Research Note: Preliminary assessment of the impact of dietary yeast products on egg production and cecal microbial profiles of laying hens.

The objective of the current study was to conduct an initial comparison of commercial yeast products in layer hen diets on egg production parameters and the corresponding impact on the cecal microbiota. A short-term feeding study was conducted with 35 laying hens receiving either a control, or 1 of 4 different yeast fermentation products, Immunowall, Hilyses (both from ICC, São Paulo, Brazil), Citristim (ADM, Decatur, IL), and Maxi-Gen Plus (CBS Bio Platforms, Calgary, Canada) with 7 hens per treatment from 40 to 46 wk of age. At the end of the trial, hens were euthanized, the ceca removed and prepared for denatured gradient gel electrophoresis (DGGE) microbial compositional analyses. Although initial shell weight and shell thickness were similar among the treatment groups, hens fed Hilyses had lower shell weight and thickness at the end of the experiment. The most predominant DGGE bands with the strongest intensity were identified as Lactobacillus species and excised double bands were identified as Bacillus, Clostridium, or Lachnospiraceae. In this short-term feeding trial, the commercial yeast products tested had little effect on egg production and shell quality, and only moderately impacted the composition of mature layer hen cecal microbiota.

Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

Isolation and characterization of novel microsatellite loci in the wrinkled frog.

The wrinkled frog, Rana rugosa, is a species complex that inhabits plains and mountains near freshwater bodies throughout East Asia, encompassing China, Korea, Japan, and the Russian Primorye region. Although extensive efforts are required to estimate cryptic diversity in the R. rugosa complex, no specifically designed microsatellite loci are available. Here, novel and polymorphic microsatellites were isolated based on the construction of a microsatellite-enriched library and characterized using R. rugosa specimens collected on the Korean Peninsula. A total of 72 primer sets were designed from approximately 400 positive clones, and 22 were validated as being reliably amplified and polymorphic. Overall, high genetic variability was observed (mean number of alleles per locus = 22.23; mean observed and expected heterozygosities = 0.770 and 0.816, respectively) from a total of 60 individuals sampled from two geographically isolated localities. In the two sites analyzed, an extremely low level of relatedness was inferred from the estimation of pairwise relatedness, and no evidence of a genetic bottleneck was detected. The two sites showed a high level of genetic differentiation, suggesting a clear signature of isolation following colonization. With high statistical power in parentage and sibship exclusion, these microsatellite loci will be suitable for the identification of cryptic diversity and population structure as well as the recognition of individuals in social interaction and captive breeding practice.

Cost-effectiveness of pediatric heart transplantation across a positive crossmatch for high waitlist urgency candidates.

Allosensitized children listed with a requirement for a negative prospective crossmatch have high mortality. Previously, we found that listing with the intent to accept the first suitable organ offer, regardless of the possibility of a positive crossmatch (TAKE strategy), results in a survival advantage from the time of listing compared to awaiting transplantation across a negative crossmatch (WAIT). The cost-effectiveness of these strategies is unknown. We used Markov modeling to compare cost-effectiveness between these waitlist strategies for allosensitized children listed urgently for heart transplantation. We used registry data to estimate costs and waitlist/posttransplant outcomes. We assumed patients remained in hospital after listing, no positive crossmatches for WAIT, and a base-case probability of a positive crossmatch of 47% for TAKE. Accepting the first suitable organ offer cost less ($405 904 vs. $534 035) and gained more quality-adjusted life years (3.71 vs. 2.79). In sensitivity analyses, including substitution of waitlist data from children with unacceptable antigens specified during listing, TAKE remained cost-saving or cost-effective. Our findings suggest acceptance of the first suitable organ offer for urgently listed allosensitized pediatric heart transplant candidates is cost-effective and transplantation should not be denied because of allosensitization status alone.

Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines

Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.

Comparison of listing strategies for allosensitized heart transplant candidates requiring transplant at high urgency: a decision model analysis.

Allosensitized children who require a negative prospective crossmatch have a high risk of death awaiting heart transplantation. Accepting the first suitable organ offer, regardless of the possibility of a positive crossmatch, would improve waitlist outcomes but it is unclear whether it would result in improved survival at all times after listing, including posttransplant. We created a Markov decision model to compare survival after listing with a requirement for a negative prospective donor cell crossmatch (WAIT) versus acceptance of the first suitable offer (TAKE). Model parameters were derived from registry data on status 1A (highest urgency) pediatric heart transplant listings. We assumed no possibility of a positive crossmatch in the WAIT strategy and a base-case probability of a positive crossmatch in the TAKE strategy of 47%, as estimated from cohort data. Under base-case assumptions, TAKE showed an incremental survival benefit of 1.4 years over WAIT. In multiple sensitivity analyses, including variation of the probability of a positive crossmatch from 10% to 100%, TAKE was consistently favored. While model input data were less well suited to comparing survival when awaiting transplantation across a negative virtual crossmatch, our analysis suggests that taking the first suitable organ offer under these circumstances is also favored.

Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines.

Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.

Different risk factors for candidemia occur for Candida species belonging to the C. parapsilosis complex.

Previous studies have demonstrated reduced virulence in the species that comprise the Candida parapsilosis complex. We investigated a cohort of 93 patients with candidemia caused by this complex. Most infections were caused by C. parapsilosis (80.6%), followed by C. orthopsilosis (18.3%) and C. metapsilosis (1.1%). Renal failure (P < 0.001) and chronic liver diseases (P = 0.019) were more frequently encountered with infections caused by the C. orthopsilosis group, suggesting an association with patients who had a greater state of immune suppression in comparison with infections caused by C. parapsilosis sensu stricto.

Exclusive radiotherapy for gliomatosis cerebri: long-term follow-up at a single institution.

PURPOSE: To evaluate the efficacy of radiotherapy and factors affecting the prognosis of gliomatosis cerebri. METHODS: Twenty-eight patients with pathologically confirmed gliomatosis cerebri underwent radiotherapy between August 1988 and September 2003. The median age of the patients was 39 years (range 18-67). Performance status was good (ECOG score ≤2) in 23 patients (82 %). The extent of radiotherapy was partial brain in 17 patients, whole brain in 2 patients, and whole brain followed by partial brain in 9 patients. The median radiation dose was 55.8 Gy (range 46.8-70.4). The median duration of follow-up was 136 months for survivors (range 39-191). RESULTS: The median overall and progression-free survival times of all patients were 20 and 11 months, respectively. When initial response to radiotherapy was grouped as improved, stationary, and aggravated, the median overall survival times in patients with improved, stationary, and aggravated responses were 76, 20, and 7 months, respectively (p = 0.0129). However, radiation parameters such as dose and irradiation volume had no impact on overall survival. On multivariate analysis, both performance status and initial response to radiotherapy were significant prognostic factors affecting overall survival (p = 0.0249 and 0.0065, respectively). CONCLUSIONS: This study showed that gliomatosis cerebri could be effectively treated with radiotherapy and that initial response to radiotherapy was a significant prognostic factor affecting the survival.

Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.

We identified new gene fusions in patients with lung cancer harboring the kinase domain of the NTRK1 gene that encodes the high-affinity nerve growth factor receptor (TRKA protein). Both the MPRIP-NTRK1 and CD74-NTRK1 fusions lead to constitutive TRKA kinase activity and are oncogenic. Treatment of cells expressing NTRK1 fusions with inhibitors of TRKA kinase activity inhibited autophosphorylation of TRKA and cell growth. Tumor samples from 3 of 91 patients with lung cancer (3.3%) without known oncogenic alterations assayed by next-generation sequencing or fluorescence in situ hybridization demonstrated evidence of NTRK1 gene fusions.

Molecular phylogenetic relationships among members of the family Phytolaccaceae sensu lato inferred from internal transcribed spacer sequences of nuclear ribosomal DNA.

The phylogeny of a phylogenetically poorly known family, Phytolaccaceae sensu lato (s.l.), was constructed for resolving conflicts concerning taxonomic delimitations. Cladistic analyses were made based on 44 sequences of the internal transcribed spacer of nuclear ribosomal DNA from 11 families (Aizoaceae, Basellaceae, Didiereaceae, Molluginaceae, Nyctaginaceae, Phytolaccaceae s.l., Polygonaceae, Portulacaceae, Sarcobataceae, Tamaricaceae, and Nepenthaceae) of the order Caryophyllales. The maximum parsimony tree from the analysis resolved a monophyletic group of the order Caryophyllales; however, the members, Agdestis, Anisomeria, Gallesia, Gisekia, Hilleria, Ledenbergia, Microtea, Monococcus, Petiveria, Phytolacca, Rivinia, Schindleria, Seguieria, Stegnosperma, and Trichostigma, which belong to the family Phytolaccaceae s.l., did not cluster under a single clade, demonstrating that Phytolaccaceae is polyphyletic.

Genetic variants of AICDA/CASP14 associated with childhood brain tumor.

We conducted a hospital-based case-control study in Korea to investigate whether apoptosis- and cell cycle control-related genes are associated with childhood brain tumor. Incident brain tumor cases (N = 70) and non-cancer controls (N = 140), frequency-matched by age and gender, were selected from 3 teaching hospitals in Seoul between 2003 and 2006. Tag single nucleotide polymorphisms (SNPs) (N = 297) in 30 genes related to apoptosis and cell cycle control were selected using a pairwise linkage-disequilibrium-based algorithm. Five tag SNPs in 2 genes (AICDA and CASP14) remained significant after adjusted multiple tests. The most significant association with childhood brain tumor risk was for IVS1-401G>C in the AICDA gene [odds ratio (OR) = 2.8; 95% confidence interval (95%CI) = 1.25-6.46]; the polymorphism *9276A>C of CASP14 was associated with decreased brain tumor risk (OR = 0.4; 95%CI = 0.19-0.95). We concluded that genetic polymorphisms in AICDA and CASP14 are associated with risk for brain tumor in Korean children.

Phylogeny and systematics of Indian Polygonum sensu lato in the subfamily Polygonoideae based on ITS sequences of nuclear ribosomal DNA.

The nuclear ribosomal DNA internal transcribed spacer (ITS) sequences from 44 Indian Polygonum taxa were examined to investigate relationships among various sections proposed by earlier researchers. The maximum parsimony trees obtained from analysis of the ITS sequences suggested eight major groups of the Indian Polygonum spp. The relationships among different sections were largely congruent with those inferred from morphological characters as described by Hooker. Also, the treatment of the Persicaria suggested by Haraldson on the basis of anatomical characters proved to be nearly in line with that based on our molecular data. We provide a high resolution of phylogeny of the Himalayan Polygonum sensu lato and support merger of the section Amblygonon in the section Persicaria. Moreover, we made the first phylogenetic analysis of many of the less known Himalayan Polygonums, including Polygonum microcephalum, P. assamicum, P. recumbens, and P. effusum. Molecular differences were detected among Persicaria barbata collected from different geographical locations of India, although these were not differentiated at the morphological level.

Combined analysis of the MspI and XbaI polymorphisms in intron 22 of the factor VIII gene for detection of hemophilia A in a Korean population.

To determine the usefulness of MspI/int22h-1 (intron 22 homologous region-1) polymorphism of the factor VIII gene for molecular genetic diagnosis of hemophilia A in the Korean population, MspI/intron 22 and XbaI/intron 22 polymorphisms were analyzed in 101 unrelated Korean families with severe hemophilia A. The expected heterozygosity rates of MspI/int22h-1 and XbaI/int22h-1 polymorphisms were 49.5 and 43.6%, respectively; these polymorphisms were not in complete linkage disequilibrium. Combined analysis using both polymorphisms provided an informative rate of 66.3%. These results suggest that PCR analysis of the MspI/int22h-1 polymorphism of the factor VIII gene would be useful for carrier detection and prenatal diagnosis of hemophilia A in the Korean population.

Lipid profile changes during the first year after kidney transplantation: risk factors and influence of the immunosuppressive drug regimen.

AIM: This study analyzed the incidence, time course, and risk factors associated with dyslipidemia during the first year after kidney transplantation among patients receiving various immunosuppressive regimens. METHODS: The analysis included 474 kidney transplant recipients receiving cyclosporine (CSA) combined with sirolimus (SRL; n=137) or mycophenolate (MMF, n=58) or everolimus (EVR, n=47); or SRL combined with MMF (n=32); or tacrolimus (TAC) combined with SRL (n=86) or MMF (n=114). All patients received prednisone. We evaluated the influence of demographic features, clinical outcomes, and statin use on lipid profiles during the first year after transplantation. total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (hdl-C), low-density lipoprotein cholesterol (ldl-C), non-HDL-C, TC:HDL-C, LDL-C:HDL-C, TG:HDL-C. RESULTS: Lipid profiles were within the recommended ranges in 28% of patients pretransplantation and in 10% at 1 year; 27% of them received statins. At 1 year, LDL-C<100 mg/dL was observed in 31.8% of patients but more than 35% of these patients still showed other lipid fractions or ratios outside recommended target concentrations. Among all patients with LDL-C>100 mg/dL, almost 70% to 80% had other lipid fractions or ratios within target ranges. A logistic regression analysis showed age, gender, time on dialysis, diabetes, type of calcineurin inhibitor (CSA vs TAC), adjunctive therapy (SRL/EVR vs MMF) and prednisone dose to be associated with dyslipidemia. CONCLUSION: Dyslipidemia is frequent at 1 year after transplantation. The lack of agreement among changes observed in lipid fractions and ratios suggests that more studies are necessary to guide therapy besides targeting LDL-C concentrations as recommended by current guidelines.

Risk factors associated with graft loss and patient survival after kidney transplantation.

OBJECTIVE: To evaluate the influence of traditional risk factors on major kidney transplantation outcome. PATIENTS AND METHODS: Data from kidney transplantation procedures performed between 2003 and 2006 were retrospectively analyzed for the influence of traditional risk factors on transplantation outcome. Of 2364 transplants, 67% were from living donors, 27% were from donors who met standard criteria, and 6% were from donor who met expanded criteria. Two hundred thirty-nine procedures (10%) were performed in pediatric patients. Immunosuppression was selected on the basis of subgroup population. RESULTS: At 1 year posttransplantation, cumulative freedom from a treated acute rejection episode (ARE) was 76.7%, with no difference between black vs nonblack recipients (75.0% vs 73.4%; P = .79). At 2 years, survival for patients (95.3% vs 88.3% vs 82.1%; P < .001) and grafts 92.3% vs 80.3% vs 70.9%; P < .001) was better in recipients of living donor grafts compared with donors who met standard or expanded criteria, respectively. Moreover, graft survival was poorer in black vs nonblack patients (83.6% vs 88.7%; P < .05) because of high mortality (13% vs 7%; P<.001). Risk factors associated with death included cadaveric donor organ (odds ratio [OR], 2.4) and black race (OR, 1.8), and risk factors associated with graft loss included cadaveric donor organ (OR, 2.1), extended-criteria criteria donor organ (OR, 2.0), delayed graft function (OR, 1.8), and any ARE (OR, 3.5). At 6 months posttransplantation, risk factors associated with death included cadaveric donor organ (OR, 2.5) or ARE (OR, 2.4), and risk factors associated with graft loss included cadaveric donor organ (OR, 2.0), extended-criteria donor organ (OR, 2.6), ARE (OR, 9.5), and impaired graft function (creatinine concentration >1.5 mg/dL; OR, 2.1). CONCLUSION: Traditional risk factors are still associated with transplantation outcome. Poorer graft survival in black vs nonblack recipients was due to higher mortality rather than graft loss.

Clinical impact of polymorphisms of transport proteins and enzymes involved in the metabolism of immunosuppressive drugs.

Individualization of immunosuppressive therapy after solid organ transplantation is a goal that has been pursued for a long time. Nevertheless, in clinical practice, we are still stratifying patients in subgroups in which risk is assessed using demographic information and population analysis. Then, a combination of immunosuppressive drugs is chosen and doses are individualized to compensate for intra- and interindividual variabilities in drug pharmacokinetics, to obtain similar plasma/blood concentrations that are believed to be therapeutic, again based on data derived from population analysis. One step further in this strategy is to recognize, before initiation of immunotherapy, those patients at higher risk to be either under- or overexposed to currently used immunosuppressive drugs. Several studies have been undertaken to correlate single nucleotide polymorphisms in genes encoding transport proteins and metabolizing enzymes involved in the disposition of immunosuppressive drugs. Overall, the results from these studies have been mixed. The causes of these sometimes conflicting results include methodologic, genetic, or nongenetic factors. The degree of linkage disequilibrium, the measure of nonrandom associations between polymorphisms at different loci, not necessarily on the same chromosome, is perhaps the main genetic factor. The influence of the environment, physiology (such as kidney and liver functions), disease state, use of multidrug regimens, and inherent drug-to-drug interactions are present nongenetic factors. Moreover, it is also important to increase our knowledge of the genetic factors involved in the variabilities observed in drug responses of pharmacodynamics. True individualized therapy, with the ability to improve health outcomes of each transplant recipient, will depend on our knowledge of the genetic factors involved in immunological response and drug pharmacokinetics and pharmacodynamics.

Exploratory calcineurin inhibitor-free regimens in living-related kidney transplant recipients.

Chronic allograft nephropathy is among the major causes of graft loss even in low-risk kidney transplant recipients and correlates with acute nephrotoxic events during the first year post-transplant. Therefore, calcineurin inhibitor-free regimens may improve patient and graft survival among recipients of living-related kidney transplants. To confirm this hypothesis, we evaluated the efficacy and safety of two calcineurin inhibitor-free regimens in 92 low-risk recipients of one-haplotype living-related kidney transplants. Immunosuppression consisted of tacrolimus, azathioprine and prednisone (group I, GI, N = 38), 2 doses of daclizumab, mycophenolate mofetil (MMF), and prednisone (GII, N = 33) and 2 doses of daclizumab, MMF, sirolimus and prednisone (GIII, N = 21). At 12 months, treatment failure (biopsy-confirmed acute rejection, graft loss or death) was higher in GII compared to GIII and GI (54.5 vs 24.0 vs 13.1%, P < 0.01, respectively). In patients of black ethnicity the incidence of acute rejection was 25 vs 83.3 vs 20% (P = 0.055), respectively. Patient and graft survival was comparable. There were no differences in mean creatinine or calculated creatinine clearance at 12 months. Overall incidence of post-transplant diabetes mellitus (3.3%) and cytomegalovirus disease (4.3%) was similar in all groups. Further development of effective calcineurin inhibitor-free regimens should exclude patients of black ethnicity and may need full-induction therapy, perhaps with depleting agents, and concentration-controlled use of sirolimus and MMF.

Exploratory calcineurin inhibitor-free regimens in living-related kidney transplant recipients

Chronic allograft nephropathy is among the major causes of graft loss even in low-risk kidney transplant recipients and correlates with acute nephrotoxic events during the first year post-transplant. Therefore, calcineurin inhibitor-free regimens may improve patient and graft survival among recipients of living-related kidney transplants. To confirm this hypothesis, we evaluated the efficacy and safety of two calcineurin inhibitor-free regimens in 92 low-risk recipients of one-haplotype living-related kidney transplants. Immunosuppression consisted of tacrolimus, azathioprine and prednisone (group I, GI, N = 38), 2 doses of daclizumab, mycophenolate mofetil (MMF), and prednisone (GII, N = 33) and 2 doses of daclizumab, MMF, sirolimus and prednisone (GIII, N = 21). At 12 months, treatment failure (biopsy-confirmed acute rejection, graft loss or death) was higher in GII compared to GIII and GI (54.5 vs 24.0 vs 13.1 percent, P < 0.01, respectively). In patients of black ethnicity the incidence of acute rejection was 25 vs 83.3 vs 20 percent (P = 0.055), respectively. Patient and graft survival was comparable. There were no differences in mean creatinine or calculated creatinine clearance at 12 months. Overall incidence of post-transplant diabetes mellitus (3.3 percent) and cytomegalovirus disease (4.3 percent) was similar in all groups. Further development of effective calcineurin inhibitor-free regimens should exclude patients of black ethnicity and may need full-induction therapy, perhaps with depleting agents, and concentration-controlled use of sirolimus and MMF.

Thymoglobulin and rate of infectious complications after transplantation.

UNLABELLED: Thymoglobulin is used as an induction agent in kidney transplantation, but the optimal dose is not well established. However, its use may be associated with increased infectious complications after transplantation. METHODS: This retrospective study of 61 high-risk renal recipients of transplants from deceased donors performed between June 2001 and April 2004 included patients treated with thymoglobulin. Patients were divided into two groups according to the total thymoglobulin dose (G1, n = 30, <7 mg/kg; G2, n = 31, >7 mg/kg) and followed for at least 1 year. RESULTS: Mean recipient age was 43 +/- 14 years; 41% were males; 63% non-Whites. Mean cold ischemia time was 26.3 +/- 7 hours. Mean PRA was 23% (0-100%). Second transplantation was performed in 18 (29.5%) patients. Mean donor age was 42.1 +/- 16 years, and 59% had a cerebral vascular accident as the cause of death. Patient- and death-censored graft survival at 12 months were 86% and 88%, respectively. There were 149 infectious episodes among 47 (78%) patients. The incidence of infection was 1.7 +/- 0.24 infections per patient per year in G1 (lower dose) vs 3.12 +/- 0.23 in G2 (P < .001). Bacterial (0.66 +/- 1.0 vs 1.48 +/- 1.26 infections per patient per year, P = .009) and viral infections (0.9 +/- 0.71 vs 1.41 +/- 0.71; P = .006) were more frequent in the higher dose group. CONCLUSION: This study suggested that a greater number of infectious episodes were present when the total dose of thymoglobulin was higher than 7 mg/kg.