Procoagulant activity of reversibly acylated human factor Xa

The plasma clotting factors used to treat hemophiliacs who have developed inhibitory antibodies have a shared history of limited clinical safety and utility. To improve on existing bypass factors, we have developed a reversibly acylated form of human plasma factor Xa capable of providing a time-dependent release of procoagulant activity. Factor Xa was treated with p-amidinophenyl p'-anisate to generate anisoyl Xa. The chemical modification of the protein involves acylation of the active site serine residue of factor Xa. Anisoyl Xa deacylated in a time, pH, and temperature-dependent manner. Active factor Xa generated on deacylation of anisoyl Xa exhibited amidolytic and prothrombinase complex activities in in vitro assays, the level being comparable to those of untreated factor Xa. When Anisoyl Xa was infused into rabbits, active factor Xa was generated on deacylation of the acylated enzyme, which shortened the activated partial thromboplastin time (APTT) in a dose-dependent manner. The duration of effect on rabbit APTT could be directly correlated to the level of human plasma factor Xa. Because anisoyl Xa bypasses the "tenase" complex that is compromised in hemophilia A and B and is unaffected by inhibitory antibodies, it has the potential to be used as an effective bypass therapy.     

防己黄芪汤对单侧输尿管梗阻大鼠肾组织TGF-β1、BMP-7的影响

目的：研究防己黄芪汤对肾组织转化生长因子β1（TGF-β1）、骨形态发生蛋白-7（BMP-7）影响,进一步探讨其祛风化湿的作用机制。方法：采用大鼠单侧输尿管结扎（UUO）模型,予防己黄芪汤低、中、高剂量干预,设蒙诺对照组。肾组织切片染色观察病理,免疫组织化学方法、逆转录-聚合酶链反应（RT-PCR）检测TGF-β1、BMP-7蛋白及基因表达水平。结果：防己黄芪汤干预组大鼠的肾间质纤维化有所改善,与模型组比较,其肾组织TGF-β1表达下降、BMP-7表达上调。结论：防己黄芪汤下调UUO大鼠肾组织TGF-β1、上调BMP-7的表达,可能是其改善肾间质纤维化、发挥祛风化湿作用的机制之一。     

The acceptance and feasibility of breast cancer screening in the East

Breast cancer, traditionally a disease prevalent among women in the West, has become an increasing disease burden in the East. In Hong Kong, breast cancer is the number one incident cancer in women. In Asian countries, due to the lower incidence rate, population screening is still controversial. Most screening programs are not population-based, and are either self-financed privately or partially subsidized by the government. Since the first government-subsidized screening program was set up in 1991 in Hong Kong, numerous private and government health centres for women have been set up. A dedicated private Breast Care Centre was set up at the Hong Kong Sanatorium and Hospital (HKSH) in 1999. Over an 8-year period from October 1999 to September 2006, 14,596 women were screened, of whom 11,408 were asymptomatic. This study aims to produce the first report on breast screening experience in the largest cohort of asymptomatic Chinese women in the private sector. An overall malignancy detection rate of 2.3 per 1000 screens and a recall rate of 9.2% were found. Despite culture differences and differences in breast characteristics (denser and smaller breasts), breast screening is feasible and acceptable in the East.     

Dynamic gadolinium-enhanced echo-planar MR imaging of the liver: Effect of pulse sequence and dose on enhancement

To develop guidelines for clinical magnetic resonance imaging of the liver, the authors undertook an animal study to investigate the effect of dose and pulse sequence on liver signal intensity in gadopentetate dimeglumine—enhanced echo-planar imaging. Serial imaging of the liver was performed in anesthetized rats after intravenous administration of five different doses (0.01, 0.05, 0.1, 0.2, and 0.5 mmol/kg) of contrast agent, with six different pulse sequences. The results show that gadopentetate dimeglumine—enhanced echo-planar images obtained during the perfusion phase can yield either positive (due to increased T1 relaxation rates) or negative (due to susceptibility-induced increased T2 relaxation rates) liver enhancement depending on choice of pulse sequence and dose. At the current clinically recommended dose of 0.1 mmol/kg, maximal liver signal enhancement was seen with a T1-weighted inversion-recovery sequence, while maximal liver signal diminution was seen with a T2*-weighted gradient-echo sequence. The authors conclude that gadopentetate dimeglumine—enhanced echo-planar imaging can provide T1, T2, and T2* contrast that may be exploited for both lesion detection and lesion characterization.     

Improvement in treatment results and long-term survival of patients with esophageal cancer: impact of chemoradiation and change in treatment strategy

OBJECTIVE: To identify prognostic factors and reasons for improved survival over time in patients with esophageal cancer. SUMMARY BACKGROUND DATA: Management strategies for esophageal cancer have evolved with time. The impact of chemoradiation in the overall treatment results has not been adequately studied. METHODS: From 1990 to 2000, 399 (62.4%) of 639 patients with intrathoracic squamous cancers underwent resection. Two study periods were analyzed: period I (01/1990-06/1995), and period II (07/1995-12/2000); during period II, chemoradiation was introduced. Prognostic factors were identified by multivariate analysis and the 2 periods compared. RESULTS: Hospital mortality rate after resection decreased from 7.8% to 1.2%, P = 0.002. Five favorable prognostic factors were identified: female gender (female vs. male, HR = 0.66), infracarinal tumor location (infra vs. supra-carinal, HR = 0.63), low pTNM stage (III/IV vs. 0/I/II/T0N1, HR = 1.76), pM0 stage (M1a/b vs. M0, HR = 1.56), and R0 category (R1/2 vs. R0, HR = 2.49). Median survival was 15.8 and 25.6 months in periods I and II, respectively, P = 0.02. More R0 resections were evident in period II, being possible in 63% (period I) and 79% (period II) of patients, P = 0.001. This was attributed to tumor downstaging by chemoradiation and more stringent patient selection for resection in period II. Performing less R1/2 resections in period II coincided with using primary chemoradiation in treating advanced tumors. In patients treated without resection, survival also improved from 3 (period I) to 5.8 months (period II), P < 0.01. CONCLUSIONS: Survival has improved; chemoradiation enabled better patient selection for curative resections and also resulted in more R0 resections by tumor downstaging. This treatment strategy led to overall better outcome for the whole patient cohort, even in those treated by nonsurgical means.     

特发性脊柱侧凸患者脊柱畸形段凸侧及凹侧关节突松质骨三维微结构比较

目的比较青少年特发性脊柱侧凸(AIS)患者脊柱畸形顶椎区和端椎区两侧关节突松质骨的三维微结构。方法AIS患者9例,均为女性,年龄12～17岁,平均14.9岁;Cobb角48°～84°,平均56°。患者均接受后路矫形融合内固定手术,术前与患者家长签署同意书,在去皮质手术时取下顶椎区和上下端椎区两侧关节突。标本取材后用中性福尔马林固定,然后用解像度为20μm的微焦点CT扫描,三维图像重组进行骨形态计量学测量对比。结果顶椎区凸侧与凹侧相比有显著差异,分别为:骨量容积比BV/TV为0.268/0.354(P<0.05),骨小梁厚度TbTh为0.20/0.24(P<0.05),骨小梁分离度TbSP为0.66/0.56(P<0.05),骨小梁面积体积比BS/BV为12.7/10.4,P<0.05)。端椎区左右两侧关节突松质骨骨小梁无明显差异,上胸椎和胸腰椎关节突骨小梁微结构比较未见差异。结论由于脊柱侧凸凹侧承受不同应力,凹侧关节突出现更多的骨小梁,骨小梁间的连接更紧密,而且骨小梁更粗,从而可使脊椎楔形变的速度变缓,提示脊柱的骨骼本身并不是AIS脊柱侧凸畸形进展的促进因素。     

Analyzing treatment aggressiveness and identifying high‐risk patients in diabetic foot ulcer return to care

Rates of diabetes and its associated comorbidities have been increasing in the United States, with diabetic foot ulcer treatment representing a large cost to the patient and healthcare system. These ulcers often result in multiple hospital admissions. This study examined readmissions following inpatient care for a diabetic foot ulcer and identified modifiable factors associated with all‐cause 30‐day readmissions to the inpatient or emergency department (ED) setting. We hypothesized that patients undergoing aggressive treatment would have lower 30‐day readmission rates. We identified patient discharge records containing International Classification of Disease ninth revision codes for both diabetes mellitus and distal foot ulcer in the State Inpatient and Emergency Department databases from the Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project in Florida and New York, 2011–2012. All‐cause 30‐day return to care visits (ED or inpatient) were analyzed. Patient demographics and treatment characteristics were evaluated using univariate and multivariable regression models. The cohort included 25,911 discharges, having a mean age of 63 and an average of 3.8 comorbidities. The overall rate of return to care was 30%, and 21% of subjects underwent a toe or midfoot amputation during their index stay. The most common diagnosis codes upon readmission were diabetes mellitus (19%) and infection (13%). Patients with a toe or midfoot amputation procedure were less likely to be readmitted within 30 days (odds ratio: 0.78; 95% confidence interval: 0.73, 0.84). Presence of comorbidities, black and Hispanic ethnicities, and Medicare and Medicaid payer status were also associated with higher odds of readmission following initial hospitalization (p < 0.05). The study suggests that there are many factors that affect readmission rates for diabetic foot ulcer patients. Understanding patients at high‐risk for readmission can improve counseling and treatment strategies for this fragile patient population.     

Perception and Awareness of Bariatric Surgery in Canada: a National Survey of General Surgeons

Background

The objective of this study was to assess Canadian general surgeons’ knowledge of bariatric surgery and perceived availability of resources to manage bariatric surgery patients.

Methods

A self-administered questionnaire was developed using a focus group of general surgeons. The questionnaire was distributed at two large general surgery conferences in September and November 2012. The survey was also disseminated via membership association electronic newsletters in November and December 2012.

Results

One hundred sixty-seven questionnaires were completed (104 practicing surgeons, 63 general surgery trainees). Twenty respondents were bariatric surgeons. Among 84 non-bariatric surgeons, 68.3 % referred a patient in the last year for bariatric surgery, 79 % agreed that bariatric surgery resulted in sustained weight loss, and 81.7 % would consider referring a family member. Knowledge gaps were identified in estimates of mortality and morbidity associated with bariatric procedures. The majority of surgeons surveyed have encountered patients with complications from bariatric surgery in the last year. Over 50 % of surgeons who do not perform bariatric procedures reported not feeling confident to manage complications, 35.4 % reported having adequate resources and equipment to manage morbidly obese patients, and few are able to transfer patients to a bariatric center. Of the respondents, 73.3 % reported residency training provided inadequate exposure to bariatric surgery, and 85.3 % felt that additional continuing medical education resources would be useful.

Conclusions

There appears to be support for bariatric surgery among Canadian general surgeons participating in this survey. Knowledge gaps identified indicate the need for more education and resources to support general surgeons managing bariatric surgical patients.