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.

Risk-mitigating behaviours in people with inflammatory skin and joint disease during the COVID-19 pandemic differ by treatment type: a cross-sectional patient survey.

BACKGROUND: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments. OBJECTIVES: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. METHODS: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model. RESULTS: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations. CONCLUSIONS: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues.

Non-contrast computed tomography is comparable to contrast-enhanced computed tomography for aortic volume analysis after endovascular abdominal aortic aneurysm repair.

OBJECTIVES: To evaluate whether non-contrast computed tomography (NCCT) images are as reliable as contrast-enhanced computed tomography (CECT) images for the measurement of aortic volume (AV). MATERIALS AND METHODS: A total of 316 pairs of AVs were retrospectively measured from 316 consecutive patients, who underwent endovascular aneurysm repair (EVAR). A standardised multidetector computed tomography protocol was used to obtain precontrast, arterial and delay-phase images. A single blinded, experienced observer measured the AV from the lowest renal artery to the aortic bifurcation by means of the disc-summation method, using the precontrast and arterial-phase images. A second blinded observer measured the AV again in 16 randomly chosen cases. RESULTS: Both NCCT and CECT yielded similar AVs that were highly correlated (r(2) = 0.99; P < 0.0001). Bland and Altman analysis revealed a small bias (mean ± 2 standard deviations: -0.9 ± 8 ml). The intraclass correlation coefficients (all >0.99; P < 0.0001) and low repeatability coefficients indicated that the AVs were reproducible with both methods. CONCLUSIONS: The AVs measured from NCCT images were accurate and highly reproducible compared with those from CECT images. Therefore, NCCT can be a reasonable alternative to CECT for AV assessment after EVAR. This is particularly important for patients with renal insufficiency (potentially sparing them from nephrotoxic contrast agents and unnecessary radiation) or allergy to contrast agents.

Depression among Patients Presenting with Gastrointestinal Symptoms: Prevalence and Associated Factors.

Gastrointestinal diseases frequently affect patients' physical and emotional wellbeing as being heavily affected by stress. This study was conducted to find out prevalence and severity of depressive symptoms among patients presenting with gastrointestinal symptoms. This cross sectional study was conducted at Outpatients Department jointly by Department of Gastroenterology and Department of Psychiatry of a tertiary care hospital in north east part of Bangladesh from November 2011 to June 2012. Consecutive patients with gastrointestinal symptoms underwent psychiatric evaluation using HDRS and analyzed. 442 patients, 38(8.6%) were found normal. Among the rest 128(28.96%), 138(31.22%), 72(16.29%) and 66(14.93%) had mild, moderate, severe and very severe depressive symptoms respectively. Female sex (95.03% vs. 89.32%), married people (93.77 vs. 86.13%), older age (98.24%), rural people (94.26% vs. 84.36%), farmers (96.36%) and house wives (96.24%) were more affected. Prevalence of depression was also higher among patients with lower socioeconomic class, less educated people and rural background. Depressive symptoms are very common in patients presenting with gastrointestinal symptoms. Awareness regarding psychiatric assessment and intervention may reduce sufferings and thus improve wellbeing of these patients.

Assessment of the impact of flares in ankylosing spondylitis disease activity using the Flare Illustration.

OBJECTIVES: Many AS patients report periods of perceived higher disease activity (flares). This pilot study aims to document disease activity patterns reported by AS patients and examine associations with disease-specific health status measures. METHODS: Consecutive AS patients (n = 114) were asked whether they experience flares, and if they experience symptoms of AS between flares. They were shown the Flare Illustration of disease patterns over time and asked to select the pattern that best described their disease (i) since symptom onset and (ii) in the past year. Associations between reported disease pattern and disease activity (Bath AS Disease Activity Index, BASDAI); functional impairment (Bath AS Functional Index, BASFI); AS Quality of Life (ASQoL); Back Pain (Nocturnal and Overall) and demographic features were assessed in a subsample (n = 83) (statistical significance defined at P 70% of patients) and patterns with constant symptoms since onset (vs intermittent symptoms) were associated with worse health status (ASQoL: P = 0.007; BASDAI: P = 0.029; BASFI: P = 0.013, overall back pain: P = 0.025). CONCLUSIONS: Almost all AS patients report flares in disease activity: 70-80% report constant symptoms with single/repeated flares, while 20-30% report flares with no intermittent symptoms. The former is associated with a significantly poorer health status. These findings will be validated in a prospective study.

Modified constructs of the tRNA TPsiC domain to probe substrate conformational requirements of m(1)A(58) and m(5)U(54) tRNA methyltransferases.

The TPsiC stem and loop (TSL) of tRNA contains highly conserved nucleoside modifications, m(5)C(49), T(54), Psi(55)and m(1)A(58). U(54)is methylated to m(5)U (T) by m(5)U(54)methyltransferase (RUMT); A(58)is methylated to m(1)A by m(1)A(58)tRNA methyltransferase (RAMT). RUMT recognizes and methylates a minimal TSL heptadecamer and RAMT has previously been reported to recognize and methylate the 3'-half of the tRNA molecule. We report that RAMT can recognize and methylate a TSL heptadecamer. To better understand the sensitivity of RAMT and RUMT to TSL conformation, we have designed and synthesized variously modified TSL constructs with altered local conformations and stabilities. TSLs were synthesized with natural modifications (T(54)and Psi(55)), naturally occurring modifications at unnatural positions (m(5)C(60)), altered sugar puckers (dU(54)and/or dU(55)) or with disrupted U-turn interactions (m(1)Psi(55)or m(1)m(3)Psi(55)). The unmodified heptadecamer TSL was a substrate of both RAMT and RUMT. The presence of T(54)increased thermal stability of the TSL and dramatically reduced RAMT activity toward the substrate. Local conformation around U(54)was found to be an important determinant for the activities of both RAMT and RUMT.

The role of histone modifications in epigenetic transitions during normal and perturbed development.

Epigenetic mechanisms control eukaryotic development beyond DNA-stored information. DNA methylation, histone modifications and variants, nucleosome remodeling and noncoding RNAs all contribute to the dynamic make-up of chromatin under distinct developmental options. In particular, the great diversity of covalent histone tail modifications has been proposed to be ideally suited for imparting epigenetic information. While most of the histone tail modifications represent transient marks at transcriptionally permissive chromatin, some modifications appear more robust at silent chromatin regions, where they index repressive epigenetic states with functions also outside transcriptional regulation. Under-representation of repressive histone marks could be indicative of epigenetic plasticity in stem, young and tumor cells, while committed and senescent (old) cells often display increased levels of these more stable modifications. Here, we discuss profiles of normal and aberrant histone lysine methylation patterns, as they occur during the transition of an embryonic to a differentiated cell or in controlled self-renewal vs pro-neoplastic or metastatic conditions. Elucidating these histone modification patterns promises to have important implications for novel advances in stem cell research, nuclear reprogramming and cancer, and may offer novel targets for the combat of tumor cells, potentially leading to new diagnostic and therapeutic avenues in human biology and disease.

Non-articular Felty's syndrome: An uncommon diagnosis.

Felty's syndrome is a triad of rheumatoid arthritis, neutropenia, and splenomegaly. We hereby report an unusual case of non-articular Felty's syndrome and its management along with discussing the importance of appropriately ruling out alternate causes of neutropenia with splenomegaly.

Aminoacyl-tRNA synthetase and U54 methyltransferase recognize conformations of the yeast tRNA(Phe) anticodon and T stem/loop domain.

The enzyme-catalyzed posttranscriptional modification of tRNA and the contributions of modified nucleosides to tRNA structure and function can be investigated with chemically synthesized domains of the tRNA molecule. Heptadecamer RNAs with and without modified nucleosides and DNAs designed as analogs to the anticodon and T stem/loop domains of yeast tRNA(Phe) were produced by automated chemical synthesis. The unmodified T stem/loop domain of yeast tRNA(Phe) was a substrate for the E coli m5U54-tRNA methyltransferase activity, RUMT. Surprisingly, the DNA analog of the T stem/loop domain composed of d(A,U,G,C) was also a substrate. In addition, the DNA analog inhibited the methylation of unfractionated, undermodified E coli tRNA lacking the U54 methylation. RNA anticodon domains and DNA analogs differentially and specifically affected aminoacylation of the wild type yeast tRNA(Phe). Three differentially modified tRNA(Phe) anticodon domains with psi 39 alone, m1G37 and m5C40, or psi 39 with m1G37 and m5C40,stimulated phenylalanyl-tRNA synthetase (FRS) activity. However, one anticodon domain, with m5C40 as the only modified nucleoside and a closed loop conformation, inhibited FRS activity. Modified and unmodified DNA analogs of the anticodon, tDNA(PheAC), inhibited FRS activity. Analysis of the enzyme activity in the presence of the DNA analog characterized the DNA/enzyme interaction as either partial or allosteric inhibition. The disparity of action between the DNA and RNA hairpins provides new insight into the potential allosteric relationship of anticodon binding and open loop conformational requirements for active site function of FRS and other aaRSs. The comparison of the stimulatory and inhibitory properties of variously modified RNA domains and DNA analogs demonstrates that conformation, in addition to primary sequence, is important for tRNA-protein interaction. The enzyme recognition of various DNA analogs as substrate and/or inhibitors of activity demonstrates that conformational determinants are not restricted to ribose and the standard A-form RNA structure.

P elements are found in the genomes of nematoceran insects of the genus Anopheles.

We report the identification of genomic sequences in various anopheline mosquitoes (family Culicidae: suborder Nematocera: order Diptera) showing homology to the class II, short inverted-terminal-repeat (ITR) transposable element P from Drosophila melanogaster (family Drosophilidae; suborder Brachycera: order Diptera). Anopheles gambiae appears to have at least six distinct P elements. Other anopheline species, including four additional members of the An. gambiae species complex (An. arabiensis, An. merus, An. melas and An. quadriannulatus), Anopheles stephensi (all subgenus Cellia), An. quadrimaculatus (subgenus Anopheles) and Anopheles albimanus (subgenus Nyssorhynchus) also possess P elements similar to those found in An. gambiae. Ten distinct P element types were identified in the genus Anopheles. At least two of the An. gambiae elements appears to be intact and potentially functional. Phylogenetic analysis of the anopheline P elements reveals them to belong to a distinctly different clade from the brachyceran P elements.

Simple peroperative antimicrobial chemoprophylaxis in elective neurosurgical operations.

From August 1981 to February 1982 postoperative infections due to different strains of penicillin-resistant Staphylococcus aureus occurred in 20 of 467 patients (4.3%) undergoing elective cranial and spinal operations. These infections were not attributable to defects in procedures or the theatre environment, therefore chemoprophylaxis was instituted. In the following 8 months, when patients were given penicillin G and sulphadiazine for 5 days commencing immediately postoperatively, S. aureus infections occurred in five of 579 patients (0.9%). In a subsequent randomized uncontrolled study, infections occurred in six of 265 patients receiving penicillin (2.3%), three of 270 receiving penicillin and sulphadiazine (1.1%) and one of 45 receiving erythromycin (2.2%) immediately postoperatively for 5 days. In a further study in which 587 patients received penicillin for 5 days commencing immediately preoperatively, infections due to S. aureus occurred in six (1.1%). Infections due to gram-negative organisms were seen in five (0.4%) of 1167 patients in the two uncontrolled studies.

Quality of survival following direct surgery for anterior communicating artery aneurysms.

The authors describe a series of 32 patients with ruptured aneurysms of the anterior communicating artery who were admitted during a 3-year period. In 28, the aneurysms were treated by direct surgery with no deaths; 26 of these patients were studied psychometrically from 4 to 33 months after operation. There was no evidence of postoperative intellectual impairment; however, there were personality changes associated with loss of interest, initiative, and energy. Analysis of the different factors involved suggests to the authors that the outcome of surgery depends mainly on preoperative clinical condition which, in turn, reflects the severity of the hemorrhage.

Use of epsilon aminocaproic acid (EACA) in the preoperative management of ruptured intracranial aneurysms.

The authors report their experience with the use of epsilon aminocaproic acid (EACA) in the preoperative management of a series of patients with ruptured intracranial aneurysms. A similar series of patients was taken as control. They found that EACA is of definite value in preventing recurrent hemorrhage in the preoperative period. The significance of antifibrinolytic therapy in ruptured intracranial aneurysms is discussed.

Treatment of internal carotid bifurcation aneurysms by direct surgery.

Carotid bifurcation aneurysms have, as a group, certain characteristics. They account for about 7% of all intracranial aneurysms. They appear to be mostly leftsided and there does not seem to be any particular sex predominance. When associated with other aneurysms, the carotid bifurcation aneurysm was the symptomatic lesion. Demonstration of small aneurysms may be difficult and accurate definition of the neck may not be possible at angiography. They appear to associate themselves with one or the other division of the internal carotid artery. With careful exposure and appropriate positioning of the head it is possible to occlude these aneurysms with a clip, but we feel that the inexperienced surgeon should not tackle these cases. Carotid artery ligation may not prevent rebleeding in this group of aneurysms.

Influence of adrenal cortex on testicular activity in the toad during the breeding season.

The aim of the present study was to determine the role of adrenals in gonadal activity in the male toad during the breeding season. Exogenous administration of corticosterone or metapyrone for 6 days inhibited adrenal delta5-3beta(delta 5-3 beta) hydroxysteroid (delta5-3beta-HSD) and testicular 17beta (17 beta) hydroxysteroid dehydrogenase (17beta-HSD) activities, decreased the serum levels of testosterone and inhibited spermatogenesis. When toads were treated with corticosterone a significant rise of serum corticosterone was noted while metapyrone treatment appeared to decrease serum corticosterone levels. It is concluded that adrenocortical hormone plays an indirect role in testicular activity in toads during the breeding season.

Risk Score Estimation: a new method to determine optimal timing of aneurysm clipping for improved management outcome.

The outcome of 703 patients who underwent surgery following aneurysmal subarachnoid hemorrhage were analyzed with regards to age, associated medical conditions, vasospasm and clinical status at the time of operation. Patients with Hunt and Hess grade I, II, and III had a 96%, 90% and 93% favorable (good and fair) outcome respectively. In contrast only 58% of patients with grade IV had the same result. The outcome was unfavorable in 13% of the patients who were older than 60 years of age and only in 9% of the patients between 30-59 years of age. All the patients younger than 30 years old had a good outcome. Associated medical condition increased the incidences of poor outcome (7% vs. 12%). Patients harboring vertebro basilar aneurysms had a poorer outcome, as opposed to those with aneurysms located in the anterior circulation (20% vs. 8%). The presence of angiographic vasospasm alone did not influence outcome. A proposed point value was given for each of the adverse factors and from this the optimal surgical time was determined for each individual patient. This concept of Risk Score Estimation approach may improve the management outcome of patients with ruptured intracranial aneurysms.

Focal infections of the central nervous system due to Propionibacterium acnes.

Propionibacterium acnes as the single cause of intracranial infections has rarely been described. We present four patients in whom the infection arose as a result of a breach of skin tegument, and postulate that P. acnes is an under-recognised pathogen.