Toxic megacolon associated Clostridium difficile colitis

Toxic megacolon is a severe complication of Clostridium difficile (C.difficile) colitis.As the prevalence of C. difficile colitis increases and treatments become more refractory, clinicians will encounter more patients with C. difficile associated toxic megacolon in the future. Here, we review a case of toxic megacolon secondary to C. difficile colitis and review the current literature on diagnosis and management. We identify both clinical and radiologic criteria for diagnosis and discuss both medical and surgical options for management. Ultimately, we recommend using the Jalen criteria in conjunction with daily abdominal radiographs to help establish the diagnosis of toxic megacolon and to make appropriate treatment recommendations. Aggressive medical management using supportive measures and antibiotics should remain the mainstay of treatment. Surgical intervention should be considered if the patient does not clinically improve within 2-3 d of initial treatment.

Deciphering the dual role and prognostic potential of PINK1 across cancer types

Metabolic rewiring and deregulation of the cell cycle are hallmarks shared by many cancers.Concerted mutations in key tumor suppressor genes,such as PTEN,and oncogenes predispose cancer cells for marked utilization of resources to fuel accelerated cell proliferation and chemotherapeutic resistance.Mounting research has demonstrated that PTEN-induced putative kinase 1(PINK1)acts as a pivotal regulator of mitochondrial homeostasis in several cancer types,a function that also extends to the regulation of tumor cell proliferative capacity.In addition,involvement of PINK1 in modulating inflammatory responses has been highlighted by recent studies,further expounding PINK1’s multifunctional nature.This review discusses the oncogenic roles of PINK1 in multiple tumor cell types,with an emphasis on maintenance of mitochondrial homeostasis,while also evaluating literature suggesting a dual oncolytic mechanism based on PINK1’s modulation of the Warburg effect.From a clinical standpoint,its expression may also dictate the response to genotoxic stressors commonly used to treat multiple malignancies.By detailing the evidence suggesting that PINK1 possesses distinct prognostic value in the clinical setting and reviewing the duality of PINK1 function in a context-dependent manner,we present avenues for future studies of this dynamic protein.

抗生素治疗对冠心病患者预后的影响:对随机对照试验的荟萃分析

Context Although Chlamydia pneumoniae infection has been associated with the initiation and progression of atherosclerosis, results of clinical trials investigating antichlamydial antibiotics as adjuncts to standard therapy in patients with coronary artery disease(CAD) have been inconsistent. Objective To conduct a meta-analysis of clinical trials of antichlamydial antibiotic therapy in patients with CAD. Data Sources The MEDLINE and Cochrane Central Register of Controlled Trials databases were searched from 1966 to April 2005 for English-language trials of antibiotic therapy in patients with CAD. Bibliographies of retrieved articles were searched for further studies. Presentations at major scientific meetings(2003-2004) were also reviewed. Search terms included antibacterial agents, myocardial infarction, unstable angina, and coronary arteriosclerosis. Study Selection Eligible studies were prospective, randomized, placebo-controlled trials of antichlamydial antibiotic therapy in patients with CAD that reported all-cause mortality, myocardial infarction, or unstable angina. Of the 110 potentially relevant articles identified, 11 reports enrolling 19217 patients were included. Data Extraction Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points. End points of interest included all-cause mortality, myocardial infarction(MI), and a combined end point of Ml and unstable angina. Data Synthesis Event rates were combined using a random-effects model. Antibiotic therapy had no impact on all-cause mortality among treated vs untreated patients(4.7%vs 4.6%; odds ratio OR , 1.02; 95%confidence interval CI , 0.89-1.16; P=.83), on the rates of MI(5.0%vs 5.4%; OR, 0.92; 95%CI, 0.81-1.04; P=.19), or on the combined end point of MI and unstable angina(9.2%vs 9.6%; OR, 0.91; 95%CI, 0.76-1.07; P=.25). Conclusion Evidence available to date does not demonstrate an overall benefit of antibiotic therapy in reducing mortality or cardiovascular events in patients with CAD.

小剂量阿司匹林在稳定型心血管疾病患者中的使用:一项荟萃分析

在心血管疾病和血栓形成的病理生理学中,血小板的重要性不言而喻[1-5].具有抗血小板活性的药物可降低心血管疾病的患病率和死亡率,这在不同类型的患者中都已得到了证实[6-11].

Comparative analysis of the effectiveness of abiraterone before and after docetaxel in patients with metastatic castration-resistant prostate cancer

AIM: To study the efficacy and safety of abiraterone in patients with and without prior chemotherapy.METHODS: The databases including Pub Med and abstracts presented at the American Society of Clinical Oncology meetings up to April 2014 were systematically searched. Eligible studies included randomized controlled trials(RCTs) in which abiraterone plus prednisone was compared to placebo plus prednisone in metastatic castration-resistant prostate cancer(CRPC) patients. The summary incidence, relative risk, hazard ratio and 95%CI were calculated using random or fixed-effects models. Heterogeneity test was performed to test between-study differences in efficacy and toxicity.RESULTS: A total of two phase III RCTs were included in our analysis, with metastatic CPRC patients before(n = 1088) and after chemotherapy(n = 1195). Prior chemotherapy did not significantly alter the effect of abiraterone on overall survival(P = 0.92) and prostatespecific antigen(PSA) progression-free survival(P = 0.13), but reduced its effect on radiographic-prog-ression-free survival(P = 0.04), objective response rate(P < 0.001), and PSA response rate(P < 0.001). Prior chemotherapy significantly increased the specific risk of fluid retention and edema(P < 0.001) and hypokalemia(P < 0.001), but decreased the risk of all-grade hypertension(P < 0.001) attributable to abiraterone. There was no significant difference of cardiac disorders associated with abiraterone between the two settings(P = 0.58). CONCLUSION: Prior chemotherapy may reduce the effectiveness of abiraterone in patients with metastatic CRPC.

Role of leptin in the progression of psoriatic,rheumatoid and osteoarthritis

Leptin,an adipokine responsible for body weight regulation,may be involved in pathological processesrelated to inflammation in joint disorders including rheumatoid arthritis(RA),osteoarthritis,and psoriatic arthritis(PsA).These arthropathies have been associated with a wide range of systemic and inflammatory con-ditions including cardiovascular disease,obesity,and metabolic syndrome.As a potent mediator of immune responses,leptin has been found in some studies to play a role in these disorders.Furthermore,current potent biologic treatments effectively used in Ps A including ustekinumab(an interleukin 12/23 blocker) and ada-limumab(a tumor necrosis factor-alpha blocker also used in RA) have been found to increase leptin receptor expression in human macrophages.This literature review aims to further investigate the role leptin may play in the disease activity of these arthropathies.

Does Current Nephrology Fellowship Training Affect Uti-lization of Peritoneal Dialysis in the United States?

Background: The 2010 US Renal Data System annual report revealed that peritoneal dialysis is used by only 7% of end-stage renal disease patients on chronic dialysis vs. hemodialysis which is used by 93% of such patients, despite documented benefits of peritoneal dialysis over hemodialysis in these cases. Purpose: We examined whether education of nephrology fellows contributed to underutilization of peritoneal dialysis in the US. Methods: Self-report questionnaires were administered electronically to nephrology fellowship training program directors, October 2010-March 2011 (55% response). Results: Median number of training faculty and patients/fellow were significantly lower for peritoneal-dialysis vs. hemodialysis training. Hours of didactic teaching for fellows over their 2-year training period were significantly lower for peritoneal dialysis vs. hemodialysis. Peritoneal dialysis training was 20% of total training vs. 80% for hemodialysis. Most program directors (87%) believed lack of trained faculty in peritoneal dialysis and insufficient peritoneal dialysis patient population contributed to inadequate fellows’ peritoneal dialysis training. Conclusions: Findings suggest that current nephrology fellowship training in peritoneal dialysis is inadequate and contributes to its underutilization.

Anesthesia Management for Pulmonary Cryoablation

Lung tumors represent a major health impact globally. Pulmonary cryoablation treatment as a palliative measure for patients with non-operable pulmonary lesions has gained popularity over the last decade. With increasing case load and patients medical status becoming more complex, preparation for pulmonary cryoablation requires the implementation of an enhanced perioperative anesthetic plan. Current literature as well as our institutional experience shows that this patient population presents with multiple comorbidities raising the challenge of providing anesthetic care. These procedures are done under challenging conditions with limited resources and in remote locations in the hospital. A team approach by the anesthesiologist, thoracic surgeon, and interventional radiologist is critical to the success of this treatment. The present review examines our institution’s anesthetic management of percutaneous cryoablation treatment (PCT) in the treatment of non-operable lung cancer and metastases. The objective of this article is to review the current literature guidelines and to discuss our retrospective institutional experience in anesthesia management of PCT procedures.

The assessment of atrial function by velocity-encoded magnetic resonance imaging

Introduction: The purpose of this study was to assess velocity-encoded cardiac magnetic resonance imaging (Ve-CMR) in a population of patients referred for cardiac magnetic resonance imaging (CMR), to determine the variability of atrial function, and to identify clinical parameters associated with left atrial function. Methods: This is a prospective study evaluating patients who were referred to our CMR center for a clinical CMR. Left atrial function was obtained via Ve-CMR thru-plane images across the mitral valve after acquiring 2 perpendicular in-plane images as “scouts”. The atrial function and mitral inflow were quantified by computer analysis (Argus, Siemens). Atrial function was defined as atrial contraction (A-wave) volume divided by total inflow volume. Left atrial volumes were calculated via computer analysis. Mitral regurgitation and left ventricular ejection fractions were assessed visually. Results: Thirty-nine patients, with mean age 56 +/- 10 years, were enrolled. The mean left atrial function was 22.9% +/-14.5%;the range in left atrial function was 0% - 57%. There was a significant positive correlation between atrial function and increased left ventricular ejection fraction (r = 0.44, P < 0.01). There was a significant negative correlation between atrial function and severity of mitral regurgitation (r = -0.60, P < 0.01), as well as left atrial volume (r = -0.36, P = 0.02). Conclusion: Our results indicate a wide variability in left atrial function and a significant association between left atrial function and left ventricular ejection fraction, left atrial volume and mitral regurgitation.

性别对当代经皮冠状动脉介入术后院内预后和长期生存率的影响

背景:早期研究提示女性的经皮冠状动脉介入术(PCI)后患病率和死亡率均高于男性。然而近期研究报道,由于女性患者预后的改善,这种短期预后上的性别差异缩小。目的:在一项针对行当代PCI的患者的大型队列研究中评估性别对长期死亡率的影响。方法:前瞻性收集1998—1999年间在纽约市3所医院接受PCI的4284例连续患者的基本资料。

对患有呼吸窘迫综合征早产儿气管内给予重组人Clara细胞蛋白的安全性、药代动力学特性以及抗炎效果

Clara cell 10-kD protein (CC10) is a potent anti-inflammatory protein that i s normally abundant in the respiratory tract. CC10 is deficient and oxidized in premature infants with poor clinical outcome (death or the development of bronch opulmonary dysplasia). The safety, pharmacokinetics, and anti-inflammatory acti vity of recombinant human CC10 (rhCC10) were evaluated in a randomized, placebo -controlled, double-blinded, multicenter trial in premature infants with respi ratory distress syndrome. A total of 22 infants (mean birth weight: 932 g; gesta tional age: 26.9 wk) received one intratracheal dose of placebo (n = 7) or 1.5 m g/kg (n = 8) or 5 mg/kg (n = 7) rhCC10 within 4 h of surfactant treatment. Pharm acokinetic analyses demonstrated that the serum half-life was 11.6 (1.5mg/kg gr oup) and 9.9 h (5 mg/kg group). Excess circulating CC10 was eliminated via the u rine within 48 h. rhCC10-treated infants showed significant reductions in total cell count (p < 0.0002), neutrophil counts (p < 0.001), and total protein conce ntrations (p < 0.01) and tended to have decreased IL-6 (p < 0.07) in tracheal a spirate fluid collected over the first 3 d of life. Infants in all three groups showed comparable growth. At 36 wk postmenstrual age, five of seven infants were still hospitalized and two of seven infants were receiving oxygen in the placeb o group compared with two of seven hospitalized and one of seven receiving oxyge n in the 1.5-mg/kg group and four of six hospitalized and three of six receivin g oxygen in the 5 mg/kg group. A single intratracheal dose of rhCC10 was well to lerated and had significant antiinflammatory effects in the lung. Multiple doses of rhCC10 will be investigated for efficacy in reducing pulmonary inflammation and ameliorating bronchopulmonary dysplasia in future s tudies.

A Survey of Non-Monetary Institutional Infrastructural Support of Academic Anesthesia Departments in the United States

Financial pressure of multifactorial etiology promises to create new obstacles for academic anesthesia departments. Integrating the priorities of the academic and clinical mission of the anesthesia department, the medical school, and the university hospital will require that anesthesia departments operate with maximal operational efficiency. Maintenance or expansion of institutional infrastructural support of the university anesthesia department will be necessary to achieve operational efficiencies, and to ensure that the safety of our patients is in no way compromised by financial concerns. Previous studies have documented increasing need for monetary institutional supports of academic anesthesia departments [1]. The purpose of this study is to delineate non-monetary institutional support afforded to academic anesthesia departments by their University Hospitals. After IRB approval, we electronically solicited the response to a 63 question survey (43 of which were used for the present study) from all 133 chairpersons of academic anesthesia departments in the United States. The remaining 20 questions were unrelated to the topics presented in this manuscript. 62 responded electronically, for an overall response rate of 46.6%. This study establishes the current state of infrastructural support afforded to academic anesthesia departments in the United States.

Practice patterns in FNA technique: A survey analysis

AIM: To ascertain fine needle aspiration(FNA) tech-niques by endosonographers with varying levels of ex-perience and environments.METHODS: A survey study was performed on United States based endosonographers. The subjects complet-ed an anonymous online electronic survey. The main outcome measurements were differences in needle choice, FNA technique, and clinical decision making among endosonographers and how this relates to years in practice, volume of EUS-FNA procedures, and prac-tice environment.RESULTS: A total of 210(30.8%) endosonographers completed the survey. Just over half(51.4%) identified themselves as academic/university-based practitioners. The vast majority of respondents(77.1%) identified themselves as high-volume endoscopic ultrasound(EUS)(> 150 EUS/year) and high-volume FNA(> 75 FNA/year) performers(73.3). If final cytology is non-diagnostic, high-volume EUS physicians were more likely than low volume physicians to repeat FNA with a core needle(60.5% vs 31.2%; P = 0.0004), and low volume physicians were more likely to refer patients for either surgical or percutaneous biopsy,(33.4% vs 4.9%, P < 0.0001). Academic physicians were more likely to repeat FNA with a core needle(66.7%) compared to community physicians(40.2%, P < 0.001). CONCLUSION: There is significant variation in EUS-FNA practices among United States endosonographers. Differences appear to be related to EUS volume and practice environment.

The interdependent networked community resilience modeling environment(IN-CORE)

In 2015,the U.S National Institute of Standards and Technology(NIST)funded the Center of Excellence for Risk-Based Community Resilience Planning(CoE),a fourteen university-based consortium of almost 100 col-laborators,including faculty,students,post-doctoral scholars,and NIST researchers.This paper highlights the scientific theory behind the state-of-the-art cloud platform being developed by the CoE-the Interdisciplinary Networked Community Resilience Modeling Environment(IN-CORE).IN-CORE enables communities,consul-tants,and researchers to set up complex interdependent models of an entire community consisting of people,businesses,social institutions,buildings,transportation networks,water networks,and electric power networks and to predict their performance and recovery to hazard scenario events,including uncertainty propagation through the chained models.The modeling environment includes a detailed building inventory,hazard scenario models,building and infrastructure damage(fragility)and recovery functions,social science data-driven house-hold and business models,and computable general equilibrium(CGE)models of local economies.An important aspect of IN-CORE is the characterization of uncertainty and its propagation throughout the chained models of the platform.Three illustrative examples of community testbeds are presented that look at hazard impacts and recovery on population,economics,physical services,and social services.An overview of the IN-CORE technology and scientific implementation is described with a focus on four key community stability areas(CSA)that encompass an array of community resilience metrics(CRM)and support community resilience informed decision-making.Each testbed within IN-CORE has been developed by a team of engineers,social scientists,urban planners,and economists.Community models,begin with a community description,i.e.,people,businesses,buildings,infras-tructure,and progresses to the damage and loss of functions caused by a hazard scenario,i.e.,a flood,tornado,hurricane,or earthquake.This process is accomplished through chaining of modular algorithms,as described.The baseline community characteristics and the hazard-induced damage sets are the initial conditions for the recovery models,which have been the least studied area of community resilience but arguably one of the most important.Communities can then test the effect of mitigation and/or policies and compare the effects of“what if”scenarios on physical,social,and economic metrics with the only requirement being that the change much be able to be numerically modeled in IN-CORE.

中国上海即食牛肉制品微生物污染情况的随机研究（英文）

本文研究了上海即食牛肉样品中微生物的污染情况。从上海的5个国际超市和5个街头摊贩随机抽取20份即食牛肉样品,采用培养法分析样本的菌落总数,并从每份样品中随机抽取10个菌落采用16S r RNA基因测序法对细菌进行分类鉴定。超市牛肉样本的菌落总数平均为(1.08±1.73)×108 CFU/g,街头摊贩样本菌落总数平均为(2.84±8.49)×10~8 CFU/g,二者在统计学上无显著性差异(p>0.05),但均高于国家标准(≤8×104 CFU/g)。所有样本均未检出能引起严重食物中毒的病原体,但检测到种类多样且与食物中毒、尿路感染、肺炎、乳腺炎以及菌血症等疾病相关的多种病原菌操作分类单元(OTU)。结果表明,即食食物是一个经常被忽视的致病微生物的储存库,我国应加强对即食食物的卫生管理,从而降低即食食品引起的食源性疾病传播几率。

老龄化与就业不振：警惕“未富先老”的低生育率陷阱

人口预期寿命延长是人类迈入现代化最宝贵的成就之一。但人口老龄化会使一个国家的人口年龄结构和劳动年龄结构发生变化,老年人口相对数量和绝对数量的增加会对经济发展造成了一系列影响。西方的经验表明人口老龄化对国家社会养老保障体系和劳动力市场造成显著负面冲击:经济增速下降,就业市场低迷,社会保障支出沉重且收支平衡日益恶化。

Nanocrystal technology for drug formulation and delivery

With the development of modem technology like high throughput screening, combinatorial chemistry and computer aid drug design, the drug discovery process has been dramatically accelerated. However, new drug candidates often exhibit poor aqueous or even organic medium solubility. Additionally, many of them may have low dissolution velocity and low oral bioavailability. Nanocrystal formulation sheds new light on advanced drug development. Due to small （nano- or micro- meters） sizes, the increased surface-volume ratio leads to drama- tically enhanced drug dissolution velocity and saturation solubility. The simplicity in preparation and the potential for various administration routes allow drug nanocrystals to be a novel drug delivery system for specific diseases （i.e. cancer）. In addition to the comprehensive review of different technologies and methods in drug nanocrystal preparation, suspension, and stabilization, we will also compare nano- and micro-sized drug crystals in pharma- ceutical applications and discuss current nanocrystal drugs on the market and their limitations.

New discovery rarely runs smooth： an update on progranulin/TNFR interactions

Progranulin （PGRN） is a growth factor implicated in various pathophysiological processes, including wound healing, inflammation, tumorigenesis, and neurodegeneration. It was previously reported that PGRN binds to tumor necrosis factor receptors （TNFR） and has thera- peutic effects in inflammatory arthritis （Tang et. al, in Science 332：478-484, 2011）; however, Chen et al. reported their inability to demonstrate the PGRN-TNFR interactions under their own conditions （Chert et. al, in J Neurosci 33：9202-9213, 2013）. A letter-to-editor was then published by the original group in response to the Chen et al. paper that discussed the reasons for the latter＇s inability to recapitulate the interactions. In addition, the group published follow-up studies that further reinforced and dissected the interactions of PGRN- TNFR. Recently, the dispute about the legitimacy of PGRN-TNFR interactions appears to be finally settled with independent confirmations of these interactions in various conditions by numerous laboratories. This review presents a chronological update on the story of PGRN-TNFR interactions, highlighting the independent confirmations of these interactions in various diseases and conditions.

Loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer

Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.

Treatment of pemphigus herpetiformis with minocycline and nicotinamide

To the editor： Pemphigus herpetiformis （PH） is a rare form f pemphigus with distinctive clinical appearance of dermatitis herpetiformis and histological features of eosinophilic spongiosis. Treatment of PH is restricted to systemic steroids and immunosuppressants. Paradoxically, mortality and morbidity related to PH are more likely caused by side-effects associated with steroid treatment, such as hypertension and osteoporosis, rather than the disease itself＇. The combination use of minocycline and nicotinamide have been reported beneficial for patients with pemphigus vulgaris （PV）, pemphigus vegetans （PVeg） and pemphigus foliaceus （PF）.1.2 Here, we report a patient of PH who was successfully treated with a combination of minocycline and nicotinamide. A 74-year-old woman presented with a one-year history of generalized pruritic erythema （Figure IA）. Flaccid vesicles were observed on the medial aspect of her let1 lower leg and excised for histopathological examination. Mucosal involvement was absent. Histopathological examination of a bulla showed intraepidermal blister with eosinophil infiltration （Figure I B）. Eosinophils were also present in the dermis （Figure I B）. Direct immunofluorescence demonstrated deposition of IgG and C3 throughout the epidermis （data not shown）. Enzyme-linked immunosorbent assays （ELISA） revealed elevated level of Dsgl antibody （408.68; normal 〈20）. Dsg3, BP180 and BP230 antibodies were not detected. Based on these findings, a diagnosis ofpemphigus herpetiformis was made. Oral corticosteroid （60 mg prednisolone per day） was prescribed, however, rejected by the patient in consideration of its side-effects. In light of previous reports,1.2 we prescribed a combination of minocycline, 100 mg bid, and nicotinamide, 500 mg tid, to this patient. Within 2 weeks of treatment, pruritus alleviated and erythema and vesicles decreased. ELISA demonstrated that the level of Dsgl antibodies decreased to 336.26. At the end of 6 weeks, an almost complete clinical remission was achieved （Figure 1C）; Dsgl antibody level further decreased to 237.03. The patient has been followed up for 1 year. No local or systemic side-effects were observed. The doses of minocycline and nicotinamide were subsequently tapered.