Quantification of the expression level of integrin receptor alpha(v)beta3 in cell lines and MR imaging with antibody-coated iron oxide particles.

Targeted imaging requires site-specific accumulation of a contrast agent (CA), and the properties of that agent must be selected according to the abundance of the target to obtain a signal above the detection limit of the instrument. However, numerical estimates of receptors per cell are rarely found in the literature. Integrin receptors would be particularly promising targets because of their accessibility from the blood stream and expression on activated neovascular endothelial cells. We systematically estimated the number of integrin receptors of cell lines and primary cells by flow cytometry analysis. Since integrin receptors are heterodimeric molecules, and alpha(v) forms complexes with various beta subunits, the numbers of alpha(v) and beta(3) subunits are therefore dissimilar. The observed values are 3 . 10(3)-1.4 . 10(4)/cell for alpha(v), and 5.3 . 10(2)-1.1 . 10(4)/cell for beta(3). Despite the low number of exposed receptors, we show that up to single-cell MR visualization can be achieved with the use of iron oxide beads complexed with antibodies as CAs.     

Significance and clinical impact of routinely tested urinary ethyl glucuronide after liver transplantation – development of a risk score

Alcohol abuse after liver transplantation can seriously impact graft and patient survival. However, to date, there is no defined standard procedure to identify patients consuming alcohol after liver transplantation. The aim of this study was to analyze the diagnostic value and clinical impact of routinely measured urinary ethyl glucuronide (uEtG) – a metabolite of ethanol – in patients after liver transplantation. Data of 362 consecutive patients after liver transplantation who visited the University Hospital of Tuebingen for outpatient follow-up were analyzed. Forty-eight patients (13%) displayed positive uEtG results. The uEtG positive group contained significantly more patients with pretransplant alcoholic liver disease. However, two thirds of the uEtG positive patients had no history of pretransplant alcoholic liver disease. Several clinical parameters were significantly associated with positive uEtG. In order to enable a more cost-effective application of uEtG in the future, a clinical risk score was developed (specificity 0.95). In conclusion, routine testing for uEtG reveals a considerable percentage of patients practicing alcohol intake after liver transplantation. Application of our proposed risk score could help focusing uEtG testing on patients at risk.     

Optimization of the future remnant liver: review of the current strategies in Europe

Liver resection still represent the treatment of choice for liver malignancies, but in some cases inadequate future remnant liver (FRL) can lead to post hepatectomy liver failure (PHLF) that still represents the most common cause of death after hepatectomy. Several strategies in recent era have been developed in order to generate a compensatory hypertrophy of the FRL, reducing the risk of post hepatectomy liver failure. Portal vein embolization, portal vein ligation, and ALLPS are the most popular techniques historically adopted up to now. The liver venous deprivation and the radio-embolization are the most recent promising techniques. Despite even more precise tools to calculate the relationship among volume and function, such as scintigraphy with ^99mTc-mebrofenin (HBS), no consensus is still available to define which of the above mentioned augmentation strategy is more adequate in terms of kind of surgery, complexity of the pathology and quality of liver parenchyma. The aim of this article is to analyse these different strategies to achieve sufficient FRL.     

Neoral dose adjustment after conversion from C0 to C2 monitoring in stable renal transplant recipients: a prospective single center study

To determine the clinical impact of conversion from C0 to C2 Neoral monitoring, we conducted a 6-month prospective study in 62 stable renal transplant recipients. Neoral was given alone (19%), with steroids (31%), combined with azathioprine (Aza) or mycophenolate mofetil (MMF) (50%). C0 and C2 target ranges were, respectively, 130-190 and 700-900 ng/mL. Neoral dosages were adjusted according to the C2 range. At baseline, mean C0 and C2 were 157 and 762 ng/mL. After 6 months C0 was 173 ng/mL (p<0.02) and C2 was 804 ng/mL (ns). Although the mean Neoral dose at 6 months was unchanged from baseline, the dose was reduced in 24 patients from 3.6+/-1.2 to 3.0+/-0.9 mg/kg/day, with a mean reduction in serum creatinine (Cr) from 1.4+/-0.4 to 1.3+/-0.3 mg/dL (p<0.001), stable in 8 patients and increased in 30 patients from 3.3+/-1.0 to 3.8+/-1.2 mg/kg/day with no change in serum Cr. Serum transaminases and blood pressure (BP) were unchanged in the three groups. C0 and C2 showed a positive correlation, but with a large dispersion of values (r2=0.14, p<0.001). Overall concordance between the C0 and C2 ranges was 49%. Therefore, in stable transplant patients C0 cannot be considered a C2 surrogate. The conversion from C0 to C2 led to a Neoral dose reduction in approximately 40% of patients with significant improvement in renal function. Most of the remaining patients required an increased dose; however, without an increased incidence of cyclosporin-induced side-effects.     

Surgical treatment of complicated sigmoid diverticulitis: our experience

Traditionally, surgical sigmoid diverticular emergencies used to be treated in stages, but more recently there has been a trend towards definitive surgery with immediate resection plus anastomosis under certain conditions. The aim of this study was to define the morbidity and mortality of resection plus anastomosis with on-table antegrade irrigation and of the Hartmann procedure for complicated sigmoid diverticulitis in relation to the type of peritonitis and to the American Society of Anesthesiologists (ASA) grade of the patients. From April 1999 to April 2002, 38 emergency operations for complicated sigmoid diverticulitis were performed at the San Sebastiano Hospital in Caserta. Six patients underwent operations for obstructions and 32 for perforation (19 Hinchley stage III and 13 Hinchley stage IV). Surgical therapy for obstruction consisted in 4 resections plus anastomosis, 1 subtotal colectomy and 1 Hartmann procedure. Surgical therapy for perforation consisted in 14 resections plus anastomosis and 18 Hartmann procedures. There was 1 case (5%) of anastomotic dehiscence out of 19 primary anastomoses versus 2/19 surgical complications (10%) after the Hartmann procedure. The mortality amounted to 1 death out of 38 (2.6%) in a patient treated with the Hartmann procedure. Left-sided colonic obstruction should be treated by resection plus anastomosis or by subtotal colectomy for ASA II-III patients and by Hartmann's procedure for ASA IV-V patients. ASA II-III patients with localised or generalised non-faecal peritonitis should be treated by resection plus anastomosis, while a Hartmann procedure should be the reasonable option for generalised faecal peritonitis and for ASA IV-V patients with localised or generalised non-faecal peritonitis.     

Step‐by‐step: The effects of physical practice on the neural correlates of locomotion imagery revealed by fMRI

Previous studies have shown that mental imagery is a suitable tool to study the progression of the effect of practice on brain activation. Nevertheless, there is still poor knowledge of changes in brain activation patterns during the very early stages of physical practice. In this study, early and late practice stages of different kinds of locomotion (i.e., balanced and unbalanced) have been investigated using functional magnetic resonance imaging during mental imagery of locomotion and stance. During the task, cardiac activity was also recorded. The cerebral network comprising supplementary motor area, basal ganglia, bilateral thalamus, and right cerebellum showed a stronger activation during the imagery of locomotion with respect to imagery of stance. The heart beat showed a significant increase in frequency during the imagery of locomotion with respect to the imagery of stance. Moreover, early stages of practice determined an increased activation in basal ganglia and thalamus with respect to late stages. In this way, it is proposed the modulation of the brain network involved in the imagery of locomotion as a function of physical practice time. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Tractostorm: The what,why, and how of tractography dissection reproducibility

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called “virtual dissection.” Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC‐ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real‐life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and “virtual dissection” across various laboratories and hospitals. Intra‐rater agreement (Dice score) was approximately 0.77, while inter‐rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.     

Long-term effects of eating sucrose on metabolic control of type 1 (insulin-dependent) diabetic outpatients

Summary The aim of the study was to investigate the effects of regularly eating a moderate amount of sucrose (30 g/day) in 12 type 1 (insulin-dependent, IDDM) diabetic outpatients in fair blood glucose and lipid control. Two diets, each lasting two month, were compared in a randomized cross-over study. The former was a high-carbohydrate high-fiber diet for diabetic patients with Italian alimentary habits, the latter had the same composition except that 30 g of sucrose replaced 30 g of complex carbohydrates with high glycemic index (bread). The two diets contained equal amounts of carbohydrates, proteins and lipids; the only difference being the contribution of oligosaccharides to total carbodhydrates (22%vs 34%) and cholesterol amount. During the control diet, glycosylated hemoglobin was substantially unchanged in both control and sucrose diet periods (control diet: 6.91±0.29 (SE)vs 6.80±0.25%; sucrose diet: 6.75±0.31vs 6.91±0.36%). This was true also for fructosamine (control diet: 3.92±0.21vs 3.76±0.18%; sucrose diet: 3.50±0.14vs 3.64±0.20 mmol/l). Circulating blood lipid levels, body weight and daily insulin dose did not show any significant variations during the study. Moderate amounts of sucrose may be allowed to IDDM patients with Italian alimentary habits without worsening diabetic control.     

Safety and efficacy of eculizumab for the prevention of antibody‐mediated rejection after deceased‐donor kidney transplantation in patients with preformed donor‐specific antibodies

The presence of preformed donor‐specific antibodies in transplant recipients increases the risk of acute antibody‐mediated rejection (AMR). Results of an open‐label single‐arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased‐donor kidney transplants with preformed donor‐specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy‐proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow‐up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24‐70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P < .001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010‐019631‐35).