Comparison of the binding and internalization properties of 12 DOTA-coupled and ¹¹¹In-labelled CCK2/gastrin receptor binding peptides: a collaborative project under COST Action BM0607

Specific overexpression of cholecystokinin 2 (CCK2)/gastrin receptors has been demonstrated in several tumours of neuroendocrine origin. In some of these cancer types, such as medullary thyroid cancer (MTC), a sensitive diagnostic modality is still unavailable and therapeutic options for inoperable lesions are needed. Peptide receptor radionuclide therapy (PRRT) may be a viable therapeutic strategy in the management of these patients. Several CCK2R-targeted radiopharmaceuticals have been described in recent years. As part of the European Union COST Action BM0607 we studied the in vitro and in vivo characteristics of 12 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated CCK2R binding peptides. In the present study, we analysed binding and internalization characteristics. Stability, biodistribution and imaging studies have been performed in parallel by other centres involved in the project.

Comparative biodistribution of 12 ¹¹¹In-labelled gastrin/CCK2 receptor-targeting peptides

Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed and some have been tested in patients. Here we aimed to compare the in vivo tumour targeting properties of 12 (111)In-labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated gastrin/CCK2 receptor-binding peptides.

Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial

This phase I trial was designed to develop a new effective and well-tolerated regimen for patients with aggressive B cell lymphoma not eligible for front-line anthracycline-based chemotherapy or aggressive second-line treatment strategies. The combination of rituximab (375 mg/m(2) on day 1), bendamustine (70 mg/m(2) on days 1 and 2), and lenalidomide was tested with a dose escalation of lenalidomide at three dose levels (10, 15, or 20 mg/day) using a 3 + 3 design. Courses were repeated every 4 weeks. The recommended dose was defined as one level below the dose level identifying ≥2/6 patients with a dose-limiting toxicity (DLT) during the first cycle. Thirteen patients were eligible for analysis. Median age was 77 years. WHO performance status was 0 or 1 in 12 patients. The Charlson Comorbidity Index showed relevant comorbidities in all patients. Two DLTs occurred at the second dose level (15 mg/day) within the first cycle: one patient had prolonged grade 3 neutropenia, and one patient experienced grade 4 cardiac adverse event (myocardial infarction). Additional grade 3 and 4 toxicities were as follows: neutropenia (31 %), thrombocytopenia (23 %), cardiac toxicity (31 %), fatigue (15 %), and rash (15 %). The dose of lenalidomide of 10 mg/day was recommended for a subsequent phase II in combination with rituximab 375 mg/m(2) on day 1 and bendamustine 70 mg/m(2) on days 1 and 2.

Learning styles vary among general surgery residents: analysis of 12 years of data

PURPOSE: Understanding the learning styles of individuals may assist in the tailoring of an educational program to optimize learning. General surgery faculty and residents have been characterized previously as having a tendency toward particular learning styles. We seek to understand better the learning styles of general surgery residents and differences that may exist within the population. METHODS: The Kolb Learning Style Inventory was administered yearly to general surgery residents at the University of Cincinnati from 1994 to 2006. This tool allows characterization of learning styles into 4 groups: converging, accommodating, assimilating, and diverging. The converging learning style involves education by actively solving problems. The accommodating learning style uses emotion and interpersonal relationships. The assimilating learning style learns by abstract logic. The diverging learning style learns best by observation. Chi-square analysis and analysis of variance were performed to determine significance. RESULTS: Surveys from 1994 to 2006 (91 residents, 325 responses) were analyzed. The prevalent learning style was converging (185, 57%), followed by assimilating (58, 18%), accommodating (44, 14%), and diverging (38, 12%). At the PGY 1 and 2 levels, male and female residents differed in learning style, with the accommodating learning style being relatively more frequent in women and assimilating learning style more frequent in men (Table 1, p < or = 0.001, chi-square test). Interestingly, learning style did not seem to change with advancing PGY level within the program, which suggests that individual learning styles may be constant throughout residency training. If a resident's learning style changed, it tended to be to converging. In addition, no relation exists between learning style and participation in dedicated basic science training or performance on the ABSIT/SBSE. CONCLUSIONS: Our data suggests that learning style differs between male and female general surgery residents but not with PGY level or ABSIT/SBSE performance. A greater understanding of individual learning styles may allow more refinement and tailoring of surgical programs.

The 2011-12 pilot European Sentinel Registry of Transcatheter Aortic Valve Implantation: in-hospital results in 4,571 patients

AIMS The aim of this prospective multinational registry is to assess and identify predictors of in-hospital outcome and complications of contemporary TAVI practice. METHODS AND RESULTS The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospective independent consecutive collection of individual patient data entered into a web-based case record form (CRF) or transferred from compatible national registries. A total of 4,571 patients underwent TAVI between January 2011 and May 2012 in 137 centres of 10 European countries. Average age was 81.4±7.1 years with equal representation of the two sexes. Logistic EuroSCORE (20.2±13.3), access site (femoral approach: 74.2%), type of anaesthesia and duration of hospital stay (9.3±8.1 days) showed wide variations among the participating countries. In-hospital mortality (7.4%), stroke (1.8%), myocardial infarction (0.9%), major vascular complications (3.1%) were similar in the SAPIEN XT and CoreValve (p=0.15). Mortality was lower in transfemoral (5.9%) than in transapical (12.8%) and other access routes (9.7%; p<0.01). Advanced age, high logistic EuroSCORE, pre-procedural ≥grade 2 mitral regurgitation and deployment failure predicted higher mortality at multivariate analysis. CONCLUSIONS Increased operator experience and the refinement of valve types and delivery catheters may explain the lower rate of mortality, stroke and vascular complications than in historical studies and registries.

Nonanimal stabilized hyaluronic acid for tissue augmentation of the dorsal hands: a prospective study on 38 patients

BACKGROUND Often ignored, hands are one of the most telltale signs of aging. This prospective study was initiated to evaluate the effect of subcutaneous hyaluronic acid (HA) injections in aging hands, with special attention to complications and long-term outcomes. METHODS Between January 2010 and December 2010, a total of 38 patients with skin phototypes II-IV and between 58 and 76 years old were treated with HA injection for aging hands. The quantity of injection never exceeded 1.0-1.5 ml HA per hand. A clinical follow-up was performed at 2 weeks, 4 weeks, 3 months, and 6 months after injection. Complications were reviewed for the whole series. At the first follow-up, 2 weeks after the procedure, ultrasound was carried out to determine if additional filling material was required. At each follow-up, patients were asked to fill out a satisfaction questionnaire. RESULTS Nine patients developed slight ecchymosis that disappeared after 1 week. No other complications were seen in the series. Pain during the injection and discomfort after the procedure were minimal. At the 2-week follow-up, after ultrasound control, nine patients received a complementary injection. At each follow-up, overall patient satisfaction was high and was validated by clearance of rhytids, veins, bony prominences, and dermal and subcutaneous atrophy. CONCLUSION Skin revitalization with injectable HA can improve the clinical appearance of the back of the hands. However, this therapy requires knowledge of the possible complications and their remediation as well as knowledge and respect of injected doses. Moreover, despite excellent results at each follow-up, the results of our series are not as good after 6 months, and a longer follow-up would be needed to determine if this procedure provides long-lasting benefit. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Language lateralisation increases with age in very preterm born 7-12 year-olds but not in term born control children

Background: Neural structural abnormalities as well as cognitive difficulties in language processing have been described in children born very preterm (<32 weeks of gestational age and/or <1500 g birth weight). These findings raise the question how premature birth is related to neural language organisation and lateralisation. The aim of the study was to test the following hypotheses: a) VPT/VLBW and control children show different language organisation b) language organisation in VPT/VLBW children is more bilateral compared to language organisation in control children c) positive correlations between language performance measures and language lateralisation exist in VPT/VLBW children and controls. Method: Brain activity was measured during a phonologic detection task in 56 very preterm born children and 38 term born control children aged 7 to 12 years using functional Magnetic Resonance Imaging. General IQ, verbal IQ, verbal fluency and reading comprehension were assessed outside the scanner. Results: Language organisation and lateralisation did not differ in very preterm and control children in overall comparisons. However, in very preterm children lateralisation increased between the age of 7 to 12 years. This correlation was not found in control children. Language organisation in very preterm children was bilateral in young children and left-sided in old children, whereas language organisation in control children was left-sided in the young and old age group. Frontal lateralisation correlated with General IQ in controls, but no other correlations between lateralisation and verbal performance were found. Discussion: The results of this study suggest different developmental patterns of language processing in very preterm born and term born control children. While very preterm born children showed atypical language organisation and lateralisation in younger years, typical left-sided patterns were found at the age of 12 years.

Clinical outcomes and revascularization strategies in patients with low-flow, low-gradient severe aortic valve stenosis according to the assigned treatment modality

OBJECTIVES This study compared clinical outcomes and revascularization strategies among patients presenting with low ejection fraction, low-gradient (LEF-LG) severe aortic stenosis (AS) according to the assigned treatment modality. BACKGROUND The optimal treatment modality for patients with LEF-LG severe AS and concomitant coronary artery disease (CAD) requiring revascularization is unknown. METHODS Of 1,551 patients, 204 with LEF-LG severe AS (aortic valve area <1.0 cm(2), ejection fraction <50%, and mean gradient <40 mm Hg) were allocated to medical therapy (MT) (n = 44), surgical aortic valve replacement (SAVR) (n = 52), or transcatheter aortic valve replacement (TAVR) (n = 108). CAD complexity was assessed using the SYNTAX score (SS) in 187 of 204 patients (92%). The primary endpoint was mortality at 1 year. RESULTS LEF-LG severe AS patients undergoing SAVR were more likely to undergo complete revascularization (17 of 52, 35%) compared with TAVR (8 of 108, 8%) and MT (0 of 44, 0%) patients (p < 0.001). Compared with MT, both SAVR (adjusted hazard ratio [adj HR]: 0.16; 95% confidence interval [CI]: 0.07 to 0.38; p < 0.001) and TAVR (adj HR: 0.30; 95% CI: 0.18 to 0.52; p < 0.001) improved survival at 1 year. In TAVR and SAVR patients, CAD severity was associated with higher rates of cardiovascular death (no CAD: 12.2% vs. low SS [0 to 22], 15.3% vs. high SS [>22], 31.5%; p = 0.037) at 1 year. Compared with no CAD/complete revascularization, TAVR and SAVR patients undergoing incomplete revascularization had significantly higher 1-year cardiovascular death rates (adj HR: 2.80; 95% CI: 1.07 to 7.36; p = 0.037). CONCLUSIONS Among LEF-LG severe AS patients, SAVR and TAVR improved survival compared with MT. CAD severity was associated with worse outcomes and incomplete revascularization predicted 1-year cardiovascular mortality among TAVR and SAVR patients.

Repatriations and 28-day mortality of ill and injured travellers: 12 years of experience in a Swiss emergency department

QUESTIONS UNDER STUDY Many persons are travelling all over the world; the elderly with pre-existing diseases also travel to places with less developed health systems. Reportedly, fewer than 0.5% of all travellers need repatriation. We aimed to analyse and examine people who are injured or ill while abroad, where they travelled to and by what means they were repatriated. METHODS Retrospective cross-sectional study with adult patients repatriated to a single level 1 trauma centre in Switzerland (2000-2011). RESULTS A total of 372 patients were repatriated, with an increasing trend per year. Of these, 67% were male; the median age was 56 years. Forty-nine percent sustained an injury, and 13% had surgical and 38% medical pathologies. Patients with medical conditions were older than those with injuries or surgical emergencies (p <0.001). Seventy-three percent were repatriated from Europe. For repatriation from Africa trauma was slightly more frequent (53%, n = 17) than illnesses, whereas for most other countries illnesses and trauma were equally distributed. Injured patients had a median Injury Severity Score of 8. The majority of illnesses involved the nervous system (38%), mainly stroke. Forty-five percent were repatriated by Swiss Air Ambulance, 26% by ground ambulance, 18% by scheduled flights with or without medical assistance and two patients injured near the Swiss boarder by helicopter. The 28-day mortality was 4%. CONCLUSIONS The numbers of travellers repatriated increased from 2000 to 2011. About half were due to illnesses and half due to injuries. The largest group were elderly Swiss nationals repatriated from European countries. As mortality is relatively high, special consideration to this group of patients is warranted.