Impact on grafted kidney function of rocuronium-sugammadex vs cisatracurium-neostigmine strategy for neuromuscular block management. An Italian single-center, 2014-2017 retrospective cohort case-control study.

BACKGROUND: The impact of sugammadex in patients with end-stage renal disease undergoing kidney transplantation is still far from being defined. The aim of the study is to compare sugammadex to neostigmine for reversal of rocuronium- and cisatracurium-induced neuromuscular block (NMB), respectively, in patients undergoing kidney transplantation. METHODS: A single-center, 2014-2017 retrospective cohort case-control study was performed. A total of 350 patients undergoing kidney transplantation, equally divided between a sugammadex group (175 patients) and a neostigmine group (175 patients), were considered. Postoperative kidney function, evaluated by monitoring of serum creatinine and urea and estimated glomerular filtration rate (eGFR), was the endpoint. Other endpoints were anesthetic and surgical times, post-anesthesia care unit length of stay, postoperative intensive care unit admission, and recurrent NMB or complications. RESULTS: No significant differences in patient or, with the exception of drugs involved in NMB management, anesthetic, and surgical characteristics, were observed between the two groups. Serum creatinine (median [interquartile range]: 596.0 [478.0-749.0] vs 639.0 [527.7-870.0] µmol/L, p = 0.0128) and serum urea (14.9 [10.8-21.6] vs 17.1 [13.1-22.0] mmol/L, p = 0.0486) were lower, while eGFR (8.0 [6.0-11.0] vs 8.0 [6.0-10.0], p = 0.0473) was higher in the sugammadex group than in the neostigmine group after surgery. The sugammadex group showed significantly lower incidence of postoperative severe hypoxemia (0.6% vs 6.3%, p = 0.006), shorter PACU stay (70 [60-90] min vs 90 [60-105] min, p < 0.001), and reduced ICU admissions (0.6% vs 8.0%, p = 0.001). CONCLUSIONS: Compared to cisatracurium-neostigmine, the rocuronium-sugammadex strategy for reversal of NMB showed a better recovery profile in patients undergoing kidney transplantation.

Protective effects induced by the food supplement Fluxonorm® in the lower urinary tract.

OBJECTIVE: Fluxonorm® is a dietary supplement that includes water-soluble extracts of Solidago virga-aurea, Phyllantus niruri, Epilobium angustifolium, Peumus boldus and Ononis spinosa. The aim of the present study was to evaluate the tolerability and efficacy of Fluxonorm® in improving lower urinary tract symptoms in patients with benign prostatic hyperplasia (BPH) in combination with standard of care. PATIENTS AND METHODS: Lower urinary tract symptoms can be improved by a marked anti-inflammatory action on the lower urinary tract (irritative symptoms) and/or by an anti-proliferative action (obstructive symptoms) on the prostate. Thirty patients were enrolled to evaluate the effect of Fluxonorm® on improving lower urinary tract symptoms. All patients complained of lower urinary tract symptoms (LUTS), such as hesitancy, poor flow, intermittent flow, incomplete voiding (obstructive symptoms), as well as increased frequency, nocturia and urgency (storage symptoms). All patients were treated with one tablet of Fluxonorm® (1200 mg) daily for 30 days to corroborate the results of our observation in which the food supplement (800 µg/mL) was also studied on the human prostate cancer PC3 cell line (antiproliferative activity) and on prostaglandin (PG)E2 production (anti-inflammatory activity). In addition, the effect of this compound on cyclooxygenase-2 (COX-2) gene expression was investigated. Finally, a bioinformatic analysis was conducted with the aim of unravelling the mechanism of action underlying the observed bio-pharmacological effects. RESULTS: As hypothesized in our preclinical research, adding Fluxonorm® to the therapy of enrolled patients improved all studied clinical parameters, including maximum flow (Qmax), after one month of treatment. In the preclinical evaluation, this formulation reduced PC3 cell viability and PGE2 production. The effects were also paralleled by reduced COX-2 gene expression and Fluxonorm®'s partly related content of catechin. While docking studies pointed out to the putative inhibition of matrix metalloproteinse-2 by gallic acid, as a further mechanism underlying the observed anti-proliferative effects, in PC3 cells exposed to Fluxonorm®. CONCLUSIONS: Fluxonorm® improved the efficacy of standard therapy, in terms of antioxidant/anti-inflammatory effects, for the management of lower urinary tract symptoms (LUTS). This could be related, albeit partially, to the blunting effect of this compound on PGE2 production.

Absence of interaction between rivaroxaban, tacrolimus and everolimus in renal transplant recipients with deep vein thrombosis or atrial fibrillation.

No data are available on rivaroxaban use in renal transplant recipients and on its surmised interaction with immunosuppressants. The aim was to investigate potential interactions between rivaroxaban and immunosuppressants in this setting. Renal transplant recipients with a stable renal function treated with rivaroxaban and tacrolimus with or without everolimus were investigated. All drugs and creatinine concentrations were determined daily for 2 weeks after the start of anticoagulation. Blood samples were drawn at 8.00 am and 3-4 h later for trough and peak concentrations, respectively. Bleeding and thrombotic events were recorded during a minimum follow-up of 6 months. In 8 renal transplant patients, rivaroxaban levels showed a predictable pharmacokinetic trend, both at Ctrough (30-61 µg/L) and at Cpeak (143-449 µg/L), with limited variability in the 25th-75th percentile range. Tacrolimus (Ctrough 3-13 µg/L; Cpeak 3-16 µg/L), everolimus (Ctrough 3-11 µg/L; Cpeak 5-17 µg/L) and creatinine concentrations were stable as well. Immunosuppressors variability before and after rivaroxaban were 30% and 30% for tacrolimus, 27% and 29% for everolimus, respectively, as well as 14% and 3% for creatinine. For rivaroxaban monitoring, the reference change value better performed in identifying significant variations of its concentration. No patient had bleeding or thrombotic events, worsening of renal graft function, and signs of immunosuppressants toxicity during a mean follow-up of 23 (9-28) months. In conclusion, rivaroxaban does not seem to interact with tacrolimus and everolimus in renal transplant recipients. Both anticoagulant and immunosuppressive effects seem warranted, without major bleeding complications and effect on the graft function.

Bio-hybrid gold nanoparticles as SERS probe for rapid bacteria cell identification.

This study reports the utilization of engineered molecular networks between bacteriophage (or phage) and gold nanoparticles (AuNPs) prepared ablating a high purity gold target in water by nanosecond laser source. Gold colloids are assembled with P9b phage clone, displaying the specific peptide (QRKLAAKLT), able to bind P. aeruginosa. The single components and assembled systems were characterized by spectroscopic and electronic techniques, such as the conventional optical absorption and micro-Raman spectroscopies as well as the Dynamic Light Scattering (DLS) and Scanning Transmission Electron Microscopy (STEM) techniques. The performance of the AuNPs-phage assembly as substrate for Surface-Enhanced Raman Spectroscopy (SERS) was tested against the detection of the characteristics Raman vibrational features of the Pseudomonas aeruginosa bacteria.

Cognitive Enhancement via Network-Targeted Cortico-cortical Associative Brain Stimulation.

Fluid intelligence (gf) represents a crucial component of human cognition, as it correlates with academic achievement, successful aging, and longevity. However, it has strong resilience against enhancement interventions, making the identification of gf enhancement approaches a key unmet goal of cognitive neuroscience. Here, we applied a spike-timing-dependent plasticity (STDP)-inducing brain stimulation protocol, named cortico-cortical paired associative stimulation (cc-PAS), to modulate gf in 29 healthy young subjects (13 females-mean ± standard deviation, 25.43 years ± 3.69), based on dual-coil transcranial magnetic stimulation (TMS). Pairs of neuronavigated TMS pulses (10-ms interval) were delivered over two frontoparietal nodes of the gf network, based on individual functional magnetic resonance imaging data and in accordance with cognitive models of information processing across the prefrontal and parietal lobe. cc-PAS enhanced accuracy at gf tasks, with parieto-frontal and fronto-parietal stimulation significantly increasing logical and relational reasoning, respectively. Results suggest the possibility of using SPTD-inducing TMS protocols to causally validate cognitive models by selectively engaging relevant networks and manipulating inter-regional temporal dynamics supporting specific cognitive functions.

Reduction of intratumoral brain perfusion by noninvasive transcranial electrical stimulation.

Malignant brain neoplasms have a poor prognosis despite aggressive treatments. Animal models and evidence from human bodily tumors reveal that sustained reduction in tumor perfusion via electrical stimulation promotes tumor necrosis, therefore possibly representing a therapeutic option for patients with brain tumors. Here, we demonstrate that transcranial electrical stimulation (tES) allows to safely and noninvasively reduce intratumoral perfusion in humans. Selected patients with glioblastoma or metastasis underwent tES, while perfusion was assessed using magnetic resonance imaging. Multichannel tES was applied according to personalized biophysical modeling, to maximize the induced electrical field over the solid tumor mass. All patients completed the study and tolerated the procedure without adverse effects, with tES selectively reducing the perfusion of the solid tumor. Results potentially open the door to noninvasive therapeutic interventions in brain tumors based on stand-alone tES or its combination with other available therapies.

ß-Bi2O3 reduction by laser irradiation in a liquid environment.

This study reports the structural and stoichiometric modifications of bismuth oxide nanoparticles in the ß phase (ß-Bi2O3) by UV pulsed laser irradiation in water or ethanol solutions. Scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, UV-vis diffuse reflectance and high-resolution transmission electron microscopy were used to characterize the synthesized nanomaterials. The various analyses demonstrate that the laser irradiation of ß-Bi2O3 nanospheres is a green, fast and effective method to produce Bi2O2CO3 nanosheets or metallic Bi nanoparticles depending on the liquid environment used. Bi subcarbonate is obtained by laser irradiation in water, whereas metallic Bi is produced by laser irradiation in ethanol, and in particular the relative amount of metallic Bi is found to depend on the laser fluence. These typologies of materials find application in several fields, such as photocatalytic processes, light filters and environmental sensors.

Clonal analysis as a prognostic factor in multiple oral squamous cell carcinoma.

OBJECTIVES: A novel classification based on molecular methods to assess clonality defines three types of secondary oral squamous cell carcinoma (OSCC): second primary tumour (SPT) independent from the index tumour, local recurrence (LR), clonally related to the primary tumour, and second field tumour (SFT), derived from the same genetically altered mucosal field as the primary tumour. The present study applied mtDNA analysis in a group of patients experiencing a second loco-regional neoplastic manifestation. The purpose was to differentiate secondary tumours into LRs, SPTs and SFTs and evaluate the prognostic impact in terms of survival rate. MATERIAL AND METHODS: The study population comprised 23 patients who experienced a second neoplastic lesion after a surgical resection of primary OSCC. mtDNA D-loop analysis was applied in paired neoplastic lesions and in clinically and histologically normal mucosa. On the basis of mtDNA results, the second OSCC was classified as LR or SPT or SFT. Disease-free survival was defined as the duration between the appearance of the second neoplastic lesion and death of disease, or last follow-up visit. RESULTS: Seven secondary tumours were classified as LR, 12 as SFT, 4 as SPT. An altered mucosal field proved a variable significantly related to a better survival rate (p<0.05); 2/12 (16.6%) SFT events failed as compared to 5/7 LRs (71.4%) and 3/4 SPTs (75%). CONCLUSION: mtDNA analysis may be considered a useful tool to differentiate secondary tumours and might influence the choice of the most appropriate treatment in patients with multiple OSCCs.

Mutations in NOTCH1 PEST domain orchestrate CCL19-driven homing of chronic lymphocytic leukemia cells by modulating the tumor suppressor gene DUSP22.

Even if NOTCH1 is commonly mutated in chronic lymphocytic leukemia (CLL), its functional impact in the disease remains unclear. Using CRISPR/Cas9-generated Mec-1 cell line models, we show that NOTCH1 regulates growth and homing of CLL cells by dictating expression levels of the tumor suppressor gene DUSP22. Specifically, NOTCH1 affects the methylation of DUSP22 promoter by modulating a nuclear complex, which tunes the activity of DNA methyltransferase 3A (DNMT3A). These effects are enhanced by PEST-domain mutations, which stabilize the molecule and prolong signaling. CLL patients with a NOTCH1-mutated clone showed low levels of DUSP22 and active chemotaxis to CCL19. Lastly, in xenograft models, NOTCH1-mutated cells displayed a unique homing behavior, localizing preferentially to the spleen and brain. These findings connect NOTCH1, DUSP22, and CCL19-driven chemotaxis within a single functional network, suggesting that modulation of the homing process may provide a relevant contribution to the unfavorable prognosis associated with NOTCH1 mutations in CLL.

Immediate delivery or expectant management in gestational diabetes at term: the GINEXMAL randomised controlled trial.

OBJECTIVE: To evaluate maternal and perinatal outcomes after induction of labour versus expectant management in pregnant women with gestational diabetes at term. DESIGN: Multicentre open-label randomised controlled trial. SETTING: Eight teaching hospitals in Italy, Slovenia, and Israel. SAMPLE: Singleton pregnancy, diagnosed with gestational diabetes by the International Association of Diabetes and Pregnancy Study Groups criteria (IADPSGC), between 38+0 and 39+0 weeks of gestation, without other maternal or fetal conditions. METHODS: Patients were randomly assigned to induction of labour or expectant management and intensive follow-up. Data were analysed by 'intention to treat'. MAIN OUTCOME MEASURES: The primary outcome was incidence of caesarean section. Secondary outcomes were maternal and perinatal mortality and morbidity. RESULTS: A total of 425 women were randomised to the study groups. The incidence of caesarean section was 12.6% in the induction group versus 11.7% in the expectant group. No difference was found between the two groups (relative risk, RR 1.06; 95% confidence interval, 95% CI 0.64-1.77; P = 0.81). The incidence of non-spontaneous delivery, either by caesarean section or by operative vaginal delivery, was 21.0 and 22.3%, respectively (RR 0.94; 95% CI 0.66-1.36; P = 0.76). Neither maternal nor fetal deaths occurred. The few cases of shoulder dystocia were solved without any significant birth trauma. CONCLUSIONS: In women with gestational diabetes, without other maternal or fetal conditions, no difference was detected in birth outcomes regardless of the approach used (i.e. active versus expectant management). Although the study was underpowered, the magnitude of the between-group difference was very small and without clinical relevance. TWEETABLE ABSTRACT: Immediate delivery or expectant management in gestational diabetes at term?

Determining exhaust fumes exposure in chainsaw operations.

The objective of this study was to investigate the inhalation exposure of forest operators to polycyclic aromatic hydrocarbons (PAHs) and BTEX (benzene, toluene, ethylbenzene and total xylenes) contained in the exhaust fumes released from chainsaws and to suggest possible countermeasures. The study was carried out in four silvicultural treatments (coppice clearcut, conifer thinning, conifer pruning, and sanitary cut), using three types of chainsaw fuel (normal two-stroke petrol mix and two alkylate fuels). Eighty personal air samples were collected; IOM samplers combined with Amberlite XAD-2 sorbent tubes were used for collecting PAHs and Radiello® samplers were used for BTEX. Results indicate that none of the four silvicultural treatments significantly affected the PAHs and BTEX inhalation exposure of forest workers. On the other hand, statistically significant differences were recorded in the inhalation exposure to PAHs and BTEX when using different fuel types. In particular, the inhalation exposure to PAHs and BTEX was generally one order of magnitude lower when using modern alkylate fuels as compared to the traditional oil and lead-free petrol mixture. The small, non-statistically significant differences in inhalation exposure recorded between the two alkylate fuels suggests that the two fuels might be equivalent in terms of quality. Our study indicates that while forest workers are exposed to PAHs and BTEX, the maximum values are generally well below accepted occupational exposure limits.

Coronary Microvascular Dysfunction Predicts Long-Term Outcome in Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: Patients with diabetes are at increased cardiovascular risk. Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice in patients with type 1 diabetes mellitus and diabetic nephropathy. We assessed coronary flow reserve (CFR) by transthoracic echocardiography as a marker of major adverse cardiac events (MACE) in SPKT patients. METHODS: We studied 48 consecutive SPKT patients (28 male, age at SPKT 54 ± 8 years). Time from transplantation was 8.5 ± 3 years. Follow-up was 4.6 ± 1.8 years. Coronary flow velocity in the left anterior descending coronary artery was detected by Doppler echocardiography at rest and during adenosine infusion. CFR was the ratio of hyperemic diastolic flow velocity (DFV) to resting DFV. A CFR ≤ 2 was considered abnormal and a sign of coronary microvascular dysfunction. MACE were cardiac death, myocardial infarction, and heart failure. RESULTS: CFR was 2.55 ± 0.8. CFR was ≤2 in 13 (27%) patients. CFR was lower in SPKT patients with MACE (2.1 ± 0.7 vs 2.7 ± 0.8, P = .03) and patients with MACE had a higher incidence of CFR ≤ 2 (P = .03). Time from transplantation was shorter in patients with MACE (P < .0001). Patients with CFR ≤ 2 had a lower MACE-free survival (P = .03). CFR ≤ 2 predicted the risk of MACE (P = .007) independently from coronary artery disease and metabolic control. However, this predicted role is lost when adjusted for the time from transplantation, which plays a protective role (P = .001). CONCLUSIONS: In SPKT, CFR ≤ 2 may be a reliable marker for MACE, independent of coronary artery disease diagnosis. However, this role seems to be reduced over time. This finding suggests a gradual reduction of cardiovascular risk in SPKT patients.

Snai1 represses Nanog to promote embryonic stem cell differentiation.

Embryonic stem cell (ESC) self-renewal and pluripotency is maintained by an external signaling pathways and intrinsic regulatory networks involving ESC-specific transcriptional complexes (mainly formed by OCT3/4, Sox2 and Nanog proteins), the Polycomb repressive complex 2 (PRC2) and DNA methylation [1-8]. Among these, Nanog represents the more ESC specific factor and its repression correlates with the loss of pluripotency and ESC differentiation [9-11]. During ESC early differentiation, many development-associated genes become upregulated and although, in general, much is known about the pluripotency self-renewal circuitry, the molecular events that lead ESCs to exit from pluripotency and begin differentiation are largely unknown. Snai1 is one the most early induced genes during ESC differentiation in vitro and in vivo [12,13]. Here we show that Snai1 is able to directly repress several stemness-associated genes including Nanog. We use a ESC stable-line expressing a inducible Snai1 protein. We here show microarray analysis of embryonic stem cells (ESC) expressing Snail-ER at various time points of induction with 4-OH. Data were deposited in Gene Expression Omnibus (GEO) datasets under reference GSE57854 and here: http://epigenetics.hugef-research.org/data.php.

Laser light triggered smart release of silibinin from a PEGylated-PLGA gold nanocomposite.

In this work a new remotely-triggered drug delivery system based on PEG-PLGA_Au nanocomposite is proposed. Due to the optical properties of gold nanoparticles (Au NPs), the nanovector allows on-demand control of the dose, the timing and the duration of the drug release, upon irradiation with red laser light. The Au NPs are synthesized by laser ablation and subsequently embedded into the PEG-PLGA copolymer via a modified emulsion-diffusion method, devised in such a way that both Au NPs and silibinin (SLB), a flavonolignan with promising anti-neoplastic effects, can be co-loaded into the polymeric system in a single step procedure. A combination of analytical techniques including nuclear magnetic resonance (NMR), static and dynamic light scattering (SLS, DLS), gel permeation chromatography (GPC), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), infrared (FTIR) spectroscopy and scanning/transmission electron microscopies (SEM/STEM/TEM), have been used to study the structural and morphological properties of the nanocomposite. The loading efficiency and the drug content, evaluated by UV-vis absorption optical spectroscopy, are 89% and 8.8%, respectively. Upon laser irradiation the system releases the encapsulated drug with a higher efficiency (∼10%) than that without irradiation. This behaviour indicates that our nanoplatform is responsive to light and it could be considered a promising new type of light-activated drug delivery carrier applicable to the biomedical field.

TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway.

Ten eleven translocation (TET) enzymes catalyse the oxidative reactions of 5-methylcytosine (5mC) to promote the demethylation process. The reaction intermediate 5-hydroxymethylcytosine (5hmC) has been shown to be abundant in embryonic stem cells and tissues but strongly depleted in human cancers. Genetic mutations of TET2 gene were associated with leukaemia, whereas TET1 downregulation has been shown to promote malignancy in breast cancer. Here we report that TET1 is downregulated in colon tumours from the initial stage. TET1 silencing in primary epithelial colon cells increase their cellular proliferation while its re-expression in colon cancer cells inhibits their proliferation and the growth of tumour xenografts even at later stages. We found that TET1 binds to the promoter of the DKK gene inhibitors of the WNT signalling to maintain them hypomethylated. Downregulation of TET1 during colon cancer initiation leads to repression, by DNA methylation, the promoters of the inhibitors of the WNT pathway resulting in a constitutive activation of the WNT pathway. Thus the DNA hydroxymethylation mediated by TET1 controlling the WNT signalling is a key player of tumour growth. These results provide new insights for understanding how tumours escape cellular controls.

Splenogonadal fusion mimicking a testis tumor.

The presence of ectopic splenic tissue in the scrotum is attributed to splenogonadal fusion, a rare congenital anomaly. This ectopic splenic tissue can be an incidental finding or less often present as a scrotal mass later in adult life. Given the rarity of splenogonadal fusion, especially in the adult population, this case highlights the clinical characteristics of the condition, with a special focus on the signs and findings that might help prevent unnecessary orchiectomy.

Decreased whole-blood global DNA methylation is related to serum hormones in anorexia nervosa adolescents.

OBJECTIVES: The one-carbon metabolism, also known as methionine-homocysteine cycle, governs the dynamics of DNA methylation, epigenetically regulating gene expression, and has been reported altered in anorexia nervosa (AN) adult patients. The aim of this study consisted in assessing whole-blood DNA methylation in adolescent AN patients, assessing its significance in relationship to clinical and hormonal variables. METHODS: Whole-blood global DNA methylation was measured as incorporation of [(3)H]dCTP following HpaII cut in 32 adolescent females affected by restrictive type AN and compared to 13 healthy controls. Homocysteine, vitamin B12 and folate plasma levels were assessed as well as fasting plasma levels of leptin and steroid hormones. Clinical variables, including severity and associate states and traits, were assessed by means of the EDI-3, CDI and STAI-Y scales. RESULTS: We confirm that whole-blood global DNA methylation is modestly albeit significantly reduced in AN adolescents with respect to controls, correlating with plasma leptin and steroid hormone levels. Conversely, clinical traits did not correlate with the outcome variable. CONCLUSIONS: A better definition of the epigenetic dysregulation underlying AN pathology or vulnerability might lead to develop useful markers for diagnosis, prognostic classification and tailored therapeutic interventions in these vulnerable patients since the earliest phases of their disease.

Percolation-based risk index for pathogen invasion: application to soilborne disease in propagation systems.

Propagation systems for seedling growth play a major role in agriculture, and in notable cases (such as organic systems), are under constant threat from soil and seedborne fungal plant pathogens such as Rhizoctonia solani or Pythium spp. Yet, to date little is known that links the risk of disease invasion to the host density, which is an agronomic characteristic that can be readily controlled. We introduce here, for the first time in an agronomic system, a percolation framework to analyze the link. We set up an experiment to study the spread of the ubiquitous fungus R. solani in replicated propagation systems with different planting densities, and fit a percolation-based epidemiological model to the data using Bayesian inference methods. The estimated probability of pathogen transmission between infected and susceptible plants is used to calculate the risk of invasion. By comparing the transmission probability and the risk values obtained for different planting densities, we are able to give evidence of a nonlinear relationship between disease invasion and the inter-plant spacing, hence to demonstrate the existence of a spatial threshold for epidemic invasion. The implications and potential use of our methods for the evaluation of disease control strategies are discussed.

Induction therapy with alemtuzumab (campath) in combined liver-kidney transplantation: University of Bologna experience.

BACKGROUND: Combined liver-kidney transplantation (LKT) is considered to be a safe procedure, but the appropriate immunosuppressive regimen is unclear. PATIENTS AND METHODS: Between January 1997 and October 2011, 55 patients were listed for LKT: 45 (82%) were effectively transplanted, 5 (9.2%) died whereon here the waiting list, 3 (5.5%) temporarily out of waiting list, 1 (1.8%) was on waiting list and 1 (1.8%) refused LKT. Five LKTs treated with cyclosporine (CyA) were excluded from the analysis. Mean recipient age was 50.32 ± 10.32 years (14-65), MELD score at time of LKT was 19.22 ± 4.69 (8-29), mean waiting list time was 8.14 ± 9.50 months (0.1-35.76), and follow-up, 4.09 ± 3.02 years (0.01-10.41). Main indications for LKT were policystic disease (n = 15; 37%), hepatitis virus C (HCV)-related cirrhosis (n = 9; 22%) metabolic disease (n = 5; 13%), hepatitis virus B (HBV) cirrhosis (n = 4; 10%), alcoholic cirrhosis (n = 4; 10%), and cholestatic disease (n = 3; 8%). Immunosuppressive regimen was based on tacrolimus and steroids in 40 cases with induction therapy with alemtuzumab (Campath; 0.3 mg/kg) in 13 of 40 instances cases administered on day 0 and day 7. RESULTS: Postoperative mortality was 2.5%. Acute cellular rejection episodes were biopsy-proven in 2 (5%) cases, post-LKT infections developed in 17 cases (42.5%), and de novo cancer developed in 3 (7.5%) cases. Similar 5-year overall survivals were obtained irrespective of the LKT indication: 100% in cholestatic and alcoholic cirrhosis patients, 86% in policystic disease, 75% in metabolic disease and HBV patients, and 66% in HCV cirrhosis. Overall survivals for the alemtuzumab vs without-induction therapy groups at 1, 3, and 5-years were 100%, 85.7%, and 85.7% vs 76%, 76%, and 70%, respectively (P = .04). CONCLUSION: An immunosuppressive regimen based on tacrolimus and steroids with induction therapy with alemtuzumab was safe, with excellent long-term results for combined LKT.