pinecone/core-2020-05-10-deduplication huggingface dataset:
Long-term results of liver transplantation from donation after circulatory death

Donation after circulatory death (DCD) liver transplantation (LT) may imply a risk for decreased graft survival, caused by post-transplantation complications such as primary non-function or ischemic-type biliary lesions. However, similar survival for DCD and donation after brain death (DBD) LT has been reported. Objective of this study is to determine long-term outcome of DCD LT in the Eurotransplant region corrected for Eurotransplant donor risk index (ET-DRI). Transplants performed in Belgium and The Netherlands (1.1.2003 - 31.12.2007) in adult recipients were included. Graft failure was defined as either date of recipient death or retransplantation; death un-censured graft survival. Mean follow-up was 7.2 years. In total 126 DCD and 1264 DBD LT's were performed. Kaplan-Meier survival analyses showed different graft survival for respectively DBD and DCD at one (78% vs. 75%, p=0.71), five (66% vs. 54%, p=0.02) and ten (47% vs. 44%, p=0.55) years (Log Rank p=0.038). Although there was an overall significant difference, the survival curves almost reach each other after 10 years, most probably caused by lower other risk factors in DCD livers. Patient survival was not significantly different (p=0.59). Multivariate Cox-regression analysis showed a HR 1.7 (p<0.001) for DCD (corrected for ET-DRI and recipient factors). First warm ischemia time (1(st) WIT) over 25 minutes was associated with a lower graft survival in univariate analysis of all DCD transplants (p=0.002).status: publishe
Vena cava encirclement predicts difficult native hepatectomy

International audienceRecipient hepatectomy is a challenging liver transplantation (LT) procedure that has life-threatening complications. The current predictive mortality clinic-biological scores (Child/Model for End-Stage Liver Disease [MELD]) do not take into consideration the recipient's liver anatomy. The aim of this study was to evaluate the impact of the dorsal sector anatomy of a cirrhotic liver on the morbidity/mortality rates of hepatectomy. A multicenter retrospective study (clinic-biological and morphologic) was performed from 2013 to 2014. The degree of encirclement of the inferior vena cava (IVC) by the dorsal sector of the liver was measured. The study population included 320 patients. Seventy-four (23%) patients had complete IVC encirclement. A correlation (P=0.01) has been reported between the existence of a circular dorsal sector and the number of transfusions during LT (4 packed red blood cell [PRBC] transfusions in the group without IVC versus 7 PRBC transfusions in the other group). The existence of such anatomy increases the relative risk of early reoperation for IVC bleeding by 31% (P=0.05). There is a correlation between alcoholic cirrhosis and dorsal-sector hypertrophy (126 cc versus 147.5 cc; P=0.05). Concerning surgical time, we found no significant between-group differences. Compared to the severity of cirrhosis, an inverse correlation was observed between the MELD and Child scores and the dorsal sector hypertrophy (P<0.001). No significant difference in terms of transfusion was found between the temporary portocaval shunt group (n=168) and the other group (n=152). The presence of a circular sector is associated with an increased risk of hemorrhage during hepatectomy, as well as an immediate postoperative risk of reoperation. Liver Transplantation 22 906-913 2016 AASL
Multidrug-resistant organisms in liver transplant: mitigating risk and managing infections

Liver transplant (LT) recipients are vulnerable to infections with multidrug-resistant (MDR) pathogens. Risk factors for colonization and infection with resistant bacteria are ubiquitous and unavoidable in transplantation. During the past decade, progress in transplantation and infection prevention has contributed to the decreased incidence of infections with methicillin-resistant Staphylococcus aureus. However, even in the face of potentially effective antibiotics, vancomycin-resistant enterococci continue to plague LT. Gram-negative bacilli prove to be more problematic and are responsible for high rates of both morbidity and mortality. Despite the licensure of novel antibiotics, there is no universal agent available to safely and effectively treat infections with MDR gram-negative organisms. Currently, efforts dedicated toward prevention and treatment require involvement of multiple disciplines including transplant providers, specialists in infectious diseases and infection prevention, and researchers dedicated to the development of rapid diagnostics and safe and effective antibiotics with novel mechanisms of action. Liver Transplantation 22 1143-1153 2016 AASLD
Pilot study of living donor liver transplantation for patients with HCC exceeding Milan criteria

BACKGROUND & AIMS: A subset of patients with hepatocellular carcinoma (HCC) beyond Milan criteria might obtain acceptable survival outcomes after liver transplantation. Living donor liver transplantation (LDLT) has emerged as a feasible alternative to overcome the paucity of donors. METHODS: In 2001 we started a protocol for LDLT in Child A-B patients with HCC fulfilling a set of criteria - the BCLC expanded criteria- that expanded the conventional indications of transplantation: 1 tumor ≤ 7cm, 5 tumors ≤ 3cm, 3 tumors ≤ 5cm without macrovascular invasion or down-staging to Milan after loco-regional therapies. RESULTS: We present a prospective cohort of 22 patients with BCLC extended indications based on size/number (17) or down-staging (5) treated with LDLT between 2001 and 2014. Characteristics of the patients were as follows: median age: 57yr old; males/female: 20/2, Child-Pugh A/B: 16/6, AFP <100ng/mL: 21. Twelve patients received neo-adjuvant loco-regional therapies. At the time of transplantation, 12 patients had HCC staging beyond Milan criteria and 10 within. Pathological reports showed that 50% exceeded BCLC expanded criteria. Perioperative mortality was 0%. After a median follow up of 81 months, the 1-, 3-, 5- and 10-year survival was 95.5%, 86.4%, 80.2% and 66.8%, respectively. Overall, seven patients recurred (range 9-108 mo), and the 5-y and 10-yr actuarial recurrence rate was of 23.8% and 44,4%, respectively. CONCLUSION: A proper selection of candidates for extended indications of living donor liver transplantation for HCC patients provide survival outcomes comparable
Incidence and severity of acute allograft rejection in liver transplant recipients treated with alfa interferon

Interferon alfa-2b (IFN-α) therapy has been shown to be effective in the treatment of viral hepatitis B (HBV) or viral hepatitis C (HCV) in patients who did not undergo transplantation. However, in allograft recipients, treatment with IFN-α often leads to allograft rejection. The aim of the present study was to determine if IFN-α therapy increases the incidence or severity of acute rejection in human liver allograft recipients. One hundred five orthotopic liver transplant (OLT) recipients with HBV (n = 32), HCV (n = 58), or Non A Non B Non C (n = 15) viral infections were treated with a 6-month course of IFN-α, 5 million U subcutaneously three times a week, which began 2 to 97 months after transplantation. The mean hepatitis activity index (HAI) at the beginning of the therapy was 10.1 ± 3.0. The baseline immunosuppression was achieved by tacrolimus in 77 patients and by cyclosporine A (CyA) in 28 patients. Contemporaneous controls consisted of 132 OLT patients (100 who received tacrolimus and 32 who received CyA) who did not receive IFN-α. A retrospective analysis was performed on this group of patients. The incidence of rejection and the baseline immunosuppression were compared. All biopsies were reviewed without knowledge of clinical data and scored for HAI and for rejection activity index (RAI). The biochemical response to IFN-α was also examined. The mean baseline maintenance dose of prednisone was greater by 2 mg daily in patients who received IFN-α with tacrolimus compared with control patients who did not receive IFN-α with tacrolimus (IFN-α 5.3 ± 5.2 mg daily v controls 3.3 ± 4.9 mg daily; P ≤ .05). Similarly, the mean maintenance dose of prednisone was greater by 2.5 mg daily in patients who received IFN-α compared with controls who received CyA-based immunosuppression (IFN-α 9.8 ± 3.1 mg daily v controls 7.3 ± 3.3 mg daily; P = .01). Acute rejection episodes were detected in 10.5% (n = 11) of IFN-α-treated patients compared with 8.8% of controls for the similar time period from OLT and period of exposure to risk of rejection. Mean RAI was 2.0 ± 2.4 for the IFN-α- treated group and 2.1 ± 1.7 for controls. Rejection episodes with IFN-α treatment were mild and responded to steroid therapy. In OLT recipients, the risk of acute rejection was not increased by the introduction of IFN-α. However, in this study, patients were exposed to greater levels of immunosuppression
Clinical outcome of patients infected with hepatitis C virus infection on survival after primary liver transplantation under tacrolimus

The outcome of hepatitis C virus (HCV) infection on patient and graft survival after orthotopic liver transplantation (OLT) has been controversial. An earlier experience with a higher dose of tacrolimus (≥0.1 mg/kg/d intravenously and ≥0.2 mg/kg/d orally) was associated with a worse clinical outcome in patients infected with HCV. The clinical outcome of 183 liver transplant recipients with end-stage liver disease (ESLD) secondary to HCV infection (HCV group) was compared with a contemporary cohort of 556 patients with HCV infection who underwent transplantation for nonviral, nonmalignant ESLD (control group). All patients were prospectively screened for anti-HCV antibodies and HCV RNA by reverse-transcriptase polymerase chain reaction. All OLT patients were receiving low-dose tacrolimus immunosuppression. Cumulative patient survival rates for the HCV group were 80% after I year and 75% after 3 years compared with rates of 84% and 78%, respectively, in the control group (P = .452). Primary graft survival rates at the same time intervals for the HCV group and the control group were 72% and 77.5% at 1 year and 67% and 72% at 3 years, respectively (P = .144). The incidence of re-transplantation (re-OLT) in the HCV group and the control group was 12.6% and 10.4%, respectively (P = .42). Chronic HCV infection as an indication for OLT with a lower dose of tacrolimus immunosuppression (≤0.05 mg/kg/d intravenously and ≤0.1 mg/kg/d orally) is associated with a similar patient and graft survival as those without HCV infection
Primary adult liver transplantation under tacrolimus: More than 90 months actual follow-up survival and adverse events

The introduction of tacrolimus has shown decreased rates of acute and steroid-resistant rejection after liver transplantation (LTx). The aim of the present study is to examine the long-term efficacy and safety of tacrolimus in primary liver transplant recipients. The first 121 consecutive adults (aged > 16 years) who underwent primary LTx at a single center from August 1989 to February 1990 were followed up until August 1997. The mean follow-up was 93.2 ± 1.2 months (range, 90.5 to 96.5 months). Patient survival, graft survival, rate of rejection, and adverse events were examined. The actual 7- year patient survival rate was 67.8%, and the graft survival rate was 63.6%. Infections, recurrence of disease, de novo malignancies, and cardiovascular events constituted the main causes of graft loss and death in the long term. Graft loss related to acute or chronic rejection was rare. The rate of acute rejection beyond 2 years was approximately 3% per year, and most rejections were steroid responsive. Approximately 70% of the patients received only tacrolimus after 1 year. Four patients developed endstage renal disease, and 2 patients underwent kidney transplantation. Hyperkalemia and hypertension were observed in one third of the patients New-onset insulin-dependent diabetes mellitus was observed in 9% and 13% of the patients at the 1-year and 7-year follow-up, respectively. Seven patients developed de novo malignancies, including two skin malignancies. Six patients developed posttransplantation lymphoproliferative disorder during the entire follow-up period. Actual patient and graft survival at 7 years was excellent, and few adverse events developed after the first year. Graft loss from acute or chronic rejection was rare under tacrolimus, and approximately 70% of the patients were steroid free on tacrolimus monotherapy after the first year after LTx
Leadership Sustainability

Today's leaders require leadership sustainability, the ability to make personal improvements stick over the long term. Ulrich and Smallwood contend that leaders fail at the stage of implementation, even after enthusiastically embracing coaching, learning, and other performance improvement efforts. The challenge, they write, “is how to turn these events into an ongoing pattern.” Their research found seven principles driving sustainability: simplicity, time, accountability, resources, tracking, melioration (“a new term for a whole complex of actions and attitudes designed to make things better”), and emotion. They also list more than 20 crucial books on such subjects as change, influence, and self‐discipline
Controlled delivery achieved with bi-layer matrix devices produced by co-injection moulding

The aim of this study was to design new soy protein-based bi-layered co-injection moulded matrix systems aimed to achieve controlled drug delivery. The devices consisted of a drug-free outer layer (skin) and a drug-containing core. The systems overcame the inherent disadvantage of non-linear release associated with diffusion-controlled single-layer matrix devices by providing additional releasing area with time to compensate for the decreasing release rate. As expected, the bi-layer devices presented a significant decrease in drug release rate when compared with a correspondent single layer matrix system. The skin thickness and the degree of crosslinking of the core appeared to be very important tools to tailor the release patterns. Furthermore, due to the amphoteric nature of the soy protein, the developed devices evidenced a pH-dependent behaviour. The mechanisms of drug release were also elucidated at two different pH values: i) pH 5.0, near the isoelectric point of soy (low matrix solubility); and ii) pH 7.4, physiological pH (high matrix solubility). Consequently, changing the release medium from pH 5.0 to pH 7.4 after two hours, led to an abrupt increase in drug release and the devices presented a typical controlled drug delivery profile: slow release/fast release. These evidences may provide for the development of individual systems with different release onsets that in combination may exhibit drug releases at predetermined times in a pre-programmed way. Another possibility is the production of three-layer devices presenting bimodal release profiles (fast release/slow release/fast release) by similar technologies.Portuguese Foundation for Science and Technology (FCT), Ministry of Science and Technology, Portugal
Production and characterization of chitosan fibers and 3-D fiber mesh scaffolds for tissue engineering applicattions

This study reports on the production of chitosan fibers and 3-D fiber meshes for the use as tissue engineering scaffolds. Both structures were produced by means of a wet spinning technique. Maximum strain at break and tensile strength of the developed fibers were found to be 8.5% and 204.9 MPa, respectively. After 14 d of immersion in simulated body fluid (SBF), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and inductively coupled plasma emission (ICP) spectroscopy analyses showed that a bioactive Ca-P layer was formed on the surface of the fibers, meaning that they exhibit a bioactive behavior. The samples showed around 120% max. swelling in physiological conditions. The pore sizes of 3-D chitosan fiber mesh scaffolds were observed to be in the range of 100-500 m by SEM. The equilibrium-swelling ratio of the developed scaffolds was found to be around 170% (w/w) in NaCl solution at 37 °C. Besides that, the limit swelling strain was less than 30%, as obtained by mechanical spectroscopy measurements in the same conditions. The viscoelastic properties of the scaffolds were also evaluated by both creep and dynamic mechanical tests. By means of using short-term MEM extraction test, both types of structures (fibers and scaffolds) were found to be non-cytotoxic to fibroblasts. Furthermore, osteoblasts directly cultured over chitosan fiber mesh scaffolds presented good morphology and no inhibition of cell proliferation could be observed.FCT Foundation for Science and Technology, through funds from the POCTI and/or FEDER programmes
Synthesis and characterization of polymeric linseed oil grafted methyl methacrylate or styrene

Syntheses of wholly natural polymeric linseed oil (PLO) containing peroxide groups have been reported. Peroxidation, epoxidation and/or perepoxidation reactions of linseed oil, either under air or under oxygen flow at room temperature, resulted in polymeric peroxides, PLO-air and PLO-ofl, containing 1.3 and 3.5 wt.% of peroxide, with molecular weights of 2100 and 3780 Da, respectively. PLO-air contained cross-linked film up to 46.1 wt.% after a reaction time of 60 d, associated with a waxy, soluble part (PLO-air-s) that was isolated with chloroform extraction. PLO-ofl was obtained as a waxy, viscous liquid without any cross-linked part at the end of 24 d under visible irradation and oxygen flow. Polymeric peroxides, PLO-air-s and PLO-ofl initiated the free radical polymerization of both methyl methacrylate (MMA) and styreine (S) to give PMMA-graft-PLO and PS-graft-PLO graft copolymers in high yields with M-w varying from 37 to 470 kDa. The polymers obtained were characterized by FT-IR. H-1 NMR, TGA, DSC and GPC techniques. Cross-linked polymers were also studied by means of swelling measurements. PMNA-graft-PLO graft copolymer film samples were also used in cell-culture studies. Fibroblast cells were well adhered and proliferated on the copolymer film surfaces, which is important in tissue engineering
Fibers and 3D mesh scaffolds from biodegradable starch-based blends : production and characterization

The aim of this work is the production of fibers
from biodegradable polymers to obtain 3D scaffolds for
tissue engineering of hard tissues. The scaffolds required for
this highly demanding application need to have, as well as the
biological and mechanical characteristics, a high degree of
porosity with suitable dimensions for cell seeding and proliferation.
Furthermore, the open cell porosity should have
adequate interconnectivity for a continuous flow of nutrients
and outflow of cell metabolic residues as well as to allow cell
growth into confluent layers. Blends of corn starch, a natural
biodegradable polymer, with other synthetic polymers (poly-
(ethylene vinyl alcohol), poly(e-caprolactone), poly(lactic
acid)) were selected for this work because of their good balance
of properties, namely biocompatibility, processability
andmechanical properties. Melt spinning was used to produce
fibers fromall the blends and 3Dmeshes fromone of the starchpoly(
lactic acid) blends. The experimental characterization
includedthe evaluationof the tensilemechanicalpropertiesand
thermal properties of the fibers and the compression stiffness,
porosity and degradation behavior of the 3Dmeshes
Bone tissue engineering : state of the art and future trends

Although several major progresses have been introduced in the field of bone regenerative medicine during the years, current therapies, such as bone grafts, still have many limitations. Moreover, and in spite of the fact that material science technology has resulted in clear improvements in the field of bone substitution medicine, no adequate bone substitute has been developed and hence large bone defects/injuries still represent a major challenge for orthopaedic and reconstructive surgeons. It is in this context that TE has been emerging as a valid approach to the current therapies for bone regeneration/substitution. In contrast to classic biomaterial approach, TE is based on the understanding of tissue formation and regeneration, and aims to induce new functional tissues, rather than just to implant new spare parts. The present review pretends to give an exhaustive overview on all components needed for making bone tissue engineering a successful therapy. It begins by giving the reader a brief background on bone biology, followed by an exhaustive description of all the relevant components on bone TE, going from materials to scaffolds and from cells to tissue engineering strategies, that will lead to engineered bone.Portuguese Foundation for Science and Technology through funds from POCTI and/or FEDER programs
Synthesis and endosomolytic properties of poly(amidoamine) block copolymers

The poly(amidoamine)s (PAAs) ISA 1 and ISA 23 display pH-dependent conformational change and pH-dependent membrane perturbation. These properties confer potential for use as endosomolytic polymers for intracytoplasmic delivery of toxins and genes. Both polymers are relatively non-toxic, and moreover ISA 23 has the beneficial property in vivo, of being non hepatotropic when administered intravenously. Although ISA 23 and ISA 1 demonstrate ability to transfect cells, ISA 1 is also able to promote intracellular delivery of non-permeant toxins. The aim of this study was to synthesise random and block copolymers of ISA 1 and ISA 23 and investigate whether these second generation hybrids would allow optimisation of PAA biological characteristics. Random and block copolymers of ISA 1 and ISA 23 were synthesised by hydrogen transfer polyaddition to generate a library of PAAs with an ISA 23:ISA 1 molar ratios of 2:1 to 4: 1. The resultant polymers have a pI slightly below 7.4 and a (M) over bar (w) of 19900-49000 g/mol and a (M) over bar (n) of 13100-24100 g/mol. Whereas none of the random or block copolymers were haemolytic at pH 7.4 all demonstrated pH-dependent membrane activity. At pH 5.5 they caused 50-60% haemoglobin (Hb) release over 1 h. This was slightly less than that seen for ISA 23 (80% Hb release). None of the copolymers were cytotoxic against B16F10 cells during a 72 h incubation (IC50 > 2 mg/ml; MTT assay). The ability of the random and block copolymer PAAs to deliver the toxin gelonin was also examined, but only ISA 1 and the block copolymer B2 (ISA 23:ISA 1 at a 2:1 molar ratio) were able to promote intracellular delivery, as measured by cytotoxic activity. It would be interesting to study the body distribution of B2 and determine whether this toxin-delivering PAA is able to escape liver capture