Mannose-derived FimH antagonists: a promising anti-virulence therapeutic strategy for urinary tract infections and Crohn’s disease

Introduction: Type 1 pili are utilized by Gram-negative bacteria to adhere to host tissue and thus are a key virulence factor in urinary tract infections (UTIs) and Crohn’s disease (CD). This adhesion is mediated through specific binding of the terminal adhesin, FimH, to mannosylated host glycoproteins. FimH is essential for UTI pathogenesis and thus is a promising therapeutic target.

Areas Covered: Herein, we review the structural frameworks of FimH antagonists disclosed in the patent literature. X-ray crystallographic binding studies of D-mannose and early FimH antagonists have uncovered key molecular interactions. Exploiting this knowledge, mannosides with extraordinarily high binding affinities have been designed. Structure-activity relationships (SAR) and structure-property relationship (SPR) studies have resulted in the rapid development of orally bioavailable FimH antagonists with promising therapeutic potential for UTI and CD.

Expert opinion: It is our opinion that biaryl or ‘two-ring’ mannosides, which represent the largest and most thoroughly tested class of FimH antagonists, also hold the most promise as a novel treatment for UTIs. These antagonists have also been shown to have efficacy in treating CD. Judging from the strong preclinical data, we predict that one or more FimH antagonists will be entering the clinic within the next 1–2 years.     

三项尿蛋白相关检测在肾小球疾病中的诊断价值

目的探讨24小时尿蛋白、肾病指数及尿蛋白肌酐比对肾小球疾病的诊断价值。方法选取四川大学华西医院收治的疑似肾小球疾病患者71例(观察组),同期健康体检者71例(对照组),检测24小时尿蛋白、肾病指数及尿蛋白肌酐比情况。结果观察组三项尿蛋白相关测定诊断的准确度、灵敏度、特异度比较,差异无统计学意义(P>0.05);观察组三项尿蛋白检测水平均高于对照组(P<0.05)。观察组24小时尿蛋白与尿蛋白肌酐比、肾病指数呈正相关(P<0.05)。结论三项尿蛋白相关测定均可完成对肾小球疾病患者病情的掌握程度,可根据患者实际情况选择适宜的检测方法,提升检测效率。     

经尿道前列腺切除术后尿路感染的危险因素及病原菌分布

 目的 探讨经尿道前列腺电切术（TURP）后尿路感染的危险因素及病原菌构成特征。方法 回顾性收集某院泌尿外科良性前列腺增生行TURP患者的临床资料，采用单因素和多因素logistic回归分析TURP术后尿路感染的危险因素，并分析患者尿标本中病原菌构成情况。结果 155例接受TURP患者中，24例患者（15.5%）发生术后尿路感染。单因素分析结果显示，尿路感染组与非感染组患者年龄、前列腺大小、术前留置导尿管，曾行泌尿道医疗操作、糖尿病史、电切镜鞘尺寸、手术时间和灌洗液温度各项比较，差异均有统计学意义（均P<0.05）；多因素logistic回归分析结果显示，患者的年龄>65岁（OR=4.18，95% CI：1.19~14.75，P=0.026）、前列腺>55 g（OR=3.92，95% CI：1.11~13.83，P=0.034）、术前留置导尿管（OR=0.28，95% CI：0.11~0.70，P=0.006）、曾行泌尿道医疗操作（OR=4.70，95% CI：1.85~11.94，P=0.001）、有糖尿病史（OR=2.54，95% CI：1.00~6.48，P=0.050）、电切镜鞘尺寸26F（OR=9.05，95% CI：1.18~69.48，P=0.034）、手术时间>60 min（OR=10.48，95% CI：1.37~80.25，P=0.024）和灌洗液温度<37℃（OR=4.06，95% CI：1.57~10.50，P=0.004）是TURP术后尿路感染的独立危险因素。感染患者尿标本共检出病原菌23株，主要为革兰阴性菌（78.26%），其中大肠埃希菌占比达52.17%（12株）。结论 TURP术后尿路感染与手术时间、电切镜鞘尺寸、曾有泌尿道医疗操作、前列腺大小等相关，感染病原菌仍以大肠埃希菌为主，有效避免高危因素及合理预防性使用抗菌药物，可有助于预防TURP术后尿路感染的发生。     

Modified technique for robot-assisted laparoscopic infantile ureteral reimplantation for obstructive megaureter

PurposeTo describe a novel modification of technique to improve efficacy of robot-assisted laparoscopic extravesical ureteral reimplantation (RALUR-EV) in infants.Materials and methodsBetween April 2017 and July 2019, sixteen infants with primary obstructive megaureter (POM) (Age range: 4–12 months) underwent robot-assisted ureteral reimplantation were reviewed in this series. In addition to the conventional Lich-Gregoir technique, the detrusor tunnel has been extended to the mobilized anterior bladder wall to guarantee sufficient tunnel length/ureter diameter ratio and avoid ureteral angulation. All patients underwent repeated ultrasound, diuretic renal dynamic imaging and voiding cystourethrography (VCUG) perioperatively and the outcomes were documented.ResultsAll operations were completed with robotic assisted approach without conversion. Bilateral and unilateral reimplantation were respectively performed in two and fourteen patients. The mean operative time was 115.0 ± 19.5 min and the mean blood loss was 10.0 ± 1.8 ml. There were no high-grade complications (III–IV on Clavien-Dindo classification) except for one patient. The distal ureteric diameter was reduced from pre operative 1.7 ± 0.5 to 0.6 ± 0.5 cm 6 months post operatively (p < 0.05). One child (6.3%) required the second reimplantation for stenosis. The overall operative success rate was 94.4% (17 of 18 ureters) with a mean follow-up of 15.9 ± 7.4 months with no flux detected.ConclusionOur preliminary experience suggests that our modified robot-assisted laparoscopic extravesical ureteral reimplantation is feasible in infants with good results.