Tripodal BODIPY-Tagged and Functional Molecular Probes: Synthesis, Computational Investigations and Explorations by Multiphoton Fluorescence Lifetime Imaging Microscopy.

A range of novel BODIPY derivatives with a tripodal aromatic core was synthesized and characterized spectroscopically. These new fluorophores showed promising features as probes for in vitro assays in live cells and offer strategic routes for further functionalization towards hybrid nanomaterials. Incorporation of biotin tags facilitated proof-of-concept access to targeted bioconjugates as molecular probes. Computational explorations using DFT and TD-DFT calculations identified the most stable tripodal linker conformations and predicted their absorption and emission behavior. The uptake and speciation of these molecules in living prostate cancer cells was imaged by single- and two-photon excitation techniques coupled with two-photon fluorescence lifetime imaging (2P FLIM).

Recurrence of hepatocellular carcinoma after liver transplantation: clinical patterns and hierarchy of salvage treatments.

STRUCTURED ABSTRACT Introduction: The multiparametric nature of recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) still leads to uncertainty with its practical management. This study aims to characterize the main post-transplant recurrence patterns of HCC and to explore the therapeutic modalities targeting recurrence. METHODS: Consecutive patients who underwent LT for HCC at a single tertiary center were analyzed. The time from first recurrence to death was investigated for each site of presentation. The impact of each recurrence targeted treatment on survival was studied. RESULTS: Of 660 patients with HCC, any recurrence occurred in 96 (15.4%) patients with a median time to recurrence of 20.0 months (95% CI 15.6-23.8). Patients recurred across different patters including solitary distant locations (30.8%, n=28), liver only (24.2%, n=22), lung (18.7%, n=17), multiorgan disease (17.6%, n=16), and bone (8.8%, n=8). Multiorgan and bone recurrences had the poorest survival, while solitary distant lesions and pulmonary recurrences had the best outcomes. Each treatment modality carried a distinctive survival. CONCLUSIONS: Patients recurred across 3 patterns with different prognostic implications. The benefit of each treatment option on distinct recurrence patterns appears to be influenced by the biological behavior inherent in the recurrence pattern itself.

Safe Procedure for Efficient Hydrodynamic Gene Transfer to Isolated Porcine Liver in Transplantation.

Although calcineurin inhibitors are very effective as immunosuppressants in organ transplantation, complete graft acceptance remains as a challenge. Transfer of genes with immunosuppressant functions could contribute to improving the clinical evolution of transplantation. In this sense, hydrodynamic injection has proven very efficacious for liver gene transfer. In the present work, the hIL-10 gene was hydrofected 'ex vivo' to pig livers during the bench surgery stage, to circumvent the cardiovascular limitations of the procedure, in a model of porcine orthotopic transplantation with a 10-day follow-up. We used IL-10 because human and porcine proteins can be differentially quantified and for its immunomodulatory pleiotropic functions. Safety (biochemical parameters and histology), expression efficacy (RNA transcription and blood protein expression), and acute inflammatory response (cytokines panel) of the procedure were evaluated. The procedure proved safe as no change in biochemical parameters was observed in treated animals, and human IL-10 was efficaciously expressed, with stationary plasma protein levels over 20 pg/mL during the follow-up. Most studied cytokines showed increments (interferon-α, IFN-α; interleukin-1ß, IL-1ß; tumor necrosis factor α, TNFα; interleukin-6, IL-6; interleukin-8, IL-8; interleukin-4, IL-4; and transforming growth factor-ß, TGF-ß) in treated animals, without deleterious effects on tissue. Collectively, the results support the potential clinical interest in this gene therapy model that would require further longer-term dose-response studies to be confirmed.

Biocompatible Probes Based on Rare-Earth Doped Strontium Aluminates with Long-Lasting Phosphorescent Properties for In Vitro Optical IMAGING.

In recent decades, the demand for biomedical imaging tools has grown very rapidly as a key feature for biomedical research and diagnostic applications. Particularly, fluorescence imaging has gained increased attention as a non-invasive, inexpensive technique that allows real-time imaging. However, tissue auto-fluorescence under external illumination, together with a weak tissue penetration of low wavelength excitation light, largely restricts the application of the technique. Accordingly, new types of fluorescent labels are currently being investigated and, in this search, phosphorescent nanoparticles promise great potential, as they combine the interesting size-dependent properties of nanoscale materials with a long-lasting phosphorescence-type emission that allows optical imaging well after excitation (so avoiding autofluorescence). In this work, core-shell structures consisting of SrAlO:Eu,Dy luminescent cores encapsulated within a biocompatible silica shell were prepared, showing a green persistent phosphorescence with an afterglow time of more than 1000 s. A high-energy ball milling procedure was used to reduce the size of the starting phosphors to a size suitable for cellular uptake, while the silica coating was produced by a reverse micelle methodology that eventually allows the excitation and emission light to pass efficiently through the shell. Confocal fluorescence microscopy using HeLa cancer cells confirmed the potential of the all-ceramic composites produced as feasible labels for in vitro optical imaging.

Tailoring the visible light photoactivity of un-doped defective TiO2 anatase nanoparticles through a simple two-step solvothermal process.

Anatase TiO2 has become a material of great interest for photocatalytic production of hydrogen, environmental purification and solar energy conversion. Among the key parameters boosting the photocatalytic efficiency of the anatase nanoparticles, an increased light absorption to expand its optical response to the visible region, together with an improved charge separation of the photo-generated electrons and holes, can be enumerated. In this work, yellow-coloured, single-phase anatase nanoparticles have been obtained using a simple two-step solvothermal routine which requires no external addition of dopants, nor the use of a harassing/aggressive synthesis atmosphere. The obtained powders display a lowered bandgap (<3.0 eV) and significantly reduce the recombination processes, eventually leading to an improved photocatalytic performance under visible light, as exemplified by an enhanced degradation of phenol. This exceptional response is linked to the presence of intrinsic defects in the yellowish particles and, hence, the specific conditions of the proposed methodology become crucial to produce a propitious TiO2-defective nanomaterial capable of photo-degrade the phenol molecule, in contrast with the lack of photocatalytic activity currently exhibited by commercial photocatalysts under visible light.

Benefits of laparoscopic liver resection in patients with hepatocellular carcinoma and portal hypertension: a case-matched study.

BACKGROUND: The advantages of laparoscopy over open liver resection in patients with cirrhosis have been widely demonstrated. On the other hand, information on the role of minimally invasive liver surgery in the presence of clinically significant portal hypertension (CSPH) is scarce. The aim of this study was to evaluate the role of laparoscopic liver resection in selected cirrhotic patients with CSPH. METHODS: A retrospective case-control study of cirrhotic patients with hepatocellular carcinoma who were treated with laparoscopic liver resection was conducted from December 2005 to April 2016. A total of 45 patients were included. Patients were divided into two groups according to the presence or absence of clinically significant portal hypertension. Fifteen cirrhotic patients with CSPH were matched with 30 patients without CSPH. RESULTS: Overall, there were no differences in intraoperative results. No conversion to open surgery occurred in the CSPH group, and 3 patients were converted in the Non-CSPH group (0 vs. 10% p = 0.57). Only 2 (7%) patients in the Non-CSPH group and 1 (7%) in the CSPH group had relevant complications (modified Clavien-Dindo classification III). Two patients in the Non-CSPH group and one in the CSPH group developed transient ascites (7 vs. 7%). Postoperative hospital stay was similar in both groups, with a median of 4 days in the CSPH group and 3 days in the Non-CSPH group (p = 0.37). The median follow-up of the entire cohort was 38 months (range 7-100). Overall survival rates at 1 and 3 years were 100 and 87%, respectively. There was no significant difference between the groups in terms of survival (p = 0.8). CONCLUSION: This initial study showed that laparoscopic resection in patients with CSPH can be performed safely in well-selected patients and expand the current surgical indications in patients with CSPH. Prospective trials with a larger sample size are necessary to confirm these results.

Fluorescence-Lifetime Imaging and Super-Resolution Microscopies Shed Light on the Directed- and Self-Assembly of Functional Porphyrins onto Carbon Nanotubes and Flat Surfaces.

Functional porphyrins have attracted intense attention due to their remarkably high extinction coefficients in the visible region and potential for optical and energy-related applications. Two new routes to functionalised SWNTs have been established using a bulky ZnII -porphyrin featuring thiolate groups at the periphery. We probed the optical properties of this zinc(II)-substituted, bulky aryl porphyrin and those of the corresponding new nano-composites with single walled carbon nanotube (SWNTs) and coronene, as a model for graphene. We report hereby on: i) the supramolecular interactions between the pristine SWNTs and ZnII -porphyrin by virtue of π-π stacking, and ii) a novel covalent binding strategy based on the Bingel reaction. The functional porphyrins used acted as dispersing agent for the SWNTs and the resulting nanohybrids showed improved dispersibility in common organic solvents. The synthesized hybrid materials were probed by various characterisation techniques, leading to the prediction that supramolecular polymerisation and host-guest functionalities control the fluorescence emission intensity and fluorescence lifetime properties. For the first time, XPS studies highlighted the differences in covalent versus non-covalent attachments of functional metalloporphyrins to SWNTs. Gas-phase DFT calculations indicated that the ZnII -porphyrin interacts non-covalently with SWNTs to form a donor-acceptor complex. The covalent attachment of the porphyrin chromophore to the surface of SWNTs affects the absorption and emission properties of the hybrid system to a greater extent than in the case of the supramolecular functionalisation of the SWNTs. This represents a synthetic challenge as well as an opportunity in the design of functional nanohybrids for future sensing and optoelectronic applications.

Hepatic resection: a safe and effective surgery. / Resección hepática mayor: una cirugía segura y eficaz.

INTRODUCTION: We analyze major liver resections performed in 10 years, with the objective of evaluating perioperative results. As secondary objectives, factors related to major complications and comparative analyses of 25-year periods are evaluated. METHODS: Retrospective analysis of patients undergoing major hepatic resection (3 or more segments) from January 2005 to December 2014, from pre, intra and postoperative data. The Clavien classification is used for postoperative morbidity. RESULTS: A total of 416 major hepatectomies were performed. Transfusions were performed in 38 patients (9.1%). A Pringle maneuver was used in 47.7% of the cases. Half of the patients had no complications, and only 96 patients (23%) had a major complication. Bile leakage was the most frequent complication (n=72, 17.3% of patients), especially due to malignant disease and biliary reconstruction, high risk ASA (III-IV) and prolonged surgical time. Thirteen patients met criteria for liver failure, of which 7died (5 associated a bacterial infection). The mean hospital stay was 12.5 days, with an 11,8% readmission rate. When comparing 25-year periods, at present more complex patients are operated on, with a lower incidence of transfusions and complications (ns). CONCLUSIONS: Liver surgery has increased significantly in recent years. Surgical management of the liver now allows safe and effective surgery, with a very low complication rate. The limit of resectability depends on the residual hepatic volume.

Analysis of the long-term results of living donor liver transplantation in adults. / Análisis de los resultados a largo plazo del trasplante hepático de donante vivo en adulto.

INTRODUCTION: Living donor liver transplantation (LDLT) is an alternative to conventional transplantation given its excellent results. The aim of this study is to evaluate long-term outcomes in LDLT recipients. METHODS: 100 consecutive THDV recipients from the Hospital Clínic of Barcelona from March 2000 to October 2015 were included. The main indication for transplantation was end-stage liver disease (58%) followed by hepatocellular carcinoma (41%). 95% of grafts consisted of the right liver of the donor and the 5% of the left liver. RESULTS: After a median follow-up of 65.5 months, patient and graft survival at 1, 3, and 5 years was 93%, 80% and 74% and 90%, 76%, and 71%, respectively. The overall re-transplant rate was 9%. The most common long-term complication was biliary stenosis (40%) with an average time of onset of 13.5±12 months, with repeated admissions and an average of 1.9±2 endoscopic procedures and 3.5±3 Radiological procedures per patient. The definitive treatment was radiological dilation in 40% of cases, surgical intervention in 22.5% and re-transplantation in 7.5%. CONCLUSIONS: Given the long-term results, LDLT is confirmed as an alternative to conventional transplantation. However, the high rate of late biliary complications involves repeated admissions and invasive treatments that, while not compromising survival, can affect the patient's quality of life.

Applications of "Hot" and "Cold" Bis(thiosemicarbazonato) Metal Complexes in Multimodal Imaging.

The applications of coordination chemistry to molecular imaging has become a matter of intense research over the past 10 years. In particular, the applications of bis(thiosemicarbazonato) metal complexes in molecular imaging have mainly been focused on compounds with aliphatic backbones due to the in vivo imaging success of hypoxic tumors with PET (positron emission tomography) using (64) CuATSM [copper (diacetyl-bis(N4-methylthiosemicarbazone))]. This compound entered clinical trials in the US and the UK during the first decade of the 21(st) century for imaging hypoxia in head and neck tumors. The replacement of the ligand backbone to aromatic groups, coupled with the exocyclic N's functionalization during the synthesis of bis(thiosemicarbazones) opens the possibility to use the corresponding metal complexes as multimodal imaging agents of use, both in vitro for optical detection, and in vivo when radiolabeled with several different metallic species. The greater kinetic stability of acenaphthenequinone bis(thiosemicarbazonato) metal complexes, with respect to that of the corresponding aliphatic ATSM complexes, allows the stabilization of a number of imaging probes, with special interest in "cold" and "hot" Cu(II) and Ga(III) derivatives for PET applications and (111) In(III) derivatives for SPECT (single-photon emission computed tomography) applications, whilst Zn(II) derivatives display optical imaging properties in cells, with enhanced fluorescence emission and lifetime with respect to the free ligands. Preliminary studies have shown that gallium-based acenaphthenequinone bis(thiosemicarbazonato) complexes are also hypoxia selective in vitro, thus increasing the interest in them as new generation imaging agents for in vitro and in vivo applications.

Beneficial Effect of a Resorbable Biliary Stent in Living Donor Liver Transplantation.

BACKGROUND: Living donor liver transplantation (LDLT) entails a significant number of bile duct complications. We aimed to diminish the biliary complication rate with the use of a resorbable biliary stent (RBS) during LDLT. The objective of this study is to describe the surgical techniques and the associated outcomes, especially in terms of safety, of RBS use in LDLT. METHODS: From 2011 to 2014, 12 LDLT recipients were enrolled in a clinical trial with the use of a specifically designed RBS. These patients were followed according to the clinical protocol. Specific complications derived from RBS as well as biliary complications were recorded. RESULTS: One patient underwent early retransplantation due to a small-for-size syndrome. None of the patients had a complication attributable to the placement, remaining in place, or degradation of the stent. Four of the remaining patients presented with a biliary complication: 1 (9.1%) with a biliary leak alone, 1 (9.1%) with a biliary stenosis alone, and 2 (18.2%) with both. However, none of the leaks could be directly attributed to the RBS. Patient and graft 1-year survival was 100 and 91.7%, respectively. CONCLUSION: The use of an RBS in LDLT is not associated with complications, and initial results regarding efficacy and safety are encouraging. The need for a larger and prospective study is warranted.

Results of laparoscopic radiofrequency ablation for HCC. Could the location of the tumour influence a complete response to treatment? A single European centre experience.

INTRODUCTION: In selected patients, radiofrequency ablation (RFA) is a well-established treatment for hepatocellular carcinoma (HCC). However, subcapsular or lesions close to adjacent viscera preclude a percutaneous approach. In this setting laparoscopic-RFA (LRFA) is a potential alternative. The aim of this study was to analyse the safety and feasibility of LRFA in patients with HCC. PATIENTS AND METHODS: Retrospective study of patients with HCC meeting strict inclusion criteria who underwent LRFA at a single Institution from December 2000 to March 2013. RESULTS: Forty-one patients underwent 42 LRFA of 51 nodules. The median size of the nodule was 2.5 (range 1.2-4.7) cm. Thirty-one tumours were subcapsular and 17 located near the gallbladder. Major complications occurred in 17 patients. The initial complete response (ICR) rate was 94% and was lower among tumours located adjacent to the gallbladder. At the end of the follow-up period, the sustained complete response (SCR) rate was 70% and was lower in tumours adjacent to the gallbladder while increased for subcapsular tumours. The 1-, 3- and 5-year overall survival rate was 92.6%, 64.5% and 43%, respectively. CONCLUSION: LRFA of HCC is safe, feasible and achieves excellent results in selected patients. LRFA should be the first-line technique for subcapsular lesions as it minimizes the risk of tumoural seeding and improves ICR. Proximity to gallbladder interferes in treatment efficacy (lower rate of ICR and lower rate of SCR).

Klatskin tumor: Diagnosis, preoperative evaluation and surgical considerations.

Hiliar cholangiocarcinoma is the most common type of cholangiocarcinoma, an represent around 10% of all hepatobiliary tumors. It is an aggressive malignancy, resectable in around 47% of the patients at diagnosis. Complete resection is the most effective and only potentially curative therapy, with a survival rate of less than 12 months in unresectable cases. Axial computerized tomography and magnetic resonance are the most useful image techniques to determine the surgical resectability. Clinically, jaundice and pruritus are the most common symptoms at diagnosis;preoperative biliary drainage is recommended using endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography. Surgery using extended liver resections with an en bloc resection of the liver with vascular reconstruction is the technique with the highest survival. Complete resection with histologically negative resection margins (R0), nodal involvement and metastases are the most important prognostic factors.

Shedding light on the use of graphene oxide-thiosemicarbazone hybrids towards the rapid immobilisation of methylene blue and functional coumarins.

Coumarins, methylene blue derivatives, as well as related functional organic dyes have become prevalent tools in life sciences and biomedicine. Their intense blue fluorescence emission makes them ideal agents for a range of applications, yet an unwanted facet of the interesting biological properties of such probes presents a simultaneous environmental threat due to inherent toxicity and persistence in aqueous media. As such, significant research efforts now ought to focus on their removal from the environment, and the sustainable trapping onto widely available, water dispersible and processable adsorbent structures such as graphene oxides could be advantageous. Additionally, flat and aromatic bis(thiosemicarbazones) (BTSCs) have shown biocompatibility and chemotherapeutic potential, as well as intrinsic fluorescence, hence traceability in the environment and in living systems. A new palette of graphene oxide-based hierarchical supramolecular materials incorporating BTSCs were prepared, characterised, and reported hereby. We report on the supramolecular entrapping of several flat, aromatic fluorogenic molecules onto graphene oxide on basis of non-covalent interactions, by virtue of their structural features with potential to form aromatic stacks and H-bonds. The evaluations of the binding interactions in solution by between organic dyes (methylene blue and functional coumarins) and new graphene oxide-anchored Zn(ii) derivatised bis(thiosemicarbazones) nanohybrids were carried out by UV-Vis and fluorescence spectroscopies.

Importance of the temporary portocaval shunt during adult living donor liver transplantation.

Adult living donor liver transplantation (aLDLT) is associated with surgical risks for the donor and with the possibility of small-for-size syndrome (SFSS) for the recipient, with both events being of great importance. An excessively small liver graft entails a relative increase in the portal blood flow during reperfusion, and this factor predisposes the recipient to an increased risk of SFSS in the postoperative period, although other causes related to recipient, graft, and technical factors have also been reported. A hemodynamic monitoring protocol was used for 45 consecutive aLDLT recipients. After various hemodynamic parameters before reperfusion were analyzed, a significant correlation between the temporary portocaval shunt flow during the anhepatic phase and the portal vein flow (PVF) after reperfusion of the graft (R(2) = 0.3, P < 0.001) was found, and so was a correlation between the native liver portal pressure and PVF after reperfusion (R(2) = 0.21, P = 0.007). The identification of patients at risk for excessive portal hyperflow will allow its modulation before reperfusion. This could favor the use of smaller grafts and ultimately lead to a reduction in donor complications because it would allow more limited hepatectomies to be performed.

Robot-assisted renal artery aneurysm repair with a saphenous vein Y-graft interposition.

BACKGROUND: Renal artery aneurysms (RAA) treatment includes both surgical repair and endovascular techniques, mostly depending on the location of aneurysm. For complex RAA located at renal artery bifurcation or distally, open surgical repair represents the gold standard of treatment. However, the transperitoneal open access to the renal artery requires a wide laparotomy--hence the attempt to be minimally invasive with the first reports of laparoscopic approach. Even if it represents a possibility, laparoscopy has not yet gained widespread acceptance for the technical difficulties in performing vascular anastomosis. We herein describe the repair of a complex RAA using the Da Vinci Surgical System. METHODS: A 41-year-old woman had an accidentally discovered saccular aneurysm of the right renal artery with a maximum diameter of 20 mm, with one in and four out. A laparoscopic robot-assisted approach was planned. Intraoperatively, we confirm the strategy to group the four output branches in two different patches. Thus, a Y-shaped autologous saphenous graft was prepared and introduced through a trocar. For the three anastomoses, a polytetrafluoroethylene running suture was preferred. RESULTS: The total operation time was 350 min, and the estimated surgical blood loss was about 200 ml. Warm ischemia time was 58 min for the posterior branch and 24 min for the second declamping. The patient resumed a regular diet on postoperative day 2, and the hospital stay lasted 4 days. No intraoperative or postoperative morbidity was noted. A CT scan performed 2 months later revealed the patency of all the reconstructed branches. CONCLUSIONS: The experience of our group counts five other renal aneurysm repair performed with a robot-assisted technique. The presence of five different arterial branches involved in the reconstruction makes this procedure difficult. Robot-assisted laparoscopic technique represents a valid alternative to open surgery in complex cases.

[Hemodynamic monitoring protocol during living donor liver transplantation]. / Protocolo de monitorización hemodinámica hepática en el trasplante hepático de donante vivo en adultos.

INTRODUCTION: The recipient of an adult living donor liver transplant (ALDLT) is subjected to great haemodynamic changes that could lead to the appearance of a "small-for-size" syndrome in the post-operative period due to portal hyperflow. The aim of this article is to evaluate these changes, and try to correlate them with portal vein flow during reperfusion. MATERIAL AND METHODS: A protocol for monitoring various liver haemodynamic data of the ALDLT recipient before, during and after surgery has been used since the year 2003. The haemodynamic outcome of the recipient after the transplant, as well as the correlation between the portal vein flow during reperfusion and the collected haemodynamic data is analysed. RESULTS: There was no small for size syndrome. A significant relationship was found between the portal flow during reperfusion and the portal vein pressure at the beginning of the operation (r=0.46, P<.006) and with the portocaval shunt flow during the anhepatic phase (r=0.55, P<.001). The recipients showed a normal splanchnic hemodynamic state at 3 months after the transplant. CONCLUSIONS: Haemodynamic monitoring of the ALDLT recipient is essential to prevent portal hyperflow. The relationship between flow during reperfusion and flow through the portocaval shunt means that patients with a higher risk of hyperflow can be identified and can be modified before reperfusion.

[The biliary complications in live donor liver transplant do not affect the long-term results]. / Las complicaciones biliares en el trasplante hepático de donante vivo no afectan los resultados a largo plazo.

INTRODUCTION: Living donor liver transplantation (LDLT) is an effective treatment for patients with terminal chronic liver disease, despite the high incidence of biliary complications. The objective is to evaluate the results and long-term impact of biliary complications after THDV. PATIENTS AND METHODS: From 2000 to 2010, 70 right lobe LDLT were performed. Biliary complications (leakage and stenosis) of the 70 LDLT recipients were collected prospectively and analyzed retrospectively. RESULTS: A total of 39 patients (55.7%) had some type of biliary complication. Twenty nine presented a leak, and of these, 14 subsequently developed a stricture. In addition, 10 patients had a stenosis without prior leakage. The median time to onset of stenosis was almost a year. Patients with previous biliary leakage were more likely to develop stenosis (58% vs. 29.5% at 5 years, P=.05). With a median follow up of 80 months, 70.8% of patients were successfully treated by interventional radiology. After excluding early mortality, there were no differences in survival according to biliary complications. A decrease of biliary complications was observed in the last 35 patients compared with the first 35. CONCLUSIONS: LDLT is associated with a high incidence of biliary complications. However, long-term outcome of patients is not affected. After a median follow-up time of nearly seven years, no differences were found in survival according to the presence of biliary complications.

Functional Diversity in Radiolabeled Nanoceramics and Related Biomaterials for the Multimodal Imaging of Tumors.

Nanotechnology advances have the potential to assist toward the earlier detection of diseases, giving increased accuracy for diagnosis and helping to personalize treatments, especially in the case of noncommunicative diseases (NCDs) such as cancer. The main advantage of nanoparticles, the scaffolds underpinning nanomedicine, is their potential to present multifunctionality: synthetic nanoplatforms for nanomedicines can be tailored to support a range of biomedical imaging modalities of relevance for clinical practice, such as, for example, optical imaging, computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). A single nanoparticle has the potential to incorporate myriads of contrast agent units or imaging tracers, encapsulate, and/or be conjugated to different combinations of imaging tags, thus providing the means for multimodality diagnostic methods. These arrangements have been shown to provide significant improvements to the signal-to-noise ratios that may be obtained by molecular imaging techniques, for example, in PET diagnostic imaging with nanomaterials versus the cases when molecular species are involved as radiotracers. We surveyed some of the main discoveries in the simultaneous incorporation of nanoparticulate materials and imaging agents within highly kinetically stable radio-nanomaterials as potential tracers with (pre)clinical potential. Diversity in function and new developments toward synthesis, radiolabeling, and microscopy investigations are explored, and preclinical applications in molecular imaging are highlighted. The emphasis is on the biocompatible materials at the forefront of the main preclinical developments, e.g., nanoceramics and liposome-based constructs, which have driven the evolution of diagnostic radio-nanomedicines over the past decade.

Successful conversion from twice-daily to once-daily tacrolimus in liver transplantation: observational multicenter study.

BACKGROUND: Compliance with immunosuppressive therapy in liver transplant patients is critical to prevent acute organ rejection and/or late graft loss. Strategies to simplify the therapeutic regimen may improve adherence. AIM: To evaluate the safety and efficacy of conversion from a twice-daily to once-daily tacrolimus formulation in adult liver transplant patients. PATIENTS AND METHODS: This prospective observational multicenter study included 187 liver transplant patients with at least 10 months post-transplant follow-up, no rejection episodes in the last three months, and creatinine levels <2 mg/dL. Conversion from a twice-daily to a once-daily formulation was based on a 1:1 proportion. RESULTS: Median age was 61 yr (range: 28-80 yr); 64% were men and 36% women. The main indications for liver transplant were alcoholic cirrhosis in 30%. Median conversion time was 55 months (range: 10-215 months). Serum tacrolimus levels decreased at one month after conversion (pre-conversion levels = 5.4 ± 3.0 ng/mL vs. post-conversion levels = 4.4 ± 2.4 ng/mL, p = 0.013); however, these values normalized at six months post-conversion with no changes in liver function and rejection episodes were observed only in two patients. CONCLUSION: Conversion from a twice-daily to a once-daily tacrolimus formulation is a safe, effective strategy in the management of stable liver transplant patients.