Chih-Yuan Lee

Expanding the donor pool: use of renal transplants from non-heart-beating donors supported with extracorporeal membrane oxygenation

Abstract:  In response to organ shortage, we used the renal grafts from non‐heart‐beating donors (NHBDs). Extracorporeal membrane oxygenation (ECMO) was used to maintain NHBDs before organ procurement. We compared the results of renal transplantation from different donors, including heart‐beating donors (HBDs), living‐related donors (LDs), and NHBDs supported with ECMO. From February 1998 to June 2003, we recruited 219 patients receiving renal transplantation at National Taiwan University Hospital. Among them, 31 received kidneys from NHBDs supported with ECMO, 120 from HBDs, and 68 from LDs. Multiple organ transplant recipients were not included in this study. We compared the graft survival, serum creatinine levels, and estimated glomerular filtration rates of the three groups. The rate of delayed graft function was higher in NHBD recipients (41.9%) than in HBD recipients (27.0%) and LD recipients (10.9%) (p = 0.003). In the NHBD group, the recipients of grafts with delayed function had significantly longer ECMO runs (63.1 ± 3.0 min) than those without delayed function (53.7 ± 2.5 min) (p = 0.024). Estimated glomerular filtration rate (p = 0.472) and mean serum creatinine level (p = 0.286) were not significantly different between the three groups using a longitudinal approach. The 5‐yr graft survival rates for NHBD (88.4%, 95% CI: 0.680–0.962), HBD (83.2%, 95% CI: 0.728–0.899), and LD transplant recipients (89.3%, 95% CI: 0.619–0.974) were not significantly different (p = 0.239). The 5‐yr patient survival rates for NHBD, HBD, and LD transplant recipients were 100, 93.0 (95% CI: 0.859–0.966) and 100% respectively. The long‐term allograft survival and function of kidneys from NHBDs supported by ECMO, HBD, and LD did not differ significantly. Long ECMO running time tended to delay graft function.

Prescription pattern of traditional Chinese medicine for climacteric women in Taiwan.

Background Traditional Chinese medicine (TCM) has become more popular as a therapy for symptom relief among menopause-aged women. The aim of this study was to analyze the utilization of TCM for climacteric women in Taiwan. Methods The study analyzed frequency distributions among 19 379 women aged 45–55 years, recruited from a random-sampled cohort of 200 000 people from the National Health Insurance database. Data mining was conducted to explore the co-prescription patterns for finished herbal products (FHP). Result There were 19 379 women aged 45–55 years in the sample; of these, 12 572 (64.9%) utilized TCM services at least once. A total of 4078 (21.0%) of the 19 379 climacteric women utilized 145 200 (79.2%) TCM visits. Of these, 39 802 (21.7%) visits were because of diseases of the musculoskeletal system and connective tissue, of which more than half were treated with acupuncture and traumatology manipulative therapies. There were 28 154 visits with FHP prescriptions because of non-specific symptoms and ill-defined conditions, and Jia-wei-xiao-yao-san was the most frequent formula. Nearly two-thirds of FHP contained more than two herbal formulae. Conclusions Women of climacteric age in Taiwan utilized TCM more often than other age groups. To deal with multiple symptoms and/or diseases among climacteric women, new prescription patterns of combining two or more herbal formulae have evolved. Studies on safety issues and drug–herb interactions are warranted for future research.

Peginterferon alfa-2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 2 receiving haemodialysis: a randomised trial

Objective Data comparing the efficacy and safety of combination therapy with peginterferon plus low-dose ribavirin and peginterferon monotherapy in treatment-naive haemodialysis patients with hepatitis C virus genotype 2 (HCV-2) infection are limited. Design In this randomised trial, 172 patients received 24 weeks of peginterferon alfa-2a 135 μg/week plus ribavirin 200 mg/day (n=86) or peginterferon alfa-2a 135 μg/week (n=86). The efficacy and safety endpoints were sustained virological response (SVR) rate and adverse event (AE)-related withdrawal rate. Results Compared with monotherapy, combination therapy had a greater SVR rate (74% vs 44%, relative risk (RR): 1.68 [95% CI 1.29 to 2.20]; p<0.001). The beneficial effect of combination therapy was more pronounced in patients with baseline viral load ≥800 000 IU/mL than those with baseline viral load <800 000 IU/mL (RR: 3.08 [95% CI 1.80 to 5.29] vs RR: 1.11 [95% CI 0.83 to 1.45]; interaction p=0.001). Patients receiving combination therapy were more likely to have a haemoglobin level of <8.5 g/dL (70% vs 8%, risk difference (RD): 62% [95% CI 50% to 73%]; p<0.001) and required a higher dosage [mean: 13 417vs 6667 IU/week, p=0.027] of epoetin β to manage anaemia than those receiving monotherapy. The AE-related withdrawal rates were 6% and 3% in combination therapy and monotherapy groups, respectively (RD: 2% [95% CI −4% to 9%]). Conclusions In treatment-naive haemodialysis patients with HCV-2 infection, combination therapy with peginterferon plus low-dose ribavirin achieved a greater SVR rate than peginterferon monotherapy. Most haemodialysis patients can tolerate combination therapy. Trial registration number ClinicalTrial.gov number, NCT00491244.

MINI-LAPAROTOMY IMPLANTATION OF PERITONEAL DIALYSIS CATHETERS: OUTCOME AND RESCUE

♦ Background: Continuous ambulatory peritoneal dialysis is one of the main treatments for end-stage renal disease. To correct mechanical outflow obstruction after open surgical methods of catheter insertion, laparoscopic techniques are widely employed. ♦ Methods: Between January 2001 and December 2006, 228 open Tenckhoff catheter implantations were carried out by mini-laparotomy in 218 patients at our medical center. The procedures were all performed by an experienced surgeon, and the postoperative care, patient education, and long-term follow-up were all conducted by the same peritoneal dialysis team. ♦ Results: Infection of the exit site or tunnel was the most common complication (27/228, 11.8%), followed by peritonitis (18/228, 7.9%) and refractory mechanical catheter obstruction (9/228, 3.9%). The main causes of catheter removal were successful renal transplantation (21/228, 9.2%), peritonitis (18/228, 7.9%), and infection of the exit site or tunnel (7/228, 3.1%). In the 9 cases of refractory mechanical catheter obstruction, laparoscopic surgery was performed to identify the pathology and to rescue the catheter at the same time. Omental wrapping was the major cause (8/9) of catheter obstruction, with blood clot in the lumen and tube migration occurring in the remaining case (1/9). Partial omentectomy was performed in 5 patients to prevent recurrent obstruction. Neither technique failure nor operation-related complications were noted in our laparoscopic rescue group. For 20 of the 25 patients with refractory infection of the exit site or tunnel, the salvage technique of partial re-plantation was performed, with an 85% (17/20) technique survival rate. ♦ Conclusions: With an experienced surgeon and a good postoperative care team, open paramedian placement is a simple, safe, and effective method for Tenckhoff catheter insertion, with a low complication rate. Laparoscopic surgery is effective as rescue for mechanical obstruction, and partial re-plantation is effective as salvage for exit-site or tunnel infection.

Robot‐assisted renal transplantation in the retroperitoneum

Minimally invasive surgery for renal transplantation is still under development. We employed the robotic surgical system to perform renal transplantation with a minimally invasive wound. The operation was performed with a Gibson incision and two working ports. The space for the transplantation was created by retroperitoneal dissection with the robot lifting the abdominal wall. Vascular reconstruction was performed with two robotic needle drivers. We successfully performed robot‐assisted renal transplantation in five female and five male patients with an average wound length of 7.7 ± 1.04 cm. Nine of the renal allografts functioned immediately, but one with prolonged warm ischemia during the live donor nephrectomy had delayed function. The average creatinine level and estimated glomerular filtration rate at discharge were 1.31 ± 0.31 mg/dl and 58.2 ± 8.1 ml/min, respectively. All the transplants are currently functioning at 6.9 ± 3.9 months after operations. In conclusion, with robot assistance, minimal invasive renal transplantation can be performed successfully in the retroperitoneum.

De novo malignancy is associated with renal transplant tourism

Despite the objections to transplant tourism raised by the transplant community, many patients continue travel to other countries to receive commercial transplants. To evaluate some long-term complications, we reviewed medical records of 215 Taiwanese patients (touring group) who received commercial cadaveric renal transplants in China and compared them with those of 321 transplant recipients receiving domestic cadaveric renal transplants (domestic group) over the same 20-year period. Ten years after transplant, the graft and patient survival rates of the touring group were 55 and 81.5%, respectively, compared with 60 and 89.3%, respectively, of the domestic group. The difference between the two groups was not statistically significant. The 10-year cumulative cancer incidence of the touring group (21.5%) was significantly higher than that of the domestic group (6.8%). Univariate and multivariate stepwise regression analyses (excluding time on immunosuppression, an uncontrollable factor) indicated that transplant tourism was associated with significantly higher cancer incidence. Older age at transplantation was associated with a significantly increased cancer risk; however, the risk of de novo malignancy significantly decreased with longer graft survival. Thus, renal transplant tourism may be associated with a higher risk of post-transplant malignancy, especially in patients of older age at transplantation.

Ge-on-glass detectors

A single crystalline thin film of Ge on glass is fabricated using wafer bonding and smart cut. A simple metal-insulator-semiconductor detector is demonstrated for visible light and telecommunication wavelength. The implantation damage of separated Ge film bonded on glass is removed by chemical etching, and the surface roughness is reduced from 14to4nm. The defect removal reduces the dark current by a factor of 30 and increases the responsivity by a factor of 1.85 at visible wavelength. The responsivity of 0.27A∕W at 1.3μm wavelength for an unetched device does not increase after damage removal due to the decrease of the absorption layer thickness.

Gender differences in renal transplant graft survival

BACKGROUND/PURPOSE A long-term retrospective study was conducted to assess the risk factors of renal transplant graft failure focusing on the effects of gender of both the donor and the recipient. METHODS Medical records of primary renal transplantation performed in a single transplant hospital were reviewed. Cases of ABO incompatibility, positive cross-matches, or multiple organ transplants were excluded. A total of 766 patient records were reviewed, and variables were analyzed with Kaplan-Meier survival curves and Cox regression to determine the independent factors associated with graft survival. RESULTS The overall 5-year graft and patient survival rates were 84.7% and 92.2%, respectively. Univariate analysis showed significantly poorer prognosis in male patients and in those with acute rejection, delayed function, or more mismatches in human lymphocyte antigens. Multivariate analysis with step-wise regression identified three independent prognostic factors for poor graft survival (male gender, acute rejection, and delayed function). The 5-year graft survival rates for female and male patients were 87.9% and 81.3%, respectively. The risk ratio of graft failure for male renal transplant recipients was 1.3732, when compared with that for female patients. The risk ratios for those with acute rejection and delayed function were 1.8330 and 1.5422, respectively. CONCLUSION Male gender, in addition to acute rejection and delayed function, was found to be an independent prognostic factor for poor renal transplant survival in this long-term retrospective study.

Conversion to combined therapy with sirolimus and mycophenolate mofetil improved renal function in stable renal transplant recipients.

BACKGROUND/PURPOSE Information is needed on renal function improvement after late elimination of calcineurin inhibitors (CNIs) and conversion to combined therapy of sirolimus (SRL) and mycophenolate mofetil (MMF) in Asian renal transplant recipients. METHODS A single-arm prospective study was undertaken to assess the outcome of stable Taiwanese renal transplant recipients who had CNI withdrawn and received combined SRL and MMF therapy. The primary endpoints were acute rejection and renal function. The secondary endpoints were graft and patient survival, side effects and infectious complications. Therapeutic drug monitoring of SRL and MMF was conducted during the study period. RESULTS Thirty patients were recruited at 9-72 (31.7+/-18.6) months post-transplantation. The graft and patient survival rates were both 100% at 12 months, though one of the 30 patients (3.33%, 1/30) had biopsy-proven acute rejection. On paired t test, the estimated glomerular filtration rates (GFR) from 4 to 12 months were significantly higher than the baseline GFR. The average trough level of SRL was 7.38+/-3.74 ng/mL at 12 months and the average abbreviated area under the concentration curve of mycophenolic acid was 64.86+/-36.62 mg/L*hour at an average MMF dose of 1.56+/-0.45 g/day. However, two patients (6.67%, 2/30) had tuberculosis (TB) reactivation at 3 and 4 months, respectively, after the combined SRL and MMF therapy. CONCLUSION Conversion to combined SRL and MMF therapy improved renal function in stable renal transplant recipients, though the risk of TB reactivation should be kept in mind when the combined therapy is employed in the Asian countries with a high prevalence of TB.

Risk of Tuberculosis Among Patients on Dialysis: The Predictive Value of Serial Interferon-Gamma Release Assay.

AbstractPatients on long-term dialysis are at high risk for tuberculosis (TB). Although latent tuberculosis infection (LTBI) is good target for TB eradication, interferon-gamma release assay-defined LTBI has a high proportion of negative conversion and lacks active TB correlation among patients on dialysis.Patients on long-term dialysis were screened in multiple centers in Taiwan. QuantiFERON-TB Gold In-tube (QFT-GIT) was used to define LTBI and was performed thrice at 6-month intervals. The primary outcome was active TB diagnosed after LTBI screening. The incidence and predictive value of QFT-GIT were analyzed.The 940 dialysis patients enrolled had an average age of 59.3 years. The initial QFT-GIT results were positive in 193, including 49.6% with persistent positive results on second check. In an average follow-up period of 3 years, 7 patients had TB. Three (319.1 per 100,000 person-yrs) and 4 (141.8 per 100,000 person-yrs) of them were prevalent and incident TB cases, respectively. Persistent positive QFT-GIT for 2 and 3 times correlated with increased hazard ratio for TB (14.44 and 20.29, respectively) compared with a single positive result (hazard ratio 10.38). Among those with 3 positive QFT-GIT results, TB development rate was 4.5% and incidence rate was 1352.3 per 100,000 person-years. In contrast, none of the incident TB occurred in those with initial positive and then negative conversion of QFT-GIT.In an area of intermediate TB incidence, dialysis patients have high TB risk. LTBI status is a good predictor of TB development, especially for those with more than 1 positive result. After excluding prevalent TB cases, serial follow-up of LTBI may narrow the target population to reduce treatment costs.