Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.

Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.

Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ETA R) and the angiotensin II receptor type 1 (AT1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ETA R and anti-AT1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient.

Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss.

Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens. A significantly higher homing capability was expressed by class II sDSAs endowed with high mean fluorescence intensity and C3d- and/or C1q-fixing properties. In patients with available sequential biopsy specimens, we detected gDSAs before the appearance of antibody-mediated rejection. In sDSA-positive patients, gDSA positivity did not allow stratification for antibody-mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management.

Acquisition of C3d-Binding Activity by De Novo Donor-Specific HLA Antibodies Correlates With Graft Loss in Nonsensitized Pediatric Kidney Recipients.

Alloantibody-mediated graft injury is a major cause of kidney dysfunction and loss. The complement-binding ability of de novo donor-specific antibodies (dnDSAs) has been suggested as a prognostic tool to stratify patients for clinical risk. In this study, we analyzed posttransplant kinetics of complement-fixing dnDSAs and their role in antibody-mediated rejection development and graft loss. A total of 114 pediatric nonsensitized recipients of first kidney allograft were periodically monitored for dnDSAs using flow bead assays, followed by C3d and C1q assay in case of positivity. Overall, 39 patients developed dnDSAs, which were C1q(+) and C3d(+) in 25 and nine patients, respectively. At follow-up, progressive acquisition over time of dnDSA C1q and C3d binding ability, within the same antigenic specificity, was observed, paralleled by an increase in mean fluorescence intensity that correlated with clinical outcome. C3d-fixing dnDSAs were better fit to stratify graft loss risk when the different dnDSA categories were evaluated in combined models because the 10-year graft survival probability was lower in patients with C3d-binding dnDSA than in those without dnDSAs or with C1q(+) /C3d(-) or non-complement-binding dnDSAs (40% vs. 94%, 100%, and 100%, respectively). Based on the kinetics profile, we favor dnDSA removal or modulation at first confirmed positivity, with treatment intensification guided by dnDSA biological characteristics.

Posttransplant de novo donor-specific hla antibodies identify pediatric kidney recipients at risk for late antibody-mediated rejection.

The emerging role of humoral immunity in the pathogenesis of chronic allograft damage has prompted research aimed at assessing the role of anti-HLA antibody (Ab) monitoring as a tool to predict allograft outcome. Data on the natural history of allografts in children developing de novo Ab after transplantation are limited. Utilizing sera collected pretransplant, and serially posttransplant, we retrospectively evaluated 82 consecutive primary pediatric kidney recipients, without pretransplant donor-specific antibodies (DSA), for de novo Ab occurrence, and compared results with clinical-pathologic data. At 4.3-year follow up, 19 patients (23%) developed de novo DSA whereas 24 had de novo non-DSA (NDSA, 29%). DSA appeared at a median time of 24 months after transplantation and were mostly directed to HLA-DQ antigens. Among the 82 patients, eight developed late/chronic active C4d+ antibody-mediated rejection (AMR), and four C4d-negative AMR. Late AMR correlated with DSA (p < 0.01), whose development preceded AMR by 1-year median time. Patients with DSA had a median serum creatinine of 1.44 mg/dL at follow up, significantly higher than NDSA and Ab-negative patients (p < 0.005). In our pediatric cohort, DSA identify patients at risk of renal dysfunction, AMR and graft loss; treatment started at Ab emergence might prevent AMR occurrence and/or progression to graft failure.

Post-COVID-19 Lung Transplantation Italian Pivotal Protocol: Some Ethical Considerations.

SARS­CoV­2 mostly affects the respiratory system with clinical patterns ranging from the common cold to fatal pneumonia. During the first wave of the COVID-19 pandemic, owing to the high number of patients who were infected with SARS­CoV­2 and subsequently recovered, it has been shown that some patients with post-COVID-19 terminal respiratory failure need lung transplantation for survival. There is increasing evidence coming from worldwide observations that this procedure can be performed successfully in post-COVID-19 patients. However, owing to the scarcity of organs, there is a need to define the safety and efficacy of lung transplant for post-COVID-19 patients as compared to patients waiting for a lung transplant for other pre-existing conditions, in order to ensure that sound ethical criteria are applied in organ allocation. The Milan's Policlinic Lung Transplant Surgery Unit, with the revision of the National Second Opinion for Infectious Diseases and the contribution of the Italian Lung Transplant Centres and the Italian National Transplant Centre, set up a pivotal observational protocol for the lung transplant of patients infected and successively turned negative for SARS­CoV­2, albeit with lung consequences such as acute respiratory distress syndrome or some chronic interstitial lung disease. The protocol was revised and approved by the Italian National Institute of Health Ethics Committee. Description of the protocol and some ethical considerations are reported in this article.

Availability of HLA-allele-matched unrelated donors and registry size: Estimation from haplotype frequency in the Italian population.

In Italy, an HLA-matched unrelated donor is currently the primary donor when a HLA matched sibling is not found for allogeneic haematopoietic stem cell transplantation (HSCT). Better outcomes for transplantation require optimal matching between donor and recipient at least at the HLA-A, -B, -C, and -DRB1 loci; therefore, the availability of HLA-matched unrelated donors is important. The enormous HLA polymorphism has always necessitated registries with a large number of individuals in order to be able to provide well-matched donors to a substantial percentage of patients. In order to increase the efficiency of the Italian Bone Marrow Donor Registry (IBMDR) in providing Italian patients with a suitable donor, the probability of finding an HLA-A, -B, -C, and -DRB1 allele-matched (8/8) or a single mismatch unrelated donor (7/8) was estimated in this study according to IBMDR size. Using a biostatistical approach based on HLA haplotype frequencies of more than 100,000 Italian donors enrolled in the IBMDR and HLA-typed at high-resolution level, the probability of finding an 8/8 HLA-matched donor was 23.8%; 33.4%; and 41.4% in simulated registry sizes of 200,000; 500,000; and 1,000,000 donors; respectively. More than 2 million recruited donors are needed to increase the likelihood of identifying an HLA 8/8 matched donor for 50% of Italian patients. If one single mismatch at HLA I class loci was accepted, the probability of finding a 7/8 HLA-matched donor was 62.8%; 73.7%; and 80.3% in 200,000 donors; 500,000; and 1,000,000 donors; respectively. Using the regional haplotype frequencies of IBMDR donors, the probability of recruiting a donor with a new HLA phenotype, in the different Italian regions, was also calculated. Our findings are highly relevant in estimating the optimal size of the national registry, in planning a cost-effective strategy for donor recruitment in Italy, and determining the regional priority setting of recruitment activity in order to increase the phenotypic variability of IBMDR as well as its efficiency.

Dynamics of molecular motion at single-crystal surfaces.

Dramatic advances in our understanding of the motion of individual atoms and molecules at single-crystal surfaces have been made within the past 5 years. Recent experimental and theoretical studies of the interaction of nitric oxide with metal surfaces illustrate the depth of understanding now obtainable. General principles, applicable to a broader range of molecule-surface encounters, have begun to emerge out of the systematic and in-depth analyses of these and related studies.

Time-resolved electron energy loss spectroscopy.

Two recent instrumental improvements in high-resolution electron energy loss spectroscopy make possible the recording of complete surface vibrational spectra on the millisecond time scale. This is the first spectroscopic probe capable of directly measuring fundamental surface rate processes in real time with a resolution less than or equal to 1 millisecond. Such measurements are the key to understanding surface kinetics at the molecular level. This article summarizes experiments on the adsorption and decomposition of formic acid on Cu(100) to investigate the temperature and coverage dependence of the formate intermediate. Other results are cited that provide a detailed description of the decomposition of methanol on Ni(110). Also reported are direct measurements of the residence time of carbon monoxide on Cu(100) and the associated desorption kinetics.

Acute rejection features in dual kidney transplant recipients from elderly donors: comparison of calcineurin inhibitor-based and calcineurin inhibitor-free immunosuppressive protocols.

Features of acute rejection in dual kidney transplant have not been studied. The aim of this study is to compare acute rejections in dual kidney transplant recipients from elderly donors on different immunosuppressive protocols. Sixty-nine patients were evaluated: 28 received calcineurin inhibitor-based (group 1) and 41 received calcineurin inhibitor-free immunosuppression (group 2). Histology of all donor kidneys was evaluated before implantation. All rejections showed tubulitis in both groups, and were classified as T-cell mediated acute rejections. Incidence and Banff grade of rejections in the two groups were not significantly different. Late rejections however, were observed in group 1 (P < 0.01) whereas steroid-resistant rejections occurred in group 2 (P < 0.03). C4d deposition was only observed in group 2. Occurrence of acute rejection was significantly associated with graft loss due to interstitial fibrosis/tubular atrophy in both groups. In group 1 mean serum creatinine levels of patients with rejections at six months and one year were higher than those of patients without rejections (P < 0.03 and P < 0.009, respectively). In group 2 they were higher at six months (P < 0.01) but not at one year. In addition, graft loss due to interstitial fibrosis/tubular atrophy occurred in 3/28 patients in group 1 (10.7%, OR= 1.95, 95%CI 1.02-3.71), and in 1/41 patients in group 2 (2.4%, OR= 0.41, 95%CI 0.07-2.24). Taken together these results suggest better renal function in patients on calcineurin inhibitor-free immunosuppression. In conclusion, acute rejections were detrimental irrespective of the type of immunosuppression, but different features were observed with each therapy. A tailored approach should be advantageous for prevention and treatment of acute rejections.

Analysis of the Trend Over Time of High-Urgency Liver Transplantation Requests in Italy in the 4-Year Period 2014-2017.

BACKGROUND: The national protocol for the handling of high-urgency (HU) liver organ procurement for transplant is administered by the Italian National Transplant Center. In recent years, we have witnessed a change in requests to access the program. We have therefore evaluated their temporal trend, the need to change the access criteria, the percentage of transplants performed, the time of request satisfaction, and the follow-up. METHODS: We analyzed all the liver requests for the HU program received during the 4-year period of 2014 to 2017 for adult recipients (≥18 years of age): all the variables linked to the recipient or to the donor and the organ transplants are registered in the Informative Transplant System as established by the law 91/99. In addition, intention to treat (ITT) survival rates were compared among 4 different groups: (1) patients on standard waiting lists vs (2) patients on urgency waiting lists, and (3) patients with a history of transplant in urgency vs (4) patients with a history of transplant not in urgency. RESULTS: Out of the 370 requests included in the study, 291 (78.7%) were satisfied with liver transplantation. Seventy-nine requests (21.3%) have not been processed, but if we consider only the real failures, this percentage falls to 13.1% and the percentage of satisfied requests rises to 86.9%. The average waiting period for liver transplantation (LT) is 1.7 days and most requests (74%) are met in less than 24 hours, if we consider the hours between the registration of the request and the donor reporting . The percentage of late retransplantations is 2.1%. The clinical indication for HU-LT that appears to improve over time is hepatic artery thrombosis (82.5%). The overall 1-year patient survival is 68.3%. The overall 1-year graft survival, performed on all the patients, is 89% and all the indications for HU-LT appear to go well over time with an average survival rate greater than 85%. CONCLUSIONS: The indications for HU-LT are changing according to the changes in the hepatologic field in recent years. The centralized management of requests has proven to be successful in optimizing responses. Urgent LT is confirmed to be lifesaving in its timeliness.

Pretransplant Single Antigen Bead-Detected HLA Antibodies in Kidney Transplant Long-term Outcome: A Single-Center Cohort Experience.

Single-antigen bead (SAB) platform permits the identification of antibodies not detectable by complement-dependent lymphocytotoxicity test, but their clinical significance is not completely understood. The aim of this study was to evaluate whether the presence of pretransplant SAB-detected antibodies is associated with the development of allograft failure. This is a single-center cohort study with 10-year follow-up in which 573 kidney recipients with negative pretransplant complement-dependent lymphocytotoxicity crossmatch who received transplants at the Kidney Transplant Center of Policlinico, Milan, from deceased donors between 1996 and 2005 were evaluated. Pretransplant plasma samples were retrospectively analyzed by SAB assay. Survival analyses were performed to assess the risk of allograft failures by SAB-detected antibodies. Pretransplant antibodies were found in 160 (28.0%) recipients, of whom 42 subsequently developed an allograft failure for a survival rate of 70.9% (95% confidence interval [CI), 63.5-78.4). Among those without antibodies, 58 (14.0%) returned to dialysis with a survival rate of 84.7% (95% CI, 81.0-88.4). In Cox regression analyses, patients with SAB-positivity had 2-fold higher risk of allograft failure than those who were SAB-negative (hazard ratio, 2.07; 95% CI, 1.39-2.79). Results did not change after adjustment for putative confounders. In conclusion, in this single-center cohort, 10-year allograft survival rate was significantly influenced by the presence of SAB-detected antibodies.

The fast-slow continuum in mammalian life history: an empirical reevaluation.

Many life-history traits co-vary across species, even when body size differences are controlled for. This phenomenon has led to the concept of a "fast-slow continuum," which has been influential in both empirical and theoretical studies of life-history evolution. We present a comparative analysis of mammalian life histories showing that, for mammals at least, there is not a single fast-slow continuum. Rather, both across and within mammalian clades, the speed of life varies along at least two largely independent axes when body size effects are removed. One axis reflects how species balance offspring size against offspring number, while the other describes the timing of reproductive bouts.

Interleukin-6, interleukin-10 and heat shock protein-90 expression in renal epithelial neoplasias and surrounding normal-appearing renal parenchyma.

Cytokines, notably the interleukins IL-6 and IL-10, have an important role in the development and progression of renal-cell carcinomas, acting in the host-tumor interaction and in tumor bulk. Heat shock proteins (HSP), in particular HSP-90, may have a regulatory role in cytokine biosynthesis and prognostic implication in some tumors. To define the roles of the cytokines IL-6 and IL-10 and HSP-90 in the progression of renal-cell carcinoma we analyzed immunohistochemical expression of these proteins in human renal-cell carcinomas from 95 total nephrectomies. IL-6, IL-10 and HSP-90 proteins were more strongly expressed in epithelium and stroma of the renal tumoral compartment than in adjacent normal peritumoral tissue. But the difference reached significance only for HSP-90 protein. The percentage of cells expressing IL-6, IL-10 and HSP-90 immunoreactivity was higher in benign epithelial tumors, than in normal peritumoral tissue, but lower than in renal-cell carcinomas. Whereas HSP-90 immunoreactivity seemed higher in more aggressive histological phenotypes (collecting-duct carcinoma) of renal-cell carcinomas, IL-10 protein levels were higher in more advanced TNM stage (pT3) tumors. Our observation suggests that IL-6 and IL-10 and HSP-90 may be useful markers associated with the development and progression of renal-cell carcinomas and have independent functional roles in this malignant condition.

Quantitative immunohistochemical analysis of matrilysin 1 (MMP-7) in various renal cell carcinoma subtypes.

The role of matrilysin 1 or matrix metalloproteinase-7 (MMP-7) in cancer is extremely complex and poorly understood. In this study we investigated differential expression of MMP-7 in the epithelium and stroma of 95 paraffin-embedded renal tumor samples by immunohistochemistry and compared tumoral with normal peritumoral renal tissue. We also determined a possible correlation of the immunohistochemical findings with histological subtype, tumor grade and stage of RCC. In all areas examined MMP-7 protein expression was significantly higher in epithelium than in stroma (P less than 0.01). MMP-7 was more less expressed in peritumoral normal areas than in benign epithelial neoplasias (renal papillary and oncocytomas) and RCC carcinomas, reaching the highest immunopositive reaction in chromophobe RCC subtypes, followed by conventional clear-cell and chromophilic-papillary RCC histological subtypes and the lowest levels in more aggressive RCC histotypes (spindle-cell and collecting-duct RCCs). MMP-7 reached their highest levels in high-grade and high-stage RCCs. Our observation suggests an important role of MMP-7 in the development and progression of renal cancer. The differential expression of MMP-7 in the various histological RCC subtypes may reflect the malignant phenotype and more aggressive behavior of RCCs.

Histological markers of humoral rejection in renal transplant patients.

Diagnosis of "suspicious humoral rejection" can be formulated in the presence of peritubular capillary (PTC) C4d deposition and one of the following tissue changes: (1) acute tubular necrosis, (2) glomerulitis or presence of polymophonuclear leukocytes or monocytes in PTC, or (3) arteritis. From January 2004 to October 2006, we performed immunohistochemical staining with anti-C4d antibody on 54 renal biopsies from 39 renal transplant patients. In 25 biopsies we observed diffuse (n = 13) or focal (n = 12) C4d deposition. Based on C4d-positivity, patients were divided into three groups: group 1 included 19 C4d-negative patients; group 2, 10 patients with diffuse C4d-positivity; and group 3, 10 patients with focal C4d-positivity. Panel-reaction antibody-positive tests were associated with diffuse C4d-positivity: 50% of group 2 patients showed a positive test, while no group 1 or 3 patients had a positive test (P < .001). Glomerulitis was observed in six biopsies and associated with diffuse C4d staining. Graft loss occurred in 3/10 group 2 patients (30%); 2/19 group 1 patients (10.5%), and 1/10 group 3 patients (10%). Viral infections were experienced in the year of the biopsy by 50% of group 1 patients 80% of group 2 patients, and 100% of group 3 patients (P < .025), indicating a significantly greater number of infections among patients with C4d-positive biopsies. In eight cases, anti-thymocyte globulin was administered less than 21 days before the biopsy: four had diffuse and four had focal C4d positivity.

Prostate--specific G protein couple receptor genes and STAG1/PMEPA1 in peripheral blood from patients with prostatic cancer.

We investigated whether prostate - specific G protein couple receptor genes and STAG1/PMEPA1 gene expression in peripheral- blood could be useful as a diagnostic or prognostic marker of prostate cancer. Circulating cells were identified by reverse transcription-polymerase chain reaction (RT-PCR) to detect PSGR and STAG1/PMEPA1 mRNA in peripheral blood (PB) from 11 patients with treated prostate cancer (CaP), 11 with newly-diagnosed untreated CaP and 20 with benign prostatic hyperplasia (BPH) (controls). RT-PCR amplified PSGR in 8 of 11 untreated and in 9 of 11 treated patients with CaP and in 16 of 20 with BPH; whereas it amplified PMEPA1 in 1 of 11 untreated and in 7 of 11 treated patients with CaP and in 4 of 20 with BPH. In our control tissues and cell lines nearly all the prostatic and non- prostatic tissues and cell lines expressed PSGR mRNA, whereas only one prostatic neoplastic tissue and the androgen-responsive (LNCaP) and androgen non-responsive (PC3) prostatic cell lines expressed PMEPA1. These findings suggest that the investigated genes are poorly specific and probably of little use as diagnostic or prognostic markers in peripheral blood for monitoring prostate cancer progression and recurrence.

Detection of human papillomavirus DNA, p53 and ki67 expression in penile carcinomas.

Our study is aimed at evaluating the presence of p53 and Ki67 expression by immunohistochemistry in a series of 11 paraffin-embedded penile carcinomas. We also investigated the presence of Human Papillomavirus (HPV) DNA in these tumours and performed an accurate typing by DNA sequencing on positive samples. Immunohistochemistry (IHC) was performed with the anti-p53 and Ki67 mouse monoclonal antibodies. DNA extracted from small sections of each specimen was submitted to amplification with HPV specific general primers; PCR products of the proper length were purified and sequenced. IHC demonstrated nuclear accumulation of mutated p53 and Ki 67 expression in 10/11 tumour samples (90.9%). The prevalence of HPV DNA was 72.7%; the most prevalent type was HPV16. Sequencing analysis revealed the presence of HPV53 (12.5%), HPV18 (25%) and HPV16 (62.5%). Out of the p53 or Ki67 positive carcinomas the percentage of HPV positives was 80% and 70% respectively. Our results indicate that penile carcinoma is frequently associated to high risk HPV and with diffuse p53 and Ki67 expression.

Mycophenolate mofetil pharmacokinetic monitoring in pediatric kidney transplant recipients.

This open-label, longitudinal, long-term study of de novo pediatric renal transplant recipients was designed to investigate the pharmacokinetics (PK) of mycophenolic acid (MPA) and its possible interaction with cyclosporine (CsA). Thirty-four children on an immunosuppressive regimen of CsA, prednisone, and mycophenolate mofetil (MMF, 300-400 mg/m2 twice daily) were investigated at 6, 30, 180, and 360 days after transplantation. Considerable interindividual variability in the areas under the concentration curve (AUC(0-12)) of MPA was observed during the follow-up, although the dose of MMF remained the same over the same time. Predose levels (C0) increased significantly during the first 6 months after transplantation: C0 at 6 and 180 days after transplantation was 0.8 +/- 0.6 and 1.9 +/- 1.1 microg/mL (P < .0001). A significant time-dependent increase in the AUC of MPA was also observed during the first 6 posttransplant months: AUC(0-12) at 6 and 180 days after transplantation was 23.3 +/- 10.8 and 40 +/- 11.6 mg*h/L (P = .003). MPA concentrations 3 and 4 hours after MMF intake were the individual time points that best correlated with the full MPA AUC (r = 0.8 and 0.79; P < .001). The abbreviated MPA AUC (0-4 hours) correlated reasonably with the full AUC (r = 0.87; P < .001). Finally, a significant reduction in CsA dose during the first 6 posttransplant months (P < .001) matched the significant increases in both MPA C0 and full MPA AUC, thus demonstrating the interaction of the 2 immunosuppressive drugs. These observations suggest the need for therapeutic drug monitoring when adjusting the dose of MMF in children.

[Renal transplantation in the North Italy Transplant program (NITp): Organ allocation and results]. / Il trapianto renale nel Nord Italia Transplant program (NITp): assegnazione degli organi e risultati.

Renal transplantation is an effective therapeutic tool for patients with end-stage renal diseases (ESRDs). Data reported in this article summarize the results obtained from 30 years' activity in the North Italy Transplant program (NITp), the first transplant organization in Italy that implemented a donor procurement and organ transplantation network. In the NITp kidney allocation is governed by a computerized algorithm, NITK3, put in place in 1997, aimed at ensuring equity, transparency and traceability during the stages of the allocation decision-making process. The NITp working group has recognized the NITK3 criteria and they are periodically reviewed following the results of the analysis of patients' transplantation odds. The results obtained with the use of the NITK3 algorithm have been very satisfactory: after 6 yrs, a significantly higher percentage of patients at immunological risk (sensitized or waiting for re-transplant), of patients waiting for >3 yrs and of patients with 0-1 HLA A,B,DR mismatches have been transplanted. Moreover, a higher percentage of kidneys were used locally (in a hospital within the procurement area), and this is known to stimulate donor procurement. Finally, we performed a preliminary statistical analysis of transplants carried out from 1998-2002 in 5/16 centers of the NITp area, demonstrating the quality of the NITp program in terms of patient and graft survival, and that donor and recipient age are the variables significantly impacting on transplant results.