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Objectives: To evaluate sensitivity and scores of vascular ultrasound (US) before and after initiating glucocorticoid (GC) treatment in patients with new-onset giant cell arteritis (GCA)., Methods: Treatment-naïve patients with GCA were prospectively included. 18F-FDG PET/CT, US and temporal artery (TA) biopsy were performed in all patients. US was repeated 3 and 10 days after GC commencement. Intima-media thickness and presence of halo signs were assessed. Sonographers were unblinded to clinical data. The OMERACT GCA Ultrasonography score (OGUS) and halo count (HC) were calculated., Results: Forty-eight patients were included. Before GC exposure, US sensitivity was 94% (95% CI: 83-99), 73% (95% CI: 58-85) and 71% (95% CI: 56-83) when assessing all vessels, TAs, and large vessels (LVs), respectively. At day 3 and 10, overall US sensitivity was 92% (95% CI: 78-98, p= 0.16) and 83% (95% CI: 69-92, p= 0.10), respectively. At day 10, TA-US and LV-US sensitivity was 53% (95% CI: 38-68, p< 0.01), and 60% (95% CI: 44-74, p= 0.13), respectively. Median OGUS decreased from 1.06 (IQR 0.83-1.24)-0.95 (IQR 0.78-1.14, p< 0.01), and 0.90 (IQR 0.73-1.01, p< 0.001) after 3 and 10 days, respectively. Median HC decreased from 3 (IQR 2-5)-2 (IQR 1-4, p< 0.01) after 10 days., Conclusion: The vasculitic US findings expressed by OGUS diminish after 3 days of GC treatment. TA-US sensitivity decreased after 10 days, whereas LV-US was less likely to change, highlighting the importance of LV-assessment. Consistent with the EULAR recommendations, these findings encourage prompt US assessment, preferably within 3 days, to ensure an accurate diagnosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Patients with giant cell arteritis (GCA) primarily have their infections managed by primary care providers and hospitalisation is rarely necessary. Existing studies in GCA focus on infection-related hospitalisations only, whereas the use of antibiotic prescriptions is largely unknown. This study aims to examine the one-year overall infection risk among patients with GCA., Methods: This nationwide observational cohort study included patients aged ≥50 years with a first-time GCA diagnosis in the Danish National Patient Registry (1996-2022). Patients with GCA were matched 1:10 by sex and date of birth with general population individuals and followed from date of diagnosis. Overall infections were defined as redeemed antibiotic prescriptions or infection-related hospitalisations. Utilising a pseudo-observation approach, we assessed 1-year cumulative incidence proportions (CIP), risk differences (RD), and relative risks (RR) of infections., Results: The study included 17 773 incident patients with GCA and 177 730 reference individuals. Patients with GCA had a 1-year CIP of 52.4% (95% CI: 51.7-53.2) for overall infections and 17.6% (95% CI: 17.1-18.2) for infection-related hospitalisations. Compared with the reference cohort, patients with GCA had a RR of 1.40 (95% CI: 1.38-1.42) for overall infections and 2.71 (95% CI: 2.61-2.82) for infection-related hospitalisations. Additionally, higher cumulative glucocorticoid doses, advanced age (≥70 years), and higher comorbidity were associated with an increased risk of infections among patients with GCA., Conclusions: The use of antibiotic prescriptions and infection-related hospitalisations in the first year after a GCA diagnosis is high compared with the background population. The cumulative glucocorticoid dose is associated with the infection risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: We evaluated sensitivity to change and discriminative abilities of vascular US scores in disease monitoring in the follow-up of a prospective cohort of new-onset cranial and large-vessel (LV) GCA patients., Methods: Baseline and follow-up (8 weeks, 24 weeks and 15 months) US of temporal arteries (TA), carotid and axillary arteries (LV) included assessment of halo and measurement of the intima media complex (IMC). Max IMC, max halo IMC, sum IMC, sum halo IMC, mean IMC, halo count and the Southend halo score were calculated. The provisional OMERACT US score, OGUS, was obtained, taking the average of temporal arteries and axillary arteries IMCs divided by their normal cut-off values., Results: Baseline US was positive in 44/47 patients (72% TA, 72% LV). Sensitivity to change of all composite US scores containing TAs was evident by week 8 onward. LVs responded poorly and new axillary US lesions emerged in six patients despite clinical remission. The OGUS showed a large magnitude of change and is considered the score least prone to potential bias. All TA-based US scores showed moderate-strong correlation with disease activity markers. OGUS, TA halo count, Southend TA halo score, TA sum IMC and TA mean IMC showed potential to discriminate remission and relapse with area under the curve ≥0.8., Conclusions: The OGUS is suggested as an outcome measurement for the assessment of treatment response in clinical trials. The abilities of US scores to discriminate remission and relapse are encouraging and should be further explored., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are age-associated inflammatory diseases that frequently overlap. Both diseases require long-term treatment with glucocorticoids (GCs), often associated with comorbidities. Previous population-based cohort studies reported that an unhealthier metabolic profile might prevent the development of GCA. Here, we report metabolic features before start of treatment and during treatment in patients with GCA and PMR., Methods: In the Dutch GCA/PMR/SENEX (GPS) cohort, we analysed metabolic features and prevalence of comorbidities (type 2 diabetes, hypercholesterolaemia, hypertension, obesity and cataract) in treatment-naïve patients with GCA (n=50) and PMR (n=42), and compared those with the population-based Lifelines cohort (n=91). To compare our findings in the GPS cohort, we included data from patients with GCA (n=52) and PMR (n=25) from the Aarhus cohort. Laboratory measurements, comorbidities and GC use were recorded for up to 5 years in the GPS cohort., Results: Glycated haemoglobin levels tended to be higher in treatment-naïve patients with GCA, whereas high-density lipoprotein, low-density lipoprotein and cholesterol levels were lower compared with the Lifelines population. Data from the Aarhus cohort were aligned with the findings obtained in the GPS cohort. Presence of comorbidities at baseline did not predict long-term GC requirement. The incidence of diabetes, obesity and cataract among patients with GCA increased upon initiation of GC treatment., Conclusion: Data from the GCA and PMR cohorts imply a metabolic dysregulation in treatment-naïve patients with GCA, but not in patients with PMR. Treatment with GCs led to the rise of comorbidities and an unhealthier metabolic profile, stressing the need for prednisone-sparing targeted treatment in these vulnerable patients., Competing Interests: Competing interests: EB, as an employee of the UMCG, received speaker/consulting fees from Roche that were paid to the UMCG. The other authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate the risk of ocular manifestations leading to hospital contacts among patients with giant cell arteritis (GCA)., Methods: A Danish, nationwide, register-based cohort study including 14,574 GCA patients diagnosed 1996-2018 and 145,740 general population referents, matched on sex and date of birth. Cumulative incidence proportions (CIPs) and relative risks (RRs) of ocular manifestations with 95% confidence intervals (CIs) were calculated using a pseudo-observation approach., Results: A total of 1026/14,574 (7.0%) GCA patients were registered with ocular manifestations within ±1 year of the diagnosis; 392/1026 (38%) being before and 634/1026 (62%) after the GCA diagnosis, and 744/1026 (73%) were registered within ±1 month of the diagnosis. The diagnoses were 336/1026 (33%) retinal vascular occlusions, 300/1026 (29%) disorders of the optic nerve, 177/1026 (17%) visual impairment, 90/1026 (9%) diplopia, and 123/1026 (12%) amaurosis fugax. The CIP for ocular manifestations among GCA patients after 3, 6, and 12 months following the diagnosis were 4.0% (95% CI: 3.6-4.3), 4.2% (95% CI: 3.9-4.6), and 4.6% (95% CI: 4.2-4.9). The 1-year RR of ocular manifestations among GCA patients was 28.0 (95% CI: 24.0-32.7), with age above 70 years, male sex, and a positive temporal artery biopsy being risk factors. Treatment with low-dose aspirin was not associated with a reduced 1-year RR of incident ocular manifestations., Conclusions: In GCA, most cases of ocular manifestations leading to hospital contacts occur close to the time of diagnosis, with over one-third of cases occurring before the diagnosis, emphasizing the need for early recognition and treatment., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the risk of aortic aneurysms (AA), aortic dissections (AD) and peripheral arterial disease (PAD) among patients with GCA., Methods: In this nationwide, population-based cohort study using Danish national health registries, we identified all incident GCA patients ≥50 years between 1996 and 2018 who redeemed three or more prescriptions for prednisolone. Index date was the date of redeeming the third prednisolone prescription. Case definition robustness was checked through sensitivity analysis. We included general population referents matched 1:10 by age, sex and calendar time. Using a pseudo-observation approach, we calculated 5-, 10- and 15-year cumulative incidence proportions (CIP) and relative risks (RR) of AA, AD and PAD with death as a competing risk., Results: We included 9908 GCA patients and 98 204 referents. The 15-year CIP of thoracic AA, abdominal AA, AD and PAD in the GCA cohort were 1.9% (95% CI 1.5, 2.2), 1.8% (1.4-2.2), 1.0% (0.7-1.2) and 4.8% (4.2-5.3). Compared with the referents, the 15-year RR were 11.2 (7.41-16.9) for thoracic AA, 6.86 (4.13-11.4) for AD, 1.04 (0.83-1.32) for abdominal AA and 1.53 (1.35-1.74) for PAD. Among GCA patients, female sex, age below 70 years and positive temporal artery findings were risk factors for developing thoracic AA. The median time to thoracic AA was 7.5 years (interquartile range 4.4-11.2) with a number needed to be screened of 250 (167-333), 91 (71-111) and 53 (45-67) after 5, 10 and 15 years., Conclusion: Patients with GCA have a markedly increased risk of developing thoracic AA and AD, but no increased risk of abdominal AA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Diagnosing patients with giant cell arteritis (GCA) remains difficult. Due to its non-specific symptoms, it is challenging to identify GCA in patients presenting with symptoms of polymyalgia rheumatica (PMR), which is a more common disease. Also, commonly used acute-phase markers CRP and ESR fail to discriminate GCA patients from PMR and (infectious) mimicry patients. Therefore, we investigated biomarkers reflecting vessel wall inflammation for their utility in the accurate diagnosis of GCA in two international cohorts., Methods: Treatment-naïve GCA patients participated in the Aarhus AGP cohort (N = 52) and the Groningen GPS cohort (N = 48). The AGP and GPS biomarker levels and symptoms were compared to patients presenting phenotypically as isolated PMR, infectious mimicry controls and healthy controls (HCs). Serum/plasma levels of 12 biomarkers were measured by ELISA or Luminex., Results: In both the AGP and the GPS cohort, we found that weight loss, elevated erythrocyte sedimentation rate (ESR) and higher angiopoietin-2/-1 ratios but lower matrix metalloproteinase (MMP)-3 levels identify concomitant GCA in PMR patients. In addition, we confirmed that elevated platelet counts are characteristic of GCA but not of GCA mimicry controls and that low MMP-3 and proteinase 3 (PR3) levels may help to discriminate GCA from infections., Conclusion: This study, performed in two independent international cohorts, consistently shows the potential of angiopoietin-2/-1 ratios and MMP-3 levels to identify GCA in patients presenting with PMR. These biomarkers may be used to select which PMR patients require further diagnostic workup. Platelet counts may be used to discriminate GCA from GCA look-alike patients., (© 2022. The Author(s).)

Objectives: To investigate whether GCA is associated with increased all-cause and cause-specific mortality., Methods: A nationwide, population-based cohort study in Denmark using medical and administrative registries. GCA cases were defined as patients aged ≥50 years from 1996-2018 with a first-time discharge diagnosis of GCA and ≥3 prescriptions for prednisolone within 6 months following diagnosis. Each GCA patient was matched based on age, sex and calendar time to 10 persons without a history of GCA. Index date was the date for the third prednisolone prescription. We used a pseudo-observation approach to calculate all-cause and cause-specific mortality, adjusted risk differences (RDs) and relative risks (RRs)., Results: We included 9908 GCA patients and 98 204 persons from the general population. The median time for GCA patients to redeem the third prednisolone prescription was 74 days [interquartile range (IQR: 49-106)]. Among GCA patients, the overall mortality was 6.4% (95% CI: 5.9, 6.9) 1 year after index date and 45% (95% CI: 44, 47) after 10 years. Compared with the reference cohort, adjusted RDs and RRs of deaths in the GCA cohort were 2.2% (95% CI: 1.7, 2.7) and 1.49 (95% CI: 1.36, 1.64) after 1 year, and 2.1% (95% CI: 1.0, 3.3) and 1.03 (95% CI: 1.00, 1.05) 10 years after index date. GCA patients had a higher risk of death due to infectious, endocrine, cardiovascular and gastrointestinal diseases., Conclusions: GCA is associated with increased all-cause mortality, particularly within the first year following the diagnosis. Cause-specific mortality indicates that mortality in GCA may in part be due to glucocorticoid-related complications., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: The study investigated the development over time of the incidence, diagnostic imaging, and treatment of giant cell arteritis (GCA)., Method: This nationwide, population-based cohort study was conducted in Denmark using medical and administrative registries. Incident GCA cases from 1996-2018 were defined as patients aged ≥50 years registered with a first-time GCA diagnosis and ≥3 prescriptions for glucocorticoids (GCs) within 6 months after diagnosis. We determined incidence rates of GCA, the proportion of patients still receiving GCs >2 years after diagnosis, the proportion of patients receiving temporal artery biopsies (TAB) and diagnostic imaging including ultrasound, positron emission tomography, magnetic resonance, and/or computed tomography angiography at the time of diagnosis., Results: We identified 9908 incident GCA cases. The incidence rates of GCA remained stable at 19-25 per 100,000 people aged >50 years from 1996-2018. The proportion of GCA patients receiving a TAB remained constant until 2016, after which it promptly declined from 70-80% to 29-39%. In contrast, the proportion of patients receiving diagnostic imaging increased from 2% to 66% from 2000-2018. The proportion of GCA patients remaining in GC treatment has steadily decreased from 1996-2016, but remains high at 64%, 40%, and 34% after 2, 5, and 10 years following the diagnosis, respectively. The cumulative GC dose has remained relatively stable., Conclusion: Incidence rates of GCA have remained stable since 1996 despite increasing use of diagnostic imaging. There is a clear discrepancy between current international GCA treatment guidelines and the clinical practice up to 2018., Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interest and the views expressed are those of the authors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: Bone erosions are the hallmark of rheumatoid arthritis (RA). High-resolution peripheral quantitative computed tomography (HR-pQCT) enables 3-dimensional visualization of arthritic bone erosions at a high resolution. However, the degree of erosive disease could influence the reliability of HR-pQCT evaluation. We aim to assess the intra- and inter-reader variability of identification of erosions in the metacarpophalangeal (MCP) joints using HR-pQCT in healthy controls and patients with RA, stratified according to van der Heijde-modified Sharp Score (HSS) of radiographic erosions., Method: We analyzed HR-pQCT images from 78 patients with RA and 25 healthy controls. Patients were allocated to one of three groups of mild, moderate or severe disease according to HSS of MCP joints 2 and 3. Total HR-pQCT scans were analyzed twice in random order by three experienced readers, blinded to group distribution. The number of cortical interruptions and their classification as either erosions or cysts according to predefined criteria were recorded. Intraclass correlation coefficients (ICC) for cortical interruptions, erosions and cysts were calculated for each group using a 2-way random-effects model for inter-reader ICC and a 2-way mixed-effects model for intra-reader ICC., Results: The intra- and inter-reader ICC were good to moderate for cortical interruptions and moderate for erosions throughout disease severity groups. The ICCs for the identification of cysts decreased with increasing degree of erosive disease., Conclusion: The detection of cortical interruptions is only minimally affected by the degree of erosive damage, whereas the distinction between erosions and cysts is more complex in patients with extensive erosive disease., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: The diagnostic accuracy of axillary artery US in the diagnosis of large-vessel (LV)-GCA using 18F-fluorodeoxyglucose (FDG) PET/CT as reference standard was prospectively evaluated in GCA-suspected patients. As an exploratory analysis, the diagnostic accuracy of cranial artery FDG PET/CT was evaluated., Methods: Briefly, the inclusion criteria were age ≥50 years, raised inflammatory markers and potential GCA symptoms. Patients in immunosuppressive therapy or with a previous diagnosis of GCA or PMR were excluded. Examinations were performed pre-treatment. LV-GCA reference diagnosis was a clinical diagnosis of GCA and PET-proven LV inflammation. GCA patients fulfilling ACR criteria were considered as cranial-GCA (c-GCA). Patients without GCA were considered controls. Receiver operating characteristic curve analysis of the US-measured axillary intima-media thickness was performed. FDG uptake in temporal, maxillary and vertebral arteries was also assessed., Results: Forty-six patients were diagnosed with LV-GCA, 10 with isolated c-GCA, and in 34 patients GCA was dismissed. Axillary US yielded a sensitivity of 76% and a specificity of 100% for LV-GCA. An axillary intima-media thickness cut-off of 1.0 mm yielded a sensitivity of 74% and a specificity of 92%. Adding LV US to temporal assessment increased sensitivity from 71% to 97% (all GCA patients). Cranial artery PET showed a diagnostic sensitivity of 78% and specificity of 100% for c-GCA., Conclusion: Axillary artery US shows high accuracy for the LV-GCA diagnosis. Building upon the recent EULAR recommendations, we propose a diagnostic algorithm with US as the first-line confirmatory test, not only in c-GCA-suspected patients, but in all patients suspected of GCA., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To investigate the positive predictive value (PPV) of the giant cell arteritis (GCA) diagnosis in the Danish National Patient Registry (DNPR)., Patients and Methods: A total of 293 patients aged ≥50 years with a first-time diagnosis of GCA in the DNPR between January 2012 and December 2017 were included. Patients were sampled from two secondary and one tertiary care hospitals in the Central Region Denmark. Two independent investigators (PH & PT) reviewed all medical files, including medical records, treatment, biochemistry, histopathology and imaging, and either confirmed or dismissed the diagnosis of GCA. In case of disagreement, a consensus agreement was reached. Sub-analyses including number of redeemed prescriptions performed temporal artery biopsies (TABs), and number of GCA-related hospital contacts were performed., Results: We confirmed the diagnosis of GCA in 183/293 patients resulting in a PPV of 62% (95% CI: 57-68). In patients with ≥3 redeemed prescriptions of glucocorticoids (GCs), we confirmed the diagnosis in 166/214 resulting in a PPV of 78% (95% CI: 71-83). In patients with ≥3 redeemed prescriptions of GCs and ≥3 GCA-related hospital contacts, we confirmed the diagnosis in 88/95 resulting in a PPV of 93% (95% CI: 85-96); however, this only included 88/183 confirmed GCA patients., Conclusion: This is the first study to validate the diagnostic code of GCA in the DNPR. The overall PPV of GCA in the DNPR was 62%. Requiring redeemed prescriptions of GCs and/or GCA-related hospital contacts increase the PPV, but also excludes a significant number of GCA patients., Competing Interests: The abstract of this paper was presented at the European Congress of Rheumatology 2019 as a poster presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in Annals of the Rheumatic Diseases (ARD): http://dx.doi.org/10.1136/annrheumdis-2019-eular.6852. Berit Dalsgaard Nielsen reports personal and speaker’s bureau fees from Roche and consulting fee from Sanofi, outside the submitted work. Ellen-Margrethe Hauge reports grants from Aarhus University and Danish Rheumatism Association, during the conduct of the study; grants from Danish Regions Medicine Grants, Novo Nordic Foundation, Roche, and Novartis, and travel expenses from Sobi, outside the submitted work. The authors report no other possible conflicts of interest in this work., (© 2020 Hjort et al.)

Objectives: To investigate the in-situ expression of acetylcholinesterase (AChE) in the inflamed vessel wall of patients with biopsy-positive giant cell arteritis (GCA) as compared to biopsy-negative non-GCA patients, and to evaluate the in-vivo expression of AChE in patients with large-vessel GCA (LVGCA) by 11C-donepezil (AChE inhibitor) positron emission tomography/computed tomography (PET/CT)., Methods: Twenty-four biopsy-positive GCA and 44 biopsy-negative non-GCA patients were included for AChE histology. Immunohistochemical methods were used to determine the AChE expression. The histological inflammation and the AChE expression were assessed by an experienced pathologist on a 3-point scale. Two patients with newly diagnosed 18F-fluorodeoxyglucose (18F-FDG) PET/CT verified LVGCA were included for 11C-donepezil PET/CT. PET images were assessed by an experienced nuclear medicine physician., Results: AChE was expressed in all 24 positive temporal artery biopsies, 10/24 showed high AChE expression (grade 2) and 14/24 showed moderate AChE expression (grade 1). No AChE expression was observed outside the media smooth muscle cells (grade 0) in any of the biopsy-negative non-GCA patients. The AChE expression was in 86% agreement with the histological inflammation. The AChE expression was not associated with any clinical or biochemical findings. In both LV-GCA patients, PET/CT revealed extensive vascular FDG uptake but no 11C-donepezil uptake., Conclusions: AChE is highly expressed in the inflamed vessel wall of patients with GCA. Although, 11C-donepezil PET/CT showed no vascular uptake in the FDG PET/CT verified LV-GCA patients, histological findings raise the possibility that AChE can be used in the development of new diagnostic and disease monitoring tools for GCA.

Purpose: To estimate the diagnostic accuracy of conventional 18F-FDG PET/CT of cranial arteries in the diagnosis of giant cell arteritis (GCA)., Methods: The study was a retrospective case-control study. The reference diagnosis was fulfillment of the 1990 ACR criteria for GCA. All patients had new-onset GCA. Conventional 18F-FDG PET/CT was performed before glucocorticoid treatment. Controls were age- and sex-matched patients with a previous history of malignant melanoma (MM) undergoing surveillance PET/CT >6 months after MM resection. PET images were evenly cropped to include only head and neck and were assessed in random order by four nuclear medicine physicians blinded to reference diagnosis. Temporal (TA), maxillary (MA) and vertebral (VA) arteries were visually rated for 18F-FDG uptake. Interreader agreement was evaluated by Fleiss kappa., Results: A total of 44 patients and 44 controls were identified. In both groups, the mean age was 69 years (p = 0.45) and 25/44 were women. 35/41 GCA patients were temporal artery biopsy positive (TAB). Considering only FDG uptake in TA and/or MA, diagnostic sensitivity and specificity was 64 and 100%. Including VA, sensitivity increased to 82% and specificity remained 100%. Interreader agreement was 91% and Fleiss kappa 0.82 for the PET diagnosis based on the cranial arteries., Conclusion: Conventional 18F-FDG PET/CT is an accurate and reliable tool to diagnose cranial arteritis in glucocorticoid-naïve GCA patients. The high diagnostic specificity suggests that TAB can be omitted in patients with 18F-FDG uptake in cranial arteries. 18F-FDG PET/CT performed in patients with suspected vasculitis should always include the head and neck.

Purpose: To evaluate the in-treatment diagnostic accuracy of FDG PET/CT in large-vessel giant cell arteritis (LV-GCA) by serial scans before and after a short course of high-dose glucocorticoid treatment., Methods: Twenty-four glucocorticoid-naïve patients with new-onset PET/CT verified LV-GCA (pre-treatment baseline PET) were prospectively included. Excluded were patients with a previous history of GCA or polymyalgia rheumatica, LV-GCA-mimicking conditions and patients on immunosuppressive therapy. All patients were treated with 60 mg of oral prednisolone daily and assigned for in-treatment FDG PET/CT after either 3 (PET3) or 10 days (PET10). Two experienced nuclear medicine physicians, blinded to patients' clinical data, reviewed the FDG PET/CT images. A visual semi-quantitative approach was used. Segmental and homogenous FDG uptake in the wall of the aorta and/or supra-aortic branches with higher uptake intensity than liver was considered consistent with vasculitis. Inter-reader reliability was evaluated., Results: Although glucocorticoid treatment attenuated FDG uptake in large vessels, LV-GCA was accurately diagnosed in 10/10 patients after 3 days of treatment, but only in 5/14 patients after 10 days of treatment (p < 0.001). Interrater reliability was substantial (agreement 87%, Cohen's weighted kappa 0.70). No correlation between CRP and FDG uptake was found., Conclusions: Within 3 days of high-dose glucocorticoid treatment, FDG PET/CT can diagnose LV-GCA with high sensitivity. This window of opportunity ensures that prompt glucocorticoid treatment can be initiated to avoid debilitating GCA complications with a limited effect on diagnostic accuracy. After 10 days of treatment, FDG PET/CT sensitivity decreases significantly.

Background: Hospital at home (HaH) is an alternative to acute admission for elderly patients. It is unclear if should be cared for a primarily by a hospital intern specialist or by the patient's own general practitioner (GP). The study assessed whether a GP based model was more effective than a hospital specialist based model at reducing number of hospital admissions without affecting the patient's recovery or number of deaths., Methods: Pragmatic, randomised, open-labelled multicentre parallel group trial with two arms in four municipalities, four emergency departments and 150 GPs in Southern Denmark, including + 65 years old patients with an acute medical condition that required acute hospital in-patient care. The patients were randomly assigned to hospital specialist based model or GP model of HaH care. Five physical and cognitive performance tests were performed at inclusion and after 7 days. Primary outcome was number of hospital admissions within 7 days. Secondary outcomes were number of admissions within 14, 21 and 30 days, deaths within 30 and 90 days and changes in performance tests., Results: Sixty seven patients were enrolled in the GP model and 64 in the hospital specialist model. 45% in the hospital specialist arm versus 24% in the GP arm were admitted within 7 days (effect size 2.7, 95% CI 1.3-5.8; p = 0.01) and this remained significant within 30 days. No differences were found in death or changes in performance tests from day 0-7 days between the two groups., Conclusions: The GP based HaH model was more effective than the hospital specialist model in avoiding hospital admissions within 7 days among elderly patients with an acute medical condition with no differences in mental or physical recovery rates or deaths between the two models., Registration: No. NCT02422849 Registered 27 March 2015. Retrospectively registered.

Background/aims: Epidermal thickness is frequently measured by light microscopy. The preservation and staining methods may alter the proportions of the specimens and thereby influence the measurements. The aim of the present study was to describe: 1) a standardized light microscopic method to quantify the thicknesses of the stratum corneum and the cellular epidermal layers, 2) the variations according to preparation and staining techniques, and 3) the observer variability., Methods: One hundred and sixty skin biopsies from 67 human volunteers were included. The cellular epidermis and the stratum corneum were estimated in sections preserved by freezing and subsequent preparation with cryostat or formalin-paraffin techniques. The slides were stained with haematoxylin-eosin or er-ythrocin, and thicknesses of the stratum corneum and the cellular epidermis were measured by a calibrated ruler and an ocular grid, respectively., Results: The formalin fixation gave slightly higher values for the cellular epidermis than the cryostat technique. In comparison to erythrocin staining, haematoxylin-eosin gave a significantly thinner stratum corneum. No significant inter- or intra-observer variation was found for the thickness of the stratum corneum assessed twice by two experienced observers. However, the two observers differed slightly from each other on the thickness of the cellular epidermis., Conclusion: It is found that thickness measurements of the stratum corneum and the cellular epidermis are reliably performed on cryostatic cut sections stained with haematoxylin-eosin.

A concept for the computer-assisted visualization of tubular organs is presented. Unmarked histological zinc-stained serial sections from the epididymis of the Wistar rat were aligned to demonstrate the concept. Virtual images were made through the aligned sections and served as controls for the alignment process. Animation of the serial sections and the virtual images revealed new information about the structure of the organ under investigation. The analysis was used to upgrade the anatomical knowledge of rat epididymis by describing how the epididymal duct runs through the structure. The proximal parts of the epididymis contain large communicating septa of connective tissue dividing the caput and the upper part of the corpus epididymidis into segments. The tortuousness was high in the caput with many turns within a small area of the epididymis, whereas longer loops were found in the lower part of the corpus and cauda epididymidis. The tube of the vas deferens was found to become an integrated part of the ductal system in the cauda epididymidis, although it was histologically easy to distinguish from the epididymal duct. The total number of cross-sections of the ductus epididymidis in the 2254, 15-microm-thick, tissue sections analysed was 104700, giving a minimum length of the ductal system of 1.5 m.

Background and Objective: To clarify whether epidermal thickness is of importance to the purpuric reaction from treatment with the pulsed dye laser (PDL)., Study Design/materials and Methods: Fifteen fairly pigmented volunteers were laser treated in two test regions of varying epidermal thicknesses: normal buttock skin and ultraviolet B (UVB)-exposed buttock skin. Laser treatments were performed with the flashlamp-pumped PDL (585 nm). Fluences ranged from 3-6.5 J/cm2, spot size was 7 mm, and each volunteer received at least six fluences in each treatment region. Assessment of the response was based on clinical evaluation (threshold dose to purpura 10 minutes and 1 day after treatment) and skin reflectance-evaluated redness (1 and 6 days, 2 and 6 weeks after treatment)., Results: The total epidermal thickness differed between the unexposed buttock skin (median, 72.7 microm) and the UVB-exposed buttock skin (87.2 microm) (P < 0.01). There was no correlation between the epidermal thickness and the threshold dose to induce purpura 10 minutes and 1 day after laser exposure. Skin reflectance revealed no correlation between the epidermal thickness and the skin reflectance evaluated redness on 1, 6 days, and 2 weeks postoperatively. A dose-response relation was seen within the two test regions; 6 weeks after laser exposure, there was no remaining laser-induced skin redness., Conclusion: The epidermal thickness is unimportant to the purpuric reaction after PDL treatment.

Urocanic acid (UCA), present in the stratum corneum as trans-UCA, absorbs ultraviolet (UV) radiation and isomerizes to cis-UCA. Cis-UCA has been demonstrated to initiate suppression of selected immune responses in several experimental systems. Topical application of UCA-containing products reduces UV-induced erythema, but a role for endogenous UCA in photoprotection has not been reported. In this study the relationship between UCA isomers, pigmentation, minimal erythema dose (MED), and stratum corneum thickness was investigated. Pigmentation, concentration of total UCA, and the percentage present as the cis-isomer was measured in 36 healthy subjects, skin type I-IV, at six UV-exposed and nonexposed body sites: forehead, chest, back, outer upper arm, inner upper arm, and buttock. The MED was determined by phototesting on buttock skin, and a punch biopsy for measurement of stratum corneum thickness was taken adjacent to the site of the phototest. The percentage of cis-UCA was significantly higher in UV-exposed than on nonexposed areas. A small intraindividual variation in total UCA was found, being high on the buttock and the arm, lowest on the forehead. The subject to subject variation of total UCA was considerable at all body sites. No correlation was found between total UCA and MED, skin type, pigmentation, or stratum corneum thickness.

The important factors for UV sensitivity in humans are considered to be the skin pigmentation and the epidermal thickness. In this study on 73 Caucasians (age 20-85 years), we investigated in UV unexposed buttock skin the relationship between the UV sensitivity and constitutive skin pigmentation and thickness of the stratum corneum and the cellular part of the epidermis, in 34 normal people and in 39 skin cancer patients (20) patients with cutaneous malignant melanoma and 19 patients with basal cell carcinoma of the skin). Skin pigmentation was measured by skin reflectance spectroscopy, and UV sensitivity by phototest with a solar simulator. Thicknesses of the stratum corneum and the cellular part of the epidermis were determined by light microscopic evaluation of skin biopsies from the phototest areas. We found that epidermal thickness was independent of skin type and was not correlated to constitutive skin pigmentation. Thickness of the stratum corneum was statistically not different in normal persons and in skin cancer patients (P = 0.41) and was independent of gender (P = 0.61) and age (P = 0.56), while thickness of the cellular epidermis decreased with age (P < 0.01). Stratum corneum thickness was found to be of minor importance for the constitutive UV sensitivity (accounting for on average 11% of the total photoprotection), which was mainly determined by the constitutive skin pigmentation (goodness-of-fit for correlation r = 0.83). A theoretical model for the relationship of UV dose to induction of clinical erythema grade and skin pigmentation and thickness of the stratum corneum was developed. Objective measurements of skin pigmentation in UV unexposed skin by skin reflectance spectroscopy in Caucasians, normal people and people with cutaneous malignant melanoma and basal cell carcinoma of the skin predicts the constitutive UV sensitivity with a high degree of precision.

Background and Objective: The intention of the present study was to clarify whether UV-exposure prior to laser treatment of albino mouse skin may influence laser-induced side effects and if a possible influence may be explained by epidermal thickening., Study Design/materials and Methods: Albino, hairless mice were irradiated 0, 8, and 22 consecutive times with simulated solar UV (1.4 J/cm2 per treatment). Subsequently, two areas on the back of the mice (1.26 cm2 each) were treated with a copper vapor laser that was connected to a Hexascan. The beam diameter was 1 mm, pulse duration 200 msec, and intensities 0.6 W, 0.8 W, and 1.0 W. Laser-induced wounds, scars, and histologically evaluated fibrosis were evaluated., Results: We found that mice irradiated with UV before laser treatment developed smaller wounds, smaller texture change areas, and less fibrosis as compared with nonirradiated control groups, and significant, negative correlations were demonstrated between epidermal thicknesses (stratum corneum, the cellular part of epidermis, and the entire epidermis) and laser-induced skin reactions. A dose response was obtained between laser intensities and laser-induced skin reactions, which tended to be more severe in the cranial back location as compared with the caudal back location. Epidermal layers increased significantly after eight consecutive times of UV irradiation and increased to a steady level after 22 times of irradiation., Conclusion: We conclude that UV exposure prior to laser treatment of albino mice reduced laser-induced side-effects, which could be explained by increased epidermal thickening. Variations in epidermal thickness might thus contribute to variations in clinical response to dermatological laser treatment with the copper vapor laser.

A teaching model, specially constructed for the purpose of training senior dental students in the use of surgical instruments, is described. The advantages of this model are inexpensiveness and reproducible simulated surgical situations securing a uniform teaching objective.

We have earlier presented evidence that adenosine may create vasodilation via presynaptic inhibition of sympathetic nerve fibers to muscle arterioles. In the present study the effect of selective adenosine antagonists on arteriolar diameter was investigated, using an autoperfused frog muscle (m. cutaneus pectoris). During application of the antagonists arteriolar diameter reductions were observed in the transparent, transilluminated muscle. The sulfonylated xanthine derivatives 8-(p-sulfo)phenyltheophylline (8-PS phi T), 8-(m-sulfo)phenyltheophylline (8-MS phi T) and 1,3-dipropyl-8-p-sulfonphenylxanthine (DPSPX) are all considered to be selective competitive adenosine antagonists without unspecific intracellular effects. Topical application of each of these compouns on resting muscle resulted in a dose-dependent arteriolar contraction. The constriction was immediately reversed by addition of the adrenergic alpha-receptor blocker phentolamine (7.1 x 10(-5) M), indicating that the arteriolar contraction was due to activation of postjunctional alpha-receptors present in vascular smooth muscle. Also, the A1-selective adenosine agonist (-)-N6-(R-phenylisopropyl)-adenosine (R-PIA) eliminated the arteriolar constriction. These effects suggest, that the xanthine derivatives release the sympathetic nerve terminals from inhibition by endogenous adenosine. When nerve fibers were blocked by tetrodotoxin (TTX), 3 x 10(-6)M or when the frogs had been chemically sympathectomized with 6-hydroxydopamine (6-OHDA), no significant arteriolar contraction was observed during adenosine antagonist administration, complying with the view that in resting muscle endogenous adenosine acts presynaptically to inhibit sympathetic nerve terminals. These results suggest that presynaptic adenosine effects are not only involved in regulation of frog skeletal muscle blood flow in response to activity, but also play a role in the control of arteriolar tone in resting muscle.

In a double-blind study dental cones containing the antifibrinolytically active propylic ester of p-hydroxybenzoic acid (PEPH), sulfanilamide and sulfathiazol or placebo were placed in dental sockets following removal of impacted mandibular third molars on 95 consecutive patients, 50 women and 45 men. The duration of the operation, the type of surgeon, preoperative symptoms and the use of peroral anticonception were recorded. The patients were asked to return to the clinic on the seventh postoperative day, and it was then noted whether the healing was disturbed by Alveolitis Sicca Dolorosa (ASD) or not. Statistical analysis showed a significantly prophylactic effect of PEPH against ASD. The prophylactic effect was most pronounced in the group of male patients without preoperative symptoms and in the group of patients operated by dental students. It could not be demonstrated that the sulfa drugs in the cones were of any benefit to the healing of the socket.