Outcome of patients with systemic light chain amyloidosis with concurrent renal and cardiac involvement

Cardiac involvement in systemic light chain amyloidosis (AL) is generally associated with a worse outcome, especially if other organs are also involved. We sought to determine whether concurrent cardiac and renal involvement were associated with a worse outcome than either organ alone. We identified 129 patients with AL, who received high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto‐HCT) at our institution between 1997 and 2014. Ninety‐nine patients had either renal (group 1: n = 62, 62%), cardiac (group 2: n = 20, 20%), or both cardiac and renal (group 3: n = 17, 17%) involvement. The overall hematological response rate (CR+VGPR+PR) post‐auto‐HCT in groups 1, 2, and 3 was 69%, 74% and 82%, respectively (P = 0.62). Overall, organ response in groups 1, 2, and 3 was 39%, 42%, and 70%, respectively. The median PFS from auto‐HCT in groups 1, 2, and 3 was not reached (NR), 13.3 and 21 months, respectively (P = 0.02). The median OS in groups 1, 2, and 3 was 120, 46, and 60 months, respectively (P = 0.1). In conclusion, median PFS and OS in patients with concurrent cardiac and renal AL were comparable to patients with cardiac AL only, but worse than patients with renal AL.     

The Changing Pattern of Renal Amyloidosis in Indian Subcontinent: Two Decades of Experience from a Single Center

Background: Renal amyloidosis is a major cause of morbidity and mortality among the patients of systemic amyloidosis. The causes of amyloidosis vary from country to country and from time to time at individual center. Aim: This study investigates the changes in epidemiological and clinical profile of renal amyloidosis in recent years. Method: Cases of biopsy-proven renal amyloidosis from January 1992 to December 2010 were studied retrospectively. They were divided into two groups: 1990s (between 1992 and 2002) and 2000s (between 2003 and 2010). The clinical characteristics of patients were studied and compared between the groups. Result: A total of 2498 (974 in 1990s and 1524 in 2000s) renal biopsies was done during the 19-year period. The incidence of amyloidosis in 1990s and 2000s was 1.74% (n = 17) and 1.9% (n = 29), respectively (p > 0.05). We noted that the incidence of renal amyloidosis increased significantly (p < 0.05) among the females in 2000s. The mean age of patients in 2000s and 1990s was 38 ± 17.9 and 39.2 ± 19 years, respectively (p = 0.83). Renal insufficiency in patients with renal amyloidosis significantly increased (p < 0.05) in 2000s (n = 14; 48.2%) in comparison to 1990s (n = 2; 12.8%). Subnephrotic proteinuria was observed in 12.8% (n = 2) and 48.82% (n = 14) of patients in 1990s and 2000s, respectively (p <?0.05). Infection (n = 10; 58.8%) was the most common cause of secondary amyloidosis during the 1990s, whereas chronic inflammation (n = 14; 48.2%) was the most common cause in 2000s. In 1990s, the incidence of ankylosing spondylitis (AS) and rheumatoid arthritis (RA) was 11.7% (n = 2) and 5.8% (n = 1), respectively, but in 2000s, their respective incidence was 17.2% (n = 5) each. Multiple myeloma (MM) was the most common cause of amyloid light chain protein (AL) amyloidosis in both the groups. We observed systemic lupus erythromatosus (SLE)-related renal amyloidosis in two cases and Hodgkin lymphoma-associated amyloidosis in one case in 2000s. Conclusion: The overall incidence of renal amyloidosis showed little change from 1990s to 2000s. Chronic inflammatory diseases were the most common cause of renal amyloidosis in 2000s in contrast to infections in 1990s. Female gender was more affected in 2000s than in 1990s. Renal insufficiency and subnephrotic-range proteinuria were more frequent clinical manifestations of renal amyloidosis in recent years (2000s) in comparison to the earlier decade (1990s).     

膀胱癌中miR-9对CBX7表达的调控作用

目的研究mi R-9在膀胱癌中对CBX7基因表达的调控作用及机制。方法应用荧光定量PCR方法检测膀胱癌及癌旁组织中mi R-9及CBX7基因的表达。培养膀胱癌T24细胞,转染mi R-9的前体pre-mi R-9,Western blot检测CBX7蛋白的表达。荧光素酶报告基因表达分析明确mi R-9与CBX7基因3'非翻译区(3'UTR)的结合。结果 mi R-9在膀胱癌组织中的表达较癌旁组织呈现显著的上调,而CBX7的表达则下调明显,二者的表达呈显著负相关。在转染后膀胱癌T24细胞中,pre-mi R-9能够分别下调T24细胞中CBX7蛋白的表达。荧光素酶报告基因表达分析明确mi R-9能够与CBX7基因的3'UTR结合并负性调节其表达。结论 mi R-9与CBX7基因的表达改变与膀胱癌相关,mi R-9能够在膀胱癌细胞中靶向负性调节CBX7基因的表达。     

The 24-h reporting of Gram stains from positive blood cultures contributes to physician's use of appropriate antimicrobials: Experience at a university hospital

Although recent technological advances for the diagnosis of bloodstream infection (BSI) provide rapid and accurate results, blood culture maintains a key role in the diagnosis of BSI. The objective of this study was to determine whether 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures (first laboratory report) affects a physician's use of appropriate antimicrobials. A total of 627 (14%) out of 4413 blood samples, excluding duplicate samples from the same patient on the same day, were positive for blood cultures between January and December 2016. The contamination rate of blood cultures during the study period was 2.3%. Among 627 patients with positive blood cultures, 538 (86%) were receiving antibiotics at the time of the first laboratory report, of which 502 (80%) thereafter continued the same antimicrobials, and the remaining 36 (6%) were changed to appropriate antimicrobials after the first laboratory report. An additional 25 (4%) were newly administered appropriate antimicrobials after the first laboratory report, whereas an additional 21 (3%) were newly administered appropriate antimicrobials after infection control team (ICT)-intervention. The median time lag (interquartile ranges) from flagging culture bottles as positive to a physician's use of appropriate antimicrobials after the first laboratory report (4 h, 2–7) was significantly (p < 0.001) shorter than that after ICT-intervention (12 h, 10–17). During the study period, no cases of discrepancy between the Gram stain morphology in the first laboratory report and definitive identification of microorganisms in the final laboratory report were observed. Because the timing of flagging culture bottles as positive tends to fall outside normal working hours, immediate 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures may contribute to an early recognition of bacteremia and the physician's use of appropriate antimicrobials.     

Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout

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大鼠脊髓圆锥损伤后大脑排尿功能区变化的实验研究

目的观察大鼠脊髓圆锥损伤后大脑排尿功能区结构变化和 Bcl-2 的表达情况，探讨大脑排尿功能区退变的可能因素。方法成年雌性 SD 大鼠 36 只，随机分为实验组（n=30）和对照组（n=6）。实验组将大鼠 L₄ 以下脊神经切断制作脊髓圆锥损伤模型，对照组不作任何处理。实验组大鼠手术全部成功，术后 3、5 个月分别死亡 1 只大鼠，原因可能是肾功能衰竭及尿路感染。实验组于术后 1 d、1 周以及 1、3、6 个月分别处死 6、6、6、5、5 只大鼠，对照组相同时间点各处死 1 只大鼠，取脑桥被盖背外侧部组织，行 HE 染色和 Bcl-2 免疫组织化学 SP 染色观察。 结果HE 染色示，术后 1 d，实验组和对照组无明显区别，神经元细胞密集，排列整齐，核仁清楚；1 周，实验组可见神经元细胞周围间隙稍增宽；1 个月，实验组部分神经元出现细胞核固缩；3、6 个月，实验组细胞核固缩的细胞越来越多，甚至部分细胞出现核消失。Bcl-2 免疫组织化学 SP 染色示，对照组 Bcl-2 表达呈弱阳性。实验组术后 1 d 即出现 Bcl-2 阳性表达，术后 7 d Bcl-2 阳性表达较对照组明显升高，并达高峰，术后 1、3、6 个月 Bcl-2 阳性表达逐渐下降，但仍高于对照组。结论大鼠脊髓圆锥损伤后大脑排尿中枢出现组织退变、细胞坏死，Bcl-2 表达升高可能与组织修复、大脑功能重塑有关。     

改良经椎间孔入路及后路腰椎椎间融合术治疗中老年轻中度腰椎滑脱症疗效比较

目的比较改良经椎间孔入路腰椎椎间融合术（transforaminal lumbar interbody fusion，TLIF）与后路腰椎椎间融合术（posterior lumbar interbody fusion，PLIF）治疗中老年轻中度腰椎滑脱症的手术疗效。方法回顾分析 2015 年 1 月—2017 年 1 月收治的符合选择标准的 106 例轻中度腰椎滑脱症（Meyerding 分度≤Ⅱ度）患者临床资料，根据手术方式不同分为改良 TLIF 组（54 例）及 PLIF 组（52 例）。两组患者性别、年龄、病程、滑脱椎体、Meyerding 分度及滑脱类型等一般资料比较，差异均无统计学意义（P>0.05）。记录并比较两组术中出血量、手术时间、术后引流量、术后卧床时间、住院时间、并发症等围术期相关指标。术前及术后 1 周，1、6、12 个月，末次随访时采用疼痛视觉模拟评分（VAS）和日本骨科协会（JOA）评分评价疼痛及功能改善情况，术前与末次随访时测量滑脱角与椎间隙高度评价椎体滑脱矫正情况，末次随访时根据 Suk 标准判定椎间融合情况。 结果所有患者均获随访，随访时间 A 组 25～36 个月，平均 32.7 个月；B 组 24～38 个月，平均 33.3 个月。改良 TLIF 组术中出血量、手术时间、术后引流量、术后卧床时间和住院时间均显著少于 PLIF 组（P<0.05）。两组患者术后各时间点 VAS 评分和 JOA 评分均较术前显著改善（P<0.05）；术后 1、6 个月改良 TLIF 组 VAS 评分和 JOA 评分显著优于 PLIF 组（P<0.05）。两组患者末次随访时滑脱角及椎间隙高度均较术前显著改善（P<0.05）；术前及末次随访时两组间滑脱角及椎间隙高度比较差异均无统计学意义（P>0.05）。末次随访时根据 Suk 标准，改良 TLIF 组椎间融合率为 96.3%（52/54），PLIF 组为 98.1%（51/52），两组比较差异无统计学意义（χ²=0.000，P=1.000）。并发症：两组患者切口感染、肺部感染及术后 1 周内健侧神经损伤发生率比较差异均无统计学意义（P>0.05）；改良 TLIF 组均未发生术中硬脊膜损伤及术后 1 周内患侧神经损伤，PLIF 组分别发生 4 例（7.7%，P=0.054）和 8 例（15.4%，P=0.002）。 结论改良 TLIF 与 PLIF 手术治疗中老年轻中度腰椎滑脱症疗效肯定，改良 TLIF 手术对脊柱后柱正常结构损伤小、出血量和引流量少，硬脊膜和神经损伤发生率低，可改善术后疼痛，促进患者术后快速康复。     

Lipocalin-2-loaded Amphiphilic Polyanhydride Microparticles Accelerate Cell Migration

This work demonstrates that amphiphilic polyanhydride microparticles based on co-polymers of 1,6-bis(p-carboxyphenoxy)hexane (CPH) and 1,6-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) provide stabilizing environments for proteins. A cryogenic atomization method was used to fabricate protein-loaded polyanhydride microparticles. These microparticles were tested for their ability to provide controlled delivery of lipocalin 2 (Lcn2) and to maintain its structure and function. Lcn2 is an acute-phase protein suspected to play a role in cell migration and tissue repair. The in vitro release kinetics of Lcn2 from the microparticles were a function of the chemistry of the polymer carrier. The biological activity of Lcn2 released from polyanhydride microparticles was investigated by its ability to stimulate migration of human colon epithelial cells (HCT116). Lcn2 released from 50:50 and 20:80 CPTEG/CPH microparticles maintained its biological activity as demonstrated by the increased rate of cell migration. In addition, the Lcn2-loaded 50:50 and 20:80 CPTEG/CPH microparticles promoted cell migration over that of the Lcn2 administered alone. This was interpreted as the ability of the amphiphilic microparticles to stabilize the encapsulated protein and release it in a controlled manner over a period of time. This work demonstrates the potential for therapeutic use of amphiphilic polyanhydride microparticles as protein/drug carriers.     

益气清利活血祛风药对治疗肾性蛋白尿临证撷英

周恩超教授从医20余载,擅长肾系疾病的中医诊治,尤其对肾性蛋白尿的治疗有较丰富的经验。他治疗肾性蛋白尿善用药对,本文介绍生黄芪-太子参,菟丝子-枸杞子,葎草-白英,桃仁-红花,桔梗-僵蚕,全蝎-地龙6组药对在治疗肾性蛋白尿中的应用。