Evaluation of the current use of MRI to aid the diagnosis of axial spondyloarthritis in the UK: results from a freedom of information request.

AIM: To evaluate the impact of recommendations from the 2019 consensus exercise conducted by radiologists and rheumatologists on the use of magnetic resonance imaging (MRI) to investigate axial spondyloarthritis (axSpA) in clinical practice. MATERIALS AND METHODS: A freedom of information (FOI) request was used to assess the use of MRI in the diagnosis of axSpA and radiologists' awareness of the 2019 guidance across all NHS Trusts and Health Boards in the UK, including England, Scotland, Northern Ireland, and Wales. RESULTS: The FOI request was sent to 150 Trusts/Health Boards, and 93 full responses were received. Of the 93 respondents (97%), 90 reported familiarity with the term axSpA and 70/93 (75%) reported familiarity with the 2019 recommendations. Awareness of recommendations regarding specific MRI features supportive of the diagnosis of axSpA was 74/93 (80%) for the sacroiliac joints (SIJs) and 66/93 (71%) for the spine. The median wait for MRI acquisition was 2-3 months. Fifty-two of the 93 (56%) reported at least some outsourcing of axSpA MRI (33%/29% for specialist/non-specialist outsourcing respectively); 32/93 (34%) reported some scans being reported in-house by non-musculoskeletal radiologists. CONCLUSION: There have been several positive developments in the understanding and use of MRI for the diagnosis of axSpA in the UK since the 2017 survey, although substantial scope for further improvement remains. Several new challenges have also emerged, including the increase in waiting times, reliance on outsourcing, and the reporting of MRI by non-musculoskeletal radiologists.

The ASAS-OMERACT core domain set for axial spondyloarthritis.

BACKGROUND: The current core outcome set for ankylosing spondylitis (AS) has had only minor adaptations since its development 20 years ago. Considering the significant advances in this field during the preceding decades, an update of this core set is necessary. OBJECTIVE: To update the ASAS-OMERACT core outcome set for AS into the ASAS-OMERACT core outcome set for axial spondyloarthritis (axSpA). METHODS: Following OMERACT and COMET guidelines, an international working group representing key stakeholders (patients, rheumatologists, health professionals, pharmaceutical industry and drug regulatory agency representatives) defined the core domain set for axSpA. The development process consisted of: i) Identifying candidate domains using a systematic literature review and qualitative studies; ii) Selection of the most relevant domains for different stakeholders through a 3-round Delphi survey involving axSpA patients and axSpA experts; iii) Consensus and voting by ASAS; iv) Endorsement by OMERACT. Two scenarios are considered based on the type of therapy investigated in the trial: symptom modifying therapies and disease modifying therapies. RESULTS: The updated core outcome set for axSpA includes 7 mandatory domains for all trials (disease activity, pain, morning stiffness, fatigue, physical function, overall functioning and health, and adverse events including death). There are 3 additional domains (extra-musculoskeletal manifestations, peripheral manifestations and structural damage) that are mandatory for disease modifying therapies and important but optional for symptom modifying therapies. Finally, 3 other domains (spinal mobility, sleep, and work and employment) are defined as important but optional domains for all trials. CONCLUSION: The ASAS-OMERACT core domain set for AS has been updated into the ASAS-OMERACT core domain set for axSpA. The next step is the selection of instruments for each domain.

Photodissociation of aqueous I 3 - observed with liquid-phase ultrafast mega-electron-volt electron diffraction.

Developing femtosecond resolution methods for directly observing structural dynamics is critical to understanding complex photochemical reaction mechanisms in solution. We have used two recent developments, ultrafast mega-electron-volt electron sources and vacuum compatible sub-micron thick liquid sheet jets, to enable liquid-phase ultrafast electron diffraction (LUED). We have demonstrated the viability of LUED by investigating the photodissociation of tri-iodide initiated with a 400 nm laser pulse. This has enabled the average speed of the bond expansion to be measured during the first 750 fs of dissociation and the geminate recombination to be directly captured on the picosecond time scale.

Initial metal-metal bond breakage detected by fs X-ray scattering in the photolysis of Ru3(CO)12 in cyclohexane at 400 nm.

Using femtosecond resolution X-ray solution scattering at a free electron laser we were able to directly observe metal-metal bond cleavage upon photolysis at 400 nm of Ru3(CO)12, a prototype for the photochemistry of transition metal carbonyls. This leads to the known single intermediate Ru3(CO)11(µ-CO)*, with a bridging ligand (µCO) and where the asterisk indicates an open Ru3-ring. This loses a CO ligand on a picosecond time scale yielding a newly observed triple bridge intermediate, Ru3(CO)8(µ-CO)3*. This loses another CO ligand to form the previously observed Ru3(CO)10, which returns to Ru3(CO)12via the known single-bridge Ru3(CO)10(µ-CO). These results indicate that contrary to long standing hypotheses, metal-metal bond breakage is the only chemical reaction immediately following the photolysis of Ru3(CO)12 at 400 nm. Combined with previous picosecond resolution X-ray scattering data and time resolved infrared spectroscopy these results yield a new mechanism for the photolysis of Ru3(CO)12.

Consistency of fish-shoal social network structure under laboratory conditions.

We investigated the consistency of association network structure for groups of sticklebacks Gasterosteus aculeatus. Each group was observed twice and we varied the duration between observations and the size of the experimental arena that they were observed in. At the dyad level, we found positive correlations between dyad interaction frequencies across observations. At the group level we found variation in four network metrics between observations, but only in treatments where the duration between observations was short. Specifically, fish formed more and smaller groups in the second observation in this treatment. Fish were also organized into more subunits in the larger arenas. Finally, we saw positive correlations between some group network metrics across observations suggesting relative consistency at the group level. There are several processes that might drive these interaction patterns. Our findings have implications for experimental design and the comparison and integration of findings of experiments from different studies carried out under different conditions.

Probing ultrafast ππ*/nπ* internal conversion in organic chromophores via K-edge resonant absorption.

Many photoinduced processes including photosynthesis and human vision happen in organic molecules and involve coupled femtosecond dynamics of nuclei and electrons. Organic molecules with heteroatoms often possess an important excited-state relaxation channel from an optically allowed ππ* to a dark nπ* state. The ππ*/nπ* internal conversion is difficult to investigate, as most spectroscopic methods are not exclusively sensitive to changes in the excited-state electronic structure. Here, we report achieving the required sensitivity by exploiting the element and site specificity of near-edge soft X-ray absorption spectroscopy. As a hole forms in the n orbital during ππ*/nπ* internal conversion, the absorption spectrum at the heteroatom K-edge exhibits an additional resonance. We demonstrate the concept using the nucleobase thymine at the oxygen K-edge, and unambiguously show that ππ*/nπ* internal conversion takes place within (60 ± 30) fs. High-level-coupled cluster calculations confirm the method's impressive electronic structure sensitivity for excited-state investigations.Many photo-induced processes such as photosynthesis occur in organic molecules, but their femtosecond excited-state dynamics are difficult to track. Here, the authors exploit the element and site selectivity of soft X-ray absorption to sensitively follow the ultrafast ππ*/nπ* electronic relaxation of hetero-organic molecules.

Identification of the dominant photochemical pathways and mechanistic insights to the ultrafast ligand exchange of Fe(CO)5 to Fe(CO)4EtOH.

We utilized femtosecond time-resolved resonant inelastic X-ray scattering and ab initio theory to study the transient electronic structure and the photoinduced molecular dynamics of a model metal carbonyl photocatalyst Fe(CO)5 in ethanol solution. We propose mechanistic explanation for the parallel ultrafast intra-molecular spin crossover and ligation of the Fe(CO)4 which are observed following a charge transfer photoexcitation of Fe(CO)5 as reported in our previous study [Wernet et al., Nature 520, 78 (2015)]. We find that branching of the reaction pathway likely happens in the (1)A1 state of Fe(CO)4. A sub-picosecond time constant of the spin crossover from (1)B2 to (3)B2 is rationalized by the proposed (1)B2 → (1)A1 → (3)B2 mechanism. Ultrafast ligation of the (1)B2 Fe(CO)4 state is significantly faster than the spin-forbidden and diffusion limited ligation process occurring from the (3)B2 Fe(CO)4 ground state that has been observed in the previous studies. We propose that the ultrafast ligation occurs via (1)B2 → (1)A1 → (1)A' Fe(CO)4EtOH pathway and the time scale of the (1)A1 Fe(CO)4 state ligation is governed by the solute-solvent collision frequency. Our study emphasizes the importance of understanding the interaction of molecular excited states with the surrounding environment to explain the relaxation pathways of photoexcited metal carbonyls in solution.

Orbital-specific mapping of the ligand exchange dynamics of Fe(CO)5 in solution.

Transition-metal complexes have long attracted interest for fundamental chemical reactivity studies and possible use in solar energy conversion. Electronic excitation, ligand loss from the metal centre, or a combination of both, creates changes in charge and spin density at the metal site that need to be controlled to optimize complexes for photocatalytic hydrogen production and selective carbon-hydrogen bond activation. An understanding at the molecular level of how transition-metal complexes catalyse reactions, and in particular of the role of the short-lived and reactive intermediate states involved, will be critical for such optimization. However, suitable methods for detailed characterization of electronic excited states have been lacking. Here we show, with the use of X-ray laser-based femtosecond-resolution spectroscopy and advanced quantum chemical theory to probe the reaction dynamics of the benchmark transition-metal complex Fe(CO)5 in solution, that the photo-induced removal of CO generates the 16-electron Fe(CO)4 species, a homogeneous catalyst with an electron deficiency at the Fe centre, in a hitherto unreported excited singlet state that either converts to the triplet ground state or combines with a CO or solvent molecule to regenerate a penta-coordinated Fe species on a sub-picosecond timescale. This finding, which resolves the debate about the relative importance of different spin channels in the photochemistry of Fe(CO)5 (refs 4, 16 - 20), was made possible by the ability of femtosecond X-ray spectroscopy to probe frontier-orbital interactions with atom specificity. We expect the method to be broadly applicable in the chemical sciences, and to complement approaches that probe structural dynamics in ultrafast processes.

Ultrafast X-ray Auger probing of photoexcited molecular dynamics.

Molecules can efficiently and selectively convert light energy into other degrees of freedom. Disentangling the underlying ultrafast motion of electrons and nuclei of the photoexcited molecule presents a challenge to current spectroscopic approaches. Here we explore the photoexcited dynamics of molecules by an interaction with an ultrafast X-ray pulse creating a highly localized core hole that decays via Auger emission. We discover that the Auger spectrum as a function of photoexcitation--X-ray-probe delay contains valuable information about the nuclear and electronic degrees of freedom from an element-specific point of view. For the nucleobase thymine, the oxygen Auger spectrum shifts towards high kinetic energies, resulting from a particular C-O bond stretch in the ππ* photoexcited state. A subsequent shift of the Auger spectrum towards lower kinetic energies displays the electronic relaxation of the initial photoexcited state within 200 fs. Ab-initio simulations reinforce our interpretation and indicate an electronic decay to the nπ* state.

Standardized grip strength as an outcome measure in early rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) suffer progressive loss of hand function and have weaker hand grip than the healthy population. In this study we aimed to validate hand grip strength standardized by age and gender (z score) against currently accepted clinical measures of disease activity. METHOD: Electronic records of patients with a diagnosis of RA seen between April 2007 and December 2011 were screened for the documentation of tender and swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), along with patient global activity score and grip strength. Bilateral grip strengths were converted to z scores on the basis of previously published age- and gender-corrected normative data for grip strength. The z scores were then correlated against components of disease activity scores. RESULTS: Ninety patients diagnosed with RA had been seen 602 times within 2 years of diagnosis. Hand grip data were available for 204 visits. There was a statistically significant inverse correlation between grip strength z scores and the tested variables. The sensitivity and specificity of a hand grip z score of -1.5 for predicting remission were, respectively, 70% and 76% for the right hand and 82% and 69% for the left hand. CONCLUSIONS: Hand grip testing and subsequent conversion to z scores corrected for age and gender correlate with disease activity in early RA. We have shown that the grip strength z scores can discriminate between various disease states, and the strength seems to return to near normative data when the disease is in remission.

Large angular jump mechanism observed for hydrogen bond exchange in aqueous perchlorate solution.

The mechanism for hydrogen bond (H-bond) switching in solution has remained subject to debate despite extensive experimental and theoretical studies. We have applied polarization-selective multidimensional vibrational spectroscopy to investigate the H-bond exchange mechanism in aqueous NaClO4 solution. The results show that a water molecule shifts its donated H-bonds between water and perchlorate acceptors by means of large, prompt angular rotation. Using a jump-exchange kinetic model, we extracted an average jump angle of 49 +/- 4 degrees, in qualitative agreement with the jump angle observed in molecular dynamics simulations of the same aqueous NaClO4 solution.

Pyloric gland metaplasia and pouchitis in patients with ileal pouch-anal anastomoses.

BACKGROUND: Diagnosis and management of chronic antibiotic-refractory pouchitis and Crohn's disease of the pouch can be challenging. Pyloric gland metaplasia is a histological feature indicative of chronic mucosal inflammation. Its value in diagnosis and prognosis of pouch disorders has not been investigated. AIM: To assess the prevalence, diagnostic and prognostic value, and risk factors of pyloric gland metaplasia in pouch patients. METHODS: Patients were identified from our prospectively maintained Pouchitis Database. Pouch biopsy specimens were re-reviewed for pyloric gland metaplasia and other histological features. Two cohorts of patients were studied: a historical cohort (n = 111) and the second, a validation cohort (n = 100). Univariate and multivariate analyses were performed to assess risk factors for pyloric gland metaplasia. RESULTS: The prevalence of pyloric gland metaplasia in the historical cohort and validation cohort was 45 (40.1%) and 24 (24.0%), respectively. The sensitivity and specificity of pyloric gland metaplasia for the diagnosis of chronic antibiotic-refractory pouchitis or Crohn's disease were 70.7% and 92.5%, respectively, for the first cohort and 39.0% and 86.4%, respectively, for the 2nd validation cohort. In multivariate analysis of the first cohort, patients with refractory pouchitis or Crohn's disease were 28 times (95% CI, 7.3-107.1) more likely to have pyloric gland metaplasia than those with a normal pouch or irritable pouch syndrome. The factor of refractory pouchitis or Crohn's disease remained in the model for the 2nd validation cohort with odds ratio of 4.58 (95% CI, 1.6-13.4). CONCLUSIONS: Pyloric gland metaplasia is associated with diagnosis of chronic antibiotic-refractory pouchitis or Crohn's disease of the pouch and appears to be a specific marker for both disease entities.

Recognition of inflammatory back pain and ankylosing spondylitis in primary care.

OBJECTIVE: The diagnosis of AS is often delayed in primary care. This may partly be due to inability to differentiate inflammatory back pain (IBP) from mechanical. The aim of this study was to assess current practice of general practitioners (GPs) in using clinical, radiological and laboratory investigations to assess patients with IBP. METHODS: A postal questionnaire was sent to all GPs in Norfolk. It was designed to test GPs ability to identify symptoms suggestive of IBP in patients with back pain. It also enquired whether GPs considered other features of SpA. Their perceptions of usefulness of various investigations when considering a diagnosis of AS, management and their unmet needs were recorded. RESULTS: A total of 62% of completed questionnaires were returned. Only 5% of GPs could identify all eight features known to be indicative of IBP, 78% between four and eight and 17% identified less than four features. GPs had a range of views regarding the utility of a positive family history, HLA-B27, use of X-ray and physiotherapy in patients with suspected IBP. GPs awareness of the associated features of SpA was low. There were inconsistencies in the use of diagnostic tests and management of AS. Improving musculoskeletal education in primary care was identified as one of the unmet needs by the majority of GPs. CONCLUSIONS: In a survey of GPs, we identified inconsistencies in their perceptions and approach to the diagnosis and management of AS. Education in primary care and the wider use of diagnostic algorithms may improve early detection and hence outcome of AS.

X-ray diffuse scattering measurements of nucleation dynamics at femtosecond resolution.

Femtosecond time-resolved small and wide angle x-ray diffuse scattering techniques are applied to investigate the ultrafast nucleation processes that occur during the ablation process in semiconducting materials. Following intense optical excitation, a transient liquid state of high compressibility characterized by large-amplitude density fluctuations is observed and the buildup of these fluctuations is measured in real time. Small-angle scattering measurements reveal snapshots of the spontaneous nucleation of nanoscale voids within a metastable liquid and support theoretical predictions of the ablation process.

Influence of biologic therapy on return to work in people with work disability due to ankylosing spondylitis.

OBJECTIVE: To answer the question 'does TNF blockade therapy enable people with severe AS to return to work or work more productively?'. METHODS: All patients with AS currently receiving anti-TNF therapy at two UK Hospitals were asked to complete a questionnaire. This asked about occupational history, type of work, degree of job-related physical activity, working hours and sickness absence from work both currently (on anti-TNF treatment) and pre-treatment. RESULTS: Sixty-five patients (72.3% male), aged 29-64 (mean 46.1) yrs, whose duration of anti-TNF treatment ranged from 3 to 56 (mean 19.1) months were studied. Twenty-four (36.9%) patients were receiving infliximab, 21 (32.3%) etanercept and 20 (30.8%) adalimumab. Pre-treatment, 46 (70.8%) were in employment (1 was a student); 38 (58.5%) were working full-time and 8 (12.3%) part-time; 19 (29.2%) were not working. On treatment, 50 (76.9%) patients were working, 44 (67.7%) full-time and 6 (9.2%) part-time. Two individuals who worked part-time pre-treatment had returned to work full-time. Thus, on treatment, 4 of the 19 patients who were previously unable to work returned to employment, and 2 others increased their work from part-time to full-time. Patients rated the effect of AS on work capacity as 7.05/10 pre-treatment and 2.92/10 post-treatment. Those who were working lost, on average, 15 days from work due to sick leave in the 12 months pre-treatment and 0.91 days in the first 12 months on treatment. CONCLUSIONS: Treatment of active AS with TNF blockade appears to be associated with improved capacity for work.