bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of PstS in the Pathogenesis of Acinetobacter baumannii Under Microaerobiosis and Normoxia
Authors: Gil-Marqués María Luisa , Labrador Herrera Gema , Miró Canturri Andrea , Pachón Jerónimo , Smani Younes , Pachón-Ibáñez María Eugenia 
Published: April 2020

Abstract
Acinetobacter baumannii is a successful pathogen responsible for infections with high mortality rate. During the course of infection it can be found in microaerobic environments, which influences virulence factor expression. From a previous transcriptomic analysis of A. baumannii ATCC 17978 under microaerobiosis, we know the gene pstS is overexpressed under microaerobiosis. Here, we studied its role in A. baumannii virulence. pstS loss significantly decreased bacterial adherence and invasion into A549 cells and increased A549 cell viability. pstS loss also reduced motility and biofilm-forming ability of A. baumannii. In a peritoneal sepsis murine model, the minimum lethal dose required by A. baumannii ATCC 17978 ΔpstS was lower compared to the wild type (4.3 vs 3.2 log colony forming units/mL, respectively), and the bacterial burden in tissues and fluids was lower. Thus, the loss of the phosphate sensor PstS produced a decrease in A. baumannii pathogenesis, supporting its role as a virulence factor.
Impacts of Low Temperatures on Wolbachia (Rickettsiales: Rickettsiaceae)-Infected Aedes aegypti (Diptera: Culicidae)
Authors: Lau Meng-Jia , Ross Perran A , Endersby-Harshman Nancy M , Hoffmann Ary A 
Published: April 2020

AbstractIn recent decades, the occurrence and distribution of arboviral diseases transmitted by Aedes aegypti mosquitoes has increased. In a new control strategy, populations of mosquitoes infected with Wolbachia are being released to replace existing populations and suppress arboviral disease transmission. The success of this strategy can be affected by high temperature exposure, but the impact of low temperatures on Wolbachia-infected Ae. aegypti is unclear, even though low temperatures restrict the abundance and distribution of this species. In this study, we considered low temperature cycles relevant to the spring season that are close to the distribution limits of Ae. aegypti, and tested the effects of these temperature cycles on Ae. aegypti, Wolbachia strains wMel and wAlbB, and Wolbachia phage WO. Low temperatures influenced Ae. aegypti life-history traits, including pupation, adult eclosion, and fertility. The Wolbachia-infected mosquitoes, especially wAlbB, performed better than uninfected mosquitoes. Temperature shift experiments revealed that low temperature effects on life history and Wolbachia density depended on the life stage of exposure. Wolbachia density was suppressed at low temperatures but densities recovered with adult age. In wMel Wolbachia there were no low temperature effects specific to Wolbachia phage WO. The findings suggest that Wolbachia-infected Ae. aegypti are not adversely affected by low temperatures, indicating that the Wolbachia replacement strategy is suitable for areas experiencing cool temperatures seasonally.
EP29 An evaluation of the use of baseline pulmonary function tests in the detection of interstitial lung disease in patients newly diagnosed with rheumatoid arthritis
Authors: Haque Ashraful , Kilding Rachael , Smith Ruth , Khalid Sameena , Sandler Robert , Cox Miriam , Hendry Thomas , Flores-Martin Andreas , Lindop Kathleen , Maxwell James 
Published: April 2020

Abstract

Background
Interstitial lung disease (ILD) is a serious extra-articular manifestation of rheumatoid arthritis (RA). Risk factors include smoking, the presence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (CCP). Pulmonary function tests (PFT) show reduced carbon monoxide diffusion capacity (DLCO) early and reduced forced vital capacity (FVC) later in disease. HRCT is the gold standard diagnostic test while chest X-ray (CXR) has low sensitivity. PFT are routinely performed in the majority of RA patients at baseline at our tertiary centre. The aim of this study was to evaluate the frequency of abnormal PFT, specificity for ILD and influence on subsequent decision-making in patients newly diagnosed with RA.

Methods
A retrospective analysis was undertaken of patients with a new diagnosis of RA between January 2016 and December 2017. Patients meeting the ACR (2010) criteria for RA, with baseline PFT data available were included. Clinic letters and the hospital electronic records were used to obtain the data.

Results
139 patients were included in the data analysis (Table 1). 23 patients had DLCO &lt;70% predicted, while 7 patients had an FVC &lt;80% predicted. Patients with abnormal PFT were more likely to be older, female, seropositive and to have smoked. Of the patients with DLCO &lt;70%, CXR was abnormal in 6 patients with changes suggesting ILD in 2 patients. 13 patients had HRCT and 7/13 patients had evidence of ILD and 6/13 patients had significant emphysema on CXR or HRCT. 1 patient with DLCO of 82% had changes of ILD on a CT scan organised for another reason. Methotrexate was commenced in 19/23 patients with DLCO&lt;70% and discontinued in 2 patients for respiratory reasons.

Conclusion
This evaluation suggests baseline PFT are more sensitive than baseline CXR in detecting ILD but that a DLCO &lt;70% is not specific for this diagnosis. The abnormal PFT lead to HRCT being requested in 13/24 patients, of whom 7 had ILD which had not been identified by CXR in 5 patients. Baseline PFT are also useful as a reference point in patients who go on to develop respiratory symptoms at a later point in their illness.

Disclosures
A. Haque None. R. Kilding None. R. Smith None. S. Khalid None. R. Sandler None. M. Cox None. T. Hendry None. A. Flores-martin None. K. Lindop None. J. Maxwell None.
O25 Quantifying and predicting the effect of anti-TNF therapy on axSpA-related fatigue: results from the BSRBR-AS registry and meta-analysis
Authors: Shim Joanna , Dean Linda , Karabayas Maira , Jones Gareth , Macfarlane Gary , Basu Neil 
Published: April 2020

Abstract

Background
Fatigue represents a critical priority among patients with axial spondyloarthritis (axSpA). Its effective management is a major unmet clinical need. Existing studies indicate that anti-TNF therapy may reduce fatigue levels, although any effect has yet to be definitively quantified. Moreover, predictors of any such improvements have not been studied.

Methods
The British Society for Rheumatology Register in Axial Spondyloarthritis (BSRBR-AS) prospectively recruited axSpA patients across 83 centres in the UK. Changes in fatigue levels (measured using the Chalder Fatigue Scale (0-33)) over 1 year were compared between those starting anti-TNF therapy at the time of recruitment and those not. Differences between treatment groups were adjusted using propensity score matching. Results were combined with other studies in a meta-analysis to calculate pooled estimates. Then, among those BSRBR-AS anti-TNF commencers with clinically relevant fatigue, baseline predictors of response were investigated.

Results
Of the 998 BSRBR-AS recruits with complete fatigue outcome data, 310 were anti-TNF commencers and 688 were not. At 1 year follow-up, the former group reported a mean change in fatigue of -2.6 (95% CI -4.1, -1.9) points while the latter reported a mean worsening of fatigue by 0.2 points. Following propensity score adjustment, those commencing anti-TNF therapy reduced fatigue by 3.0 points compared to those not 95% CI (-4.1-1.9). In the meta-analysis, including 1109 subjects across 5 observational studies and trials, treatment with anti-TNF therapy resulted in a significant improvement in fatigue (SMD 0.36, 95% CI 0.15-1.56). Of those BSRBR-AS recruits commencing anti-TNF, n = 205 (66%) reported clinically significant fatigue at baseline of whom n = 139 (68%) experienced a clinically relevant improvement in their fatigue at 1 year. Poor sleep quality at baseline was predictive of fatigue improvement.

Conclusion
Anti TNF therapy results in a significant but modest reduction in fatigue amongst axSpA patients, with those reporting poor sleep quality most likely to report improvement. Effective management will likely require additional, possibly non-pharmacological, approaches.

Disclosures
J. Shim None. L. Dean None. M. Karabayas None. G. Jones None. G. Macfarlane None. N. Basu None.
P27 A challenging case of multi-site avascular necrosis
Authors: Haque Ashraful , Coote Annabel 
Published: April 2020

Abstract

Background
A 32 year old gentleman was assessed in the rheumatology department in August 2018 having been referred for investigation into the cause of multi-site avascular necrosis (AVN).

Methods
He had mild Raynaud's symptoms in his hands and recurrent oral ulceration. He was previously fit and well without any history of thrombotic events or family history. He smoked 2 cigarettes a day and denied any alcohol intake.

Results
In February 2011 he was diagnosed with T-cell lymphoma while in the Navy. He underwent chemotherapy in a medical oncology department at a tertiary care centre. His chemotherapy regime involved 2 cycles of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) and 4 cycles of cyclophosphamide, cytarabine, vincristine, doxorubicin, methotrexate, ifosfamide, etoposide, cytarabine (CODOX-M IVAC) which finished in September 2011. He developed severe bilateral hip pain 6 months after completing his chemotherapy. X-rays revealed bilateral avascular necrosis (AVN). He was discharged from the Navy on medical grounds and underwent bilateral total hip replacements in 2013. In March 2014 he developed pain involving both shoulders. An MRI scan revealed extensive bilateral humeral head AVN. He was seen by an orthopaedic surgeon at a tertiary centre and underwent re-surfacing surgery on both shoulders. Meanwhile he was reviewed by the pain team and a palliative care consultant in June- July 2014 for ongoing widespread pain in his elbows, wrists, knees and ankles. He also suffered from depression, poor sleep and expressed frustration regarding his general health and inability to work. Multiple analgesic agents used included amitriptyline, dothiepin, pregabalin, oxycodone, oxynorm and clonazepam. He also tried cognitive behavioural therapy (CBT). He developed a headache and saw a neurologist who investigated this and concluded the patient had an analgesia overuse headache. In December 2017 he developed more pain in his knees and ankles and X-rays revealed AVN of both knees. He underwent a right total knee replacement in June 2018. An MRI scan of his ankles revealed signs of bilateral AVN with bone infarction of the distal tibia and a small area of the talus bilaterally. When he was assessed in the rheumatology clinic in August 2018, he had a number of investigations which revealed normal blood counts, haemoglobin electrophoresis and clotting screen. An autoimmune screen was negative including ANA, ENA and antiphospholipid antibodies. An infection screen including HIV was also negative. A lipid screen revealed a triglyceride level of 10.9, cholesterol 8.1 and HDL ratio of 9.3.

Conclusion
This challenging case involves a young patient with AVN in 8 sites which is rare. The AVN is likely related to chemotherapy, steroids and untreated hyperlipidaemia. There have been devastating painful and psychological consequences to his daily functioning. Ongoing issues include widespread pain and further sites of AVN.

Disclosures
A. Haque None. A. Coote None.
P28 Marfan syndrome? Think again!
Authors: Madenidou Anastasia- Vasiliki , Choida Varvara , Reddy Venkat , Kazkaz Hanadi 
Published: April 2020

Abstract

Background
A 21 year old male was referred to the adult hypermobility clinic from the local rheumatologist with a suspected diagnosis of Marfan syndrome, based on his body habitus although he had presented to his GP with painful toes.

Methods
He had a background of autism,learning difficulties and was wearing glasses due to amblyopia. He had a history of dental crowding with two previous teeth extractions. There was no family history of note. On examination, his arm span was not greater than his height, there was no arachnodactyly, his palate was normal, but he had gum hypertrophy. His skin texture was normal, with no abnormal scarring or bruising, but there was presence of striae. His Beighton score was 4/9 and he had flat feet. There was reduced muscle mass and hypotonia, which was felt to be the cause of his hypermobility, rather than increased ligamentous laxity. There was evidence of gynaecomastia and lack of facial hair. The working diagnosis was Klinefelter syndrome due to his tall stature, gynaecomastia and absence of secondary male characteristics. Subsequently, the patient was referred to endocrinology and for genetic testing.

Results
The endocrinology team recognised the clinical features of male hypogonadism with small phallus (Tanner stage 2/3) and small testes, confirmed also by ultrasound. The patient reported absence of early morning erections. Blood tests confirmed hypergonadotropic hypogonadism (high luteinizing hormone, low testosterone) and the patient was commenced on testosterone therapy. His bone mineral density values lied within the expected range for age. Karyotype analysis confirmed the presence of 48,XXYY which is a chromosomal condition characterized by the presence of an extra X and Y chromosome in males. In terms of management, he attended our Outpatient Hypermobility Exercise Programme and was given advice on footwear. He was provided with extensive written information about this condition by the Rare Chromosome Disorder Support Group, Unique.

Conclusion
Our case report illustrates the importance of considering 48,XXYY syndrome in patients with typical body habitus and joint hypermobility. Marfanoid habitus is associated with connective tissue diseases, like hypermobile Ehlers-Danlos syndrome and Marfan syndrome, but also described in homocystinuria and Klinefelter syndrome. 48,XXYY was considered previously as a variant of Klinefelter syndrome, but now it is regarded as a separate syndrome with overlapping features with the Klinefelter syndrome. As in our case, the classical phenotypic characteristicsinclude gynaecomastia, small testes and tall stature. Most affected individuals are infertile. This syndrome is also associated with behavioural problems, learning difficulties, congenital heart defects, bone abnormalities, tremor, obesity, type 2 diabetes and/orrespiratory problems. Patients have an essentially normal life expectancy but require regular medical follow-up.

Disclosures
A. Madenidou None. V. Choida None. V. Reddy None. H. Kazkaz None.
P42 Use of trametinib, a MEK1 inhibitor, to treat Erdheim Chester disease (ECD)
Authors: Alkoky Hoda , Munir Talha , Borg Frances 
Published: April 2020

Abstract

Background
Erdheim Chester disease (non-Langerhan’s cell histocytosis) is a poorly recognised rare multisystem disorder. Alfa interferon (αINF) is recommended as initial therapy. BRAFV600E and MAP2K1 mutations have been identified in this condition, for which targeted biologic therapy is now available. We present a clinically challenging case of ECD, including both small and large vessel vasculitis, intolerant of αINF, who has now responded well to MAP2KI inhibition.

Methods
A 49-year-old gentleman was referred to the rheumatology clinic in 2013 with a multisystem inflammatory condition, initially characterised by weight loss, systemic upset, cranial diabetes insipidus and hypogonadism, testicular masses, lymphadenopathy and knee arthritis. Initial PET scan demonstrated uptake in these areas, together with the typical long bone pattern of uptake of ECD with complete enhancement of the pituitary on MRI. Non-Langerhan’s cell histocytosis was confirmed histologically from synovial biopsy, with presence of the MAP2K1 mutation. He was initially treated with αINF, which he was unable to tolerate, and he was then maintained on a combination of subcutaneous methotrexate and prednisolone. In 2017, he developed transient weakness and dysarthria, and episcleritis with DSA-MRI consistent with small vessel cerebral vasculitis. This was treated with cyclophosphamide. 6 months later, he experienced amaurosis fugax. He was found to have critically stenotic carotid arteries, despite these being normal when imaged 6 months previously. Carotid artery biopsy confirmed non-giant cell vasculitic changes, and PET confirmed large vessel uptake from carotids to aortic arch.

Results
Funding for targeted biologic therapy was turned down by NHSE. Trametib, a MEK1 inhibitor was obtained on compassionate grounds. Following commencement of this, PET uptake in all areas, including the vasculature normalised, with symptomatic resolution and CRP falling from 148 to 4. At the 6-month point, he remains in remission symptomatically, radiographically and in laboratory markers.

Conclusion
ECD is a rare multi-system disorder characterised by tissue infiltration of foamy histiocytes. There are approximately 550 cases described in the literature. It is classified as an inflammatory myeloid neoplasm, with variable phenotype and prognosis. Median survival is 162 months. CNS involvement and lack of response to α-INF are both independent predictors of a poor prognosis. Two genetic mutations have been identified in these patients: BRAFV600E in over 60% and MAP2K1 in 20%. Both mutations now have targeted biologic inhibition. ECD may present in the rheumatology clinic due to its inflammatory and multisystem involvement. We hope to promote recognition of this condition through this case. Although targeted therapies exist, better avenues of funding need to be available for patients with rare conditions to access them.

Disclosures
H. Alkoky None. T. Munir None. F. Borg None.
P59 Social care use in people with chronic pain
Authors: Humphreys Jenny H , Dempsey Katy , Phelan Ollie , Boothman Laura , Cook Louise , Dixon William G 
Published: April 2020

Abstract

Background
Chronic pain is a common and disabling health problem and those affected may need support with their activities of daily living (ADLs). However currently there are no data quantifying how much social care support people with chronic pain need.

Methods
Between June-July 2019, previous participants of the Cloudy with a Chance of Pain study were invited to take part in an online survey, adapted from a validated Personal Social Services Research Unit interview survey. It collected data on whether participants with chronic pain needed help with ADLs, how frequently help was needed and who provided it (formal/informal social care). Additional data was collected on demographics, employment status, pain diagnosis, and comorbidities. Descriptive statistics described the burden of social care need and multivariable logistic regression identified factors associated with social care need.

Results
There were 981 respondents; 791 (81%) were female, median age 59 years (Table 1). In the last month 527 (61%) respondents reported needing help with ADLs. Over three-quarters of help was provided informally by family and friends (408 (77%)). For 309 (59%) respondents, help was needed at least daily. In the multivariable logistic regression model, needing help was lower with older age, (OR (95% CI) 0.96 (0.94-0.98), but higher in female gender (OR (95% CI) 1.96(1.27-3.01), fibromyalgia (OR (95% CI) 2.75 (2.53-5.54)), osteoarthritis (OR (95% CI) 1.56 (1.11-2.19)) and multi-morbidity OR (95% CI) 2.13 (1.51-3.01)). Compared to full-time work, respondents who were retired or unable to work were also significantly more likely to need help with ADLs, respective OR (95% CI) 2.16 (1.21-3.84) and 6.98 (3.72-13.08).

Conclusion
A high proportion of people with chronic pain needed support with ADLs; for more than half, on a daily or more frequent basis. Interestingly, younger patients were more likely to need help which may reflect responder bias. Most support was provided informally, and this could be for a number of reasons. For example, lack of awareness/not meeting eligibility/unable to afford formal social care, or preference to be cared for by familiar persons. This should be explored in future research. These results demonstrate the burden of social care may be significantly greater than government and social care organisations are aware, with important implications for policy and planning.

Disclosures
J.H. Humphreys None. K. Dempsey None. O. Phelan None. L. Boothman None. L. Cook None. W.G. Dixon None.
P66 Risk factors for chronic widespread pain among older workers: findings from the Health and Employment After Fifty (HEAF) study
Authors: Ntani Georgia , D'Angelo Stefania , Harris Clare , Linaker Cathy , Walker-Bone Karen 
Published: April 2020

Abstract

Background
Incident chronic widespread pain (CWP) is associated with demographic and personal risk factors such as low mood and somatisation. More recently, there has been increased focus on the role of workplace factors on CWP. However, evidence from studies exploring the interaction of demographic, personal risk factors, job activities and psychosocial aspects of work on pain in older workers is limited. We assessed several potential determinants of the onset of CWP among participants in the HEAF study, a prospective UK cohort.

Methods
A cohort of participants aged 50-64 years were recruited from 24 English general practices in 2013-14 and have been followed-up annually by postal questionnaire. At baseline, information was collected about demographic and employment circumstances, physical workload, psychosocial aspects of work and their general health, mood and well-being. At three years of follow-up, information about pain was also obtained by reporting painful sites on a body mannikin, and CWP was defined according to the ACR criteria. Associations between potential risk factors and the onset of new CWP were explored using logistic regression modelling. Effect estimates were summarised by odds ratios (OR) and 95% confidence intervals (CIs).

Results
HEAF recruited a total of 8,134 people aged 50-64 years at baseline. Among the N = 3,909 still at work at three years’ follow-up, N = 3,873 did not report CWP in the first two years of follow-up. The incidence of CWP at three years follow-up was 7.4% (males: 5.7%; females: 8.9%). Multivariate analyses showed that the strongest predictors of the onset of new CWP were: female sex (OR(95% CI): 1.7(1.2-2.3)), reporting that they have low expectations of coping with physical demands of the job (OR (95%CI): 2.1 (1.5-3.0)); somatisation (OR(95%CI): 2.1(1.3-3.2)) and poor self-rated health (OR(95%CI): 2.3(1.7-3.2)). Physical workload and other psychosocial aspects of work were also significantly associated with onset of CWP but with relatively smaller effect sizes (physical workload OR(95%CI): 1.2(1.1-1.3)); lack of appreciation OR (95% CI): 1.6(1.1-2.5))

Conclusion
Our results complement previous findings that physical loading at work independently predicts the onset of CWP. However, personal risk factors like self-rated health and work-related expectations demonstrated stronger effects. These findings can inform future interventions for prevention of CWP.

Disclosures
G. Ntani None. S. D'Angelo None. C. Harris None. C. Linaker None. K. Walker-Bone None.