Follow-up ultrasound examination in patients with newly diagnosed giant cell arteritis.

OBJECTIVES: Ultrasound is a standard tool to diagnose giant cell arteritis (GCA). Until now, only few studies investigated the role of ultrasound in the follow-up of GCA. The aim of this study was to assess the changes in the intima media thickness (IMT), total number of affected arteries and provisional OMERACT GCA ultrasonography score (OGUS) in a 12-months follow-up period. METHODS: Patients with newly diagnosed GCA were prospectively enrolled. Ultrasound examinations of facial, temporal, carotid, vertebral and axillary arteries were performed at baseline, after three, six, nine and 12 months. Changes of IMT, total number of affected arteries, and OGUS values were evaluated. In a subgroup of patients, exams were conducted weekly in the first 100 days. RESULTS: Fifty patients were enrolled, 36 completed the follow-up. Significant reductions in IMT, total number of affected arteries and OGUS were observed. Eighteen patients presented to weekly exams. The mean IMT of the axillary artery normalized after seven days, while IMT of the common temporal artery normalized after 50 days. The mean OGUS values were below one after six months. There were no differences in IMT changes between GCA patients with or without PMR or between those with and without additional tocilizumab treatment. A relapse occurred in 4 patients. At relapse, mean IMT and OGUS were higher as compared with the preceding assessment. No predictive values indicating a relapse were identified. CONCLUSION: Vascular ultrasound is sensitive to change in GCA. The presence of PMR or treatment with tocilizumab did not affect IMT decrease.

Transorbital Ultrasound in the Diagnosis of Giant Cell Arteritis.

OBJECTIVES: The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. METHODS: Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. RESULTS: We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: ß=-1.91; p=0.029; EDV: ß=-0.57; p=0.032) and significantly elevated OND (ß = 0.79; p=0.003) compared with controls. RI did not significantly differ from controls (ß=-0.06, p=0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (p=0.048) and EDV (p=0.040). No association was found with RI (p=0.249), while a positive significant association was noted with OND (p<0.001). CONCLUSIONS: This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.

Construction of the Bicyclic Carbon Framework of Euphosalicin.

Our studies toward the total synthesis of the natural product euphosalicin (1) are presented. Different approaches targeting key intermediates are described, the synthesis of which includes findings on asymmetric dihydroxylations and ring-closing enyne metatheses (RCEYM). Their connection allowed the isolation of highly advanced precursors for studies on macrocyclizations. Our efforts culminated in the preparation of the unique C11/C12 (Z) isomer of the C13 nor methyl skeleton of euphosalicin (1).

Assessing sleep-related breathing disorders among newly diagnosed rheumatoid and psoriatic arthritis patients: a cross-sectional study.

OBJECTIVES: This cross-sectional study aimed to determine the prevalence and risk factors for sleep-related breathing disorders (SRBD) in newly diagnosed, untreated rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients, and to develop a screening algorithm for early detection. METHODS: We evaluated newly diagnosed RA or PsA patients using the Epworth Sleepiness Scale (ESS) questionnaire, cardiorespiratory polygraphy (RPG), and clinical and laboratory assessments. Sleep apnea syndrome (SAS) was diagnosed based on pathological RPG findings excessive daytime sleepiness, defined as ESS score above 10. RESULTS: The study included 39 patients (22 RA, 17 PsA) and 23 controls. In RPG, SRBD was identified in 38.5% of arthritis patients compared to 39.1% of controls (p = 1.00), with male gender (p = .004) and age (p < .001) identified as risk factors. Excessive daytime sleepiness was noted in 36.4% of RA patients, 17.6% of PsA patients, and 21.7% of controls. Of the 24 patients diagnosed with SRBD, 41.6% met the criteria for SAS. SAS prevalence was 31.8% among RA patients, 0% in PsA patients, and 13% in controls. A significant association was observed between excessive daytime sleepiness and SRBD (p = .036). CONCLUSION: Our findings reveal a high prevalence of SRBD in newly diagnosed, untreated RA and PsA patients in ESS and RPG, with excessive daytime sleepiness being a reliable predictor of SRBD. Patients with RA exhibited a higher predisposition to SAS. We therefore suggest incorporating ESS and RPG as screening tools in RA or PsA for early detection and management of SRBD.

Development of a 3D-printed nuchal translucency model: a pilot study for prenatal ultrasound training.

BACKGROUND: We used two 3D ultrasound volumes of fetal heads at 13 weeks to create live-size 3D-printed phantoms with a view to training or assessment of diagnostic abilities for normal and abnormal nuchal translucency measurements. The phantoms are suitable for use in a water bath, imitating a real-life exam. They were then used to study measurement accuracy and reproducibility in examiners of different skill levels. METHODS: Ultrasound scans of a 13 + 0-week fetus were processed using 3D Slicer software, producing a stereolithography file for 3D printing. The model, crafted in Autodesk Fusion360™, adhered to FMF guidelines for NT dimensions (NT 2.3 mm). Additionally, a model with pathologic NT was designed (NT 4.2 mm). Printing was performed via Formlabs Form 3® printer using High Temp Resin V2. The externally identical looking 3D models were embedded in water-filled condoms for ultrasound examination. Eight specialists of varying expertise levels conducted five NT measurements for each model, classifying them in physiological and abnormal models. RESULTS: Classification of the models in physiological or abnormal NT resulted in a detection rate of 100%. Average measurements for the normal NT model and the increased NT model were 2.27 mm (SD ± 0.38) and 4.165 mm (SD ± 0.51), respectively. The interrater reliability was calculated via the intraclass correlation coefficient (ICC) which yielded a result of 0.883, indicating robust agreement between the raters. Cost-effectiveness analysis demonstrated the economical nature of the 3D printing process. DISCUSSION: This study underscores the potential of 3D printed fetal models for enhancing ultrasound training through high inter-rater reliability, consistency across different expert levels, and cost-effectiveness. Limitations, including population variability and direct translation to clinical outcomes, warrant further exploration. The study contributes to ongoing discussions on integrating innovative technologies into medical education, offering a practical and economical method to acquire, refine and revise diagnostic skills in prenatal ultrasound. Future research should explore broader applications and long-term economic implications, paving the way for transformative advancements in medical training and practice.

Recommendations for defining giant cell arteritis fast-track clinics. English version.

A German expert committee recommends defining fast-track clinics (FTC) for the acute diagnosis of giant cell arteritis (GCA) as follows: easy and prompt reachability at least on weekdays, scheduling appointments ideally within 24 h, examination by a specialist with GCA expertise, ≥ 2 experts per FTC, ≥ 50 patients with suspected GCA per year, sonologists with ≥ 300 (≥ 50) temporal and axillary artery examinations, adherence to standard operating procedures, availability of an ≥ 18 (≥ 15) MHz and a lower frequency linear ultrasound probe, and collaboration with partners for neurology and ophthalmology consultations, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT, possibly CT), and for temporal artery biopsy.

[Recommendations for defining giant cell arteritis fast-track clinics]. / Empfehlungen zur Definition von Riesenzellarteriitis-Fast-Track-Kliniken.

An expert committee recommends defining fast-track clinics (FTC) for the acute diagnostics of giant cell arteritis (GCA) as follows: low-threshold, easy and prompt reachability at least on weekdays, scheduling appointments ideally within 24 h, examination by a specialist with GCA expertise, ≥ 2 experts per FTC, ≥ 50 patients with suspected GCA per year, sonologists with ≥ 300 (≥ 50) temporal and axillary artery examinations, adherence to standard operating procedures, availability of an ≥ 18 (≥ 15) MHz and a lower frequency linear ultrasound probe and collaboration with partners for fast performance of neurological and ophthalmological examinations, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT, possibly CT) and for temporal artery biopsy.

Prospective double-blind study on the value of musculoskeletal ultrasound by dermatologists as a screening instrument for psoriatic arthritis.

OBJECTIVES: This study evaluated musculoskeletal ultrasound (MSUS) use by dermatologists previously trained on a novel handheld, chip-based ultrasound device (HHUD) to screen for early PsA. METHODS: Twelve dermatologists were recruited to screen psoriasis patients for PsA using the novel HHUD in one major hospital in Bonn (Germany) and six private practices in surrounding regions. Patient screening was based on medical history, clinical examination, and the GEPARD questionnaire paired with an MSUS examination of up to three painful joints. All screened patients were then referred to rheumatologists, who determined the final diagnosis. The screening effect of MSUS was assessed according to its sensitivity and specificity before and after its application. RESULTS: Between 1 October 2020 and 26 May 2021, a total of 140 psoriasis patients with arthralgia participated in this study. PsA was diagnosed in 19 (13.6%) cases. Before applying MSUS, dermatologists' screening sensitivity and specificity were recorded as 88.2% and 54.4%, respectively, while after applying MSUS the sensitivity and specificity changed to 70.6% and 90.4%, respectively. MSUS led to a change of PsA suspicion in 46 cases, with PsA no longer being suspected in 45 of them. CONCLUSION: This study was able to demonstrate that PsA screening using MSUS by previously trained dermatologists can lead to more precise PsA detection and potentially decreased rheumatologist referral rates.

Efforts toward the Total Synthesis of Elisabethin A.

We describe our efforts toward the total synthesis of the natural product elisabethin A. The first route was guided by the proposed biosynthesis, assembling the 6,6-ring system before forming the five-membered ring including the quaternary carbon. The second approach includes a high yielding cyclization under Mitsunobu conditions as a key step. It allowed the preparation of an unusual and highly functionalized bicyclic 6,5-spiro compound. Both routes share a common advanced precursor obtained from an "underdeveloped" Claisen rearrangement of an aryl dienyl ether.

[Imaging of eosinophilic fasciitis in ultrasound and MRI (magnetic resonance imaging): a case report]. / Darstellung der eosinophilen Fasziitis in Ultraschall und MRT (Magnetresonanztomographie): ein Fallbericht.

Eosinophilic fasciitis (EF, also known as Shulman syndrome) is an uncommon connective tissue disease characterized by inflammatory thickening of the fasciae as well as swelling and hardening of the skin. It mostly affects the lower extremities. Swollen and indurated skin, together with the groove sign, are typical clinical signs. So far, biopsy evidence of inflammation and thickening of the fascia has been the gold standard for diagnosis. Magnetic resonance imaging (MRI) is mentioned in the literature as an alternative method for confirming the diagnosis. We present a case of asymmetric EF in a 54-year-old German male. He came with painful induration of the right forearm, with a characteristic groove sign and limitation of motion of the right hand. The blood count revealed eosinophilia with 0.57 G/l or 9.6% (normal: 0.05-0.5 G/l and 0.5-5.5%), ANA and ENA were negative. The diagnosis was confirmed histologically and we were able to detect a thickened fascia in MRI and ultrasound imaging. The EF also appeared in the left lateral malleolus during the course of the illness. Treatment was carried out with prednisolone and methotrexate.

Asymmetric Synthesis of Merck's Potent hNK1 Antagonist and Its Stereoisomers via Tandem Acylation/[3,3]-Rearrangement of 1,2-Oxazine N-Oxides.

An asymmetric total synthesis of Merck's hNK1 antagonist and three of its stereoisomers was accomplished in 10 steps. The synthesis involves a stereoselective assembly of 1,2-oxazine N-oxide by the [4 + 2]-cycloaddition, site-selective C-H oxygenation using a novel tandem acylation/[3,3]-rearrangement process and the reductive 1,2-oxazine ring contraction into a pyrrolidine ring as key stages. Using this strategy, the fused pyrrolidine subunit was constructed with exceptionally high regio- and stereoselectivities. The approach described here can be used to access enantiopure 3,4-disubstituted prolinols, which are frequently found in pharmaceutically relevant molecules and organocatalysts.

Nucleophilic Halogenation of Cyclic Nitronates: A General Access to 3-Halo-1,2-Oxazines.

In this article, comprehensive studies on the nucleophilic chlorination and bromination of readily available six-membered cyclic nitronates (1,2-oxazine-N-oxides) are reported. Under optimized conditions (POCl3 or (COBr)2 with Hünig's base), 3-halo-substituted 1,2-oxazines, which are difficult to access by other routes, were obtained in good to high yields. The latter were shown to be convenient precursors to other 3-substituted 1,2-oxazine derivatives using Lewis/Brønsted acid-assisted substitution of the halide atom for C-, S-, and N-nucleophiles.

Tryptophan / Dextran70 Based - Fluorescent Silver Nanoparticles: Synthesis and Physicochemical Properties.

Nano-size and shape of fluorescent silver nanostructures are important for a wide range of bio-applications, especially as drug delivery systems, imaging and sensing. The aim of the work is to develop a fluorescent silver nano-structured system, synthesized by chemical reduction of aqueous AgNO3 solution by Tryptophan using Dextran 70 as stabilizing agent (SNPsFL). The formed fluorescent nano-system was analyzed by UV-Vis absorption, DLS, SEM, TEM, AFM, steady-state and time resolved fluorescence spectroscopy. TEM analysis showed multi-twined nanoparticle, with the size within 15-40 nm. SNPsFL shows the fluorescence emission at 346 nm, the fluorescence quantum yield, Φ = 0.034 and the integrated fluorescence lifetime, <τ > = 1.82 ns. Riboflavin fluorescence behaviour in the RF/SNPsFL system, has been also studied. The results have relevance in using SNPsFL as a potential marker/emissive system to solve various biological barriers in humans, like drug release and protein structure.

Acylation of Nitronates: [3,3]-Sigmatropic Rearrangement of in Situ Generated N-Acyloxy, N-oxyenamines.

Acylation of nitronates affords α-acyloxyoxime derivatives via an umpolung functionalization of the α-position. This transformation involves generation of hitherto unknown N-acyloxy, N-oxyenamines and their fast [3,3]-sigmatropic rearrangement driven by the cleavage of the weak N-O bond. The reaction has a broad scope, and it is regioselective in the case of nitronates possessing nonsymmetrically substituted α-positions. Application to the formal total synthesis of clausenamide and cis-clausenamide is presented.

Oil from transgenic Camelina sativa containing over 25 % n-3 long-chain PUFA as the major lipid source in feed for Atlantic salmon (Salmo salar).

Facing a bottleneck in the growth of aquaculture, and a gap in the supply and demand of the highly beneficial n-3 long-chain PUFA (LC-PUFA), sustainable alternatives to traditional marine-based feeds are required. Therefore, in the present trial, a novel oil obtained from a genetically engineered oilseed crop, Camelina sativa, that supplied over 25 % n-3 LC-PUFA was tested as a sole dietary-added lipid source in Atlantic salmon (Salmo salar) feed. Three groups of fish were fed three experimental diets for 12 weeks with the same basal composition and containing 20 % added oil supplied by either a blend of fish oil and rapeseed oil (1:3) (COM) reflecting current commercial formulations, wild-type Camelina oil (WCO) or the novel transgenic Camelina oil (TCO). There were no negative effects on the growth, survival rate or health of the fish. The whole fish and flesh n-3 LC-PUFA levels were highest in fish fed TCO, with levels more than 2-fold higher compared with those of fish fed the COM and WCO diets, respectively. Diet TCO had no negative impacts on the evaluated immune and physiological parameters of head kidney monocytes. The transcriptomic responses of liver and mid-intestine showed only mild effects on metabolism genes. Overall, the results clearly indicated that the oil from transgenic Camelina was highly efficient in supplying n-3 LC-PUFA providing levels double that obtained with a current commercial standard, and similar to those a decade ago before substantial dietary fishmeal and oil replacement.

Synthesis and structural elucidation of a dehydrochloromethyltestosterone metabolite.

The human urinary long-term metabolite "M3" (4-chloro-17ß-hydroxymethyl-17α-methyl-18-norandrost-13-en-3-ol) of the common doping agent DHCMT has thus far been detected via GC/MS-MS, creating ambiguities concerning its absolute configuration. Its structure was elucidated via the synthesis of all eight possible stereoisomers with 17ß-hydroxymethyl configuration. The highlights of the synthesis consist of a novel first generation approach to 4ß-chloro-5ß compounds as well as a divergent route which allows easy access to the remaining A-ring chlorohydrins.

Diastereoselective synthesis and profiling of bicyclic imidazolidinone derivatives bearing a difluoromethylated catechol unit as potent phosphodiesterase 4 inhibitors.

Metal-mediated C-H functionalization of cyclic N-oxides was exploited to access a series of new difluoromethylated analogs of imidazolidinone-based PDE4 inhibitor CMPI in a diastereoselective manner. Among the products synthesized, compounds with fine-tuned activity/selectivity profiles compared to both CMPI and the clinically applied apremilast were identified. From these studies, an unusual fused 1,2-oxazinoimidazolidinone heterocyclic system was suggested as a novel scaffold for the design of potent and selective PDE4 inhibitors. Computational studies suggest that the oxygen atom in the imidazolidinone unit can bind to the metal ion center (most likely Mg2+). DFT calculations of the relative interaction energies of inhibitors with Mg2+ and Zn2+ ions were performed on a model of the bimetal active site of PDE4.

Biogeochemical spatio-temporal transformation of copper in Aspergillus niger colonies grown on malachite with different inorganic nitrogen sources.

This work elucidates spatio-temporal aspects of the biogeochemical transformation of copper mobilized from malachite (Cu2 (CO3 )(OH)2 ) and bioaccumulated within Aspergillus niger colonies when grown on different inorganic nitrogen sources. It was shown that the use of either ammonium or nitrate determined how copper was distributed within the colony and its microenvironment and the copper oxidation state and succession of copper coordinating ligands within the biomass. Nitrate-grown colonies yielded ∼1.7× more biomass, bioaccumulated ∼7× less copper, excreted ∼1.9× more oxalate and produced ∼1.75× less water-soluble copper in the medium in contrast to ammonium-grown colonies. Microfocus X-ray absorption spectroscopy revealed that as the mycelium matured, bioaccumulated copper was transformed from less stable and more toxic Cu(I) into less toxic Cu(II) which was coordinated predominantly by phosphate/malate ligands. With time, a shift to oxalate coordination of bioaccumulated copper occurred in the central older region of ammonium-grown colonies.

Ultrasound cut-off values for intima-media thickness of temporal, facial and axillary arteries in giant cell arteritis.

Objective: To evaluate the intima-media thickness (IMT) of arteries involved in GCA for determining cut-off values. Methods: Forty newly diagnosed GCA patients in a fast-track GCA clinic and 40 age- and sex-matched controls were included. IMT measurement was performed at or within 24 h after diagnosis. The common superficial temporal arteries with their frontal and parietal branches and the facial arteries were bilaterally examined with a 10-22 MHz probe and the axillary artery with a 6-18 MHz probe. Receiver operating characteristics analysis was performed for estimating cut-off values. Results: The mean age was 72 years (s.d. 9) and 68% were females. In the control group, IMT was 0.23 mm (s.d. 0.04), 0.19 mm (s.d. 0.03), 0.20 mm (s.d. 0.03), 0.24 mm (s.d. 0.05) and 0.59 mm (s.d. 0.10) for the common superficial temporal arteries, the frontal and parietal branches, the facial arteries and the axillary arteries, respectively. In vasculitic segments of GCA patients, IMT was 0.65 mm (s.d. 0.18), 0.54 mm (s.d. 0.18), 0.50 mm (s.d. 0.17), 0.53 mm (s.d. 0.16) and 1.7 mm (s.d. 0.41), respectively. Cut-off values are 0.42, 0.34, 0.29, 0.37 and 1.0 mm, respectively, with 100% sensitivities and specificities for common superficial temporal arteries, for frontal branches and for axillary arteries and sensitivities of 97.2 and 87.5% and specificities of 98.7 and 98.8% for parietal branches and facial arteries, respectively. The intraclass correlation coefficient was between 0.87 and 0.98. Conclusion: IMT measurement can correctly distinguish vasculitic from normal arteries in suspected GCA.