Reply to the letter to the editor: Could the use of bone morphogenetic proteins in fracture healing do more harm than good to our patients?

Surger

Vitamin D in Head and Neck Cancer : a Systematic Review

Purpose of review Observational studies have shown that serum 25-OH vitamin D [25(OH)D] is inversely associated with overall cancer risk in many malignancies. We performed a systematic literature review to determine whether vitamin D deficiency is related to head and neck cancer (HNC) etiology and outcome. Recent findings The search yielded five prospective studies reporting 25(OH)D levels prior to cancer diagnosis and their effect on the risk of HNC. Eight studies were cross-sectional or case-control studies, in which 25(OH)D levels were only measured after cancer diagnosis. Two studies found an inverse association between 25(OH)D level and HNC risk, while two other prospective cohort studies demonstrated no connection between 25(OH)D and HNC risk. Several studies reported cancer patients to have significantly lower 25(OH)D levels than controls. Associations between 25(OH)D and prognosis and mortality were variable. The link between vitamin D and HNC has so far only been investigated in a few observational, prospective, and case-control studies. Vitamin D deficiency may be more common in HNC patients than in the healthy population. There is no evidence for a causal relationship. Further studies are needed to evaluate whether low 25(OH)D concentrations play a role in the development or outcome of HNCs.Peer reviewe

Preclinical evaluation of EpCAM-binding designed ankyrin repeat proteins (DARPins) as targeting moieties for bimodal near-infrared fluorescence and photoacoustic imaging of cancer

PURPOSE Fluorescence-guided surgery (FGS) can play a key role in improving radical resection rates by assisting surgeons to gain adequate visualization of malignant tissue intraoperatively. Designed ankyrin repeat proteins (DARPins) possess optimal pharmacokinetic and other properties for in vivo imaging. This study aims to evaluate the preclinical potential of epithelial cell adhesion molecule (EpCAM)-binding DARPins as targeting moieties for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of cancer. METHODS EpCAM-binding DARPins Ac2, Ec4.1, and non-binding control DARPin Off7 were conjugated to IRDye 800CW and their binding efficacy was evaluated on EpCAM-positive HT-29 and EpCAM-negative COLO-320 human colon cancer cell lines. Thereafter, NIRF and PA imaging of all three conjugates were performed in HT-29_luc2 tumor-bearing mice. At 24 h post-injection, tumors and organs were resected and tracer biodistributions were analyzed. RESULTS Ac2-800CW and Ec4.1-800CW specifically bound to HT-29 cells, but not to COLO-320 cells. Next, 6 nmol and 24 h were established as the optimal in vivo dose and imaging time point for both DARPin tracers. At 24 h post-injection, mean tumor-to-background ratios of 2.60 ± 0.3 and 3.1 ± 0.3 were observed for Ac2-800CW and Ec4.1-800CW, respectively, allowing clear tumor delineation using the clinical Artemis NIRF imager. Biodistribution analyses in non-neoplastic tissue solely showed high fluorescence signal in the liver and kidney, which reflects the clearance of the DARPin tracers. CONCLUSION Our encouraging results show that EpCAM-binding DARPins are a promising class of targeting moieties for pan-carcinoma targeting, providing clear tumor delineation at 24 h post-injection. The work described provides the preclinical foundation for DARPin-based bimodal NIRF/PA imaging of cancer

Displaced midshaft fractures of the clavicle: non-operative treatment versus plate fixation (Sleutel-TRIAL). A multicentre randomised controlled trial

Contains fulltext : 96826.pdf (publisher's version ) (Open Access)BACKGROUND: The traditional view that the vast majority of midshaft clavicular fractures heal with good functional outcomes following non-operative treatment may be no longer valid for all midshaft clavicular fractures. Recent studies have presented a relatively high incidence of non-union and identified speciic limitations of the shoulder function in subgroups of patients with these injuries. AIM: A prospective, multicentre randomised controlled trial (RCT) will be conducted in 21 hospitals in the Netherlands, comparing fracture consolidation and shoulder function after either non-operative treatment with a sling or a plate fixation. METHODS/DESIGN: A total of 350 patients will be included, between 18 and 60 years of age, with a dislocated midshaft clavicular fracture. The primary outcome is the incidence of non-union, which will be determined with standardised X-rays (Antero-Posterior and 30 degrees caudocephalad view). Secondary outcome will be the functional outcome, measured using the Constant Score. Strength of the shoulder muscles will be measured with a handheld dynamometer (MicroFET2). Furthermore, the health-related Quality of Life score (ShortForm-36) and the Disabilities of Arm, Shoulder and Hand (DASH) Outcome Measure will be monitored as subjective parameters. Data on complications, bone union, cosmetic aspects and use of painkillers will be collected with follow-up questionnaires. The follow-up time will be two years. All patients will be monitored at regular intervals over the subsequent twelve months (two and six weeks, three months and one year). After two years an interview by telephone and a written survey will be performed to evaluate the two-year functional and mechanical outcomes. All data will be analysed on an intention-to-treat basis, using univariate and multivariate analyses. DISCUSSION: This trial will provide level-1 evidence for the comparison of consolidation and functional outcome between two standardised treatment options for dislocated midshaft clavicular fractures. The gathered data may support the development of a clinical guideline for treatment of clavicular fractures. TRIAL REGISTRATION: Netherlands National Trial Register NTR2399

Use and efficacy of bone morphogenetic proteins in fracture healing

Signal transduction in aging related disease