Methicillin-resistant Staphylococcus aureus in children with cystic fibrosis: An eradication protocol

A retrospective 12-year study (May 1988-July 2000) was undertaken in children with cystic fibrosis (CF) to evaluate 1) the magnitude of methicillin-resistant Staphylococcus aureus (MRSA) in these children; 2) the clinical impact of MRSA on CF; and 3) the efficacy of an MRSA protocol aimed at the eradication of the carrier state. The study maneuver comprised of 1) surveillance cultures of throat/rectum to detect the MRSA carrier state; 2) life-long cephradine rather than flucloxacillin to lift selection pressure; 3) topical application of oral and nebulized vancomycin for 5 days to clear the carriage of MRSA; and 4) a strict antistaphylococcal hygiene program, including handwashing and device policy. Fifteen children with CF (11 boys, with median age 117 months) positive for MRSA were enrolled. The current prevalence of MRSA among children with CF in our hospital is 6.5%. Of 15 children identified, only 12 (18 episodes of MRSA colonization) were treated according to protocol. Median age of MRSA acquisition was 73 months (interquartile range, 43-134 months). In 7 patients (55%), MRSA was eradicated. Of a total of 18 MRSA episodes, the protocol was successful in 10 episodes. The mean period of MRSA-free status was 12 months (range, 6-36 months). Pulmonary function (measured by FEV(1)) was not affected (68% of predicted before treatment, and 68% of predicted after treatment). All children were oropharyngeal carriers of both MRSA and ceftazidime-resistant P. aeruginosa. We believe that an effort has to be made to limit MRSA in CF clinics for the following reasons: 1) MRSA carriage in any individual is an abnormal condition; 2) limitation of systemic vancomycin use is desirable; 3) MRSA carriage may be a contraindication for lung transplantation; and 4) epidemiologically, a CF unit with a substantial MRSA problem functions as a source of dissemination for other patients.     

Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid–Resistant Nephrotic Syndrome

Background and objectives

Treatment of congenital nephrotic syndrome (CNS) and steroid–resistant nephrotic syndrome (SRNS) is demanding, and renal prognosis is poor. Numerous causative gene mutations have been identified in SRNS that affect the renal podocyte. In the era of high–throughput sequencing techniques, patients with nongenetic SRNS frequently escape the scientific interest. We here present the long-term data of the German CNS/SRNS Follow-Up Study, focusing on the response to cyclosporin A (CsA) in patients with nongenetic versus genetic disease.

Design, setting, participants, & measurements

Cross–sectional and longitudinal clinical data were collected from 231 patients with CNS/SRNS treated at eight university pediatric nephrology units with a median observation time of 113 months (interquartile range, 50–178). Genotyping was performed systematically in all patients.

Results

The overall mutation detection rate was high at 57% (97% in CNS and 41% in SRNS); 85% of all mutations were identified by the analysis of three single genes only (NPHS1, NPHS2, and WT1), accounting for 92% of all mutations in patients with CNS and 79% of all mutations in patients with SRNS. Remission of the disease in nongenetic SRNS was observed in 78% of patients after a median treatment period of 2.5 months; 82% of nongenetic patients responded within 6 months of therapy, and 98% of patients with nongenetic SRNS and CsA–induced complete remission (normalbuminemia and no proteinuria) maintained a normal renal function. Genetic SRNS, on the contrary, is associated with a high rate of ESRD in 66% of patients. Only 3% of patients with genetic SRNS experienced a complete remission and 16% of patients with genetic SRNS experienced a partial remission after CsA therapy.

Conclusions

The efficacy of CsA is high in nonhereditary SRNS, with an excellent prognosis of renal function in the large majority of patients. CsA should be given for a minimum period of 6 months in these patients with nongenetic SRNS. In genetic SRNS, response to CsA was low and restricted to exceptional patients.     

耐甲氧西林金黄色葡萄球菌在医院的临床分布与耐药性研究

目的探讨辽河油田总医院耐甲氧西林金黄色葡萄球菌(MRSA)临床分布及耐药性特征,指导该院临床合理用药。方法对辽河油田总医院2012年1月至2013年12月临床分离的51株耐甲氧西林金黄色葡萄球菌(MRSA)标本,运用LIS系统进行回顾性分析。结果 MRSA分离率占金黄色葡萄球菌的20.6%,标本以痰及分泌物检出率最高,主要侧重于ICU及呼吸内科,对临床常用抗菌药物具有多重耐药性。结论辽河油田总医院MRSA的分离率及耐药率均较高,MRSA表现为多重耐药性,临床各科室要合理使用抗菌药物并采取有效措施以预防和控制院内感染。     

Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations

Prostate cancer (PCa) is a hormone-sensitive disease. Androgen deprivation therapy lowers serum testosterone levels (castration) or blocks the androgen receptor (AR) ligand-binding domain. Especially in metastatic disease, hormonal therapy has been able to delay disease progression, reduce symptoms, and improve overall survival. Despite subsequent disease progression and development of castration resistance, PCa remains AR driven. Secondary hormonal treatments such as abiraterone acetate or enzalutamide have demonstrated increased overall survival. However, new resistance mechanisms to these agents have been identified, and systemic chemotherapy is still needed especially in fast-progressing castration-resistant PCa. Several promising androgen synthesis inhibitors (orteronel and galeterone), AR inhibitors (ARN-509, EPI-001, AZD3514, and ODM-201), and heat shock protein modulators (AT11387, 17-DMAG, STA-9090, and OGX-427) are currently under investigation. The wide variety in upcoming systemic agents underlines the molecular heterogeneity of castration-resistant PCa. This article reviews antihormonal therapy in PCa and resistance mechanisms and focuses on novel and upcoming agents currently in clinical testing.     

Implementing newer agents for the management of castrate‐resistant prostate cancer: what is known and what is needed?

Men receiving androgen‐deprivation therapy will in time develop metastatic castrate‐resistant prostate cancer (mCRPC). Whilst effective treatment options for mCRPC have traditionally been limited, new agents are becoming available. Since 2010, the number and class of agents available to treat mCRPC has increased dramatically. As such, there is a need for clear guidance on the optimum treatment and sequence of treatments for mCRPC before and after chemotherapy. This evidence‐based statement, reflecting the views of the authors, provides suggestions on the continued relevance of conventional approaches to first‐ and second‐line treatment in mCRPC, the potential role of novel treatments, and factors that may influence the choice of hormonal agents and/or chemotherapy.     

骨松汤对去卵巢小鼠骨质疏松影响的实验研究

目的:建立去卵巢小鼠骨质疏松模型,观察骨松汤对去卵巢小鼠骨质疏松骨代谢指标及骨密度的影响,并探讨骨松汤对去卵巢骨质疏松影响的机制。方法:将40只雌性小鼠随机分为空白组、模型组、骨松汤组、钙尔奇组,每组各10只。除空白组外,其余各组经双侧卵巢切除术建立骨质疏松小鼠模型。骨松汤组在造模后灌胃骨松汤水煎剂每天早晚各3 m L(1.72 g/10 g),钙尔奇组给予钙尔奇灌胃每天早晚各3 m L(0.42 g/10 g)、空白组和模型组灌胃等量生理盐水,共12 w。12 w后测各组定小鼠血清碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRAP)、骨钙素(BGP)和雌二醇(E2)及骨密度。结果:1.血清碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRAP)、骨钙素(BGP)和血清雌二醇(E2):骨松汤组治疗前后比较血清碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRAP)、骨钙素(BGP)明显降低,雌二醇(E2)明显升高,P0.05,差异显著,有统计学意义。钙尔奇组治疗前后比较的血清碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRAP)、骨钙素(BGP)明显降低,雌二醇(E2)明显升高,P0.05,差异显著,有统计学意义。治疗后骨松汤组和钙尔奇组2组比较,血清碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRAP)、骨钙素(BGP)明显降低,雌二醇(E2)明显升高,P0.05,差异显著,有统计学意义。骨松汤可以升高去卵巢小鼠骨质疏松的血清雌二醇(E2),降低血清碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRAP)、骨钙素(BGP),改善去卵巢骨质疏松小鼠骨密度。2.骨密度:治疗后骨松汤组和钙尔奇组的骨密度与空白组接近,与模型组相比差异显著,有统计学意义。2组组间比较差异显著,P0.05。结论:骨松汤可以改善去卵巢小鼠骨密度,其机制与其减缓雌激素水平有关。