Time-average albumin predicts the long-term prognosis of IgA nephropathy patients achieved remission

Objective To clarify the long-term renal prognosis and related risk factors of progression for IgA nephropathy (IgAN) patients who achieved remission under current therapy. To identify the target value of the serum albumin level for Chinese patients with IgAN. Methods The patients with biopsy-proven primary IgAN in Nephrology Department of Renji Hospital in Shanghai were studied．The survival of renal and the relationships between clinical parameters and renal outcome were assessed. Results A total of 369 patients between Jan 2005 and Dec 2010 were included with a median follow-up time of 49.0 (38.0-65.8) months. All the subjects had achieved a complete remission (CR) or partial remission (PR) following six months’ therapy after diagnosis. Progressive renal disease had occurred in 61 cases at the end of follow-up. Three variables had a significant independent effect on renal outcome in patients achieving remission under current therapy regimen for IgAN, including time-average serum creatinine (TA-Scr) [HR(95%CI): 1.03(1.01-1.04)], time-average serum albumin (TA-Alb) [HR(95%CI): 0.83 (0.69-0.99)], and eGFR ratio within one year [HR(95%CI): 0.00(0.00-0.01)]. By multivariate Cox analyses, each 1 g/L drop of TA-Alb was related with 17.2% increase in the risk of renal progression. The ROC curve indicated that combination of serum albumin at baseline and during a long-term had a more significant value in prediction of renal outcome than independent predictor alone. By Kaplan-Meier analyses, patients with TA-Alb﹤38 g/L had a 10.4 fold sincreased risk of progressive disease compared with that of TA-Alb﹥38 g/L. Conclusions IgAN patients with lower eGFR ratio, higher TA-Scr and lower TA-Alb would progress to ESRD more quickly, and serum albumin during follow-up is important for predicting IgAN progression.     

Inhibition of Nucleic Acid Biosynthesis Makes Little Difference to Formation of Amphotericin B-Tolerant Persisters in Candida albicans Biofilm

Candida albicans persisters constitute a small subpopulation of biofilm cells and play a major role in recalcitrant chronic candidiasis; however, the mechanism underlying persister formation remains unclear. Persisters are often described as dormant, multidrug-tolerant, nongrowing cells. Persister cells are difficult to isolate and study not only due to their low levels in C. albicans biofilms but also due to their transient, reversible phenotype. In this study, we tried to induce persister formation by inducing C. albicans cells into a dormant state. C. albicans cells were pretreated with 5-fluorocytosine (planktonic cells, 0.8 μg ml⁻¹; biofilm cells, 1 μg ml⁻¹) for 6 h at 37°C, which inhibits nucleic acid and protein synthesis. Biofilms and planktonic cultures of eight C. albicans strains were surveyed for persisters after amphotericin B treatment (100 μg ml⁻¹ for 24 h) and CFU assay. None of the planktonic cultures, with or without 5-fluorocytosine pretreatment, contained persisters. Persister cells were found in biofilms of all tested C. albicans strains, representing approximately 0.01 to 1.93% of the total population. However, the persister levels were not significantly increased in C. albicans biofilms pretreated with 5-fluorocytosine. These results suggest that inhibition of nucleic acid synthesis did not seem to increase the formation of amphotericin B-tolerant persisters in C. albicans biofilms.     

Assessment of Time to Clinical Response,a Proxy for Discharge Readiness,among Hospitalized Patients with Community-Acquired Pneumonia Who Received either Ceftaroline Fosamil or Ceftriaxone in Two Phase III FOCUS Trials

The primary driver of health care costs for patients with community-acquired pneumonia (CAP) is the hospital length of stay (LOS). Unfortunately, hospital LOS comparisons are difficult to make from phase III CAP trials because of their structured designs and prespecified treatment durations. However, an opportunity still exists to draw inferences about potential LOS differences between treatments through the use of surrogates for hospital discharge. The intent of this study was to quantify the time to a clinical response, a proxy for the time to discharge readiness, among hospitalized CAP patients who received either ceftaroline or ceftriaxone in two phase III CAP FOCUS clinical trials. On the basis of the Infectious Diseases Society of America and American Thoracic Society CAP management guidelines and recent FDA guidance documents for community-acquired bacterial pneumonia, a post hoc adjudication algorithm was constructed a priori to compare the time to a clinical response, a proxy for the time to discharge readiness, between patients who received ceftaroline or ceftriaxone. Overall, 1,116 patients (ceftaroline, n = 562; ceftriaxone, n = 554) from the pooled FOCUS trials met the selection criteria for this analysis. Kaplan-Meier analyses showed that ceftaroline was associated with a shorter time, measured in days, to meeting the clinical response criteria (P = 0.03). Of the patients on ceftaroline, 61.0, 76.1, and 83.6% achieved a clinical response by days 3, 4, and 5, compared to 54.3, 69.8, and 79.3% of the ceftriaxone-treated patients. In the Cox regression, ceftaroline was associated with a shorter time to a clinical response (HR, 1.16, P = 0.02). The methodology employed here provides a framework to draw comparative effectiveness inferences from phase III CAP efficacy trials. (The FOCUS trials whose data were analyzed in this study have been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT00621504","term_id":"NCT00621504"}}NCT00621504 and {"type":"clinical-trial","attrs":{"text":"NCT00509106","term_id":"NCT00509106"}}NCT00509106.)     

IL-25 Elicits Innate Lymphoid Cells and Multipotent Progenitor Type 2 Cells That Reduce Renal Ischemic/Reperfusion Injury

IL-25 is an important immune regulator that can promote Th2 immune response-dependent immunity, inflammation, and tissue repair in asthma, intestinal infection, and autoimmune diseases. In this study, we examined the effects of IL-25 in renal ischemic/reperfusion injury (IRI). Treating IRI mice with IL-25 significantly improved renal function and reduced renal injury. Furthermore, IL-25 treatment increased the levels of IL-4, IL-5, and IL-13 in serum and kidney and promoted induction of alternatively activated (M2) macrophages in kidney. Notably, IL-25 treatment also increased the frequency of type 2 innate lymphoid cells (ILC2s) and multipotent progenitor type 2 (MPP^type2) cells in kidney. IL-25–responsive ILC2 and MPP^type2 cells produced greater amounts of Th2 cytokines that associated with the induction of M2 macrophages and suppression of classically activated (M1) macrophages in vitro. Finally, adoptive transfer of ILC2s or MPP^type2 cells not only reduced renal functional and histologic injury in IRI mice but also induced M2 macrophages in kidney. In conclusion, our data identify a mechanism whereby IL-25-elicited ILC2 and MPP^type2 cells regulate macrophage phenotype in kidney and prevent renal IRI.     

HIFU“帽式”消融方法的可行性研究

目的探索高强度聚焦超声"帽式"消融兔肝组织的可行性。方法将60只健康新西兰白兔分为A、B两组,每组30只,A组根据采用功率的不同分为A1(200 W,10只)、A2(250 W,10只)、A3(300 W,10只)3个亚组;B组根据两个辐照面的夹角不同分为B1(55°,10只)、B2(90°,10只)、B3(125°,10只)三个亚组,分别辐照兔肝组织。计算总辐照时间和超声能量,观察凝固性坏死体积大小、形态变化。结果 A2亚组能形成连续线状坏死,并能组成均匀规则的椭球形坏死体;B1亚组凝固性坏死体积为(3907.85±565.53)mm3,沿近声场形成的长轴与垂直于近声场所形成的短轴(长/短轴)之比为2.14±0.25;B2亚组凝固性坏死体积为(4431.49±721.36)mm3,其长/短轴比值为1.47±0.26;B3亚组产生的凝固性坏死大小为(3729.46±1049.29)mm3,长/短轴比值为1.06±0.12。结论 "帽式"消融方法能有效缩短辐照时间,减少能量的过度投放,降低或减少副反应的发生。     

Direct sequencing of SARS-coronavirus S and N genes from clinical specimens shows limited variation

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged, in November 2002, as a novel agent causing severe respiratory illness. To study sequence variation in the SARS-CoV genome, we determined the nucleic acid sequence of the S and N genes directly from clinical specimens from 10 patients--1 specimen with no matched SARS-CoV isolate, from 2 patients; multiple specimens from 3 patients; and matched clinical-specimen/cell-culture-isolate pairs from 6 patients. We identified 3 nucleotide substitutions that were most likely due to natural variation and 2 substitutions that arose after cell-culture passage of the virus. These data demonstrate the overall stability of the S and N genes of SARS-CoV over 3 months during which a minimum of 4 generations for transmission events occurred. These findings are a part of the expanding investigation of the evolution of how this virus adapts to a new host.     

MRI和高频超声对踝关节外侧副韧带损伤的诊断价值比较

目的:探讨MPd和高频超声对踝关节外侧副韧带损伤的诊断价值。材料与方法:采用1.5T磁共振及高频超声对95例临床怀疑踝关节侧副韧带损伤患者进行检查,对54例经手术治疗患者的检查结果与手术结果进行比较。结果:以手术结果为标准MPd诊断韧带损伤的敏感性、特异性、准确率分别为92%,100%,95%;超声诊断韧带损伤的敏感性、特异性、准确率分别为84%,93%,88%;54例侧副韧带损伤中,Ⅱ级损伤20例,Ⅲ级损伤34例,以手术结果为标准,高频超声诊断韧带Ⅱ、Ⅲ级损伤的符合率为70%,85%,MRI诊断韧带Ⅱ、Ⅲ级损伤的符合率为75%,94%。结论:MRI和高频超声对于踝关节外侧副韧带损伤的诊断均具有有较高的诊断效能,有助于准确分期,为临床早期治疗及康复提供客观依据。