Changes in International Normalized Ratio (INR) and Model for Endstage Liver Disease (MELD) Based on Selection of Clinical Laboratory

Priority for liver transplantation is based on the Model for Endstage Liver Disease (MELD) score, a mathematical function which includes international normalized ratio (INR). We present an analysis to determine the lab-to-lab variation in INR at 14 clinical laboratories across the United States. We performed a survey to identify representative clinical laboratories across the United States, where INR was measured in the determination of MELD score. Five 'standard' samples for INR were formulated and were sent to the 14 clinical laboratories to determine variation in INR and MELD score. Among the 14 clinical laboratories, the range in INR for the five samples was: sample 1 (1.2-2.0), sample 2 (1.4-2.5), sample 3 (1.7-3.4), sample 4 (1.9-3.7) and sample 5 (2.4-5.1). The range in calculated MELD score was: sample 1 (8-14), sample 2 (10-17), sample 3 (12-20), sample 4 (14-21) and sample 5 (16-25). The selection of the clinical laboratory used to determine INR may result in substantial changes in MELD score independent of severity-of-illness. These data suggest that further review of interlaboratory variation in MELD should be undertaken because of the potential impact on prioritization for liver transplantation.     

应用两种评分系统对409 例肝硬化和重型肝炎病例的评估分析

目的应用两种评分方法对409名肝硬化及重型肝炎患者进行评估比较，对两种评估结果及有关的上消化道出血及死亡等因素进行相关性分析。方法统计409名肝硬化及重型肝炎患者的相关资料，应用Child和MELD评分法分别计算后应用Chiss软件进行统计学分析。结果各种计算比较结果见表格。结论Child-Pugh分级法和MELD评分系统各有特点，将两种评分方式与多因素分析与经验有机结合，才是符合临床实际的判断严重肝病预后的较科学手段。     

The role of JOA score as an indication for surgical or conservative treatment of symptomatic degenerative lumbar spinal stenosis

Abstract The aim of this study was to evaluate the short- to medium-term results (up to 2 years) of conservative and surgical treatments of patients with symptomatic lumbar stenosis. To our knowledge, no previous study has provided strict indications for conservative or surgical treatment. We retrospectively studied 184 patients, who were divided into 3 groups according to JOA (Japanese Orthopaedic Association) score. A cutoff JOA score was arbitrarily fixed at 7. Patients with a score ≤7 (n=12; group A) underwent surgery, while patients with a score >7 (n=172) were conservatively treated. Group A included patients surgically treated within two months from diagnosis. Group B consisted of 144 patients who received conservative treatment, while group C (28 patients) represented patients who underwent surgery after a period of failed conservative treatment. The outcomes of surgical and conservative treatments were evaluated after 12 and 24 months, and were rated as satisfactory, not totally satisfactory, not satisfactory or totally unsatisfactory. Conservative treatment consisted of physical, orthotic and drug therapy, whereas surgical treatment included spinal decompression and instrumentation (if indicated), either rigidly or dynamically performed. Surgery was indicated in 22% of all patients and we obtained excellent results in 85% of them. Operative treatment provides excellent results for patients with severe clinical presentation (JOA score ≤7), while individuals with mild to moderate spinal stenosis (JOA score >7) should receive conservative treatment.     

A Note on the Asymptotic Properties of Affected-sib-pair Linkage Tests

This article concerns the asymptotic properties of linkage tests for affected‐sib‐pair data under the null hypothesis of no linkage. We consider a popular single‐locus analysis model where the unknown parameters are the disease allele frequency, the three penetrances for the three genotypes at the disease locus, and the recombination fraction between the marker locus and the disease locus. These parameters are completely confounded under the null hypothesis of no linkage. We show that 1) If the total variance of the trait (i.e., the additive variance plus the dominance variance) is “separated” from 0, then the likelihood ratio statistic has an asymptotic 0.5χ²₀+ 0.5χ²₁ distribution; 2) If the prevalence of the trait is “separated” from 0 and the recombination fraction is fixed at 0, then the likelihood ratio statistic has an asymptotic distribution which is a mixture of χ²₀, χ²₁ and χ²₂ . The implications of these results are discussed.     

Regional Variations in Peer Reviewed Liver Allocation Under the MELD System

The Model for End-Stage Liver Disease (MELD) is used to assign priority for liver transplantation candidates. The Organ Procurement and Transplantation Network (OPTN) approved recognized exceptional diagnoses (RED's) for which MELD fails to accurately measure priority. Centers can request increased MELD points in cases not recognized by this policy (non-RED's). Our aim was to compare regional practices to justify non-RED requests for MELD adjustments. The UNOS/OPTN database was queried to extract all adult cases for which a non-RED MELD adjustment was requested from 2/27/02 until 8/27/03. The data were stratified by region and justification. Data for 29,510 listings were available. 26,947 had complete diagnosis information. There were 827 non-RED requests of which 477 (57.7%) petitions were approved by the regional review boards (RRBs). The approval rate varied significantly among regions (range: 28-75%, p<0.0001). The most common non-RED's were complications of portal hypertension (48%). The percentage of patients listed with non-RED's varied significantly among regions (0.7-8.3 %, p<0.0001), as did the proportion of patients transplanted with non-RED's (2.1-31.9%, p<0.0001). Demographics did not differ among regions requesting non-REDs.Widespread regional variations exist in the handling of requests for non-REDs. These variations point to the need for reform to standard exception criteria.     

静止性脑梗死风险预测量表的构建和验证

【摘要】
目的 调查与静止性脑梗死（silent brain infarction，SBI）相关的独立影响因素，构建SBI风险预测量
表并验证。
方法 在单中心横断面研究中，前瞻性连续纳入无神经系统疾病既往史的体检者，收集其人口学
信息，高血压、糖尿病等血管危险因素，血脂、糖化血红蛋白、血浆同型半胱氨酸等化验结果录入数
据库。采用标准影像学操作规范进行头颅MRI扫描，并由影像学医师盲法判读，将受试者分为SBI组
和无SBI组。将所有受试者按照3∶1比例随机分为训练集和验证集，在训练集中采用单因素和多因素
Logistic回归分析SBI的独立影响因素，构建SBI预测量表。在训练集和验证集中应用ROC曲线检验量表
的区分度，应用Hosmer-Lemeshow分析检验量表的校准度。
结果 共有633例研究对象纳入研究，平均年龄52.0±10.5岁，女性272例（43.0%）。训练集（475
例）和验证集（158例）两个样本集合的基线特征均衡。校正混杂因素后多因素分析显示，年龄≥45
岁（OR 8.37，95%CI 1.12～62.80，P =0.039），高血压（OR 2.30，95%CI 1.08～4.90，P =0.032），同型半
胱氨酸（Q2～Q3：OR 6.89，95%CI 0.89～53.10，P =0.064；Q4：OR 13.6，95%CI 1.74～105.87，P =0.013）
与SBI风险独立相关。根据OR 值构建SBI危险评分（SBI risk score，SBI-RS）量表，量表赋值为：年龄
≥45岁赋值8分；有高血压赋值2分；同型半胱氨酸根据四分位分层分别赋值为0分、7分和14分。SBIRS
在训练集和验证集中ROC曲线显示曲线下面积分别为0.77（95%CI 0.69～0.84，P＜0.001）和0.76
（95%CI 0.63～0.88，P＜0.001），区分度良好。Hosmer-Lemeshow相关分析提示SBI-RS具有较好的校准度
（P＞0.05）。
结论 在健康体检人群中，SBI -RS具有较好的区分度和校准度，可以帮助识别SBI高危人群。     

Regional Variation and Use of Exception Letters for Cadaveric Liver Allocation in Children with Chronic Liver Disease

The Pediatric End-Stage Liver Disease (PELD) score was designed to reduce subjectivity in liver allocation and to advantage patients with a higher probability of waiting list mortality. The aims of this study were to determine the impact of PELD implementation for children with chronic liver disease and to assess whether PELD met its goal of standardization of liver allocation for children. This study used data reported to the United Network for Organ Sharing (UNOS) registry for children with chronic liver disease receiving primary cadaveric liver transplant between January 2000 and December 2001 (pre-PELD) and March 2002 and July 2003 (PELD). PELD reduced the percentage of children transplanted while in an intensive care unit and as status 1. A calculated PELD score was used for allocation in only 52% of recipients. Thirty percent were status 1 at transplant and PELD scores granted by exception were used for allocation in 18% of patients. There was regional variation in PELD score at allocation and use of exception scores with a significant relationship between PELD score and percentage of exception cases. Regional variation suggests that PELD has not resulted in standardization of listing practices in pediatric liver transplantation.     

Autologous implantation of chondrocytes on a solid collagen scaffold: clinical and histological outcomes after two years of follow-up

Abstract From our overall experience in 56 patients, we here report the treatment with matrix-induced autologous chondrocyte implantation (MACI) of 35 patients suffering from knee cartilage defects measuring about 4 cm², and followed for a minimum of 6 months. A total of 36 knees were treated (1 patient on both knees) and clinically observed for 22 months (in some cases for over 39 months), in accordance with a standardised protocol. Subjective parameters (pain, well-being, functional state, symptoms during specific activity) and objective outcomes (IKDC score and Lysholm and Tegner scores) were recorded. One or 2 years after implantation, some biopsies of the regenerated cartilage were histologically evaluated. The subjective parameters (VAS pain score, 2.80±1.49, p<0.0001; change vs. basal score, 2.72) promptly normalized after 1 month, as did the objective ones (IKDC score after 6 months, 1.53±0.59, p<0.0001; change vs. basal score, 1.78). Similar results were observed after the treatment of a femoropatellar kissing lesion. The three cartilage biopsies that were analysed from different patients showed a tissue positivity to immunohistochemical markers of hyaline cartilage. The conclusions of this preliminary analysis are that the clinical outcome and histological evaluation suggest that MACI is able to relieve pain and restore the functionality of the knee, and that the treatment appears capable of regenerating hyaline cartilage.     

Flow cytometric analysis of localized adenocarcinoma of the prostate: the use of archival DNA analysis in conjunction with pathological grading to predict clinical outcome following radical retropubic prostatectomy

Fifty-four specimens from patients undergoing radical prostatectomy for clinically confined prostate cancer between 1983 and 1987 were reviewed to determine the potential for flow cytometric (FCM) analysis of DNA ploidy and replication rate to predict disease recurrence. Each specimen was deparaffinized for FCM analysis and the pathology slides were reviewed by a single pathologist. FCM characteristics were correlated with pathological grade and stage, and both were correlated with disease status. In this series of patients, routine FCM analysis of DNA ploidy and replication rate failed to significantly enhance the ability of standard histopathological grading to predict disease recurrence in patients having clinically localized prostate cancer. Aneuploid tumors pathologically confined to the prostate did not appear to negatively affect prognosis.     

Liver and intestine transplantation

The most significant development in liver transplantation in the USA over the past year was the full implementation of the MELD- and PELD-based allocation policy in March 2002, which shifted emphasis from waiting time within broad medical urgency status to prioritization by risk of waiting list death. The implementation of this system has led to a decrease in pretransplant mortality without increasing post-transplant mortality, despite a higher severity of illness at the time of transplant.
The trend over the last few years of rapidly increasing numbers of adult living donor liver transplants was reversed in 2002 by a decline of more than 30% in the number of these procedures. In 2002, a greater percentage of women received livers from living donors (43%) than deceased donors (34%), possibly because of size considerations.
From 1993 to 2001, the waiting list increased more than sixfold, from 2902 patients to 18 047 patients. For the first time since 1993, the waiting list size decreased in 2002, dropping 6% to 16 974 candidates. The percentage of temporarily inactive liver candidates also increased from 2001, thus the net decrease in the active waiting list for 2002 was 12%. This may reflect a trend toward less pre-emptive listing practices under MELD.
Intestine transplantation remains a low-volume procedure limited to a few transplant centers and is still accompanied by significant pre- and post-transplantation risks. As this procedure matures, its application may increase to include recipients at an earlier stage of their disease with better likelihood of success.