Clinical significance of circulating plasma DNA in gastric cancer

With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5‐year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5‐year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer.     

Determining post-thaw CD34+ cell dose of cryopreserved haematopoietic progenitor cells demonstrates high recovery and confirms their integrity

Background  The acceptable dose of haematopoietic progenitor cells (HPCs) for transplantation is generally based on the number of CD34+ cells determined prior to cryopreservation. Commonly, cryopreservation is associated with total nucleated cell viability loss. Because HPCs have been shown to be more resistant to cryopreservation damage than nucleated cells overall, low viability may not reflect the quality and integrity of the thawed product.
Methods  Peripheral blood HPC products from 45 mobilized allogeneic and autologous donors were harvested by continuous flow blood separation and cryopreserved in 7·5% dimethyl sulfoxide. The number of viable CD34+ cells was determined by flow cytometry. Viability was measured by trypan blue (TB) uptake and 7-aminoactinomycin D (7-AAD) flow cytometry.
Results  Post-thaw HPC products were analysed for viability, CD34+ cell recovery and engraftment capability. The average post-thaw viable CD34+ cell recovery was 86·4%, while the average post-thaw viability, measured by TB or 7-AAD, was 74·0% and 57·0%, respectively. Most of the cells that did not survive cryopreservation were of the granulocyte series. All of the donors who underwent transplantation engrafted, mostly within 14 days.
Conclusions  Our data show that most CD34+ cells survive cryopreservation, regardless of the overall post-thaw total nucleated cell viability. Measuring the number of viable CD34 cells post-thaw might be of importance, and in cases of low viability can confirm the quality of the product issued.     

Therapeutic plasmapheresis as a bridge to liver transplantation in fulminant Wilson disease

Wilson disease is an autosomal recessive disorder of copper metabolism that leads to the accumulation of copper mainly in the liver, cornea, brain, and kidney. Rarely, Wilson disease can present as fulminant hepatic failure with direct antiglobulin test-negative hemolytic anemia and renal failure. In the absence of liver transplantation, this disease is uniformly fatal because medical therapy is ineffective. This report describes the successful use of plasmapheresis for a patient with fulminant Wilson disease as a bridge to transplantation. Five daily therapeutic plasmapheresis procedures using fresh frozen plasma as a replacement fluid were performed over 6 days. Serum copper, urinary copper excretion, and hemolysis were significantly reduced and renal function improved. The patient's clinical status improved and she remained clinically stable until a liver transplant was possible. Plasmapheresis can be a successful medical treatment in fulminant Wilson disease and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible.     

Therapeutic plasma exchange performed in parallel with extra corporeal membrane oxygenation for antibody mediated rejection after heart transplantation

We report on the feasibility, safety, and efficacy of performing therapeutic plasmapheresis (TPE) in parallel with extracorporeal membrane oxygenation (ECMO) to alleviate antibody mediated rejection (AMR) after heart transplantation. Two pediatric and one adult patient presented with severe congestive heart failure and respiratory distress after heart transplantation and required ECMO support. TPE was initiated to treat AMR while patients remained on ECMO. Each patient received three to five procedures either every day or every other day. One equivalent total plasma volume (TPV) was processed for each procedure (patient TPV + ECMO extracorporeal TPV). A total of 13 TPE procedures were performed with 12 procedures completed without complications or adverse events; one procedure was terminated before completion because of cardiac arrhythmia. Anti-HLA antibody titers decreased after TPE in all three patients. Ventricular function improved and ECMO was discontinued in 2 of 3 patients. Performing large volume TPE with a processed volume up to 2.5 times the patient's TPV is well tolerated in both pediatric (< or = 10 kg) and adult patients. TPE in parallel with ECMO is feasible, safe, and may be measurably effective at reducing anti-HLA antibodies and should be considered as part of the treatment for patients with early AMR after heart transplantation.     

染料木黄酮对乳鼠颅盖骨成骨细胞增殖分化的影响及其与白细胞介素6的关系

目的:观察染料木黄酮对成骨细胞活性的影响及其相关机制。方法:实验于2001-05/2003-05在卫生学环境医学研究所实验室完成。①成骨细胞培养:无菌条件下分离出生3d的乳鼠颅盖骨,剪碎,加入胰蛋白酶和Ⅱ型胶原酶,用含体积分数为0.1的胎牛血清的F-12培养基重悬,调整细胞浓度后接种于25mL细胞培养瓶,Ⅱ代细胞用于实验。②实验方法:实验分为染料木黄酮组、雌激素组和对照组(吐温20),染料木黄酮剂量分别为10-5,10-6、10-7mol/L,雌激素剂量分别为10-9,10-10mol/L,培养48,72h后,应用MTT和3H-TdR掺入实验观察不同剂量的染料木黄酮和雌激素对成骨细胞活性影响,免疫组化的方法测定白细胞介素6表达。结果:①A570nm值:培养48h,染料木黄酮10-5,10-6,10-7mol/L组分别比对照组增加105%,136%和143%;10-9,10-10mol/L雌激素组分别比对照组增加84%和100%;培养72h,染料木黄酮3个剂量组分别比对照组增加93%,113%和146%,各剂量组与对照组相比均有显著性差异(P<0.05)。②3H-TdR掺入量:10-5,10-6,10-7mol/L染料木黄酮组分别比对照组增加0.47,11.29,6.45倍;10-9和10-10mol/L雌激素组增加15.4倍和16.5倍(P<0.05)。③白细胞介素6表达:各组成骨细胞周围均有较强的呈棕色的阳性颗粒,但染料木黄酮组组与对照组相比无明显差别。结论:①10-5～10-7mol/L染料木黄酮和雌激素一样可促进成骨细胞增殖和DNA合成。②染料木黄酮不是通过促进白细胞介素6表达来促进成骨细胞增殖与分化。     

How do we perform and bill for blood bank physician consultative services?

Transfusion medicine (TM) physicians provide medical services that benefit all patients such as providing 24‐hour laboratory coverage, advising health care providers on test interpretation and selection, validating new methods, and supervising technical personnel. These services ensure delivery of accurate, reliable, and timely laboratory test results and blood products. TM physicians also provide consultations to individual patients by 1) interpreting and determining the clinical significance of test results (e.g., alloantibodies, direct antiglobulin tests), 2) recommending appropriate component therapy and approving deviations from laboratory policy, and 3) evaluating and recommending treatment of suspected transfusion reactions. The potential benefits of consultations are improved quality and cost of health care, enhanced provider education, and decreased inappropriate testing and product utilization. When physician services are delivered to individual patients, are appropriately requested, provide a diagnosis or recommendation, and are properly documented, TM physicians can receive professional reimbursement. While many TM physicians provide medical direction and oversight of apheresis procedures, billing in this area is sufficiently complex to be reviewed elsewhere. The objective of this article is for educational purposes to describe the 1) benefits of a consultative TM service, 2) development of reimbursement systems in the United States for professional component services and the current regulatory requirements, 3) current procedural terminology codes commonly used for TM physician services, and 4) examples of consultation documentation and daily workflow at tertiary care teaching hospitals. The information provided should help guide physicians to deliver and bill for these services.     

Heart transplantation in pediatric patients: twelve-year experience of the Asan Medical Center

Heart transplantation is a standard treatment for end-stage heart disease. Pediatric heart transplantation, however, is not frequently performed due to the shortage of pediatric heart donors. This is the first report of pediatric heart transplantation in Korea. Our retrospective study included 37 patients younger than 18 yr of age who underwent heart transplantation at Asan Medical Center between August 1997 and April 2009. Preoperative diagnosis was either cardiomyopathy (n = 29, 78.3%) or congenital heart disease (n = 8, 22.7%). Mean follow up period was 56.9 ± 44.6 months. There were no early death, but 7 late deaths (7/37, 18.9%) due to rejection after 11, 15, 41 months (n = 3), infection after 5, 8, 10 months (n = 3), suspicious ventricular arrhythmia after 50 months (n = 1). There was no significant risk factor for survival. There were 25 rejections (25/37, 67.6%); less than grade II occurred in 17 patients (17/25, 68%) and more than grade II occurred in 8 patients (8/25, 32%). Actuarial 1, 5, and 10 yr survival was 88.6%, 76.8%, and 76.8%. Our midterm survival of pediatric heart transplantation showed excellent results. We hope this result could be an encouraging message to do more pediatric heart transplantation in Korean society.