Tacrolimus Therapeutic Drug Monitoring in Stable Kidney Transplantation and Individuation of CYP3A5 Genotype.

The posology of tacrolimus (TAC) is usually guided by its therapeutic drug monitoring. Some patients reach target concentrations (CTs) quickly, others more slowly. In a retrospective study, 20 kidney transplant recipients were included (mean age, 50.7 ± 14.1 years; weight 64.0 ± 14.2 kg; patients clinically stable for over a year). We studied cytochrome CYP3A5 genotype, in particular CYP3A5 6986A>G, the most important polymorphism related to the metabolism of TAC (wild genotype CYP3A5 *1 genotype, and CYP3A5 *3 variants). One year after transplantation, the CTs were 5.0 to 8.0 ng/mL. The patients were divided into group A (TAC doses < 6.0 mg/d) and group B (TAC doses > 6.0 mg/d). All were tested for the CYP3A5 gene sequence to characterize their polymorphism. Patients with CYP3A5 *1/*1 and *1/*3 were extensive metabolizers, and those with CYP3A5 *3/*3 were poor metabolizers. In group A and group B, the average TAC doses at the time of therapeutic drug monitoring were 3.0 ± 1.4 ng/mL (0.05 ± 0.03 mg/kg) and 12.8 ± 3.7 ng/mL (0.2 ± 0.1 mg/kg), respectively (P < .001). Group A was the poor metabolizers genotype, while in group B, the extensive metabolizers genotype was present. Patients with the CYP3A5 *1/*1 or *1/*3 genotype required 1.5 to 2 times higher doses than patients *3/*3 to reach CT. This genetic test allows clinicians to know, before the kidney transplant, the patient's TAC metabolism pattern and then to optimize the drug exposure.

Innovative Approaches to Active and Healthy Ageing: Campania Experience to Improve the Adoption of Innovative Good Practices.

The demographic projections on the European population predict that people aged over 60 will increase by about two million/year in the next decades. Since 2012, the Campania Reference Site of the European Innovation Partnership on Active and Healthy Ageing supports the innovation of the Regional Health System, to face up demographic changes and sustainability. Campania Reference Site provides the opportunity to connect loco-regional stakeholders in social and health care services (universities, healthcare providers, social services, local communities and municipalities), with international organizations, in order to adopt and scale up innovative solutions and approaches. This paper describes the building process of Campania Reference Site and the main results achieved, that have been allowing it to become a hub for open innovation in the field of active and healthy aging at regional, national and international level.

MEDS score and vitamin D status are independent predictors of mortality in a cohort of Internal Medicine patients with microbiological identified sepsis.

OBJECTIVE: Sepsis is a life-threatening disease resulting from the interaction between pathogen and host response; its dysregulation causes organ dysfunction, high morbidity, and mortality. Despite the increase of septic patients admitted to Internal Medicine wards, data about clinical predictors of mortality in this setting are still lacking. The aim of this study was to evaluate the role of MEDS score and vitamin D as predictors of mortality (28-day and 90-day) in septic patients admitted to the Internal Medicine department. PATIENT S AND METHODS: Prospectively collected clinical data, lab tests including vitamin D, and clinical scores (SIRS, MEDS, SCS, REMS, SOFA, qSOFA) were retrospectively analyzed. Eighty-eight microbiologically identified septic patients (median age 75 years old, IQR 65-82 years old; range 37-94 years old) were evaluated. RESULTS: Twenty-three patients (26.1%) died at 28 days, 33 (37.5%) died at 90 days. The logistic regression showed a positive effect of MEDS score (p=0.006; OR 1.24, 95% CI 1.08-1.49), and a negative effect of low vitamin D levels (p=0.008, OR 0.83, 95% CI 0.72-0.94) on mortality. Moreover, the cut-off of 7 points for MEDS score and of 7 ng/ml for vitamin D levels significantly predicted poor prognosis at 28 and 90 days. CONCLUSIONS: MEDS score and vitamin D levels represent independent predictors of mortality in a cohort of Internal Medicine septic patients. Further studies on larger samples are needed to confirm our results and to clarify the pathophysiological mechanisms at the basis of vitamin D deficiency as a predictor of mortality in septic patients.

Kidney Transplantation in Elderly Recipients: A Single-Center Experience.

In this retrospective single-center study we evaluated the outcome after kidney transplant in recipients older than 65 years in terms of patient and graft survival and causes of death. PATIENTS AND METHODS: From 1993 to 2016, 109 consecutive first single kidney transplants in recipients older than 65 years were included. Furthermore, 2 age groups have also been identified (group A, 65-70 years old vs group B, 71-76 years old). Donor and recipient characteristics were analyzed. Other parameters were cold and warm ischemia times, delayed graft function, biopsy-proven acute rejection, and causes of death. Induction immunosuppressive therapy was performed with basiliximab or thymoglobulin. Baseline triple immunosuppression included calcineurin inhibitor, antimetabolite, and steroids. The results of preimplantation biopsies, which were performed in all expanded criteria donors were analyzed and graded according to Karpinski 2009 classification. RESULTS: Overall mortality was 39.4%: 23.2% women and 76.8% men. Causes of death were infections in 42%, tumors in 23%, cardiovascular disease in 14%, cerebrovascular disease in 7%, and unknown in 14%. The most common cause of death in men was infections (52%), and the most common cause in women was tumors (55%). At 1, 3, 5, and 10 years, overall patient survival was 89%, 84%, 72%, and 45%, and overall graft survival was 100%, 97%, 89%, and 84%, respectively. Patient and graft survival were statistically different between group A vs group B (P = .006 and P = .02, respectively). At univariate analysis significant risk factors for increased mortality were age, delayed graft function, and cold ischemia time. At multivariate analysis, delayed graft function maintained statistical significance. CONCLUSIONS: Kidney transplantation in patients older than 65 years is safe, feasible, and has good graft survival. Mortality is statistically significant in patients older than 71 years, despite a persistent low graft loss.

Androgen insensitivity syndrome.

OBJECTIVE: We provide a review of the literature about the Androgen Insensitivity Syndrome (AIS), its onset and associated developmental anomalies and the genetic alterations causing it. MATERIALS AND METHODS: We searched PubMed with a larger emphasis on the physiology, genetics and current management of AIS. RESULTS: AIS is an X-linked recessive Disorder of Sex Development (DSD). It is caused by mutations of the Androgen Receptor, and their large amount and heterogeneity (missense and nonsense mutations, splicing variants, deletions, and insertions) are responsible for the wide spectrum of possible phenotypes of patients, divided into Partial AIS (PAIS) and Complete AIS (CAIS). Once the clinical and laboratory investigations have laid the foundation for a diagnostic hypothesis, it is important to identify the actual karyotype of the individual and search for the mutation in the Androgen Receptor to diagnose with certainty the syndrome. Alternatively, in the absence of such evidence, the diagnosis should more properly be an AIS-like condition, which we describe as well in our report. CONCLUSIONS: The management of this DSD is based on pharmacotherapies, surgery and psychological support: all of them must be directed to facilitate the patient's life, considering his/her sexual identity.

De Novo Solid Tumors After Kidney Transplantation: Is It Time for a Patient-Tailored Risk Assessment? Experience From a Single Center.

BACKGROUND: Progress in immunosuppressive therapy and perioperative techniques has improved the survivals of both grafts and patients. The patient, however, is exposed to the risks of aging and side effects of immunosuppression. De novo tumors are the 2nd cause of death in the organ transplant population. The aim of this study was to evaluate whether the current accepted guidelines for the pre-transplantation study and the post-transplantation follow-up have been effective, in our kidney transplant population, regarding early detection and treatment, improving prognosis, and reducing mortality of some curable neoplastic diseases. METHODS: We considered de novo tumors in kidney transplant patients from 1995 to 2010 (n = 636) excluding hematologic and nonmelanoma skin tumors from our study. RESULTS: There were 64 de novo tumors in 59 patients out of 636 kidney transplant patients; 29.68% were urogenital cancer, 26.56% gastrointestinal cancer, 12.5% melanoma, 6.25% lung cancer, 6.25% biliopancreatic cancer, 4.68% visceral Kaposi sarcoma, 4.68% breast cancer, 4.68% thyroid cancer, 1 pleural mesothelioma, 1 meningioma, 1 merkeloma. Twenty patients died because of cancer. Ten patients had a late de novo tumor diagnosis, when the stage of tumor was advanced and not suitable for curative treatment. CONCLUSIONS: Because of the increased neoplastic risk, we consider it mandatory to carry out a meticulous screening and to implement pre-transplantation study concerning this increased neoplastic risk population to detect a subgroup of patients presenting the highest risk to improve their outcome.

Preemptive liver-kidney transplantation in von Gierke disease: a case report.

Type 1a glycogen storage disease (GSD 1a), or von Gierke disease, is a rare, autosomal-recessive disease caused by a deficiency of glucose-6-phosphatase, which leads to glycogen accumulation in the liver, kidney, and intestinal mucosa. Clinical manifestations include hypoglycemia, growth retardation, hepatomegaly, lactic acidemia, hyperlipidemia, and hyperuricemia. Long-term complications include renal disease, gout, osteoporosis, pulmonary hypertension, short stature, and hepatocellular adenomas, which may undergo malignant transformation. Herein we have described the management and the clinical course of a GSD1a patient who underwent simultaneous preemptive liver- kidney transplantation (SPLKT), which solved the liver and renal disease. We confirmed the rapid normalization of glucose metabolism, and correction of hyperlipemia after liver transplantation. In our opinion uremic patients with GSD 1a with or without adenomas must be considered for SPLKT. To our knowledge this is the fifth case of SPLKT and the first preemptive one to be described in the literature.

[Uretero-vescical anastomosis during kidney transplantation. Preliminary results of two surgical techniques]. / L'anastomosi uretero-vescicale nel trapianto di rene. Risultati preliminari di due tecniche a confronto.

AIM: The most frequent urologic complications after renal transplantation involve the uretero-vescical anastomosis (leakage, stenosis, and reflux), with a frequency of 1% to 30% in different series. METHODS: We present our results in a prospective randomized trial performed from October 2004 to September 2005, in a cohort of 36 patients, who underwent renal transplantation from cadaveric donor at our institution. A uretero-vescical anastomosis according to Lich-Gregoir was used in 18 cases (group A), whereas an anastomosis according to Knechtle was performed in other 18 patients (group B), respectively. The groups were comparable for donors and recipients characteristics. The mean donor age was 46.3 years vs 44.9 years, and the mean duration of cold ischemia was 1 086+/-296 min vs 1 100+/-381 min for group A and for group B respectively. The mean recipient age was 47.5 years vs 46.1 for group A and group B, respectively. RESULTS: No differences were evidenced between the two uretero-vescical anastomosis in term of surgical complications, infections or patient and graft survival at one year of follow-up. Stenosis and leakage involved 2 patients for each group respectively. Numbers of infections, days of antibiotic therapy were similar between the two groups. CONCLUSION: Our early experience does not evidence differences between the two types of uretero-vescical anastomosis.

Effects of successful renal transplantation on left ventricular mass.

Left ventricular hypertrophy is an independent cardiovascular risk factor in the general population and in patients with chronic renal failure. Relatively little is known about the effects of renal transplantation on left ventricular hypertrophy. The aim of this study was to determine the changes in left ventricular mass after successful renal transplantation and to evaluate the importance of some clinical, laboratory, and echocardiographic variables on the trend to left ventricular hypertrophy. Twenty-three patients with end-stage renal disease were studied by ambulatory blood pressure monitoring and echocardiography before and 2 years following renal transplantation. After 24 months of follow-up, all transplant recipients had adequate renal function (serum creatinine <2 mg/dL). At the end of the study, we observed a significant decrease in left ventricular mass and left ventricular mass index compared to the pretransplantation period. In renal transplant recipients, the prevalence of left ventricular hypertrophy significantly decreased (78% versus 44%, P < .03) after 2 years of follow-up. Systolic 24-hour blood pressure was the only predictor of left ventricular mass and of left ventricular mass index at 2 years after transplantation. In conclusion, successful renal transplantation produces a regression of left ventricular hypertrophy. This beneficial effect depends on a decrease in systolic pressure levels.

Renoprotective effect of early inhibition of the renin-angiotensin system in renal transplant recipients.

The aim of this work was to study the effect of early administration of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type-I receptors blockers (ARB) on renal function and proteinuria in renal transplant recipients with good, stable renal function and mild proteinuria. Twenty four patients started ACEI/ARB therapy within 14 months after surgery (RAS-). Before (T0) and every month for 2 years after the initiation of ACEI/ARB we evaluated creatinine clearance (CrCl), proteinuria/day (UP), UP/CrCl (FUP), arterial blood pressure, and serum lipid levels. Twenty-eight patients who never received ACEI/ARB (RAS+) were studied in the same fashion. In the RAS+ CrCl was reduced after 2 years compared with T0 (64.5 +/- 2.6 vs 75.0 +/- 3.2 mL/min, P < .003); UP and FUP were both significantly increased (666 +/- 65 vs 132 +/- 20 mg/day 8.8 +/- 1.2 vs 2.6 +/- 0.6 mg/mL x 10(3); P < .001 and .002) compared with T0. Moreover, UP (P < .04), FUP (P < .03), and the percentage reduction of CrCl (11.4% +/- 5% vs 4.6% +/- 1.8%; P < .05) were greater in RAS+ than RAS- subjects at 2 years of the study. The values of other parameters did not show significant differences between the two groups. In conclusion, this study suggested that ACEI/ARB have renoprotective effects, when used in patients with good stable renal function and mild proteinuria. These drugs may play a role to prevent chronic allograft nephropathy.

Lipomatosis pélvica: informe de un caso y revisión bibliográfica / Pelvic lipomatosis: case report and bibliography review

La prostatectomía radical está ampliamente difundida como tratamiento en el cáncer de próstata temprano. Pese a esto no queda claro su posible utilidad. Para responder a este interrogante realizamos un estu-dio randomizado. Métodos: Entre octubre de 1989 y febrero de 1996, 95 hombres con diagnóstico reciente de cáncer de próstata estadios 1 Ib, lie, o T2 fueron randomizados entre prostatectomía radical y control. Se realizó el seguimiento completo durante el ano 2000. El objetivo primario fue determinar la mortalidad por cáncer de próstata y secundaria la mortalidad gene-ral, la sobrevida libre de metástasis v la progresión local. Durante un promedio de seguimiento de 6,2 años, 62 hombres en el grupo de control y 53 en el de prostatectomía radi-ca] tallecieron. La muerte debida al cáncer de próstata ocurrió en 31 de los 348 pacientes del grupo control (8, 9 por ciento) y en 16 de los 347 asignados a prostatectomía radical (4,6 por ciento). La muerte relacionada con otras causas sobrevino en'31 de los 348 pacientes del grupo control (8,9 por ciento) y en 37 de los 347 pacientes asignados a prostatectomía radical (10,6por ciento) Los pacientes destinados a cirugía tuvieron un riesgo relativo menor para metástasis a distancia que los pacientes en el grupo control Conclusiones: En este estudio randomizado, la prostatectomía radical disminuyó significativamente la muerte asociada con la enfermedad, pero no presentó mayor diferencia con el grupo control en términos de sobrevida general.

Lipomatosis pélvica: informe de un caso y revisión bibliográfica / Pelvic lipomatosis: case report and bibliography review

La prostatectomía radical está ampliamente difundida como tratamiento en el cáncer de próstata temprano. Pese a esto no queda claro su posible utilidad. Para responder a este interrogante realizamos un estu-dio randomizado. Métodos: Entre octubre de 1989 y febrero de 1996, 95 hombres con diagnóstico reciente de cáncer de próstata estadios 1 Ib, lie, o T2 fueron randomizados entre prostatectomía radical y control. Se realizó el seguimiento completo durante el ano 2000. El objetivo primario fue determinar la mortalidad por cáncer de próstata y secundaria la mortalidad gene-ral, la sobrevida libre de metástasis v la progresión local. Durante un promedio de seguimiento de 6,2 años, 62 hombres en el grupo de control y 53 en el de prostatectomía radi-ca] tallecieron. La muerte debida al cáncer de próstata ocurrió en 31 de los 348 pacientes del grupo control (8, 9 por ciento) y en 16 de los 347 asignados a prostatectomía radical (4,6 por ciento). La muerte relacionada con otras causas sobrevino en31 de los 348 pacientes del grupo control (8,9 por ciento) y en 37 de los 347 pacientes asignados a prostatectomía radical (10,6por ciento) Los pacientes destinados a cirugía tuvieron un riesgo relativo menor para metástasis a distancia que los pacientes en el grupo control Conclusiones: En este estudio randomizado, la prostatectomía radical disminuyó significativamente la muerte asociada con la enfermedad, pero no presentó mayor diferencia con el grupo control en términos de sobrevida general. (AU)

Infiltración leucemica de la próstata: presentación de un caso / Laukemic infiltration of the prostate

La infiltración leucémica de la próstata no es un hallazgo clínico habitual. La mayoría de los casos se deben a la leucemia linfocítica crónica. Estaría indicada la realización de una biopsis prostática en todod paciente leucémico con síntomas obstructivos del tracto urinario inferior

Infiltración leucemica de la próstata: presentación de un caso / Laukemic infiltration of the prostate

La infiltración leucémica de la próstata no es un hallazgo clínico habitual. La mayoría de los casos se deben a la leucemia linfocítica crónica. Estaría indicada la realización de una biopsis prostática en todod paciente leucémico con síntomas obstructivos del tracto urinario inferior(AU)

Direct in vivo assessment of parathyroid hormone-calcium relationship curve in renal patients.

Secondary hyperparathyroidism (SHP) is a well documented finding even in the early stages of chronic renal failure (CRF). A sigmoidal relationship, fitting a four parameter model, links PTH secretion rate and calcium concentration changes. To our knowledge, PTH secretory parameters have only been studied in uremic patients who are in dialysis treatment. As a result of these studies, a possible role for derangement in setpoint values (that is, the serum calcium concentration corresponding to the mid-range value on the sigmoidal curve) has been suggested in the pathogenesis of SHP in CRF. Our study was undertaken to gain insight into the calcium-PTH relationship curve in the first course of CRF and to assess whether a change in any of the secretory parameters is related to the beginning of SHP. We studied 27 male renal patients with a variable degree of renal function (creatinine clearance 12 to 164 ml/min) and 9 control subjects. In all patients and controls the following parameters were evaluated: (1) basal 1,25(OH)2 vitamin D, 25(OH)vitamin D, calcitonin (CT), intact PTH; (2) GFR by Cr51EDTA clearance; (3) the sigmoidal PTH-ionized calcium relation curve, by means of a hypocalcemic stimulating test (Na2-EDTA 37 mg/kg body weight/2 hr) and a hypercalcemic test (Ca gluconate giving 8 mg/kg of body weight/2 hr of Ca element), performed on two consecutive days.(ABSTRACT TRUNCATED AT 250 WORDS)