The patients' experience of neuroimaging of primary brain tumors: a cross-sectional survey study.

PURPOSE: To gain insight into how patients with primary brain tumors experience MRI, follow-up protocols, and gadolinium-based contrast agent (GBCA) use. METHODS: Primary brain tumor patients answered a survey after their MRI exam. Questions were analyzed to determine trends in patients' experience regarding the scan itself, follow-up frequency, and the use of GBCAs. Subgroup analysis was performed on sex, lesion grade, age, and the number of scans. Subgroup comparison was made using the Pearson chi-square test and the Mann-Whitney U-test for categorical and ordinal questions, respectively. RESULTS: Of the 100 patients, 93 had a histopathologically confirmed diagnosis, and seven were considered to have a slow-growing low-grade tumor after multidisciplinary assessment and follow-up. 61/100 patients were male, with a mean age ± standard deviation of 44 ± 14 years and 46 ± 13 years for the females. Fifty-nine patients had low-grade tumors. Patients consistently underestimated the number of their previous scans. 92% of primary brain tumor patients did not experience the MRI as bothering and 78% would not change the number of follow-up MRIs. 63% of the patients would prefer GBCA-free MRI scans if diagnostically equally accurate. Women found the MRI and receiving intravenous cannulas significantly more uncomfortable than men (p = 0.003). Age, diagnosis, and the number of previous scans had no relevant impact on the patient experience. CONCLUSION: Patients with primary brain tumors experienced current neuro-oncological MRI practice as positive. Especially women would, however, prefer GBCA-free imaging if diagnostically equally accurate. Patient knowledge of GBCAs was limited, indicating improvable patient information.

Tick Saliva Protein Evasin-3 Allows for Visualization of Inflammation in Arteries through Interactions with CXC-Type Chemokines Deposited on Activated Endothelium.

Atherosclerosis is one of the leading causes of mortality in developed and developing countries. The onset of atherosclerosis development is accompanied by overexpression of several inflammatory chemokines. Neutralization of these chemokines by chemokine-binding agents attenuates atherosclerosis progression. Here, we studied structural binding features of the tick protein Evasin-3 to chemokine (C-X-C motif) ligand 1 (CXCL1). We showed that Evasin-3-bound CXCL1 is unable to activate the CXCR2 receptor, but retains affinity to glycosaminoglycans. This observation was exploited to detect inflammation by visualizing a group of closely related CXC-type chemokines deposited on cell walls in human endothelial cells and murine carotid arteries by a fluorescent Evasin-3 conjugate. This work highlights the applicability of tick-derived chemokine-binding conjugates as a platform for the development of new agents for inflammation imaging.

Ultrasound-Guided Nerve Blocks as Analgesia for Nonoperative Management of Distal Radius Fractures-Two Consecutive Randomized Controlled Trials.

OBJECTIVES: To investigate whether a conventional fracture hematoma block (FHB) or an ultrasound-guided peripheral nerve block has more superior analgesic effect during nonoperative management of distal radius fractures in an emergency department setting. Two peripheral nerve block types were investigated, one at the level of the elbow, or cubital nerve block (CNB), and another an axillary nerve block (ANB). DESIGN: Two prospective randomized controlled studies were performed to compare the difference in pain intensity during closed reduction of a distal radius fracture between FHB-, CNB-, and, ANB-treated patients. SETTING: Level 2 trauma center. PATIENTS: One hundred ten patients with radiographic displaced distal radius fractures were randomized. Fifty patients were randomized between FHB and CNB, and 60 patients were randomized between CNB and ANB. INTERVENTION: FHB, CNB, or ANB. These were performed by 3 physicians new to ultrasound-guided peripheral nerve blocks and trained before onset of this study. MAIN OUTCOME MEASUREMENT: Pain was sequentially measured using an NRS during closed distal radius fracture reduction. RESULTS: CNB patients experienced less pain during block procedure (P = 0.002), finger trap traction (P = 0.007), fracture reduction (P = 0.00001), after plaster cast application (P = 0.01), and after control radiography (P = 0.01). In our second study, ANB-treated patients reported less pain during block procedure (P = 0.04), during finger trap traction (P < 0.0001), fracture reduction (P < 0.0001), after plaster cast application (P = 0.0001), and after control radiography (P = 0.0005). CONCLUSIONS: Although participating clinicians had minimal expertise using ultrasound-guided peripheral nerve blocks, nonoperative management of distal radius fracture using an ANB was less painful. These block types are expected to completely eradicate sensation the best. Future studies should address technical factors including adequate placement and time to let the block set up, as well as issues such as resource utilization including time and clinician availability to better determine the relative advantages and disadvantages to other analgesia techniques such as the FHB. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Xiphoidectomy: A Surgical Intervention for an Underdocumented Disorder.

Two patients who presented with nonspecific thoracic and upper abdominal symptoms and tenderness of the xiphoid process are discussed. Both patients had undergone extensive examinations, but no source for their symptoms could be found. Plain chest radiographs revealed an anterior displacement of the xiphoid process in both patients. Physical examination confirmed this to be the primary source of discomfort. Anterior displacement of the xiphoid process may be the result of significant weight gain. Repeated trauma of the afflicted area, unaccustomed heavy lifting, exercise, and perichondritis are, amongst other causes, believed to contribute to the development of xiphodynia. Both patients were treated by performing a xiphoidectomy, resulting in disappearance of the symptoms.

Delivering therapeutics in peripheral artery disease: challenges and future perspectives.

Targeted and sustained delivery of biologicals to improve neovascularization has been focused on stimulation angiogenesis. The formation of collaterals however is hemodynamically much more efficient, but as a target of therapy has been under-utilized. Although there is good understanding of the molecular processes involving collateral formation and there are interesting drugable candidates, the need for targeting and sustained delivery is still an obstacle towards safe and effective treatment. Molecular targeting with nanoparticles of liposomes is promising and so are peri-vascularly delivered polymer-based protein reservoirs. These developments will lead to future arteriogenesis strategies that are adjunct to current revascularization.

Comparison of LDPI to SPECT perfusion imaging using (99m)Tc-sestamibi and (99m)Tc-pyrophosphate in a murine ischemic hind limb model of neovascularization.

BACKGROUND: We aimed to determine the accuracy of laser Doppler perfusion imaging (LDPI) in an animal model for hind limb ischemia. METHODS: We used a murine (C57Bl/6 mice) ischemic hind limb model in which we compared LDPI with the clinically used (99m)Tc-sestamibi SPECT perfusion imaging (n = 7). In addition, we used the SPECT tracer (99m)Tc-pyrophosphate ((99m)Tc-PyP) to image muscular damage (n = 6). RESULTS: LDPI indicated a quick and prominent decrease in perfusion immediately after ligation, subsequently recovering to 21.9 and 25.2 % 14 days later in the (99m)Tc-sestamibi and (99m)Tc-PyP group, respectively. (99m)Tc-sestamibi SPECT scans also showed a quick decrease in perfusion. However, nearly full recovery was reached 7 days post ligation. Muscular damage, indicated by the uptake of (99m)Tc-PyP, was highest at day 3 and recovered to baseline levels at day 14 post ligation. Postmortem histology supported these findings, as a significantly increased collateral diameter was found 7 and 14 days after ligation and peak macrophage infiltration and TUNEL positivity was found on day 3 after ligation. CONCLUSIONS: Here, we indicate that LDPI strongly underestimates perfusion recovery in a hind limb model for profound ischemia.

Multiple carpometacarpal dislocations and an associated fracture of the hamate: an uncommon injury.

Dislocation of the four ulnar carpometacarpal (CMC) joints with a concurrent fracture of the hamate is a rare injury, with a paucity of published cases. A great force is required to dislocate a CMC joint. Diagnosis can easily be missed, due to other serious associated injuries. Appropriate treatment of CMC joint dislocations usually leads to excellent outcomes. We present a case of dorsal dislocation of the four ulnar CMC joints after punching a wall. The injury was treated with a closed reduction and percutaneous transfixation with Kirschner-wires. Despite the extensive injury, the functional result was good (full and painless range of motion) at 12 weeks of follow-up.

CXCL1 microspheres: a novel tool to stimulate arteriogenesis.

CONTEXT: After arterial occlusion, diametrical growth of pre-existing natural bypasses around the obstruction, i.e. arteriogenesis, is the body's main coping mechanism. We have shown before that continuous infusion of chemokine (C-X-C motif) ligand 1 (CXCL1) promotes arteriogenesis in a rodent hind limb ischemia model. OBJECTIVE: For clinical translation of these positive results, we developed a new administration strategy of local and sustained delivery. Here, we investigate the therapeutic potential of CXCL1 in a drug delivery system based on microspheres. MATERIALS AND METHODS: We generated poly(ester amide) (PEA) microspheres loaded with CXCL1 and evaluated them in vitro for cellular toxicity and chemokine release characteristics. In vivo, murine femoral arteries were ligated and CXCL1 was administered either intra-arterially via osmopump or intramuscularly encapsulated in biodegradable microspheres. Perfusion recovery was measured with Laser-Doppler. RESULTS: The developed microspheres were not cytotoxic and displayed a sustained chemokine release up to 28 d in vitro. The amount of released CXCL1 was 100-fold higher than levels in native ligated hind limb. Also, the CXCL1-loaded microspheres significantly enhanced perfusion recovery at day 7 after ligation compared with both saline and non-loaded conditions (55.4 ± 5.0% CXCL1-loaded microspheres versus 43.1 ± 4.5% non-loaded microspheres; n = 8-9; p < 0.05). On day 21 after ligation, the CXCL1-loaded microspheres performed even better than continuous CXCL1 administration (102.1 ± 4.4% CXCL1-loaded microspheres versus 85.7 ± 4.8% CXCL1 osmopump; n = 9; p < 0.05). CONCLUSION: Our results demonstrate a proof of concept that sustained, local delivery of CXCL1 encapsulated in PEA microspheres provides a new tool to stimulate arteriogenesis in vivo.

Case report of nail bed injury after blunt trauma; what lies beneath the nail?

INTRODUCTION: A stable, mobile and sensate fingertip is of paramount importance to perform daily tasks and sense dangerous situations. Unfortunately, fingertips are easily injured with various extents of soft tissue damage. Delayed and inadequate treatment of nail bed injuries may cause substantial clinical problems. The aim is to increase awareness about nail bed injuries among physicians who often treat these patients. PRESENTATION OF CASE: We present a 26-year-old male with blunt trauma to a distal phalanx. Conventional radiographs showed an intra-articular, multi-fragmentary fracture of the distal phalanx. At the outpatient department the nail was removed and revealed a lacerated nail bed, more than was anticipated upon during the first encounter at the emergency department. DISCUSSION: Blunt trauma to the fingertip occurs frequently and nail bed injuries are easy to underestimate. An adequate emergency treatment of nail bed injuries is needed to prevent secondary deformities and thereby reduce the risk of secondary reconstruction of the nail bed, which often gives unpredictable results. CONCLUSION: However, adequate initial assessment and treatment are important to achieve the functional and cosmetic outcomes. Therefore awareness of physicians at the emergency department is essential.

Wound Infections Following Implant removal below the knee: the effect of antibiotic prophylaxis; the WIFI-trial, a multi-centre randomized controlled trial.

BACKGROUND: In the Netherlands about 18,000 procedures with implant removal are performed annually following open or closed reduction and fixation of fractures, of which 30-80% concern the foot, ankle and lower leg region. For clean surgical procedures, the rate of postoperative wound infections (POWI) should be less than ~2%. However, rates of 10-12% following implant removal have been reported, specifically after foot, ankle and lower leg fractures. Currently, surgeons individually decide if antibiotics prophylaxis is given, since no guideline exists. This leads to undesirable practice variation. The aim of the study is to assess the (cost-)effectiveness of a single intravenous gift of Cefazolin prior to implant removal following surgical fixation of foot, ankle and/or lower leg fractures. METHODS: This is a double-blind randomized controlled trial in patients scheduled for implant removal following a foot, ankle or lower leg fracture. Primary outcome is a POWI within 30 days after implant removal. Secondary outcomes are quality of life, functional outcome and costs at 30 days and 6 months after implant removal. With 2 x 250 patients a decrease in POWI rate from 10% to 3.3% (expected rate in clean-contaminated elective orthopaedic trauma procedures) can be detected (Power = 80%, 2-sided alpha = 5%, including 15% lost to follow up). DISCUSSION: If administration of prophylactic antibiotics prior to implant removal reduces the infectious complication rate, this will offer a strong argument to adopt this as standard practice of care. This will consequently lead to less physical and social disabilities and health care use. A preliminary, conservative estimation suggests yearly cost savings in the Netherlands of € 3.5 million per year. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov ( NCT02225821 ) and the Netherlands Trial Register ( NTR4393 ) and was granted permission by the Medical Ethical Review Committee of the Academic Medical Centre on October 7 2014.

CXCL1 promotes arteriogenesis through enhanced monocyte recruitment into the peri-collateral space.

AIMS: The mechanisms of monocyte recruitment to arteriogenic collaterals are largely unknown. We investigated the role of chemokine (C-X-C-motif) ligand 1 (CXCL1) and its cognate receptor, chemokine (C-X-C-motif) receptor 2 (CXCR2) in arteriogenesis. METHODS AND RESULTS: After femoral artery ligation in Sprague-Dawley rats, either native collaterals were harvested or placebo, CXCL1 or CXCR2 blocker was administered via an osmopump. Perfusion recovery was measured with Laser Doppler, leukocyte populations were analyzed by fluorescence-activated cell sorting, and hind limb sections were stained for macrophage marker cluster of differentiation 68 (CD68). In vitro, fluorescent CXCL1 or human acute monocytic leukemia cell line (THP-1) monocytic cells were flown over shear-stressed endothelium. CXCL1 mRNA expression in collaterals was dramatically upregulated already 1 h after ligation (ratio ligated/sham 5.73). CD68 mRNA was upregulated from 12 h until 3 days after ligation (peak ratio ligated/sham 2.65). CXCL1 treatment augmented perfusion recovery at 3 and 7 days (p < 0.05) after ligation, and a significant increase in the number of peri-collateral macrophages was evident concomitantly (p < 0.05). Conversely, CXCR2 antagonist treatment caused a decrease in perfusion recovery both at 7 and 10 days postligation (p = 0.01) and also significantly reduced the number of peri-collateral macrophages (p < 0.05). In vitro, CXCL1 tethered to and was taken up by endothelial cells under shear stress conditions and enhanced THP-1 adherence compared to control (p < 0.05). In contrast, CXCR2 antagonist compromised THP-1 adherence to endothelial cells (p < 0.05). CONCLUSION: CXCL1 presented on the luminal endothelial surface leads to an increase in the number of peri-collateral macrophages, thus improving the arteriogenic response after arterial ligation.

A hybrid vanadium fluoride with structurally isolated S = 1 kagome layers.

A new organically-templated vanadium(III) fluoride, (NH4)2(C2H8N)[V3F12], has been prepared using an ionothermal approach. This compound has a unique layered structure featuring distorted S = 1 kagome planes separated by the cationic species. The compound exhibits magnetic frustration, with a canted antiferromagnetic ground state. On further cooling in the ground state a pronounced change in magnetisation kinetics is observed.

Angular malalignment as cause of limitation of forearm rotation: an analysis of prospectively collected data of both-bone forearm fractures in children.

INTRODUCTION: Although limitation of pronation/supination following both-bone forearm fractures in children is often attributed to an angular malunion, no clinical study has compared pronation/supination and angular malalignment of the same child by analysis of prospectively collected clinical data. AIM: The purpose of this trial is to explore whether limitation of pronation/supination can be predicted by the degree of angular malalignment in children who sustained a both-bone forearm fracture. METHODS: In four Dutch hospitals, children aged ≤16 years with a both-bone forearm fracture were prospectively followed up consecutive children for 6-9 months. At the final follow-up, pronation/supination and angular malunion on radiographs were determined. RESULTS: Between January 2006 and August 2010, a total of 410 children were prospectively followed up, of which 393 children were included for analysis in this study. The mean age of the children was 8.0 (±3.5) years, of which 63% were male and 40% fractured their dominant arm. The mean time to final examination was 219 (±51) days. Children with a metaphyseal both-bone fracture of the distal forearm with an angular malalignment of ≤15° had a 9-13% chance of developing a clinically relevant limitation (i.e., <50° of pronation and/or supination), while children with an angular malalignment of ≥16° had a 60% chance. Children with diaphyseal both-bone forearm fractures with ≤5° of angular malalignment had a 13% chance of developing a clinically relevant limitation, which showed no significant increase with a further increase of angular malalignment. CONCLUSIONS: Children who sustained a both-bone forearm fracture localised in the distal metaphysis have a higher chance of developing a clinically relevant limitation of forearm rotation in case of a more severe angular malalignment, while children with a diaphyseal both-bone forearm fracture had a moderate chance of limitation, irrespective of the severity of the angular malalignment.

Which factors affect limitation of pronation/supination after forearm fractures in children? A prospective multicentre study.

INTRODUCTION: Both-bone forearm fractures in children frequently result in a limitation of pronation/supination, which hinders daily activities. The purpose of this prospective multicentre study was to investigate which clinical factors are related to the limitation of pronation/supination in children with a both-bone forearm fracture. METHODS: In four Dutch hospitals, consecutive children (<16 years) who sustained a both-bone forearm fracture were included. Children were followed up for 6-9 months and data from questionnaires, physical examination and X-rays were collected. Univariate and multivariate logistic regression analyses were used to assess the relationship between limitation of pronation/supination (≥20°) and several clinical factors. RESULTS: A group of 410 children with both-bone forearm fractures were included, of which 10 children missed the final examination (follow-up rate of 97.6%). We found that a re-fracture (odds ratio (OR) 11.7, 95% confidence interval (CI) 1.2; 118.5), a fracture in the diaphysis (OR 3.3, 95% CI 1.4; 7.9) and less physiotherapy during follow-up (OR 0.90, 95% CI 0.82; 0.98) were independently associated with a limitation of pronation/supination of 20° or more. CONCLUSIONS: These findings imply that a re-fracture and a diaphyseal located fracture were associated independently of each other with a limitation of pronation/supination in children with a both-bone forearm fracture. Furthermore, in children with severe limitation extensive physiotherapy is associated with better functional outcome.

Conversion to below-elbow cast after 3 weeks is safe for diaphyseal both-bone forearm fractures in children.

BACKGROUND: It is unclear whether it is safe to convert above-elbow cast (AEC) to below-elbow cast (BEC) in a child who has sustained a displaced diaphyseal both-bone forearm fracture that is stable after reduction. In this multicenter study, we wanted to answer the question: does early conversion to BEC cause similar forearm rotation to that after treatment with AEC alone? CHILDREN AND METHODS: Children were randomly allocated to 6 weeks of AEC, or 3 weeks of AEC followed by 3 weeks of BEC. The primary outcome was limitation of pronation/supination after 6 months. The secondary outcomes were re-displacement of the fracture, limitation of flexion/extension of the wrist and elbow, complication rate, cast comfort, complaints in daily life, and cosmetics of the fractured arm. RESULTS: 62 children were treated with 6 weeks of AEC, and 65 children were treated with 3 weeks of AEC plus 3 weeks of BEC. The follow-up rate was 60/62 and 64/65, respectively with a mean time of 6.9 (4.7-13) months. The limitation of pronation/supination was similar in both groups (18 degrees for the AEC group and 11 degrees for the AEC/BEC group). The secondary outcomes were similar in both groups, with the exception of cast comfort, which was in favor of the AEC/BEC group. INTERPRETATION: Early conversion to BEC cast is safe and results in greater cast comfort.

Sputter growth and characterization of metamagnetic B2-ordered FeRh epilayers.

Chemically ordered alloys are useful in a variety of magnetic nanotechnologies. They are most conveniently prepared at an industrial scale using sputtering techniques. Here we describe a method for preparing epitaxial thin films of B2-ordered FeRh by sputter deposition onto single crystal MgO substrates. Deposition at a slow rate onto a heated substrate allows time for the adatoms to both settle into a lattice with a well-defined epitaxial relationship with the substrate and also to find their proper places in the Fe and Rh sublattices of the B2 structure. The structure is conveniently characterized with X-ray reflectometry and diffraction and can be visualised directly using transmission electron micrograph cross-sections. B2-ordered FeRh exhibits an unusual metamagnetic phase transition: the ground state is antiferromagnetic but the alloy transforms into a ferromagnet on heating with a typical transition temperature of about 380 K. This is accompanied by a 1% volume expansion of the unit cell: isotropic in bulk, but laterally clamped in an epilayer. The presence of the antiferromagnetic ground state and the associated first order phase transition is very sensitive to the correct equiatomic stoichiometry and proper B2 ordering, and so is a convenient means to demonstrate the quality of the layers that can be deposited with this approach. We also give some examples of the various techniques by which the change in phase can be detected.

Early conversion to below-elbow cast for non-reduced diaphyseal both-bone forearm fractures in children is safe: preliminary results of a multicentre randomised controlled trial.

INTRODUCTION: This multicentre randomised controlled trial was designed to explore whether 6 weeks above-elbow cast (AEC) or 3 weeks AEC followed by 3 weeks below-elbow cast (BEC) cause similar limitation of pronation and supination in non-reduced diaphyseal both-bone forearm fractures in children. MATERIALS AND METHODS: Children were randomly allocated to 6 weeks AEC or to 3 weeks AEC followed by 3 weeks BEC. The primary outcome was limitation of pronation and supination after 6 months. The secondary outcomes were re-displacement of the fracture, complication rate, limitation of flexion and extension of wrist and elbow, cast comfort, cosmetics, complaints in daily life and assessment of radiographs. RESULTS: A group of 23 children was treated with 6 weeks AEC and 24 children with 3 weeks AEC and 3 weeks BEC. The follow-up rate was 98 % with a mean follow-up of 7.0 months. The mean limitation of pronation and supination was 23.3 ± 22.0 for children treated with AEC and 18.0 ± 16.9 for children treated with AEC and BEC. The other study outcomes were similar in both groups. CONCLUSIONS: Early conversion to BEC is safe in the treatment of non-reduced diaphyseal both-bone forearm fractures in children. LEVEL OF EVIDENCE: Multicentre randomised controlled trial, Level II.

Single-bone intramedullary fixation of unstable both-bone diaphyseal forearm fractures in children leads to increased re-displacement: a multicentre randomised controlled trial.

INTRODUCTION: Both-bone diaphyseal forearm fractures in children can be stabilised without cast by a flexible intramedullary nail in both the radius and the ulna. Adequate results with single-bone fixation combined with a complementary cast are also reported. However, because those results are based on a selection of children, this trial investigates whether single-bone intramedullary fixation, compared with both-bone intramedullary fixation, results in similar pronation and supination in children with an unstable diaphyseal both-bone forearm fracture. MATERIALS AND METHODS: In four Dutch hospitals, 24 consecutive children aged <16 years with a displaced unstable both-bone diaphyseal forearm fracture were randomly allocated to single-bone or both-bone intramedullary fixation. Primary outcome was limitation of pronation and supination 9 months after initial trauma. Secondary outcomes were limitation of flexion/extension of wrist/elbow, complication rate, operation time, cosmetics of the fractured arm, complaints in daily life, and assessment of radiographs. RESULTS: Between January 2006 and August 2010, 11 children were randomised to single-bone fixation and 13 to both-bone fixation. In the both-bone fixation group, two fractures were stabilized by only one nail. In both groups, median limitation of pronation/supination at 9-month follow-up was 5°-10°. In both groups operation time was similar but in the single-bone fixation group cast immobilisation was longer (median of 37 vs. 28 days). In four children, re-displacement of the fracture occurred in those fractures without an intramedullary nail. CONCLUSIONS: These results caution against the use of single-bone fixation in all both-bone forearm fractures. This method may lead to increased re-displacement and reduced clinical results.