Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European Liver Transplant Registry.

This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with <1 month of follow-up were excluded from the analyses. In total, 4367 patients (prolonged-release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score-matched patients confirmed the significant survival advantages observed in the prolonged-release tacrolimus- versus tacrolimus BD-treated group. This large retrospective analysis from the ELTR identified significant improvements in long-term graft and patient survival in patients treated with prolonged-release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data.

Analysis of disease-free survival and overall survival in patients with luminal a breast cancer stratified according to TNM.

BACKGROUND AND AIM: The TNM classification of malignant tumours is the most commonly used system to assess the stage as well as the prognosis of cancer. However, one of the biggest challenges in treatment of breast cancer is the understanding of tumour heterogeneity typical of these carcinomas. The aim of this study was to analyse the disease-free survival and overall survival in patients with luminal A subtype of breast cancer, stratified by TNM staging system. METHODS AND STUDY DESIGN: A total of 363 medical records from January 2001 to May 2006 were evaluated for data collection. There were 136 patients with luminal A breast cancer, selected for the cohort. The main objective was the analysis of disease-free survival (DFS) and overall survival (OS) in patients with luminal A breast cancer, stratified according to the TNM classification. RESULTS: The group of 136 patients with immunohistochemically defined luminal A subtype represented 53% of the 253 patients with breast cancer. There was no significant difference in the number and type of patients as for TNM stage and histological grading among patients treated with chemotherapy and HT in comparison to patients treated with HT alone. CONCLUSION: Our analysis did not prove any significant difference in survival of patients treated with chemotherapy followed by hormone therapy in comparison to patients treated with HT alone. We suggest that the IHC luminal A subtype of breast cancer generally warrants a good prognosis independently on other prognostic factors such as TNM stage. We conclude that patients might not benefit of adding a chemotherapy to hormonal therapy in adjuvant settings.

Increased Gene Expression of RUNX2 and SOX9 in Mesenchymal Circulating Progenitors Is Associated with Autophagy during Physical Activity.

Lack of physical exercise is considered an important risk factor for chronic diseases. On the contrary, physical exercise reduces the morbidity rates of obesity, diabetes, bone disease, and hypertension. In order to gain novel molecular and cellular clues, we analyzed the effects of physical exercise on differentiation of mesenchymal circulating progenitor cells (M-CPCs) obtained from runners. We also investigated autophagy and telomerase-related gene expression to evaluate the involvement of specific cellular functions in the differentiation process. We performed cellular and molecular analyses in M-CPCs, obtained by a depletion method, of 22 subjects before (PRE RUN) and after (POST RUN) a half marathon performance. In order to prove our findings, we performed also in vitro analyses by testing the effects of runners' sera on a human bone marrow-derived mesenchymal stem (hBM-MSC) cell line. PCR array analyses of PRE RUN versus POST RUN M-CPC total RNAs put in evidence several genes which appeared to be modulated by physical activity. Our results showed that physical exercise promotes differentiation. Osteogenesis-related genes as RUNX2, MSX1, and SPP1 appeared to be upregulated after the run; data showed also increased levels of BMP2 and BMP6 expressions. SOX9, COL2A1, and COMP gene enhanced expression suggested the induction of chondrocytic differentiation as well. The expression of telomerase-associated genes and of two autophagy-related genes, ATG3 and ULK1, was also affected and correlated positively with MSC differentiation. These data highlight an attractive cellular scenario, outlining the role of autophagic response to physical exercise and suggesting new insights into the benefits of physical exercise in counteracting chronic degenerative conditions.

Pancreas Transplantation: Small-Center Experience in Type 1 Diabetes Mellitus in a High-Incidence Region.

BACKGROUND: Pancreas transplantation (PT) is the best option of care for patients with type I diabetes mellitus (T1DM). METHODS: From July 2005 to September 2014, we performed 27 PT from deceased donors (24 simultaneous pancreas-kidney transplantations [SPKT] and 3 pancreas transplantations alone) in a region with a high incidence of T1DM. RESULTS: Enteric drainage and systemic venous derivation were accomplished for all PT. Cold and warm ischemia times were 291 ± 70 minutes and 32 ± 9 minutes, respectively. The rate of early re-operations was 33%, mainly because of bleeding occurrence. Mean donor age was 31 ± 11 years; all patients had ABO compatibility and negative cross-match. With a mean follow-up time of 2.3 years, no death was registered. Graft survival of PT was 96.7%, with 1 graft loss in the SPKT group (3.7%) after acute rejection. Nine patients were submitted successfully to re-operation for no life-threatening complications within 30 post-operative days. No early or late episode of vascular thrombosis, pancreatitis, or pancreatic fistula was observed. All patients with a functioning graft had excellent metabolic control, with mean glycosylated hemoglobin level at last follow-up of 5.5% and median fasting glucose level of 95 ± 13 mg/dL, comparable to that in the non-diabetic population. CONCLUSIONS: In our experience, PT is an excellent therapeutic solution for patients with T1DM. Despite fewer than 5 PT performed per year, graft and patient outcomes were similar to those in high-volume centers.

Use of arterial conduit as an alternative technique in arterial revascularization during orthotopic liver transplantation.

BACKGROUND: The risk of hepatic artery thrombosis after orthotopic liver transplantation is higher in cases of poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, unsafe native hepatic arteries. AIMS: To assess the use of arterial conduits as alternative technique for graft revascularization. PATIENTS: At the Liver Transplant Center of the "S. Giovanni Battista" Hospital in Torino, a review has been made of 600 consecutive orthotopic liver transplantations in 545 adult patients from 1990 to 1999. METHODS: In 95 orthotopic liver transplantations (15.8%) in 88 patients, the graft was supplied by infrarenal conduit, while in 505 orthotopic liver transplantations (84.2%) in 457 patients, a direct anastomosis was used. RESULTS AND CONCLUSIONS: The overall incidence of hepatic artery thrombosis in our series was 3.5% (21/600): 5.3% (5/91) for conduits and 3.2% (16/505) for standard technique (p=ns, chi2 test). The actuarial 5-year graft survival was 67.7% for conduits and 68.6% for the standard technique; p (log rank): ns. The iliac prosthesis torsion was the only complication related to the use of infrarenal iliac conduit. The arterial conduit, performed with donor iliac artery, is an effective and safe revascularization technique in patients at high risk of arterial thrombosis.

[Glypressin and emergency sclerotherapy, deferred emergency shunt (Warren, portacaval, mesocaval): new tactics in the treatment of severe hemorrhage by esophagogastric varices in cirrhotic patients]. / Glipressina e sclerosi mirata in urgenza, intervento di derivazione (Warren, porta-cava, meso-cava) in urgenza differita: nuova tattica per il trattamento delle gravi emorragie da varici esofago-gastriche nel cirrotico.

Transplenic decompression of esophageal varices by distal splenorenal shunt according to Warren (DSRS) aims to a selective detention of the esophago-gastric varices, also assuring an adequate portal perfusion and hypertensive state of the porto-mesenteric district. The DSRS though, should and must not be performed in emergency as a high mortality rate is registered in all cases of emergency porto-systemic derivations. A mortality risk is reported even during endoscopic sclerosis if performed in emergency compared to the elective procedure. The scope of our study was to test the validity of a new approach of the hemorrhagic cirrhotic patient: the end point was to stop the bleeding with Glypressin and deferred sclerotherapy, associating a selective shunt at 40-60 days. Out of 32 patients with esophago-gastric variceal bleeding, 8 were selected also for derivative surgery. Results show Glypressin as the first and best therapeutic approach. The drug in many cases stops bleeding or at least reduces the blood loss allowing an easier endoscopic sclerosis. Further sclerosis and/or surgical therapy may assure variceal eradication.

Bio-electrospraying of human mesenchymal stem cells: An alternative for tissue engineering.

Bio-electrospraying (BES) is a technique used for the processing of cells and can be applied to tissue engineering. The association of BES with scaffold production techniques has been shown to be an interesting strategy for the production of biomaterials with cells homogeneously distributed in the entire structure. Various studies have evaluated the effects of BES on different cell types. However, until the present moment, no studies have evaluated the impact of BES time on mesenchymal stem cells (MSC). Therefore, the aim of this work was to standardise the different parameters of BES (voltage, flow rate, and distance of the needle from the collecting plate) in relation to cell viability and then to evaluate the impact of BES time in relation to viability, proliferation, DNA damage, maintenance of plasticity and the immunophenotypic profile of MSC. Using 15 kV voltage, 0.46 ml/h flow rate and 4 cm distance, it was possible to form a stable and continuous jet of BES without causing a significant reduction in cell viability. Time periods between 15 and 60 min of BES did not cause alterations of viability, proliferation, plasticity, and immunophenotypic profile of the MSC. Time periods above 30 min of BES resulted in DNA damage; however, the DNA was able to repair itself within five hours. These results indicate that bio-electrospraying is an adequate technique for processing MSC which can be safely applied to tissue engineering and regenerative medicine.

De novo malignancies following liver transplantation: results from a multicentric study in central and southern Italy, 1990-2008.

OBJECTIVE: The objective of this study was to quantify incidence rates (IR) and risks of de novo tumors (except nonmelanoma skin cancers) in patients who underwent orthotopic liver transplantation (OLT) in central and southern Italy. METHODS: Data were collected on 1675 patients (75.5% males) who underwent OLT in six Italian transplantation centers in central and southern Italy (1990-2008). The time at risk of cancer (person years [PY]) was computed from OLT to the date of cancer diagnosis, death, or last follow-up, whichever occurred first. The number of observed cancer cases were compared with the expected one using data from population-based cancer registries. We computed gender- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: During 10,104.3 PYs (median follow-up, 5.2 years), 98 patients (5.9% of the total) were diagnosed with a de novo malignancy (for a total of 100 diagnoses). Twenty-two of these cancers were post-transplantation lymphoproliferative disorders (PTLD; 18 non-Hodgkin lymphoma [NHL] and 2 Hodgkin's lymphoma [HL]), 6 were Kaposi's sarcoma (KS), and 72 were solid tumors (19 head and neck [H&N], 13 lung, 11 colon-rectum, 6 bladder, and 4 melanoma). The overall incidence was 9.9 cases/10(3) PYs, with a 1.4-fold significantly increased SIR (95% CI, l.2-1.7). Significantly increased SIRs were observed for KS (37.3), PTLD (3.9), larynx (5.7), melanoma (3.1), tongue (7.1), and H&N (4.5) cancers. CONCLUSIONS: These results confirmed that OLT patients are at greater risk for cancer, mainly malignancies either virus-associated or related to pre-existent factors (eg, alcohols). These observations point to the need to improve cancer surveillance after OLT. The on-going enrollment of patients in the present cohort study will help to elucidate the burden of cancer after OLT and better identify risk factors associated with its development.

Bacterial contamination in soft contact lens wearers.

We prospectively analyzed bacterial contamination in 15 soft contact lens wearing subjects. Contact lenses, cases, tips of saline solution bottles, and conjunctiva were cultured. Cultures were positive for 13 subjects (86.6%). Contamination was present in 13 contact lens cases (86.6%), 12 contact lenses (80.0%), nine saline solution bottles (60.0%), and in the conjunctiva of three patients (20.0%). Gram-negative bacteria (Pseudomonas aeruginosa and Proteus mirabilis) were the most frequently isolated organisms. Staphylococcus aureus was the only gram-positive organism isolated. We discuss the possible sources of contamination, and emphasize the importance of contact lens care instruction.

Clinical study of disposable contact lens wear: Brazilian experience.

PURPOSE: The objective of this study was to analyze prospectively the continuous use of disposable contact lenses. METHODS: We conducted a clinical study of extended wear of disposable contact lenses for a period of 7 days and 6 nights by 25 patients during a 90-day period. Factors such as visual acuity, keratometry, complications, and contamination were analyzed. RESULTS: Visual acuity and keratometry measurements did not present significant alterations during the study. Complications related to the use of disposable contact lenses were not observed. Analysis of cultures did not present any significant microbiological alterations due to contact lens use. All of the patients were satisfied with the wear schedule and considered the Acuvue lenses comfortable. CONCLUSIONS: Our results may be useful in increasing the level of acceptance of extended wear of disposable contact lenses in Brazil.

Effect of macrovescicular steatosis and other donor and recipient characteristics on the outcome of liver transplantation.

The influence of steatosis and of other donor and recipient characteristics in affecting liver performance post-orthotopic liver transplantation (OLT) was evaluated in 311 consecutive liver transplantations made in 278 patients. Donor variables considered were age, sex, blood group, cause of death, intensive care unit (ICU) days, need for vasopressors, hepatic enzymes and bilirubin, total and warm ischemia time, and macro- and microvescicular steatosis. Recipient variables considered were age, sex, blood group, biliary output, and post-OLT peak levels of hepatic enzymes. Patient and graft survival were the main outcome indicators. In the multivariate analysis, macrovescicular steatosis involving 25% or more of the hepatocytes was the only variable independently associated with shorter patient survival (p < 0.05). Five (62.5%) of the eight livers with macrovescicular steatosis involving 25% or more of the hepatocytes incurred in a delayed non-function (DNF) and one (12.5%) in a primary non-function (PRNF). The incidence of DNF and PRNF in the group with macrovescicular steatosis involving less than 25% of the liver cells was 1.6% (p < 0.001) and 2.3%, respectively. Microvescicular steatosis of any degree was not associated with a worse prognosis. Macrovescicular steatosis involving 25% or more of the hepatocytes identifies marginal livers, the use of which significantly increases the risk of graft non-function post-OLT.

Recurrence of hepatitis B in liver transplants treated with antiviral therapy.

BACKGROUND AND AIMS: In patients with terminal Hepatitis B Virus-related liver diseases, liver transplantation carries a consistent risk of Hepatitis B Virus recrudescence in the graft. In the attempt to reduce the reinfection rate with antiviral therapy, we studied a total of 16 viraemic patients. PATIENTS AND METHODS: Twelve patients received Ganciclovir, starting 4-67 days (mean 25 days) before transplantation and prolonged for 10 days after transplantation; four patients were treated with Lactosaminated Arabinoside-Monophosphate 6 hours before surgery and prolonged for 28 days after surgery. All received hepatitis B immunoglobulins. RESULTS: At transplantation, HBV-DNA had decreased to about 10(4) virus/ml (as assessed by the polymerase chain reaction assay) in 10 of the 12 patients treated with Ganciclovir. Of these patients, 4 died perioperatively from causes unrelated to Hepatitis B Virus reinfection. Of the eight survivors, only the patient who maintained a titre of 10(6) virus/ml at the time of transplantation developed viral recurrence 4 months after surgery. Before transplantation, 2 of the patients treated with Lactosaminated Arabinoside-Monophosphate had a viraemic load of 10(6) and 2 of 10(4) virus/ml. In all cases, viraemia became undetectable at the end of therapy. None died and Hepatitis B Virus recurred 2 months after transplantation in one. The overall rate of Hepatitis B Virus recurrence was 16.6%. The recurrence rate decreased to 9% in patients in whom the viraemic load decreased to around 10(4) virus/ml following treatment, compared to an overall recurrence rate of 50% in our historical series of patients transplanted for Hepatitis B Virus-related cirrhosis. CONCLUSION: Antiviral therapy was effective in decreasing the risk of Hepatitis B Virus reinfection of the liver graft by decreasing the viral load before surgery.

Efeito da compressao ocular continua sobre a pressao intra-ocular. / Effect of the continuous ocular compression on the intraocular pressure

Foi realizado um estudo com o balao de compressao ocular continua em 40 pacientes com idade variando entre 43 e 67 anos. Aplicou-se nesse balao uma pressao constante de 40 mmHg por trinta minutos, obtendo-se com isso uma reducao significativa (p < 0,001) da pressao intra-ocular (ao redor de 06 mmHg) por mais de vinte minutos em todos os pacientes.Alem de apresentar baixo custo e nenhuma complicacao o metodo mostrou ser eficiente, podendo, portanto ser usado como alternativa ao manitol no pre-operatorio da cirurgia intra-ocular