Effect of high-dose glucocorticoid treatment on human brown adipose tissue activity: a randomised, double-blinded, placebo-controlled cross-over trial in healthy men.

BACKGROUND: Glucocorticoids (GCs) are widely applied anti-inflammatory drugs that are associated with adverse metabolic effects including insulin resistance and weight gain. Previous research indicates that GCs may negatively impact brown adipose tissue (BAT) activity in rodents and humans. METHODS: We performed a randomised, double-blinded cross-over trial in 16 healthy men (clinicaltrials.govNCT03269747). Participants received 40 mg of prednisone per day for one week or placebo. After a washout period of four weeks, participants crossed-over to the other treatment arm. Primary endpoint was the increase in resting energy expenditure (EE) in response to a mild-cold stimulus (cold-induced thermogenesis, CIT). Secondary outcomes comprised mean 18F-FDG uptake into supraclavicular BAT (SUVmean) as determined by FDG-PET/CT, volume of the BAT depot as well as fat content determined by MRI. The plasma metabolome and the transcriptome of supraclavicular BAT and of skeletal muscle biopsies after each treatment period were analysed. FINDINGS: Sixteen participants were recruited to the trial and completed it successfully per protocol. After prednisone treatment resting EE was higher both during warm and cold conditions. However, CIT was similar, 153 kcal/24 h (95% CI 40-266 kcal/24 h) after placebo and 186 kcal/24 h (95% CI 94-277 kcal/24 h, p = 0.38) after prednisone. SUVmean of BAT after cold exposure was not significantly affected by prednisone (3.36 g/ml, 95% CI 2.69-4.02 g/ml, vs 3.07 g/ml, 95% CI 2.52-3.62 g/ml, p = 0.28). Results of plasma metabolomics and BAT transcriptomics corroborated these findings. RNA sequencing of muscle biopsies revealed higher expression of genes involved in calcium cycling. No serious adverse events were reported and adverse events were evenly distributed between the two treatments. INTERPRETATION: Prednisone increased EE in healthy men possibly by altering skeletal muscle calcium cycling. Cold-induced BAT activity was not affected by GC treatment, which indicates that the unfavourable metabolic effects of GCs are independent from thermogenic adipocytes. FUNDING: Grants from Swiss National Science Foundation (PZ00P3_167823), Bangerter-Rhyner Foundation and from Nora van der Meeuwen-Häfliger Foundation to MJB. A fellowship-grant from the Swiss National Science Foundation (SNF211053) to WS. Grants from German Research Foundation (project number: 314061271-TRR 205) and Else Kröner-Fresenius (grant support 2012_A103 and 2015_A228) to MR.

Humor in radiological breast cancer screening: a way of improving patient service?

BACKGROUND: Breast cancer screening is essential in detecting breast tumors, however, the examination is stressful. In this study we analyzed whether humor enhances patient satisfaction. METHODS: In this prospective randomized study 226 patients undergoing routine breast cancer screening at a single center during October 2020 to July 2021 were included. One hundred thirty-two were eligible for the study. Group 1 (66 patients) received an examination with humorous intervention, group 2 (66 patients) had a standard breast examination. In the humor group, the regular business card was replaced by a self-painted, humorous business card, which was handed to the patient at the beginning of the examination. Afterwards, patients were interviewed with a standardized questionnaire. Scores between the two study groups were compared with the Mann-Whitney U test or Fisher's exact test. P-values were adjusted with the Holm's method. Two-sided p-values < 0.05 were considered significant. RESULTS: One hundred thirty-two patients, 131 female and 1 male, (mean age 59 ± 10.6 years) remained in the final study cohort. Patients in the humor group remembered the radiologist's name better (85%/30%, P < .001), appreciated the final discussion with the radiologist more (4.67 ± 0.73-5;[5, 5] vs. 4.24 ± 1.1-5;[4, 5], P = .017), felt the radiologist was more empathetic (4.94 ± 0.24-5;[5, 5] vs.4.59 ± 0.64-5;[4, 5], P < .001), and rated him as a humorous doctor (4.91 ± 0.29-5;[5, 5] vs. 2.26 ± 1.43-1;[1, 4], P < .001). Additionally, patients in the humor group tended to experience less anxiety (p = 0.166) and felt the doctor was more competent (p = 0.094). CONCLUSION: Humor during routine breast examinations may improve patient-radiologist relationship because the radiologist is considered more empathetic and competent, patients recall the radiologist's name more easily, and value the final discussion more. TRIAL REGISTRATION: We have a general approval from our ethics committee because it is a retrospective survey, the patient lists for the doctors were anonymized and it is a qualitative study, since the clinical processes are part of the daily routine examinations and are used independently of the study. The patients have given their consent to this study and survey.

In vivo 3D tomography of the lumbar spine using a twin robotic X-ray system: quantitative and qualitative evaluation of the lumbar neural foramina in supine and upright position.

OBJECTIVES: Supine lumbar spine examinations underestimate body weight effects on neuroforaminal size. Therefore, our purpose was to evaluate size changes of the lumbar neuroforamina using supine and upright 3D tomography and to initially assess image quality compared with computed tomography (CT). METHODS: The lumbar spines were prospectively scanned in 48 patients in upright (3D tomographic twin robotic X-ray) and supine (30 with 3D tomography, 18 with CT) position. Cross-sectional area (CSA), cranio-caudal (CC), and ventro-dorsal (VD) diameters of foramina were measured by two readers and additionally graded in relation to the intervertebral disc height. Visibility of bone/soft tissue structures and image quality were assessed independently on a 5-point Likert scale for the 18 patients scanned with both modalities. Descriptive statistics, Wilcoxon's signed-rank test (p < 0.05), and interreader reliability were calculated. RESULTS: Neuroforaminal size significantly decreased at all levels for both readers from the supine (normal intervertebral disc height; CSA 1.25 ± 0.32 cm2; CC 1.84 ± 0.24 cm2; VD 0.88 ± 0.16 cm2) to upright position (CSA 1.12 ± 0.34 cm2; CC 1.78 ± 0.24 cm2; VD 0.83 ± 0.16 cm2; each p < 0.001). Decrease in intervertebral disc height correlated with decrease in foraminal size (supine: CSA 0.88 ± 0.34 cm2; CC 1.39 ± 0.33 cm2; VD 0.87 ± 0.26 cm2; upright: CSA 0.83 ± 0.37 cm2, p = 0.010; CC 1.32 ± 0.33 cm2, p = 0.015; VD 0.80 ± 0.21 cm2, p = 0.021). Interreader reliability for area was fair to excellent (0.51-0.89) with a wide range for cranio-caudal (0.32-0.74) and ventro-dorsal (0.03-0.70) distances. Image quality was superior for CT compared with that for 3D tomography (p < 0.001; κ, CT = 0.66-0.92/3D tomography = 0.51-1.00). CONCLUSIONS: The size of the lumbar foramina is smaller in the upright weight-bearing position compared with that in the supine position. Image quality, especially nerve root delineation, is inferior using 3D tomography compared to CT. KEY POINTS: • Weight-bearing examination demonstrates a decrease of the neuroforaminal size. • Patients with higher decrease in intervertebral disc showed a narrower foraminal size. • Image quality is superior with CT compared to 3D tomographic twin robotic X-ray at the lumbar spine.

Comparison of 3D X-ray tomography with computed tomography in patients with distal extremity fractures.

OBJECTIVE: To compare fracture detection, image quality, and radiation dose in patients with distal extremity fractures using 3D tomography and computed tomography (CT). MATERIALS AND METHODS: IRB approval was obtained including informed consent for this prospective study from June to December 2016. Patients diagnosed with an acute fracture at CT were consecutively scanned on the same day using 3D tomography. Anatomical location (effected bone and location within the bone) and morphological characteristics of fractures (avulsion, articular involvement, mono- vs. multifragmented, displacement), visibility of bone/soft tissue structures, and image quality were assessed independently by two blinded readers on a 5-point Likert scale. Dose-length-product (DLP; mGy*cm) was compared between both modalities. Descriptive statistics, Wilcoxon signed rank test (P < 0.05), Student's t test (P < 0.05), and Cohen's kappa (κ) for interreader reliability were calculated. RESULTS: In 46 patients (28 males; 18 females; mean age, 53 ± 20 years) with 28 hand/wrist and 18 foot/ankle examinations, 86 out of 92 fractures were diagnosed with 3D tomography compared with CT. No false-positive finding occurred at 3D tomography. The six missed fractures on 3D tomography were five avulsion fractures of the carpals/metacarpals or tarsals/metatarsals, respectively, and one nondisplaced fracture of the capitate. Interreader agreement of anatomical location and morphological characteristics was substantial to almost perfect for upper (κ = 0.80-0.96) and lower (κ = 0.70-0.97) extremity fractures. Visibility of bone and soft tissue structures and image quality were slightly inferior using 3D tomography compared with CT (upper extremity P < 0.001-0.038 and lower extremity P < 0.001-0.035). DLP of a comparable scan coverage was significantly lower for 3D tomography (P < 0.001) for both upper (3D mean, 19.4 ± 5.9 mGy*cm; estimated CT mean, 336.5 ± 52.2 mGy*cm) and lower extremities (3D mean, 24.1 ± 11.1 mGy*cm; estimated CT mean, 182.9 ± 6.5 mGy*cm). Even the highest DLP with 3D tomography was < 30% of the mean estimated CT dose of a comparable area of coverage. CONCLUSION: Fracture assessment of peripheral extremities is reliable utilizing a low-dose 3D tomography X-ray system, with slightly reduced image quality.

Initial Assessment of a Prototype 3D Cone-Beam Computed Tomography System for Imaging of the Lumbar Spine, Evaluating Human Cadaveric Specimens in the Upright Position.

OBJECTIVES: The aims of this study were to assess feasibility, image quality, and radiation dose and to estimate the optimal dose protocol for the lumbar spine of cadaveric specimens with different body mass indices (BMIs) in the upright position using a prototype 3-dimensional cone-beam computed tomography (CT) software implemented on a robotic x-ray system and compare with CT. MATERIALS AND METHODS: The lumbar spine of 5 formalin-fixed human cadaveric specimens (BMI, 22-35 kg/m) was prospectively assessed in the upright position using prototype software for 3-dimensional tomography implemented on a robotic x-ray system. Specimens were scanned with varying kilovolt values (70, 81, 90, 100, 109, 121 kV) and thereafter with 80 kV (BMI ≤30 kg/m) and 121 kV (BMI >30 kg/m) and varying dose levels (DLs; 0.278, 0.435, 0.548, 0.696, 0.87, 1.09). Computed tomography data were acquired with a standard clinical protocol. Two independent readers rated visibility of the cortex, endplates, facet joints, trabeculae, neuroforamina, posterior alignment, and spinal canal as well as nerve roots. Radiation dose was measured with a cylindrical CTDI phantom. Descriptive statistics and analysis of variance were used (P < 0.05). RESULTS: Average intraclass correlation was excellent (0.94). The lowest technically possible kilovolt and the highest technically possible DL yielded the best image quality. In specimens with a BMI of 30 kg/m or less, depiction of all structures was good and comparable to CT, except for nerve roots. For specimens with a BMI greater than 30 kg/m, image quality was limited. CONCLUSIONS: Three-dimensional cone-beam CT of the lumbar spine in cadaveric specimens in the upright position is feasible. An optimal dose protocol was estimated. Depiction of osseous structures is comparable to CT in specimens with BMI of 30 kg/m or less. Image quality is limited for soft tissue structures and specimens with BMI greater than 30 kg/m.

Epineural adipose-derived stem cell injection in a sciatic rodent model.

BACKGROUND: The aim was to evaluate the regenerative effect of epineural injection of rat ASCs (rASCs) in three different settings of acute and chronic compression in a rat sciatic nerve model. METHODS: Acute compression (60 s) with a vessel clamp over a distance of 1 mm (group 1) or 10 mm (group 2), as well as chronic compression with a permanent remaining, nonabsorbable polymeric clip over a distance of 1 mm (group 3) was performed. Depending on the group, either 5 × 106 rASCs or the same volume (25 µl) of culture medium (CM) was injected with a 30G needle in the epineurium at the time of compression. Outcome measures were functional gait evaluations, imaging analysis, histomorphometric analyses, and muscle weight. RESULTS: The rats in group 2 had a better function than those with group 1 at one and especially at 2 weeks. After 4 weeks however, almost all rats were close to a normal function. There was a similar Muscle Weight Ratio (MWR) after 2 weeks in all groups, whereas after 4 weeks, the MWR in group 3 was lower compared with group 1 and 2. Histomorphometric analysis showed a better myelination in group 1 & 2 compared to group 3 after 4 weeks. ASCs have a beneficial effect on myelin thickness (G-Ratio). CONCLUSIONS: We successfully evaluated the regenerative effect of epineural injection of rASCs in three different settings of acute and chronic compression. However, there were no significant differences in outcomes between the ASC-treated groups and control groups.

Initial evaluation of image performance of a 3-D x-ray system: phantom-based comparison of 3-D tomography with conventional computed tomography.

Phantom-based initial performance assessment of a prototype three-dimensional (3-D) x-ray system and comparison of 3-D tomography with computed tomography (CT) were proposed. A 3-D image quality phantom was scanned with a prototype version of 3-D cone-beam CT imaging implemented on a twin robotic x-ray system using three trajectories (163 deg = table, 188 deg = upright, and 200 deg = side), six tube voltages (60, 70, 81, 90, 100, and 121 kV), and four detector doses (0.348, 0.696, 1.740, and [Formula: see text]). CT was obtained with a clinical protocol. Spatial resolution (line pairs/cm) and soft-tissue-contrast resolution were assessed by two independent readers. Radiation dose was assessed. Descriptive and analysis of variance (ANOVA) ([Formula: see text]) were performed. With 3-D tomography, a maximum of 16 lp/cm was visible and best soft-tissue-contrast resolution was 2 mm at 30 Hounsfield units (HU) for 160 projections. With CT, 10 lp/cm was visible and soft-tissue-contrast resolution was 4 mm at 20 HU. The upright trajectory yielded significantly better spatial resolution and soft tissue contrast, and the side trajectory yielded significantly higher soft tissue contrast than the table trajectory ([Formula: see text]). Radiation dose was higher in 3-D tomography (45 to 704 mGycm) than CT (44 mGycm). Three-dimensional tomography renders overall equal or higher spatial resolution and comparable soft tissue contrast to CT for medium- and high-dose protocols in the side and upright trajectories, but with higher radiation doses.

From Bedside to Bench: The Effect of Muscular Denervation on Fat Grafting to the Breast by Comparing Take Rate, Quality, and Longevity.

BACKGROUND: Autologous fat grafting (AFG) to the breast is a frequent procedure in aesthetic and reconstructive surgery. Despite pure volume gain, questions remain regarding the engraftment rate, quality, and longevity. Little is known about the role of recipient tissue or innervation of the grafted area. OBJECTIVES: The goal of this study was to determine the optimal recipient layer and muscular pretreatment of AFG. METHODS: Fat was grafted to the breast, pectoralis muscle, or adjacent subcutaneous tissue of 42 rats. Nerve treatment included excision of a nerve segment, botulinum toxin (BTX) injection, or no treatment. Magnetic resonance imaging (MRI) and histological workup were carried out after 2 and 6 weeks. RESULTS: Six weeks after AFG, the proportion of viable fat cells within the grafted fat stayed high (median, [IQR]: 81% [72% to 85%]). The signs of inflammation decreased over time. Intramuscular grafting with intact nerves had a decreasing effect on the viability of the grafted cells compared with subcutaneous treatment (-10.21%; 95% confidence interval [-21.1 to 0.68]). CONCLUSIONS: If utilized on an intact nerve, intramuscular injection may lead to inferior results. If the nerve was cut or treated with BTX; however, intramuscular injection tends to be superior. These findings may prove interesting for future studies and eventual clinical application.

Characterization of subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis.

Facet joint osteoarthritis may be a cause of low back pain in degenerative spine diseases including lumbar spinal stenosis. Subchondral bone is regarded as a potential therapeutic target for osteoarthritis treatment. The goal of this study was to characterize subchondral bone histopathology in osteoarthritic facet joints from lumbar spinal stenosis patients. Fifteen patients with degenerative spinal stenosis scheduled for transforaminal lumbar interbody fusion surgery were recruited for this study. Osteoarthritis severity was graded on T1- and T2-weighted MRI images using Weishaupt scoring system. Dissected osteoarthritic facet joints were subjected to histological and immunohistochemistry analyses to study relative abundance of osteoblast, osteoclasts, and macrophages using van Gieson's, tartrate-resistant acid phosphatase and CD68-antibody staining, respectively. Presence of nerve fibers was evaluated by PGP9.5-antibody staining. Differential bone histopathology, independent from radiological osteoarthritis grade, was observed in facet joints. Extensive de novo bone formation was found in subchondral bone tissues of eight of fifteen specimens. Regions of bone formation showed high abundance of blood vessels and CD68-positive macrophages, but were devoid of multinucleated osteoclasts. Additional pathological changes in subchondral marrow spaces, including inflammatory infiltration and enhanced osteoclast activity, were characterized by macrophage-rich tissues. PGP9.5-positive nerve fibers were detected near arterioles, but not in regions displaying bone pathology. Individual histopathological parameters did not associate with clinical features or radiological osteoarthritis severity. Subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis is characterized by marrow infiltration by macrophage-rich tissues and enhanced de novo bone formation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1475-1480, 2016.

Endovascular treatment of cervical artery dissection: ten case reports and review of the literature.

PURPOSE: The role of endovascular treatment in cases of cervical artery dissection (CeAD) is debatable. With an increasing number of endovascular therapies such as endovascular recanalization and embolization the number of complications such as iatrogenic dissection is also rising. We report our experience with endovascular stenting in the treatment of patients presenting with CeAD. METHODS: We included all consecutive patients with CeAD (n = 168) treated in our hospital between 2001 and 2010 for our retrospective study. Patients with CeAD were considered eligible for stenting: (1) in iatrogenic dissections and (2) in noniatrogenic dissections if they suffered from recurrent ischemic events despite antithrombotic treatment. RESULTS: During our observation period 10 out of 168 patients presenting with CeAD were selected for stenting. Several types of stents were used. Stenting was technically successful in 8 but unsuccessful in 2 patients with complete arterial occlusion. Stent-related clinically apparent complications occurred in 3 of the 10 patients. All were transient. During a mean follow-up of 47 (±24.8) months none of the patients had new cerebrovascular ischemic events. CONCLUSION: In our patient sample stenting due to dissection is a rare procedure performed in less than 10% of CAD patients. It should be considered as a feasible rescue treatment in cases of impending stroke despite optimal antithrombotic therapy.