Dual-Layer Detector Cone-Beam CT Angiography for Stroke Assessment: First-in-Human Results (the Next Generation X-ray Imaging System Trial).

BACKGROUND AND PURPOSE: In patients with stroke, IV cone-beam CTA in the angiography suite could be an alternative to CTA to shorten the door-to-thrombectomy time. However, image quality in cone-beam CTA is typically limited by artifacts. This study evaluated a prototype dual-layer detector cone-beam CT angiography versus CTA in patients with stroke. MATERIALS AND METHODS: A prospective, single-center trial enrolled consecutive patients with ischemic or hemorrhagic stroke on initial CT. Intracranial arterial segment vessel conspicuity and artifact presence were evaluated on dual-layer cone-beam CTA 70-keV virtual monoenergetic images and CTA. Eleven predetermined vessel segments were matched for every patient. Twelve patients were necessary to show noninferiority to CTA. Noninferiority was determined by the exact binomial test; the 1-sided lower performance boundary was prospectively set to 80% (98.75% CI). RESULTS: Twenty-one patients had matched image sets (mean age, 72 years). After excluding examinations with movement or contrast media injection issues, all readers individually considered dual-layer cone-beam CT angiography noninferior to CTA (CI boundary, 93%, 84%, 80%, respectively) when evaluating arteries relevant in candidates for intracranial thrombectomy. Artifacts were more prevalent compared with CTA. The majority assessment rated each individual segment except M1 as having noninferior conspicuity compared with CTA. CONCLUSIONS: In a single-center stroke setting, dual-layer detector cone-beam CTA virtual monoenergetic images are noninferior to CTA under certain conditions. Notably, the prototype is hampered by a long scan time and is not capable of contrast media bolus tracking. After excluding examinations with such scan issues, readers considered dual-layer detector cone-beam CTA noninferior to CTA, despite more artifacts.

Analgesic effect of intravenous dexamethasone after volar plate surgery for distal radius fracture with brachial plexus block anaesthesia: a prospective, double-blind randomised clinical trial.

Rebound pain after brachial plexus block resolution and development of long-lasting pain are problems associated with volar plate fixation for distal radius fractures. The aim of this double-blind study was to evaluate the effect of a single prophylactic intravenous dose of dexamethasone in this setting. The primary endpoint was highest pain score during the first 24 hours after surgery. We included 51 adults of ASA physical status 1-2 due to undergo planned acute fixation of the radius. All received premedication with oral paracetamol and etoricoxib, and a pre-operative brachial plexus block with ropivacaine. Patients were randomly allocated into two groups: a dexamethasone group receiving 16 mg dexamethasone intravenously at start of surgery and a control group receiving 4 ml saline. After surgery, all patients received fixed doses of paracetamol, etoricoxib and oxycodone, with further oxycodone added as needed in the first 48 hours. Pain, analgesic consumption and daily function were registered at predefined times up to 1 year after surgery. Median (IQR [range]) worst pain score in the first 24 hours, as assessed by verbal numeric rating scale (0-10), was 4 (2-6 [0-7]) in the dexamethasone group compared with 8 (5-8 [2-10]) in the placebo group (p < 0.001). Average pain score, 2 (1-4 [0-5]) vs. 5 (3-6 [0-8]), p = 0.001 and rescue oxycodone consumption, 5 (0-10 [0-35]) mg vs. 10 (5-15 [0-50]) mg, p = 0.037), respectively, were both significantly lower in the dexamethasone group compared with control from 8 to 24 hours. Brachial plexus block duration was 69% longer in the dexamethasone group, 21.5 (19.1-23.4 [12.9-24.1]) hours vs. 12.7 (11.9-15.3 [7.4-26.6]) hours, p < 0.001. Two patients (9%) in the dexamethasone group compared with 12 (50%) in the placebo group experienced worst pain scores of 8-10 during the first 36 hours (p = 0.002). At 3 and 7 days postoperatively, there were no significant differences between groups for pain scores or opioid consumption. At 6 months, 27 patients (57%) reported pain at the site of surgery, with significantly higher average pain score (p = 0.024) in the placebo group. At 1 year, two patients in the dexamethasone group reported pain compared with 10 in the placebo group (p = 0.015), and worst pain score was significantly higher in the placebo group (p = 0.018). We conclude that intravenous dexamethasone improves early postoperative analgesia and may also improve clinical outcomes after 6 and 12 months.

Microcirculation and haemodynamics after infraclavicular brachial plexus block using adrenaline as an adjuvant to lidocaine: a randomised, double-blind, crossover study in healthy volunteers.

We evaluated the effect of adrenaline on human skin microcirculation (nutritive and sub-papillary) and systemic cardiovascular variables after it was added to lidocaine in infraclavicular brachial plexus blocks. Twelve healthy, non-smoking male volunteers were included, each attending two study sessions 2 weeks apart, and they were studied using a crossover design. In both sessions, they received an ultrasound-guided infraclavicular brachial plexus block in the non-dominant arm with 0.4 ml.kg-1 lidocaine, 15 mg.ml-1 with or without adrenaline 5 µg.ml-1 . Microcirculation was assessed by laser Doppler fluxmetry (sub-papillary blood flow), capillary video microscopy (nutritive blood flow) and continuous temperature measurements. Heart rate and arterial pressure were recorded continuously and non-invasively. Median (IQR [range]) sub-papillary blood flow increased substantially 30 min after the brachial plexus block, from 8.5 (4.4-13.5 [2.9-28.2]) to 162.7 (111.0-197.8 [9.5-206.7]) arbitrary units with adrenaline (p = 0.017), and from 6.9 (5.3-28.5 [1.8-42.1] to 133.7 (16.5-216.7 [1.0-445.0] arbitrary units without adrenaline (p = 0.036). Nutritive blood flow (functional capillary density, capillaries.mm-2 , measured at the dorsal side of the hand) decreased in the blocked extremity when adrenaline was used as adjuvant, from median (IQR [range]) 45 (36-52 [26-59]) to 38 (29-41 [26-42]), p = 0.028, whereas no significant change occurred without adrenaline. Median finger skin temperature (°C) increased by 44% (data pooled) with no significant differences between the groups. No significant changes were found in the systemic cardiovascular variables with or without adrenaline. We conclude that lidocaine infraclavicular brachial plexus blocks caused an increase in skin sub-papillary blood flow. The addition of adrenaline produced stronger and longer lasting blocks, but decreased the nutritive blood flow.

Proton pump inhibitor medication is associated with colonisation of gut flora in the oropharynx.

BACKGROUND: The normal body exists in mutualistic balance with a large range of microbiota. The primary goal of this study was to establish whether there is an imbalance in the oropharyngeal flora early after hospital or ICU admittance, and whether flora differs between control, ward and critically ill patients. The secondary goal was to explore whether there are patient characteristics that can be associated with a disturbed oropharyngeal flora. METHODS: Oropharyngeal cultures were obtained from three different study groups: (1) controls from the community, (2) ward patients and (3) critically ill patients, the two latter within 24 h after admittance. RESULTS: Cultures were obtained from 487 individuals: 77 controls, 193 ward patients and 217 critically ill patients. Abnormal pharyngeal flora was more frequent in critically ill and ward patients compared with controls (62.2% and 10.4% vs. 1.3%, P < 0.001 and P = 0.010, respectively). Colonisation of gut flora in the oropharynx was more frequent in critically ill patients compared with ward patients or controls (26.3% vs. 4.7% and 1.3%, P < 0.001 and P < 0.001, respectively). Proton pump inhibitor medication was the strongest independent factor associated with the presence of gut flora in the oropharynx in both ward and critically ill patients (P = 0.030 and P = 0.044, respectively). CONCLUSION: This study indicates that abnormal oropharyngeal flora is an early and frequent event in hospitalised patients and more so in the critically ill, compared to controls. Proton pump inhibitor medication is associated with colonisation of gut flora in the oropharynx.

Pre-operative brachial plexus block compared with an identical block performed at the end of surgery: a prospective, double-blind, randomised clinical trial.

We evaluated whether pre-emptive analgesia with a pre-operative ultrasound-guided infraclavicular brachial plexus block resulted in better postoperative analgesia than an identical block performed postoperatively. Fifty-two patients undergoing fixation of a fractured radius were included. All patients received general anaesthesia with remifentanil and propofol. Patients were randomly allocated into two groups: a pre-operative block or a postoperative block with 0.5 ml.kg-1 ropivacaine 0.75%. After surgery, all patients received regular paracetamol plus opioids for breakthrough pain. Mean (SD) time to first rescue analgesic after emergence from general anaesthesia was 544 (217) min in the pre-operative block group compared with 343 (316) min in the postoperative block group (p = 0.015). Postoperative pain scores were higher and more patients required rescue analgesia during the first 4 h after surgery in the postoperative block group. There were no significant differences in plasma stress mediators between the groups. Analgesic consumption was lower at day seven in the pre-operative block group. Pain was described as very strong at block resolution in 27 (63%) patients and 26 (76%) had episodes of mild pain after 6 months. We conclude that a pre-operative ultrasound-guided infraclavicular brachial plexus block provides longer and better analgesia in the acute postoperative period compared with an identical postoperative block in patients undergoing surgery for fractured radius.

Hip fracture, mortality risk, and cause of death over two decades.

UNLABELLED: Men and women with hip fracture have higher short-term mortality. This study investigated mortality risk over two decades post-fracture; excess mortality remained high in women up to 10 years and in men up to 20 years. Cardiovascular disease (CVD) and pneumonia were leading causes of death with a long-term doubling of risk. INTRODUCTION: Hip fractures are associated with increased mortality, particularly short term. In this study with a two-decade follow-up, we examined mortality and cause of death compared to the background population. METHODS: We followed 1013 hip fracture patients and 2026 matched community controls for 22 years. Mortality, excess mortality, and cause of death were analyzed and stratified for age and sex. Hazard ratio (HR) was estimated by Cox regression. A competing risk model was fitted to estimate HR for common causes of death (CVD, cancer, pneumonia) in the short and long term (>1 year). RESULTS: For both sexes and at all ages, mortality was higher in hip fracture patients across the observation period with men losing most life years (p < 0.001). Mortality risk was higher for up to 15 years (women (risk ratio (RR) 1.9 [95 % confidence interval (CI) 1.7-2.1]); men (RR 2.8 [2.2-3.5])) and until end of follow-up ((RR 1.8 [1.6-2.0]); (RR 2.7 [2.1-3.3])). Excess mortality by time intervals, censored for the first year, was evident in women (<80 years, up to 10 years; >80 years, for 5 years) and in men <80 years throughout. CVD and pneumonia were predominant causes of death in men and women with an associated higher risk in all age groups. Pneumonia caused excess mortality in men over the entire observation period. CONCLUSION: In a remaining lifetime perspective, all-cause and excess mortality after hip fracture was higher even over two decades of follow-up. CVD and pneumonia reduce life expectancy for the remaining lifetime and highlights the need to further improve post-fracture management.

Interobserver variability in the assessment of the clinical severity of superficial venous insufficiency.

BACKGROUND: The clinical class C, of the CEAP classification (Clinical-Etiology-Anatomy-Pathophysiology), is often used when selecting patients for treatment within the national healthcare system. The aim of this study was to test the interobserver reproducibility of C when used in a clinical situation where the decision for reimbursement was made. METHODS: An unselected series of 78 patients (106 limbs) with varicose veins were examined by three independent surgeons with regard to C of CEAP and whether there was a medical indication for treatment. Interobserver reproducibility was calculated with kappa statistic. RESULTS: Total agreement between the three observers for clinical class was obtained in 61% of all cases (κ .55-.68 (95% CI)) and for medical indication in 60% of all cases (κ.35-.57 (95% CI)). CONCLUSION: The reproducibility of C when deciding medical indication for treatment is moderate. This may be due to inherent difficulties in the CEAP, lack of specific training, or the simultaneous assessment of reimbursement that may influence the clinical classification.

Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses.

Whereas gut IgA responses to the microbiota may be multi-centered and diverse, little is known about IgA responses to T-cell-dependent antigens following oral immunizations. Using a novel approach, gut IgA responses to oral hapten (4-hydroxy-3-nitrophenyl)acetyl-cholera toxin (NP-CT) conjugates were followed at the cellular and molecular level. Surprisingly, these responses were highly synchronized, strongly oligoclonal, and dominated by affinity matured cells. Extensive lineage trees revealed clonal relationships between NP-specific IgA cells in gut inductive and effector sites, suggesting expansion of the same B-cell clone in multiple Peyer's patches (PPs). Adoptive transfer experiments showed that this was achieved through re-utilization of already existing germinal centers (GCs) in multiple PPs by previously activated GC GL7(+) B cells, provided oral NP-CT was given before cell transfer. Taken together, these results explain why repeated oral immunizations are mandatory for an effective oral vaccine.

High average brightness water window source for short-exposure cryomicroscopy.

Laboratory water window cryomicroscopy has recently demonstrated similar image quality as synchrotron-based microscopy but still with much longer exposure times, prohibiting the spread to a wider scientific community. Here we demonstrate high-resolution laboratory water window imaging of cryofrozen cells with 10 s range exposure times. The major improvement is the operation of a λ=2.48 nm, 2 kHz liquid nitrogen jet laser plasma source with high spatial and temporal stability at high average brightness >1.5×10(12) ph/(s×sr×µm(2)×line), i.e., close to that of early synchrotrons. Thus, this source enables not only biological x-ray microscopy in the home laboratory but potentially other applications previously only accessible at synchrotron facilities.

Different in vitro and in vivo profiles of substituted 3-aminopropylphosphinate and 3-aminopropyl(methyl)phosphinate GABA(B) receptor agonists as inhibitors of transient lower oesophageal sphincter relaxation.

BACKGROUND AND PURPOSE: Gastro-oesophageal reflux is predominantly caused by transient lower oesophageal sphincter relaxation (TLOSR) and GABA(B) receptor stimulation inhibits TLOSR. Lesogaberan produces fewer CNS side effects than baclofen, which has been attributed to its affinity for the GABA transporter (GAT), the action of which limits stimulation of central GABA(B) receptors. To understand the structure-activity relationship for analogues of lesogaberan (3-aminopropylphosphinic acids), and corresponding 3-aminopropyl(methyl)phosphinic acids, we have compared representatives of these classes in different in vitro and in vivo models. EXPERIMENTAL APPROACH: The compounds were characterized in terms of GABA(B) agonism in vitro. Binding to GATs and cellular uptake was done using rat brain membranes and slices respectively. TLOSR was measured in dogs, and CNS side effects were evaluated as hypothermia in mice and rats. KEY RESULTS: 3-Aminopropylphosphinic acids inhibited TLOSR with a superior therapeutic index compared to 3-aminopropyl(methyl)phosphinic acids. This difference was most likely due to differential GAT-mediated uptake into brain cells of the former but not latter. In agreement, 3-aminopropyl(methyl)phosphinic acids were much more potent in producing hypothermia in rats even when administered i.c.v. CONCLUSIONS AND IMPLICATIONS: An enhanced therapeutic window for 3-aminopropylphosphinic acids compared with 3-aminopropyl(methyl)phosphinic acids with respect to inhibition of TLOSR was observed and is probably mechanistically linked to neural cell uptake of the former but not latter group of compounds. These findings offer a platform for discovery of new GABA(B) receptor agonists for the treatment of reflux disease and other conditions where selective peripheral GABA(B) receptor agonism may afford therapeutic effects.

Laboratory cryo soft X-ray microscopy.

Lens-based water-window X-ray microscopy allows two- and three-dimensional (2D and 3D) imaging of intact unstained cells in their near-native state with unprecedented contrast and resolution. Cryofixation is essential to avoid radiation damage to the sample. Present cryo X-ray microscopes rely on synchrotron radiation sources, thereby limiting the accessibility for a wider community of biologists. In the present paper we demonstrate water-window cryo X-ray microscopy with a laboratory-source-based arrangement. The microscope relies on a λ=2.48-nm liquid-jet high-brightness laser-plasma source, normal-incidence multilayer condenser optics, 30-nm zone-plate optics, and a cryo sample chamber. We demonstrate 2D imaging of test patterns, and intact unstained yeast, protozoan parasites and mammalian cells. Overview 3D information is obtained by stereo imaging while complete 3D microscopy is provided by full tomographic reconstruction. The laboratory microscope image quality approaches that of the synchrotron microscopes, but with longer exposure times. The experimental image quality is analyzed from a numerical wave-propagation model of the imaging system and a path to reach synchrotron-like exposure times in laboratory microscopy is outlined.

Risk factors for cardiovascular disease and future osteoarthritis-related arthroplasty: a population-based cohort study in men and women from Malmö, Sweden.

OBJECTIVE: To investigate the hypothesis that cardiovascular risk factors increase the likelihood of future osteoarthritis (OA)-related arthroplasty in adult men and women. METHODS: Baseline cohort data on cardiovascular risk factors [age, socio-economic class, family history, obesity, smoking, glucose, cholesterol, blood pressure, and early cardiovascular disease (CVD) history] were linked to clinical registers of OA-related arthroplasty data. The study included 8749 women and 14 821 men with up to a 30-year follow-up. RESULTS: In women, higher cardiovascular risk groups were more likely to have an OA outcome compared to the lowest risk quartile group (trend p < 0.001). The estimates were as follows: second quartile risk: rate ratio (RR) 2.15, 95% confidence interval (CI) 1.6-2.9, third quartile risk: 3.32 (2.5-4.5); and highest risk quartile: 3.47 (2.6-4.7). In men, higher cardiovascular risk groups were also more likely to have an OA outcome compared to the lowest risk quartile group (trend p = 0.001). The estimates were as follows: second quartile risk: RR 1.44, 95% CI 1.1-1.9; third quartile risk: 1.38 (1.1-1.8); and highest risk quartile: 1.67 (1.3-2.2). CONCLUSIONS: Our large cohort study with up to a 30-year follow-up period provides evidence to support the hypothesis of shared risk factors in CVD and OA, and the findings suggest an alternative aetiological process in the pathogenesis of OA.

Propionibacterium acnes as an etiological agent of arthroplastic and osteosynthetic infections--two cases with specific clinical presentation including formation of draining fistulae.

This report describes two patients with orthopaedic implant infections, with specific clinical presentations including formation of draining fistulae. Propionibacterium acnes was isolated in multiple cultures in both cases. Phenotypic and genetic characterisation of the isolates clearly emphasizes the significance of P. acnes as an etiological agent of implant infections. These infections are insidious with delayed presentation of symptoms and may have been overlooked because of the consideration of P. acnes as a contaminating commensal as well as the frequent use of suboptimal culture procedures.

Biofilm formation by Propionibacterium acnes is a characteristic of invasive isolates.

Propionibacterium acnes is a common and probably underestimated cause of delayed joint prosthesis infection. Bacterial biofilm formation is central in the pathogenesis of infections related to foreign material, and P. acnes has been shown to form biofilm both in vitro and in vivo. Here, biofilm formation by 93 P. acnes isolates, either from invasive infections (n = 45) or from the skin of healthy people (n = 48), was analysed. The majority of isolates from deep infections produced biofilm in a microtitre model of biofilm formation, whereas the skin isolates were poor biofilm producers (p <0.001 for a difference). This indicates a role for biofilm formation in P. acnes virulence. The type distribution, as determined by sequencing of recA, was similar among isolates isolated from skin and from deep infections, demonstrating that P. acnes isolates with different genetic backgrounds have pathogenic potential. The biofilm formed on plastic and on bone cement was analysed by scanning electron microscopy (EM) and by transmission EM. The biofilm was seen as a 10-mum-thick layer covering the bacteria and was composed of filamentous as well as more amorphous structures. Interestingly, the presence of human plasma in solution or at the plastic surface inhibits biofilm formation, which could explain why P. acnes primarily infect plasma-poor environments of, for example, joint prostheses and cerebrospinal shunts. This work underlines the importance of biofilm formation in P. acnes pathogenesis, and shows that biofilm formation should be considered in the diagnosis and treatment of invasive P. acnes infections.

Compact Zernike phase contrast x-ray microscopy using a single-element optic.

We demonstrate Zernike phase contrast in a compact soft x-ray microscope using a single-element optic. The optic is a combined imaging zone plate and a Zernike phase plate and does not require any additional alignment or components. Contrast is increased and inversed in an image of a test object using the Zernike zone plate. This type of optic may be implemented into any existing x-ray microscope where phase contrast is of interest.

The association between hyperglycemia and fracture risk in middle age. A prospective, population-based study of 22,444 men and 10,902 women.

AIMS: Type 1 diabetes mellitus is associated with increased fracture risk, whereas the risk associated with type 2 diabetes is less obvious. Elevated fasting blood glucose and high 2-h glucose during an oral glucose tolerance test indicate impaired glucose tolerance or diabetes. The associations among fasting blood glucose, 2-h glucose, and the risk of fracture were investigated. METHODS: The Malmö Preventive Project consists of 22,444 men (44+/-6.6 yr) and 10,902 women (50+/-7.4 yr), with a follow-up of 19 yr (+/-3.9) and 15 yr (+/-4.5) for incident fractures. Baseline assessment included multiple examinations and lifestyle information. A logistic regression model was used. Adjustments were made for age, body mass index (BMI), and smoking. RESULTS: Low-energy fractures were recorded in 1246 men and 1236 women. A 2-h glucose measurement between 4.3 and 6.2 mmol/liter in men (second and third quartile), and above 6.5 mmol/liter in women (third and fourth quartile), adjusted for age, BMI, and smoking, was significantly associated with a decreased risk of multiple fractures, in men [odds ratios (ORs) 0.57-0.71] and women (ORs 0.38-0.66). In women, a 2-h glucose measurement above 7.5 mmol/liter was associated with a decreased risk of osteoporotic fractures (OR 0.57, 95% confidence interval 0.44-0.74). CONCLUSIONS: In middle-aged men and women, elevated 2-h glucose levels were associated with decreased risks of multiple and osteoporotic fractures, independent of age, BMI, and smoking. A high 2-h glucose level is characterized by peripheral insulin resistance with a high insulin level. Our findings indirectly suggest a positive effect on bone from hyperglycemia.

Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men.

UNLABELLED: Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes. Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men. INTRODUCTION: The low-density lipoprotein receptor-related protein 5 (LRP5)-Wnt signalling system is of importance for regulating osteoblastic activity, which became clear after findings that inactivating mutations in LRP5 cause osteoporosis. The overall aim of this study was to investigate the association between polymorphisms in the LRP5 gene and bone mineral density (BMD) in three large cohorts of young and elderly men. METHODS: The cohorts used were MrOS Sweden (n = 3014, aged 69-81 years) and MrOs Hong Kong (n = 2000, aged > 65 years) and the Swedish GOOD study (n = 1068, aged 18-20 years). The polymorphisms Val667Met and Ala1330Val were genotyped using a TaqMan assay. RESULTS: When combining the data from the Swedish cohorts in a meta-analysis (n = 3,800), men carrying the 667Met-allele had 3% lower BMD at lumbar spine compared with non-carriers (p < 0.05). The Val667Met SNP was not polymorphic in the Hong Kong population and thus were not included. There were no associations between the Ala1330Val SNP and bone phenotypes in the study populations. No associations between the LRP5 polymorphisms and self-reported fractures were seen in MrOs Sweden. CONCLUSIONS: Results from these three large cohorts indicate that the Val667Met polymorphism but not the Ala1330Val contributes to the observed variability in BMD in the Swedish populations.

High-resolution compact X-ray microscopy.

We demonstrate compact full-field soft X-ray transmission microscopy with sub 60-nm resolution operating at lambda= 2.48 nm. The microscope is based on a 100-Hz regenerative liquid-nitrogen-jet laser-plasma source in combination with a condenser zone plate and a micro-zone plate objective for high-resolution imaging onto a 2048 x 2048 pixel CCD detector. The sample holder is mounted in a helium atmosphere and allows imaging of both dry and wet specimens. The microscope design enables fast sample switching and the sample can be pre-aligned using a visible-light microscope. High-quality images can be acquired with exposure times of less than 5 min. We demonstrate the performance of the microscope using both dry and wet samples.