Histological Processing of CAD/CAM Titanium Scaffold after Long-Term Failure in Cranioplasty

Cranioplasty is a frequently performed procedure after craniectomy and includes several techniques with different materials. Due to high overall complication rates, alloplastic implants are removed in many cases. Lack of implant material osseointegration is often assumed as a reason for failure, but no study has proven this in cranioplasty. This study histologically evaluates the osteointegration of a computer-aided design and computer-aided manufacturing (CAD/CAM) titanium scaffold with an open mesh structure used for cranioplasty. A CAD/CAM titanium scaffold was removed due to late soft tissue complications 7.6 years after cranioplasty. The histological analyses involved the preparation of non-decalcified slices from the scaffold's inner and outer sides as well as a light-microscopic evaluation, including the quantification of the bone that had formed over the years. Within the scaffold pores, vital connective tissue with both blood vessels and nerves was found. Exclusive bone formation only occurred at the edges of the implant, covering 0.21% of the skin-facing outer surface area. The inner scaffold surface, facing towards the brain, did not show any mineralization at all. Although conventional alloplastic materials for cranioplasty reduce surgery time and provide good esthetic results while mechanically protecting the underlying structures, a lack of adequate stimuli could explain the limited bone formation found. CAD/CAM porous titanium scaffolds alone insufficiently osseointegrate in such large bone defects of the skull. Future research should investigate alternative routes that enable long-term osteointegration in order to reduce complication rates after cranioplasty. Opportunities could be found in mechano-biologically optimized scaffolds, material modifications, surface coatings, or other routes to sustain bone formation

Physical activity in 9–15 year-old pediatric cancer survivors compared to a nationwide sample

Introduction: Sufficient physical activity (PA) has the potential to mitigate late effects of cancer, but objective data of PA levels in adolescents are scarce. The aim of this study was to investigate differences in PA behavior between childhood cancer survivors (CCS) and healthy peers. Methods: PA levels of n = 74 CCS and n = 1304 healthy peers from the MoMo study aged 9–15 years were assessed with validated objective accelerometry and group means were compared. A binary multiple logistic regression was performed to investigate the potential predictors of PA. Results: CCS spent significantly more time sedentary (p < 0.001) and less time in moderate-to-vigorous physical activity (p = 0.002) compared to the healthy cohort. Subgroup analysis revealed the largest deviations of PA levels for CCS aged 9–11 years who fulfilled international PA recommendations on significantly fewer days than MoMo (p < 0.01). Health conditions seem to be a predictor concerning the fulfillment of international PA recommendations by the WHO (p = 0.015). Conclusions: Our study identified vulnerable groups which seem to require targeted exercise and health behavior change programs to increase physical activity and reduce sedentary time. The presence of treatment sequelae as a significant predictor of insufficient physical activity underlines the need of multidisciplinary supportive care approaches

Update on DLR's OSIRIS program and first results of OSIRISv1 on Flying Laptop

Optical satellite links have gained increasing attention throughout the last years. Especially for the application of optical satellite downlinks. Within the OSIRIS program, DLR's Institute of Communications and Navigation develops optical terminals and systems which are optimized for small satellites. After the successful qualification and launch of two precursor terminals, DLR currently develops OSIRISv3, a 3rd generation OSIRIS terminal with up to 10 Gbps downlink rate, and OSIRIS4Cubesat, a miniaturized version optimized for Cubesat Applications. The University of Stuttgart's Institute of Space Systems develops small satellites, which are used to demonstrate novel technologies in the Space domain. Together, DLR and University of Stuttgart integrated the first OSIRIS generation onboard the Flying Laptop satellite, which was launched in July 2017 and has been successfully operated since. This paper will give an overview about DLR's OSIRIS program. Furthermore, it will show first results of OSIRISv1 on Flying Laptop. Therefore, the Flying Laptop satellite and OSIRISv1 will be explained. Preliminary results from the validation campaign, where optical downlinks have been demonstrated, will be given. © 2019 SPIE. Downloading of the abstract is permitted for personal use only

Randomized evaluation of fibrinogen versus placebo in complex cardiovascular surgery : post hoc analysis and interpretation of phase III results

OBJECTIVES: In a multicentre, randomized-controlled, phase III trial in complex cardiovascular surgery (Randomized Evaluation of Fibrinogen vs Placebo in Complex Cardiovascular Surgery: REPLACE), single-dose human fibrinogen concentrate (FCH) was associated with the transfusion of increased allogeneic blood products (ABPs) versus placebo. Post hoc analyses were performed to identify possible reasons for this result. METHODS: We stratified REPLACE results by adherence to the transfusion algorithm, pretreatment fibrinogen level (2g/l) and whether patients were among the first 3 treated at their centre. RESULTS: Patients whose treatment was adherent with the transfusion algorithm [FCH, n=47 (60.3%); placebo, n=57 (77.0%); P=0.036] received smaller quantities of ABPs than those with non-adherent treatment (P2g/l and fewer patients undergoing thoracoabdominal aortic aneurysm repair. CONCLUSIONS: None of the patient stratifications provided a clear explanation for the lack of efficacy seen for FCH in the REPLACE trial versus the positive phase II outcomes. However, together, the 3 factors demonstrated trends favouring FCH. Less familiarity with the protocol and procedures and unavoidable differences in the study populations may explain the differences seen between the phase II study and REPLACE.Peer reviewe

Development of a Neurotensin-Derived 68Ga-Labeled PET Ligand with High In Vivo Stability for Imaging of NTS1 Receptor-Expressing Tumors

Overexpression of the neurotensin receptor type 1 (NTS1R), a peptide receptor located at the plasma membrane, has been reported for a variety of malignant tumors. Thus, targeting the NTS1R with 18F- or 68Ga-labeled ligands is considered a straightforward approach towards in vivo imaging of NTS1R-expressing tumors via positron emission tomography (PET). The development of suitable peptidic NTS1R PET ligands derived from neurotensin is challenging due to proteolytic degradation. In this study, we prepared a series of NTS1R PET ligands based on the C-terminal fragment of neurotensin (NT(8–13), Arg8-Arg9-Pro10-Tyr11-Ile12-Leu13) by attachment of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via an Nω-carbamoylated arginine side chain. Insertion of Ga3+ in the DOTA chelator gave potential PET ligands that were evaluated concerning NTS1R affinity (range of Ki values: 1.2–21 nM) and plasma stability. Four candidates were labeled with 68Ga3+ and used for biodistribution studies in HT-29 tumor-bearing mice. [68Ga]UR-LS130 ([68Ga]56), containing an N-terminal methyl group and a β,β-dimethylated tyrosine instead of Tyr11, showed the highest in vivo stability and afforded a tumor-to-muscle ratio of 16 at 45 min p.i. Likewise, dynamic PET scans enabled a clear tumor visualization. The accumulation of [68Ga]56 in the tumor was NTS1R-mediated, as proven by blocking studies

A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study

The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC). This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m(2) doxorubicin or equivalent were allowed. Left ventricular ejection fraction of > 50 % was required. Patients received PLD 50 mg/m(2) every 28 days or capecitabine 1250 mg/m(2) twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP). 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838-1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %;P = 0.31). Both PLD and capecitabine are effective first-line agents for MBC

a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma

Background Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. Methods/Design ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and - in absence of available stem cells from earlier harvesting - undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3rd (arm A + B) and the 5th lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS. Discussion This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. Trial registration: ISRCTN16345835 (date of registration 2010-08-24)