Randomized Trial of Machine Perfusion Versus Cold Storage in Recipients of Deceased Donor Kidney Transplants With High Incidence of Delayed Graft Function

BACKGROUND: This study compared the use of static cold storage versus continuous hypothermic machine perfusion in a cohort of kidney transplant recipients at high risk for delayed graft function (DGF). METHODS: In this national, multicenter, and controlled trial, 80 pairs of kidneys recovered from brain-dead deceased donors were randomized to cold storage or machine perfusion, transplanted, and followed up for 12 months. The primary endpoint was the incidence of DGF. Secondary endpoints included the duration of DGF, hospital stay, primary nonfunction, estimated glomerular filtration rate, acute rejection, and allograft and patient survivals. RESULTS: Mean cold ischemia time was high but not different between the 2 groups (25.6 ± 6.6 hours vs 25.05 ± 6.3 hours, 0.937). The incidence of DGF was lower in the machine perfusion compared with cold storage group (61% vs. 45%, P = 0.031). Machine perfusion was independently associated with a reduced risk of DGF (odds ratio, 0.49; 95% confidence interval, 0.26-0.95). Mean estimated glomerular filtration rate tended to be higher at day 28 (40.6 ± 19.9 mL/min per 1.73 m2 vs 49.0 ± 26.9 mL/min per 1.73 m2; P = 0.262) and 1 year (48.3 ± 19.8 mL/min per 1.73 m2 vs 54.4 ± 28.6 mL/min per 1.73 m2; P = 0.201) in the machine perfusion group. No differences in the incidence of acute rejection, primary nonfunction (0% vs 2.5%), graft loss (7.5% vs 10%), or death (8.8% vs 6.3%) were observed...

Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses.

This study compared the incidence of CMV infection/disease in de novo kidney transplant recipients receiving everolimus or mycophenolate and no CMV pharmacological prophylaxis. We randomized 288 patients to receive a single 3 mg/kg dose of antithymocyte globulin, tacrolimus, everolimus, and prednisone (r-ATG/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (BAS/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (BAS/MPS, n = 101). The primary end-point was the incidence of first CMV infection/disease in the intention-to-treat population at 12 months. Patients treated with r-ATG/EVR showed a 90% proportional reduction (4.7% vs. 37.6%, HR 0.10, 95% CI 0.037-0.29; p < 0.001), while those treated with BAS/EVR showed a 75% proportional reduction (10.8% vs. 37.6%, HR 0.25, 95% CI 0.13-0.48; p < 0.001) in the incidence of CMV infection/disease compared to BAS/MPS. There were no differences in the incidence of acute rejection (9.4 vs. 18.6 vs. 15.8%, p = 0.403), wound-healing complications, delayed graft function, and proteinuria. Mean estimated glomerular filtration rate was lower in BAS/EVR (65.7 ± 21.8 vs. 60.6 ± 20.9 vs. 69.5 ± 21.5 ml/min, p = 0.021). In de novo kidney transplant recipients receiving no pharmacological CMV prophylaxis, reduced-dose tacrolimus and everolimus was associated with a significant reduction in the incidence of CMV infection/disease compared to standard tacrolimus dose and mycophenolate (ClinicalTrials.gov NCT01354301).

Asynchronous kidney allograft loss after simultaneous pancreas-kidney transplantation: impact on pancreas allograft outcome at a single center.

OBJECTIVE: We analyzed the clinical evolution of pancreas allografts in simultaneous pancreas-kidney transplantation (SPKT) cases after asynchronous kidney allograft loss and kidney retransplantation at a single non-United States center. PATIENTS AND METHODS: We performed a retrospective analysis of 168 SPKT from December 2000 to June 2007. RESULTS: The 5-year kidney allograft survival rate was 71%. Excluding cases of death with a functioning graft after SPKT (n = 35; 74.4%), 12 kidney allografts were lost due to acute rejection (n = 7; 15%) or chronic allograft nephropathy (n = 5; 10.6%). Delayed graft function contributed to kidney allograft loss. Five of 12 patients underwent kidney retransplantation. Sixty percent of pancreas allografts were lost after this procedure, which was attributed to either the diabetogenic effects of the immunosuppressive regimen or to the perioperative stress. Oral glucose tolerance tests performed before kidney retransplantation identified patients with good pancreas allograft function versus those with intolerance on glucose tests who received reduced glucocorticoid doses. CONCLUSIONS: In SPKT, pancreas allograft function was seriously affected by kidney retransplantation. Oral glucose tolerance tests performed before kidney retransplantation were helpful to assess beta-cell function and suggest prescription of lower steroid doses to decrease the pancreas allograft dysfunction.

Score for Neonatal Acute Physiology and Perinatal Extension II as a predictor of retinopathy of prematurity: study in 304 very-low-birth-weight preterm infants.

AIM: To evaluate the use of the Score for Neonatal Acute Physiology and Perinatal Extension (SNAPPE-II) at admission to predict the development of retinopathy of prematurity (ROP) among very-low-birth-weight preterm babies. METHODS: A prospective cohort study included 304 infants screened for ROP from July 2004 to October 2007. The main outcomes were the development of any stage ROP and severe ROP. The main variable was the SNAPPE-II obtained at admission. Seventeen risk factors for ROP were studied by univariate analysis (chi(2) and Student's t test). A simple descriptive analysis was used for the SNAPPE-II (mean, median, standard deviation and interquartile range: p25-p75). Logistic regression and receiver-operating characteristic (ROC) curve were calculated for SNAPPE-II. Ophthalmological examinations started at the 6th week of life and were repeated until the 45th week of corrected gestational age (GA). RESULTS: The mean GA and mean birth weight of the whole cohort were 30.3 weeks (+/-2.2) and 1,209.2 g (+/-277.7), respectively. The median SNAPPE-II among non-ROP and ROP patients were 6.0 and 15.0, respectively (p = 0.001). When compared with severe ROP patients (25.0) there was also a significant difference (p = 0.003). After logistic regression, the SNAPPE-II adjusted odds ratio for ROP was 1.024. The area under the ROC curve was 0.62 (95% confidence interval: 0.55-0.70, p < 0.001). The best discriminative cutoff value was 8.5 (sensitivity: 68%; specificity: 54%; positive predictive value: 37.3%; negative predictive value: 80.6%). CONCLUSIONS: The SNAPPE-II values at admission were significantly higher among babies with ROP, suggesting a positive association between higher scores with the development of ROP, but after adjusted logistic regression and ROC curve results, the SNAPPE-II scores at admission did not enhance the assessment of risk for ROP.

Simultaneous pancreas-kidney transplantation: infectious complications and microbiological aspects.

OBJECTIVE: The purpose of this study was to describe the clinical and microbiological characteristics of the infectious complications among simultaneous pancreas-kidney transplantations (SPKT). MATERIALS AND METHODS: Among the first 45 SPKT the mean age was 34 years (range, 21 to 49) and the mean duration of follow-up 13 months (range, 2 to 27 months). RESULTS: Twenty-three patients (51%) presented at least one to three episodes (1.7 mean) of infectious complications that needed hospitalization. The etiology of the infections included 71% bacterial (44% gram-negative rods and 27% gram-positive cocci), 16% viral (12% from CMV and 4% from Herpes sp) and 13% fungal (8% by Candida sp and 4% by others fungus). Wound and urinary infections were most frequent, occurring in 22% and 28% of the patients, respectively. All patients who were submitted to vesical drainage developed infections in contrast a rate of only 44% among patients undergoing enteric drainage. CONCLUSION: Infectious complications are the main cause of morbidity and mortality following simultaneous pancreas-kidney transplantation, especially with vesical drainage. The use of enteric drainage combined with administration of broad spectrum prophylactic antibiotics is recommended.

Risk factors for the development of posttransplantation diabetes mellitus in simultaneous pancreas and kidney recipients.

We sought to determine the risk factors involved in the development of posttransplantation diabetes mellitus (PTDM) following simultaneous pancreas and kidney transplantation. Correlations were sought between tacrolimus (FK-506) levels/dose 2-hour capillary glucose (CG) and glycosylated hemoglobin (HbA(1c)), cyclosporine (CSA) levels/dose with HbA1c, 2-hour CG with prednisone dose and body mass index (BMI) and PTDM. Four patients (9.3%) developed PTDM. Three treated with FK-506 had altered 2-hour CG at 3 months after transplantation; 1 prescribed CSA displayed diabetes diagnosed after 1 year. There was no statistically significant difference among HbA(1c) values and FK-506 (P =.18) or CSA (P =.81) doses or FK-506 (P =.53) and CSA (P =.54) levels. In contrast, there was a statistically significant relationship between elevated 2-hour CG (> or =200 mg/dL) and daily prednisone dose (9.7 mg vs. 16.2 mg; P =.003). There was no correlation between 2-hour CG and FK-506 dose (P =.084) or FK-506 levels (P =.075). The greater BMI correlated with an increased risk of PTDM (21.25 +/- 3.13 kg/m(2) vs 24.67 +/- 2.38 kg/m(2); P =.034). Two-hour CG may be a useful tool to screen the diabetogenic effects of corticosteroids. A BMI increase should be discouraged due to the risk of PTDM.

Intracavernous injection in the treatment of erectile dysfunction after radical prostatectomy: an observational study.

CONTEXT: Despite the recent improvements in performing radical retropubic prostatectomy that have led to a considerable decrease in the complication rate, erectile dysfunction still represents a major problem. Moreover, less invasive treatment options that are emerging for erectile dysfunction have not shown satisfactory results in managing these patients. OBJECTIVE: To study the efficacy and side effects of self-injection therapy in the treatment of men who had become impotent after undergoing radical prostatectomy due to prostate cancer, over a study period of 96 months. DESIGN: Observational study. SETTING: University Referral Center. PARTICIPANTS: 168 patients with erectile dysfunction, aged 43 to 78 years old, who underwent radical retropubic prostatectomy due to localized prostate cancer. PROCEDURES: The patients were treated with self-injection therapy using papaverine, phentolamine and prostaglandin E1, at home. RESULTS: This study showed an acceptable 94.6% success rate, with no life-threatening complications. In addition to this, our series presented a 13.1% cure rate with this therapy. CONCLUSION: Self-injection therapy with papaverine, phentolamine and prostaglandin E1 is effective and safe in the treatment of erectile dysfunction after radical prostatectomy.

Physiological aspects involved in production of xylanolytic enzymes by deep-sea hyperthermophilic archaeon Pyrodictium abyssi.

Xylanases (EC 3.2.1.8) catalyze the hydrolysis of xylan, the major constituent of hemicellulose. The use of these enzymes could greatly improve the overall economics of processing lignocellulosic materials for the generation of liquid fuels and chemicals. The hyperthermophilic archaeon Pyrodictium abyssi, which was originally isolated from marine hot abyssal sites, grows optimally at 97 degrees C and is a prospective source of highly thermostable xylanase. Its endoxylanase was shown to be highly thermostable (over 100 min at 105 degrees C) and active even at 110 degrees C. The growth of the deep-sea archaeon P. abyssi was investigated using different culture techniques. Among the carbohydrates used, beech wood xylan, birch wood glucuronoxylan and the arabinoxylan from oats pelt appeared to be good inducers for endoxylanase and beta-xylosidase production. The highest production of arabinofuranosidase, however, was detected in the cell extracts after growth on xylose and pyruvate, indicating that the intermediate of the tricarboxylic acid cycle acted as a nonrepressing carbon source for the production of this enzyme. Electron microscopic studies did not show a significant difference in the cell surface (e.g., xylanosomes) when P. abyssi cells were grown on different carbohydrates. The main kinetic parameters of the organism have been determined. The cell yield was shown to be very low owing to incomplete substrate utilization, but a very high maximal specific growth rate was determined (micromax = 0.0195) at 90 degrees C and pH 6.0. We also give information on the problems that arise during the fermentation of this hyperthermophilic archaeon at elevated temperatures.

The Newest Findings about Viral Etiology of Chronic Fatigue Syndrome

Objetivando testar a hipótese de que os títulos elevados de anticorpos virais em pacientes com síndrome de fadiga crônica(SFC) deve-se a uma resposta imune policlonal inespecífica, foram mensurados os anticorpos para HSV1 e HSV2. Mais do que dois terços dos casos foram IgG e IgM positivos para HSV1 e HSV2. Mais do que dois terços dos casos foram IgM e IgG negativos para vírus Epstein-Barr (EBV) e, dentre os que foram sorologicamente testados para HHV-6 e enterovirosres, a totalidade foi näo reagente. O presente estudo demonstrou que as herpesviroses tipo 1 e 2(HSV1 e HSV2) podem estar associadas com a SFC na populaçäo brasileira. A ausência simultänea de elevados níveis de anticorpos para as virosesmais comuns, nos pacientes com SFC, näo dá sustentaçäo à hipótese de que uma reaçäo imune policlonal seja a causa dos altos títulos de anticorpos virais observados nos pacientes acometidos por esta condiçäo clínica. Ao contrário, os resultados sugerem que, na maioria dos casos da SFC, a elevaçäo dos títulos dos anticorpos virais näo se deve a uma resposta imune policlonal inespecífica