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Background/Purpose This study aims at investigating the epidemiological profile of chronic hepatitis C (CHC) regarding hepatitis C virus (HCV) genotype in Taiwan. Methods A total of 29,087 CHC patients with advanced fibrosis who received direct-acting antivirals (DAAs) therapy under Taiwan's National Health Insurance (NHI) during 2017–2018 were recruited. The HCV genotype distribution and its association with patients' demographic factors including age, gender, and geographical areas were examined. Results The most common genotypes were 1b (59.5%) and 2 (30.1%) with characteristics of older age (mean ± standard deviation (SD): 66.5 ± 10.7 years and 67.3 ± 10.9 years) and female gender predominant (57.1% and 59.4%), which were associated with iatrogenic infection decades ago. Most of patients with genotype 1a (5.9%) and 6 (3.7%) infection were relatively younger (59.2 ± 12.0 years and 60.0 ± 13.8 years) and male gender predominant (59.1% and 61.1%), except Liujia and Liuying districts in southern Taiwan. The youngest group (53.2 ± 11.8 years) and most male gender predominant (74.3%) was genotype 3 (0.37%). These genotypes with characteristics of being younger and male gender predominant were highly related to injection drug use in recent years. The number of genotype 4 patients were extremely rare (n = 25) and efficacy of genotype-4-specific-DAA was significantly poorer than non-genotype-4-specific DAA (P value = 0.0411). Conclusions The significant differences in demographic characteristics among CHC patients with different HCV genotypes found in this study suggest HCV genotype was highly associated with transmission pattern and may be used as a reference for HCV control.

This paper provides an introduction to laboratory databases established by Taiwan National Health Insurance Administration (NHIA) since 2015 and released for research since June 2017. The National Health Insurance (NHI) is a government-run single-payer program introduced in 1995 that now covers more than 99% of 23 million Taiwanese citizens. To prevent duplication of medication prescriptions and laboratory test and examination prescriptions, contracted health care providers are required to upload the results of laboratory tests and reports of examinations to the NHIA. The cumulative number of laboratory test results was 5.64 billion from January 2015 to the end of August 2020 for 602 types of test. There are 35 variables for each laboratory test result stored in the databases that can be used for research. However, different hospitals might use different format in reporting the results. The researchers therefore have to develop algorithms to include and exclude incompatible records and to determine whether the results are positive or negative (normal or abnormal). The NHIA suggests that researchers release their source codes of algorithms so that other researchers can modify the codes to improve inter-study comparability. Through the unique personal identification number, the laboratory data can be linked to NHI inpatient and outpatient claims data for further value-added analyses. Non-Taiwanese researchers can collaborate with Taiwan researchers to access the NHI laboratory databases.

Ji-An Liang,1,2,* Po-Chang Lee,3,* Chun-Ping Ku,3,* William Tzu-Liang Chen,2,3,* Chih-Yuan Chung,4 Yu-Cheng Kuo,1,2 Szu-Hsien Chou,5 Chia-Chin Li,6 Chun-Ru Chien1,2,6 1Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 3Department of Surgery, China Medical University Hsinchu Hospital, Hsinchu, Taiwan; 4Department of Medical Oncology, China Medical University Hsinchu Hospital, Hsinchu, Taiwan; 5Department of Medical Imaging, China Medical University Hsinchu Hospital, Hsinchu, Taiwan; 6Department of Radiation Oncology, China Medical University Hsinchu Hospital, Hsinchu, Taiwan*These authors contributed equally to this workCorrespondence: Chun-Ru ChienSchool of Medicine, College of Medicine, China Medical University, No. 91 Hsueh-Shih Road, North District, Taichung, 40402, TaiwanTel +886-4-22052121-7450Fax +886-4-22052121-7460Email d16181@gmail.comPurpose: Image-guided radiotherapy (IGRT) is an advanced radiotherapy technique to improve the radiotherapy delivery. We aimed to compare the overall survival (OS) for localized breast cancer (LBC) patient treated with adjuvant conventional fractionated radiotherapy (CFRT) using IGRT vs those without IGRT via a population-based analysis.Patients and Methods: Eligible LBC patients diagnosed between 2011 and 2013 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and other outcomes were compared between IGRT and non-IGRT. We also evaluated OS in various supplementary analyses.Results: Our primary analysis included 6490 patients in whom covariates were well balanced after PS weighing. The HR for death when IGRT was compared with non-IGRT was 1.02 (95% confidence interval 0.80– 1.31, P = 0.86). There were also no significant differences in the supplementary analyses.Conclusion: We found that OS of LBC patients treated with adjuvant CFRT was not statistically different between those treated with IGRT versus without IGRT. This was the first study in this regard to our knowledge but randomized controlled trials were needed to confirm our finding.Keywords: breast cancer, effectiveness, image-guided radiotherapy

Background Low infection and case-fatality rates have been thus far observed in Taiwan. One of the reasons for this major success is better use of big data analytics in efficient contact tracing and management and surveillance of those who require quarantine and isolation. Objective We present here a unique application of big data analytics among Taiwanese people who had contact with more than 3000 passengers that disembarked at Keelung harbor in Taiwan for a 1-day tour on January 31, 2020, 5 days before the outbreak of coronavirus disease (COVID-19) on the Diamond Princess cruise ship on February 5, 2020, after an index case was identified on January 20, 2020. Methods The smart contact tracing–based mobile sensor data, cross-validated by other big sensor surveillance data, were analyzed by the mobile geopositioning method and rapid analysis to identify 627,386 potential contact-persons. Information on self-monitoring and self-quarantine was provided via SMS, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests were offered for symptomatic contacts. National Health Insurance claims big data were linked, to follow-up on the outcome related to COVID-19 among those who were hospitalized due to pneumonia and advised to undergo screening for SARS-CoV-2. Results As of February 29, a total of 67 contacts who were tested by reverse transcription–polymerase chain reaction were all negative and no confirmed COVID-19 cases were found. Less cases of respiratory syndrome and pneumonia were found after the follow-up of the contact population compared with the general population until March 10, 2020. Conclusions Big data analytics with smart contact tracing, automated alert messaging for self-restriction, and follow-up of the outcome related to COVID-19 using health insurance data could curtail the resources required for conventional epidemiological contact tracing.

Dengue fever is an important epidemic disease with a high prevalence in tropical and subtropical countries. We aimed to investigate the effects of a treatment integrating traditional Chinese (TCM) and Western medicines on dengue inpatients with warning signs (i.e., group B) according to the World Health Organization dengue classification in this retrospective cohort study of medical records. Inpatients who were treated with conventional Western therapies in the absence or presence of TCM were assigned to the control and treatment groups, respectively. Data were compared using an analysis of variance, general linear analysis, and chi-square test. The most common clinical symptoms and signs of dengue fever were fever and muscle ache. The treatment group patients were significantly more likely to present general weakness and poor appetite than the control group patients. Patients in the treatment group were more likely to experience stomachache than those in the control group. Moreover, comparisons of the changes in hemoglobin and alanine aminotransferase levels over time revealed significant differences between the patient groups. Zhu Ye Shi Gao Tang, Gui Pi Tang, Paeonia suffruticosa, and Clerodendrum cyrtophyllum were the most commonly administered TCM formula and single herbs in this study. Patients in the treatment group experienced a resolution of symptoms, signs, and laboratory data and were discharged smoothly, without deterioration to death or critical care. Our findings suggest that the integration of TCM and Western medicine may yield an appropriate treatment for dengue fever.

Background Those taking proton pump inhibitors (PPIs) might have a higher risk of acute kidney injury. The long-term safety, especially the PPI-associated chronic kidney disease (CKD) is the subsequent concern. Objective This study explores the potential relationship between using PPIs and CKD in Taiwan. Methods Using a database collated by the Taiwan National Health Insurance programme, we conducted a population-based case-controlled study to identify 16 704 cases of patients aged 20 years or older with newly diagnosed CKD between 2000 and 2013. 16 704 controls were randomly selected and were matched by sex, age and comorbidities. 'Use' of PPIs was defined as when subjects had received at least a prescription for PPIs before the index date. 'Non-use' was defined as subjects who had never received a prescription for PPIs before the index date. The odds ratio (OR) for CKD associated with the use of PPIs was estimated by a logistic regression model. Results The OR for CKD was 1.41 for subjects using PPIs [95% confidence interval (CI) 1.34, 1.48] compared with subjects who had never used PPIs. Almost all major types of PPIs present a weak association with increased odds of CKD in cumulative duration and dosage regression analysis. The OR in relation to cumulative duration (per month) of PPIs use was 1.02 (95% CI 1.01, 1.02) and the OR in relation to cumulative dosage (per microgram) of PPIs use was 1.23 (95% CI 1.18, 1.28). Conclusions Using PPIs presented 1.4-fold higher odds of CKD in Taiwan health insurance claims data analysis.

The occurrence of dural arteriovenous fistula (DAVF) is rare. The clinical manifestation varies and depends on the location and venous drainage pattern. We present a case of a 57-year-old man with a left transverse sinus DAVF along with sigmoid thrombosis, cortical venous reflux, and congestion, that initially presented as parkinsonism. The patient was alert and fully oriented; however, decreased facial expressions were noted. His left forearm showed rigidity and bradykinesia, and it was difficult for the patient to smoothly perform rapid alternating movement testing. His complaints about hearing a rhythmic bruit above the left ear, particularly when lying down, alerted the physician of the presence of vascular lesions. Magnetic resonance imaging and angiography confirmed the diagnosis of DAVF. The patient received a combined surgical and endovascular approach to permanently block the fistula blood flow. The motion and movement of his left upper limb improved after fistula embolization. Images at the 1-month follow-up showed a decrease in the volume of tortuous vessels, and the fistula was completely occluded.

Aims and objectives. This study examined health promotion behaviours of kidney transplant recipients, 1–5 years after transplant and identified the risk factors predicting non-adherence to post-transplant recommendations. Background. Non-adherence to health care recommendations and health promotion behaviours is one of the top three reasons for graft loss following kidney transplantation. Design. A cross-sectional study. Methods. Kidney transplant recipients (n = 101) in southern Taiwan completed a self reported survey, the Kidney Transplant Health Promotion Behavior and Healthcare Provider Support survey. Results. Kidney transplant patients had better adherence with medication and least adherence with regular exercise health promotion behaviours. Age, post kidney transplant time, health care provider support and financial satisfaction accounted for 37·2% of the explained variance in monitoring and management for rejection and infection. Marital status, post kidney transplant time and gender accounted for 16·2% of the explained variance in infection prevention. Age was the sole predictor of exercise (odds ratio = 1·08, p = 0·025). Health promotion behaviours declined with time and perceived healthcare provider support decreased at the third (p = 0·04) post kidney transplant year. Conclusion. In this study, young, single, males were identified as requiring specific strategies to improve post kidney transplant health promotion behaviours. The need for health promotion must be continually reinforce by healthcare providers throughout the lifespan of a kidney transplant recipient. Relevance to clinical practice. Understanding the changes of health behaviours of post kidney transplant recipients and their risk factors, healthcare providers can be more aware of the needs of patients in maintaining health promotion behaviours.

Enzyme-linked immunosorbent assay (ELISA) and flow cytometric techniques have been introduced to overcome the limited sensitivity and specificity of the CDC assay. This retrospective study used lambda antigen tray-mixed screening and Luminex HLA class I and II specificity assays to re-examine: (1) the accuracy with which detection of HLA antibody and specificity by ELISA predicts pretransplantation National Institutes of Health (NIH)/Centers for Disease Control and Prevention (CDC) crossmatch; and (2) a comparison of Luminex and ELISA methods to detect HLA antibodies. Sera from 481 patients awaiting kidney transplantation were tested using the ELISA method lambda antigen tray-mixed and using NIH-CDC to determine how well HLA antibodies detected using ELISA predicted crossmatches using CDC. Pretransplantation sera from 48 patients with follow-up data were retested using both ELISA lambda antigen tray-mixed and Luminex to compare the efficacy of the 2 methods.

Quality of life is an important indicator for evaluating therapeutic outcomes and mortality in patients with end-stage renal disease. Few studies have explored the impact of symptom distress and social support on quality of life in this population. A correlational study was designed to examine the influence of symptom distress, social support and demographic characteristics on quality of life in renal transplant recipients. A convenience sample of 113 renal transplant recipients was recruited from a medical center in Southern Taiwan. A structured questionnaire was used to collect data. This four-part tool included: Quality of Life Index--Kidney Transplant Version III, Physical Symptom Distress Scale, Social Support Scale, and demographic characteristics. Data were analyzed by descriptive and inferential statistics (SPSS 10.1 statistical package). Percentage, rank, mean and standard deviation, t-tests, chi-square, ANOVA, Pearson's correlation and multiple regression were computed. Results showed that renal transplant recipients had a moderate quality of life. Social support and symptom distress, age, employment status, and household income significantly explained 28.8% of the variance in quality of life. Findings suggest implications for interventional programming and research aimed toward improving quality of life, including individual and family-based approaches designed to enhance recipients' social support and address effective management of symptoms. Recruiting a transplant clinical nurse specialist to design and implement an intervention program also is recommended.

This retrospective study uses the LAT-M (One Lambda Inc., Calif) screen assay to reexamine the impacts (a), of pretransplant human leukocyte antigen (HLA) antibody on long-term graft survival; (b) posttransplant HLA antibody on long-term graft survival and (c) immunosuppressive regimen on posttransplant HLA antibody development.Pretransplant sera from 222 renal transplant recipients and posttransplant sera from 216 renal transplant recipients were studied for the impact of HLA antibody on long-term graft survival.Among the patients who did not display pretransplant HLA antibodies, 85% enjoyed 5-year and 59% 10-year graft survival, whereas the patients who tested positive were 83% and 83% (P = .5596). Among the patients who did not show posttransplant HLA antibodies, 99% enjoyed 5-, 91% 10-, and 65% 15-year graft survival, whereas for the 44 patients who tested positive they were 59%, 44%, and 30%, respectively (P.0001). Patients prescribed cyclosporine + myfortic (odds ratio 0.17, P = .05) or FK + Cellcept (odds ratio 0.36, P = .04) showed the lowest posttransplant HLA antibody development.Both regimens improve graft survival.

Background. Cyclosporine A (CsA) and morphine have neurotoxic and psychiatric side effects, respectively. Endogenous opiatelike peptides can elicit a number of behavioral responses that mimic the symptoms of psychiatric illness. The purpose of this study was to quantitiate the changes of Met-enkephalin (ME) and β-endorphin (BE) after administration of CsA and morphine in surgery and to assess the antinociceptive effect. Patients and materials. Pain sensitivity, an antinociceptive indicator in rats, was determined with the hotplate test. Plasma ME and BE levels were measured with radioimmunoassays. Results. In normal unoperated rats, CsA induced a profound analgesic effect concomitant with an increased plasma ME level on day 1. Morphine produced an analgesic effect on days 1 and 2, with decreased ME levels on days 2 and 3. Coadministration of CsA and morphine prolonged the analgesia from days 1 to 4 and increased the plasma ME level on day 1. No change in plasma BE level was found. In surgically operated rats, CsA induced an analgesic effect and higher ME levels than those in unoperated rats. Interestingly, the combined use of CsA and morphine prolonged the analgesia and increased plasma ME levels from days 1 to 4, with no significant change in plasma BE levels. Conclusions. Our results showed that CsA can induce antinociception and increase plasma ME levels. This induction can be potentiated by the addition of morphine. Acute neuropsychiatric manifestations in the early posttransplant period might, therefore, be due to induction of ME after coadministration of CsA and morphine.

Julio Pascual,1 Titte R Srinivas,2 Steven Chadban,3 Franco Citterio,4 Federico Oppenheimer,5 Helio Tedesco,6 Mitchell L Henry,7 Christophe Legendre,8 Yoshihiko Watarai,9 Claudia Sommerer,10 Po-Chang Lee,11 J Mark Hexham,12 Gaohong Dong,12 Peter Bernhardt,13Flavio Vincenti14 1Nephrology Department, Hospital del Mar, Barcelona, Spain; 2Division of Nephrology, Medical University of South Carolina, Mt Pleasant, SC, USA; 3Department of Transplantation, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; 4Centro Trapianti d'Organo Istituto di Clinica Chirurgica, Università Cattolica del Sacro Cuore, Policlinico Universitario A Gemelli, Rome, Italy; 5Renal Transplant Unit, Hospital Clínic de Barcelona, Barcelona, Spain; 6Nephrology Division, Hospital do Rim, UNIFESP, São Paulo, Brazil; 7The Comprehensive Transplant Center, The Ohio State University, Wexner Medical Center, Columbus, OH, USA; 8Service de Transplantation Adultes, Université Paris Descartes and Hôpital Necker, Paris, France; 9Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya City, Aich, Japan; 10Medizinische Klinik, Sektion Nephrologie, Universitätsklinikum Heidelberg, Heidelberg, Germany; 11Medical College, National Cheng Kung University, Tainan City, Taiwan; 12Biometrics and Statistical Science, Novartis Pharmaceuticals, East Hanover, NJ, USA; 13Research and Development, Novartis Pharma AG, Basel, Switzerland; 14Kidney Transplant Service, University of California San Francisco, San Francisco, CA, USA Abstract: Two well defined, modifiable risk factors for kidney allograft failure are acute rejection and poor graft function at one year post-transplant. Regulatory bodies and expert panels in the USA and Europe have recognized that both acute rejection and one-year graft function should be assessed when evaluating immunosuppressive regimens. TRANSFORM (Clinicaltrials.gov NCT01950819) is one of the first trials to adopt this approach and the first that applies a novel combined clinically meaningful endpoint to take the first step towards changing the paradigm for immunosuppression in kidney transplant patients. Everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy is a strategy designed to reduce the risk of chronic nephrotoxicity and other dose-dependent complications associated with CNI therapy. In TRANSFORM, de novo kidney transplant patients are randomized to everolimus with reduced-exposure CNI, or mycophenolic acid with standard-exposure CNI, both with induction therapy and maintenance steroids. The primary endpoint is a composite of treated biopsy-proven acute rejection or estimated glomerular filtration rate ,50 mL/min/1.73 m2 at month 12 post-transplant, which is expected to be sensitive both to the effects of acute and chronic allograft rejection and nephrotoxic side effects of immunosuppressive therapies. The construct of this endpoint allows the integration of a continuous outcome (graft function) with a logistic outcome (rejection). The trial uses a randomized, multicenter, open-label, two-arm design. After completion of a 2-year core study, patients enter a further 3-year prospective observational study. By capturing follow-up to 5 years, TRANSFORM will provide substantial data on the incidence of graft loss, graft dysfunction, cancer, cardiovascular events, and other patient-relevant outcomes. TRANSFORM will determine whether de novo CNI reduction with an everolimus-based regimen achieves short-term outcomes compared with standard CNI. As the largest clinical trial undertaken to date in kidney transplantation, recruiting more than 2,000 patients, and with extended follow-up to 5 years, TRANSFORM will provide critical data required to help maximize long-term outcomes. Keywords: mTOR inhibitor, calcineurin inhibitor, reduced exposure

Objective Preoperative reduction of isoagglutinins leads to successful ABO-incompatible (ABOi) renal transplantation. The strategy includes pretransplantation plasmapheresis, more potent immunosuppressive drugs, splenectomy, and anti-CD20 antibody. It has been reported that low isoagglutinin antibody titers posttransplant were observed among ABOi renal transplants with favorable outcome. The isoagglutinin titers may increase slightly when plasmapheresis is discontinued; however, it never returns to the pretreatment level under immunosuppressive therapy. This raises the question of what occurs to the isoagglutinin titer in ABO-compatible renal transplants under maintenance immunosuppressive pharmacotherapy. Methods We analyzed 10 renal transplant recipients, including seven living and three cadaveric donors. Patients were treated with basiliximab (20 mg) intravenously on day 0 and day 4. Maintenance immunosuppressive therapy involved a calcineurin inhibitor, mycophenolate mofetil, and steroid. Anti-human globulin isoagglutinin titers were routinely examined 1 day before and day 0 and 1, 2, 3, 4, 8, 12, and 24 weeks posttransplant. No ALG or intravenous immunoglobulin or plasmapheresis treatment was provided in the follow-up period. Results Our preliminary data showed nearly no influence on isoagglutinin titer levels in 6-month follow-up under maintenance immunosuppressive therapy. In addition, no significant difference in isoagglutinin titer was observed between tacrolimus and cyclosporine groups. Conclusion Maintenance immunosuppressive pharmacotherapy did not affect isoagglutinin titer levels in ABO-compatible kidney transplants. Further study is needed to investigate the mechanisms of persistent low-level isoagglutinin titers among successful ABOi renal transplantation patients.

Objectives Despite the advantages of laparoscopic living donor nephrectomy (LDN), this technique is known to have a steep learning curve that makes worldwide adoption challenging, especially in institutions without a large patients volume. Herein, we have reviewed our 5-year experience of adoption and evolution of this surgical technique, examining the donor and recipient outcomes. Methods Between September 2002 and June 2007, 40 LDNs were performed consecutively. Our surgical technique was mainly derived from the University of California San Francisco method. We retrospectively reviewed the donor demographics, operative characteristics, perioperative complication of donors/recipients, and outcomes of donors and recipients. Results Among the 40 cases, 36 (90.0%) were left-sided LDNs. Mean operative time was 335.1 ± 66.9 minutes, blood loss was 303.9 ± 333.2 mL, and warm ischemia time was 243.2 ± 127.0 seconds. Multiple renal arteries required bench arterial reconstruction in 7 (17.5%) donor kidneys. Three renovascular injuries occurred intraoperatively, and 2 (5.0%) required open conversion. The overall postoperative complication rate was 20.0%. Postoperative donor serum creatinine was 1.5 times higher than preoperative serum creatinine. All but one recipient was discharged with adequate renal function. Graft function continues in 36 of the 38 harvested kidneys (94.7%) during the follow-up period. One (2.5%) recipient developed ureteral necrosis, and no recipients developed vascular thrombosis. Conclusions LDNs can be performed with careful adoption and evolution in institutions without a large patient volume. The intraoperative complication rate of LDN can be reduced with experience.

Although the operative mortality of pancreaticoduodenal resection has decreased recently, the operative morbidity resulting from a leaking pancreatic anastomosis remains high. We described our experience in 50 consecutive cases with a simple, secure end to side pancreaticojejunostomy. We used a paediatric nasogastric tube in the pancreatic remnant duct as a temporary external pancreatic drain. There were 29 men and 21 women ranging from 12 to 84 years with a median age of 61 years. Forty-two patients underwent a standard Whipple procedure and eight a pylorus preserving pancreaticoduodenectomy. Average operating time was 270 minutes with a range of 170 to 480 minutes. The pancreaticojejunostomy could be constructed in a mean of 8 minutes. Intraoperative blood loss ranged from 150 to 3500 mL with a mean of 910mL. Twenty-five patients (50 %) received no blood transfusion. The consistency of the pancreatic remnant was hard in 12 patients (24 %) and normal in 38 patients (76 %). The pancreatic duct was dilated (>4mm) in 15 patients (30 %). There was no operative mortality and only three (6.0 %) minor leaks from the pancreatic anastomosis which healed spontaneously. It was difficult to determine if the leaks were related to the consistency of the pancreatic remnant, the size of the pancreatic duct, the amount of intraoperative blood loss, operating time, sex of the patient or experience of the surgeon, as there were only three leaks. We concluded that our technique for pancreaticojejunal anastomosis following pancreaticoduodenectomy was safe and applicable to, standard Whipple or pylorus preserving pancreaticoduodenectomy, small or dilated pancreatic ducts, normal or fibrotic pancreas.

Kidney transplant recipients receiving calcineurin inhibitor-based immunosuppression incur increased long-term risks of cancer and kidney fibrosis. Switch to mammalian target of rapamycin (mTOR) inhibitors may reduce these risks. Steroid or Cyclosporin Removal After Transplant using Everolimus (SOCRATES), a 36-month, prospective, multinational, open-label, randomized controlled trial for de novo kidney transplant recipients, assessed whether everolimus switch could enable elimination of mycophenolate plus either steroids or CNI without compromising efficacy. Patients received cyclosporin, mycophenolate and steroids for the first 14 days then everolimus with mycophenolate and CNIwithdrawal (CNI-WD); everolimus with mycophenolate and steroid withdrawal (steroid-WD); or cyclosporin, mycophenolate and steroids (control). 126 patients were randomized. The steroid WD arm was terminated prematurely because of excess discontinuations. Mean eGFR at month 12 for CNI-WD versus control was 65.1 ml/min/1.73 m2 vs. 67.1 ml/min/1.73 m2 by ITT, which met predefined noninferiority criteria (P = 0.026). The CNI-WD group experienced a higher rate of BPAR(31% vs. control 13%, P = 0.048) and showed a trend towards higher composite treatment failure (BPAR, graft loss, death, loss to follow-up). The 12 month results from SOCRATES show noninferiority in eGFR, but a significant excess of acute rejection when everolimus was commenced at week 2 to enable a progressive withdrawal of mycophenolate and cyclosporin in kidney transplant recipients.

Background Predonation kidney function may be an important factor affecting graft outcome. Increased baseline allograft function may be more effective than strategies to slow the decline in glomerular filtration rate (GFR). However, the role of donor effective renal plasma flow (ERPF) on long-term outcome is less well understood. The purpose of this study was to examine the relationship between preoperative allograft function as measured by ERPF and the decline of allograft function as defined by the annualized change in GFR among living-donor kidney transplant recipients. Methods We performed a retrospective analysis of 83 patients who underwent living donor renal transplantation at our institution from March 2001 to October 2010. A time series analysis of autoregressive integrated moving average (ARIMA) model was applied to determine the annualized change in GFR after transplantation. Univariate and stepwise multivariate analyses were performed using linear regression between preoperative ERPF and annualized change in GFR after transplantation. We also investigated the influence on annualized change in GFR of other donor or recipient variables. Results The ARIMA model revealed that the annualized change in GFR was −1.344 ± 12.476 mL/min/1.73 m 2 per year. Pearson correlation coefficient for the association between predonation ERPF of the transplanted kidney and the annualized change in GFR was 0.033 ( P = .777). Conclusions Poor predonation kidney function was not associated with an increased rate of decline of allograft function. Neither donor age nor renal function (preoperative ERPF value) was a valid predictor of change in GFR among living-donor kidney transplant recipients.

Background Mycophenolic acid (MPA) pharmacokinetics using the mycophenolate mofetil (CellCept) formulation are known to differ between patients receiving tacrolimus (FK) or cyclosporine (CyA), but only limited data exist concerning concomitant use of FK or CyA with enteric-coated mycophenolate sodium (EC-MPS; Myfortic). This retrospective study compared the drug interactions with the mycophenolic acid blood levels using different immunosuppressants and their relation to graft survival. Patients and methods We studied MPA levels in posttransplant sera from 298 renal transplant recipients. Results Patients receiving immunosuppression with CyA + Myfortic showed 94% at 5- and 10-year graft survivals, which were better than CyA + CellCept (75%, 63%). This combination suppressed posttransplant human leukocyte antigen (HLA) antibody development significantly ( P = .03) with higher MPA levels. Conclusion Patients immunosuppressed with CyA + Myfortic showed higher MPA levels and lower posttransplant HLA antibody development as well as the best graft survival. CyA + Myfortic or FK + Cellcept may be better combinations.

Background. Recent studies show that almost all patients who have rejected a kidney transplant had human leukocyte antigen (HLA) antibodies. In this study, we sought to determine whether patients develop HLA antibodies before chronic rejection. Methods. For the past 8 years, 139 patients who had undergone kidney transplantation were systematically examined, using an enzyme-linked immunosorbent assay-based method, for the development of class-I and class-II HLA antibodies 3 months, 6 months, and yearly after transplantation. Chronic rejection was diagnosed by biopsy. Results. Among 29 patients with chronic rejection, 100% of the patients had HLA antibodies before rejection. Of these patients, 14 patients developed antibodies de novo. In contrast, among 110 patients with stable function, 27% of the patients developed HLA antibodies posttransplant (P

A 46-YEAR-OLD WOMAN was referred to National Cheng-Kung University Hospital in January, 1997 with a diagnosis of renal hyperparathyroidism. She was uremic and had received hemodialysis for 10 years. She had bone pain and muscular weakness for 2 years and experienced 2 episodes of fractures during this period. There were no palpable neck masses, and the remainder of the physical examination showed no significant findings. Laboratory assessments revealed a serum calcium concentration of 11.1 mg/dL (normal range, 8.1-10.1 mg/dL), a serum phosphorus concentration of 6.3 mg/dL (normal range, 2.5-5.0 mg/dL), an alkaline phosphatase level of 813 U/L (normal range, 30110 U/L), and an intact parathyroid hormone level of 1242 pg/mL (normal range, 10-65 pg/mL). Roentgenograms of the skull showed a pepper-andsalt appearance of the cranial bone and roentgenograms of the hands showed subperiosteal resorption of phalangeal bones. Sonographic examination of the neck revealed 5 hypoechoic nodules, 2 on the right and 3 on the left side. During an operation, 4 hyperplastic parathyroid glands adjacent to the thyroid gland were identified. Subtotal parathyroidectomy and cervical thymectomy were performed, leaving a wellvascularized remnant of the left superior parathyroid gland of about 60 mg. Special attention was paid to the left lateral neck because 3 hypoechoic nodules were shown by preoperative sonography. Within the left carotid sheath, a fusiform swelling of the vagus nerve that initially was thought to be a neurogenic tumor was seen opposite the upper pole of the thyroid (Figure). The perineurium was split longitudinally and a 1.0 × 0.5–cm brownish mass was carefully enucleated from between the vagus fibers. Unexpectedly, on examination of frozen and permanent sections, the intravagal tissue was proved to be hyperplastic parathyroid. Postoperatively, the serum calcium level dropped immediately to below the normal range and was maintained in the normal range with supplements of oral calcium carbonate and 1,25dihydroxyvitamin D3.

BACKGROUND Evidence shows posttransplant antibodies lead to renal allograft failure, but does the time elapsed between transplantation and antibody development impact allograft survival? This is the first study showing importance of when antibodies appear. METHODS Serial sera were collected during 17 years (1991-2008) from two groups of patients, one whose allograft failed due to chronic rejection containing 25 patients (230 sera) and a control group consisting of 25 graft functioning patients (305 sera) who were matched by transplant date to a patient whose graft failed. RESULTS The median follow-up for failure patients was 7.1+/-4.8 years and 11.8+/-4.4 years for controls. Human leukocyte antigens alloantibodies appeared in 24 of 25 (96%) of the failed patients and 48% of the controls (P

Objectives Predonation kidney function is supposed to be an important factor affecting graft outcome. Controversial evidence suggests that higher predonation glomerular filtration rate (GFR) positively correlated with posttransplant graft outcome. The purpose of this study was to examine the relationship between living donor graft kidney function as measured by effective renal plasma flow (ERPF) and short-term graft function. Methods We performed a retrospective analysis of 45 patients who underwent living donor renal transplantation at our institution from 2001 to 2007. The comprehensive nuclear medicine evaluation of donors' ERPF was performed before laparoscopic nephrectomy. The preoperative absolute ERPF–recipient body surface area (F/BSA) ratio and absolute ERPF–recipient body weight (F/Wt) ratio were determined for each donor–recipient pair. Posttransplant graft function was estimated by the four-variable Modification of Diet in Renal Disease (Chinese MDRD) equation. Results Estimated GFR correlated with F/BSA ratio at 3 months and 6 months (Pearson r = .495, P = .001 and r = .441, P = .012). Estimated GFR correlated with F/Wt ratio at 3 months and 6 months ( r = .567, P r = .453, P = .009). The correlations between the estimated GFR at 3 months and other variables were investigated. However, in the final multivariate model, F/BSA ratio and F/Wt ratio were the independent predictors of graft function. Conclusion Preoperative ERPF can be used to calculate F/BSA and F/Wt ratios before living donor kidney transplantation. Our study provided evidence that F/BSA and F/Wt ratios may be considered predictive indices for short-term outcomes. An extreme discrepancy should be avoided between preoperative allograft function (absolute ERPF) and recipient body surface area or body weight.

An increasing number of studies have demonstrated adverse graft survival in patients who have anti-HLA antibodies, whether preformed or developed posttransplantation. This retrospective study used Lambda antigen tray-mixed (LAT-M) screening and Luminex HLA class I and II specificity assay to re-examine the impact of pretransplantation HLA antibody on long-term graft survival. In this study, pretransplantation sera from 288 renal patients were tested using the enzyme-linked immunosorbent assay (ELISA) method, LAT-M. Among the 234 of the patients who did not have pretransplantation antibodies, 85% enjoyed 5-year functional graft survival, 76% 10-year functional graft survival, and 56% 15-year functional graft survival. The corresponding functional graft survival for the 54 patients who tested HLA antibody-positive was 65%, 53%, and 28%, respectively (P = .0021).

Dear Editor, In their recent large, retrospective, cross-sectional study with 7702 renal-transplant patients, Einollahi et al. showed that cyclosporine (CsA) absorption (CA) steadily increases over 3 years post transplant (1). They also indicated that despite the day-to-day and inter-individual variability in CA, the CsA levels are routinely monitored by measuring the predose blood trough level (C0) or the 2-h post-dose level (C2). Their approach was to use the C2/C0 ratio as a measure of CA because it takes into account both the elimination and absorption phases, which are required to identify high and low CsA absorbers (1). According to the convention, the therapeutic target ranges for C0 and C2 of CsA were higher during the first 3 months post-transplant. Although the CsA dose was gradually reduced thereafter, as evidenced by the decreases in C0 and C2, to avoid CsA nephrotoxicity, CA increased during the 3-year post-transplant period. This increase in CA had a significant correlation with allograft function. CA levels also correlated with lower recipient age, hypokalemia, hypernatremia, hypotriglyceridemia, anemia, higher creatinine concentration, and lower LDL levels (1). Literature suggests that increase in CA after renal transplantation is influenced by numerous factors modifying CsA pharmacokinetics, including food, concomitant medication, CsA nephropathy, and decrease in CYP3A4 and P-glycoprotein levels (1). Increased serum creatinine and triglyceride levels, and hypokalemia are also associated with increased CsA levels (1, 2). Einollahi et al., through statistical analysis, showed that many of these factors correlated with higher CA. However, an important noteworthy point is that this study included long-term transplant patients, and the changes in CsA dose at the 4 time points post transplant were associated with decreased C0 and C2 levels and increased CA over a 3-year period (1). This finding suggests that the observed increase in CA is perhaps CsA specific, and highlights the role of inter-individual variability in CsA absorption as an important factor that must be considered for preventing CsA overuse-induced nephrotoxicity. Further, CsA co-administration increases the levels of other immunosuppressants such as mycophenolic acid, showing formulation-based variations (3). Therefore, further studies are needed to clarify the effect of CA on concomitant medications. Chapman et al. discussed the causes of chronic allograft nephropathy (CAN) and concluded that late identification of CAN leading to graft loss is an indication that the intervening strategies tend to be “too little and far too late” (4). A review by Vanrenterghem suggested that an individualized regimen requires selection of an immunosuppressive protocol and monitoring of individual drug-related toxicity, risk factors, and donor organ characteristics (5). Regarding toxicity, C0 does not indicate the amount of absorption, whereas C2 lacks the trough level aspect. Therefore, in renal-transplant patients on CsA, the C2/C0 ratio is a better marker and evidence of increasing CA as it indicates a fold increase in CsA levels from trough levels. In keeping with the spirit of doing “a little more” in patient interest, monitoring the C2/C0 ratio can serve as a balanced and individualized intervention strategy, which can also be applied to other drugs with a narrow therapeutic index.

Background. Clinically, liver dysfunction in renal transplant recipients is related to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. The contribution of parvovirus B19 (B19) to liver disease in renal transplant recipients has not been studied. Here we present the association of liver dysfunction with or without the coinfection of B19, HBV, and HCV after renal transplantation. Methods. We used enzyme-linked immunosorbent assay to identify B19, HBV, and HCV infections in serum samples taken from 144 renal transplant recipients before transplantation and at 12 and 24 months after transplantation. After each patient had fasted for 12 hr, blood was taken for measurement of aspartate aminotransferase and alanine aminotransferase monthly for at least 6 months. Results. Liver dysfunction developed at the significantly higher incidence of 47% in the anti-HCV(+) patients compared with 6% in the noninfected group (P

Background/Purpose: Laparoscopic donor nephrectomy (LDN) has emerged as the preferred technique worldwide, and has contributed to a dramatic increase in living kidney donation during the past decade. We adopted LDN in 2002 with the intention of increasing living kidney donation incentive and maintaining equivalent donor/recipient outcome. Methods: Forty-five LDNs were performed between September 2002 and November 2007. Donor demographics, operative characteristics, perioperative complications and donor/recipient outcome were reviewed retrospectively. The LDN series was divided into earlier and later groups for comparison. To confirm the safety and efficacy of LDN, we compared the results with those of previous series and our open donor nephrectomy (ODN) series. Results: All 45 LDN kidneys were procured and transplanted successfully. Mean donor operation time was 327.7±10.2 minutes, blood loss was 286.0±48.3 mL, and warm ischemia time was 233.9±19.6 seconds. Two (4.4%) open conversions happened in the earlier group. There was a significant decrease in warm ischemia time and donor intraoperative complications in the later group. There was no donor mortality and there were no repeat surgical procedures. Delayed graft function occurred in 8.9% of cases and three (6.7%) recipients developed ureteral complications. All but one recipient was discharged with adequate renal function. Graft function continued in 41 of the 43 harvested kidneys (95.3%). Compared with ODN, there was a significant decrease in donor postoperative stay in the LDN series (p = 0.00). There was no difference between the series with regard to donor safety, donor outcome, and immediate and long-term recipient outcome. Conclusion: The number of living kidney donations increased significantly after adopting LDN in our series. The equivalent donor/recipient outcome of the LDN series compared with that of previous and ODN series was achieved with increasing experience.