism and SLE / LN, and to explore whether STAT4 gene polymorphism could become a predictive marker for SLE / LN risk. METHODS: Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2013, and eligible investigations were synthesized using meta-analysis method. RESULTS: 24 investigations were identified for the analysis of association between STAT4 gene polymorphism and SLE, consisting of 31190 patients with SLE and 43940 controls. In STAT4 rs7574865, there was a marked association between T allele or TT genotype and SLE susceptibility (T: OR=1.53, 95% CI: 1.30-1.79, P<0.00001; TT: OR=1.60, 95% CI: 1.34-1.92, P<0.00001), and GG homozygous was associated with SLE risk (OR=0.62, 95% CI: 0.51-0.75, P<0.00001). Furthermore, rs8179673, rs7582694, or rs3821236 minor allele frequency was associated with the risk of SLE, but this association was not found in rs16833431, rs11889341, rs10168266, rs7601754, however, the number of included studies was small and the results were less robust. In addition, STAT4 rs7574865 gene polymorphism was not associated with the LN risk. CONCLUSIONS: Our results indicate that T allele or TT homozygous is a significant risk genetic molecular marker to predict the SLE susceptibility and GG genotype is a valuable marker to against the SLE risk, but the association was not found for LN. However, more investigations are required to further clarify the association of the T allele or TT homozygous with SLE / LN susceptibility.

Higher D-dimer and activated partial thromboplastin time are poor prognostic factors in patients with peritoneal dialysis-related peritonitis.

INTRODUCTION: Coagulation system dysfunction is associated with adverse outcomes of peritoneal dialysis (PD) and bacterial infection. We investigated the association between coagulation system and treatment failure of peritoneal dialysis-related peritonitis (PDRP). METHODS: We collected records of patients aged ≥18 years with PDRP. PDRP episodes were divided into: shortened activated partial thromboplastin time (APTT) group and prolonged APTT group, low D-dimer (DD) group and high DD group. The baseline characteristics of the groups were collected and compared. The association between APTT, DD and treatment failure of PDRP was analyzed using logistic regression analysis. RESULTS: Thirty episodes of treatment failure were observed in 110 episodes of PDRP in our study. After adjusting for variables, prolonged APTT (OR = 1.166 [1.049-1.296], p = 0.004) or high level of DD (OR = 1.374 [1.057-1.787], p = 0.017) was associated with treatment failure of PDRP. CONCLUSION: Prolonged baseline APTT or high level of DD increased the risk of treatment failure of PDRP.

Comprehensive Analysis of CRIP1 Expression in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy that imposes great challenges in terms of drug resistance and relapse. Previous studies revealed heterogeneous leukemia cells and their relevant gene markers, such as CRIP1 as clinically prognostic in t (8;21) AML patients. However, the expression and role of CRIP1 in AML are poorly understood. We used the single-cell RNA sequencing and gene expression data from t (8;21) AML patients to analyze the immune and regulation networks of CRIP1. Two independent cohorts from GSE37642 and The Cancer Genome Atlas (TCGA) datasets were employed as validation cohorts. In addition, the methylation data from TCGA were used to analyze the methylation effect of the CRIP1 expression. Gene expression profile from t (8;21) AML patients showed that the CRIP1-high group exhibited an enrichment of immune-related pathways, including tumor necrosis factor (TNF)α signaling via nuclear factor kappa B (NFκB) pathways. Further studies using CIBERSORT showed that the CRIP1-high group had a significantly higher infiltration of exhausted CD8 T cells and activated mast cells. The CRIP1 expression was validated in the GSE37642-GPL96, GSE37642-GPL570, and TCGA datasets. In addition, with the methylation data, four CpG probes of CRIP1 (cg07065217, cg04411625, cg25682097, and 11763800) were identified as negatively associated with the CRIP1 gene expression in AML patients. Our data provide a comprehensive overview of the regulation of CRIP1 expression in AML patients. The evaluation of the TNFα-NFκB signaling pathway as well as the immune heterogeneity might provide new insights for exploring improvements in AML treatment.

Identification of the Thyrotropin-Releasing Hormone (TRH) as a Novel Biomarker in the Prognosis for Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a biologically and genetically heterogeneous hematological malignance with an unsatisfactory risk stratification system. Recently, through the novel single-cell RNA sequencing technology, we revealed heterogeneous leukemia myeloblasts in RUNX1-RUNX1T1 AML. Thyrotropin-releasing hormone (TRH), as biomarkers of CD34+CD117bri myeloblasts, were found to be prognostic in RUNX1-RUNX1T1 AML. However, the clinical and genetic features of TRH in AML patients are poorly understood. Here, with data from TCGA AML, TRH was found to be downregulated in patients older than 60 years old, with DNMT3A and NPM1 mutations, while overexpressed in patients with KIT mutations. This was further validated in three other cohorts of primary AML including Beat AML (n = 223), GSE6891 (n = 461), and GSE17855 (n = 237). Furthermore, we demonstrated that the expression of TRH in AML could be used to improve the ELN 2017 risk stratification system. In conclusion, our preliminary analysis revealed that TRH, a novel biomarker for AML patients, could be used to evaluate the survival of AML.

Casticin protected against neuronal injury and inhibited the TLR4/NF-κB pathway after middle cerebral artery occlusion in rats.

Although stroke is a major human neurological disease, there is a paucity of effective neuroprotectants that can improve its treatment. Casticin is a natural monomer drug with many biological effects such as anti-inflammatory and anti-tumor actions. However, it is not clear whether it has a neuroprotective effect in ischemic stroke. In this study, the neuroprotective effect of casticin in a rat middle cerebral artery occlusion (MCAO) model was investigated. Results showed that casticin reduced the volume of the cerebral infarction, mNSS scores, swimming distance, time to find the submerged platform, and serum concentrations of TNF-α, TGF-ß, IL-6 in MCAO rats. Moreover, casticin also decreased the expression of TLR4, NF-κB p65, and NF-κB p50 proteins and reversed the reduced expression of IκB protein in the brain tissue of MCAO rats. The in vitro study revealed that casticin decreased apoptosis of OGD/R-PC12 cells, reduced the expression of TLR4, NF-κB p65, and NF-κB p50, while increased IκB protein expression. In conclusion, casticin improved the neurological functions of MCAO rats via inhibiting the TLR4/NF-κB pathway and might have the potential to be developed into a neuroprotective agent for stroke patients.

Elevated baseline serum IgA may predict earlier proteinuria remission in IgA nephropathy patients.

The goals of this work were to investigate the correlations of elevated serum IgA with renal pathology and outcome of proteinuria in IgA nephropathy patients. Retrospective cohort analysis enrolled 90 IgA nephropathy patients (proteinuria ≥0.5 g/24 hr, estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2) who were admitted to The Sixth Affiliated Hospital of Sun Yat-sen University from 2013.01 to 2017.04. The elevated serum IgA level was found in 20 (22.2%) patients. In clinical characteristics, serum IgG, ratio of IgA/C3 and recurrent mucosal infection rate were increased obviously in high serum IgA group compared with normal serum IgA group (serum IgG, 14.90±3.50 g/L vs. 10.27±3.49 g/L, P<0.001, IgA/C3, 4.45±1.21 vs. 2.77±0.75, P<0.001, recurrent mucosae infection rate, 40.0% vs. 14.3%, P=0.027). In kidney biopsy, mesangial proliferation was significantly more common in normal serum IgA group (81% vs. 50% in high serum IgA group, P=0.028). The proportion of crescent less than 25% more often occurred in elevated IgA group (81.3% vs. 63.8% in normal IgA group). The Kaplan-Meier curves showed that proteinuria remission rate for patients with high serum IgA was 80%, 85%, 90%, 95% and 95% after 3, 6, 9, 12 and 15 months compared with patients with normal serum IgA (proteinuria remission rate, 45%, 64%, 75%, 86% and 93%, P=0.020). Cox proportional hazard regression model indicated that elevated serum IgA (RR=1.984, P=0.040) and steroids therapy (RR=2.192, P=0.030) were independent predictors for proteinuria remission in IgA nephropathy patients. In view of our data, more active treatments may improve outcome of IgA nephropathy patients with elevated serum IgA. We conclude that elevated serum IgA may indicate a higher proteinuria remission rate within a shorter period of time in IgA nephropathy patients.

RETRACTED: Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy.

The following article has been included in a multiple retraction: Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System ( JRAAS) 1470320314563424, first published 18 December 2014. DOI: 10.1177/1470320314563424 . This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the JRAAS (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer-review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online-first articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy JRAAS 1470320314563426, first published 18 December 2014. DOI: 10.1177/1470320314563426 . Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy JRAAS 1470320314563424, first published 18 December 2014. DOI: 10.1177/1470320314563424 . Weiqiang Zhong, Zongpei Jiang and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population JRAAS1470320314566019, first published 26 January 2015. DOI: 10.1177/1470320314566019 . Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population JRAAS 1470320314563425, first published 1 February 2015. DOI: 10.1177/1470320314563425 . Chun-Hua Yang and Tian-Biao Zhou Relationship between the angiotensinogen A1166C gene polymorphism and the risk of diabetes mellitus developing into diabetic nephropathy JRAAS 1470320314566221, first published 1 February 2015. DOI: 10.1177/1470320314566221 . Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression JRAAS 1470320314568521, first published 3 February 2015. DOI: 10.1177/1470320314568521 . Articles published in an issue Guohui Liu, Tian-Biao Zhou, Zongpei Jiang and Dongwen Zheng Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population JRAAS March 2015; 16: 165-171, first published 14 November 2014. DOI: 10.1177/1470320314557849 . Weiqiang Zhong, Zhongliang Huang, Yong Wu, Zongpei Jiang and Tian-Biao Zhou Association of aldosterone synthase ( CYP11B2) gene polymorphism with IgA nephropathy risk and progression of IgA nephropathy JRAAS September 2015; 16: 660-665, first published 20 August 2014. DOI: 10.1177/1470320314524011 .

Relationship between chemokine receptor 5 Δ32/W gene polymorphism and lupus nephritis.

Results from the published studies on the association between chemokine receptor 5 (CCR5) Δ32/W gene polymorphism and lupus nephritis (LN) are still conflicting. This meta-analysis was performed to evaluate the relationship between CCR5 Δ32/W gene polymorphism and LN and to explore whether CCR5 Δ32 allele, Δ32/Δ32 and W/W genotypes could become a predictive marker for systemic lupus erythematosus (SLE) developing into LN. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of March 1, 2014, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Five investigations were identified for the analysis of association between CCR5 Δ32/W gene polymorphism and LN. In the overall populations, Asians, Caucasian population, the association between CCR5 Δ32/W gene polymorphism and LN susceptibility was not found. Interestingly, a trend toward an association of Δ32 allele and W/W genotype with LN risk was observed in African population. However, this meta-analysis only included one study for the study in Africans. We also found that the gene distribution of CCR5 Δ32/W gene polymorphism between SLE group and LN group were not different. In conclusion, our results indicate that CCR5 Δ32/W gene polymorphism was not associated with LN risk and might be no a significant genetic molecular marker to predict the SLE patients developing into LN. However, more investigations are required to further clarify this association.