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BackgroundJAK inhibitor uptake has increased in recent years, and recent NICE (National Institute for Health and Care Excellence) approval of certain JAK inhibitors for moderate rheumatoid arthritis disease activity will likely increase this further. The EULAR guidance on the management of rheumatoid arthritis recommends JAK inhibitors as part of the treat-to-target strategy, provided certain risk factors are considered [1]. However, there remains limited data on discontinuation rates for this drug class.ObjectivesThis retrospective study aimed to measure the discontinuation rates of the four UK approved JAK inhibitors in a multi-ethnic population at a UK tertiary centre, thereby providing real-world data on the durability of the different JAK inhibitors.MethodsAll patients ever prescribed a JAK inhibitor at University Hospitals of Leicester were identified on a drug monitoring database. Discontinuation rates were calculated for each JAK inhibitor, as well as the median duration of time on each drug prior to discontinuation. The baseline characteristics of the patients who discontinued a JAK inhibitor were documented, as well as reason for discontinuation. These were categorized as either primary inefficacy, secondary inefficacy, toxic adverse events, non-toxic reasons, and disease remission.ResultsIn total, 375 patients had been prescribed a JAK inhibitor since 2018. Discontinuation rates and duration of time prior to discontinuation for each drug are shown in Table 1.Table 1.JAK inhibitor discontinuation rates and duration of use.Duration prior to discontinuation (weeks)DrugNumber of patientsProportion discontinuedMedianMinimumQ1Q3MaximumMeanStandard deviationStandard error of meanBaricitinib23351/233 (21.89%)35.000.8618.4368.14230.1049.5548.686.82Tofacitinib6133/61 (54.09%)70.295.2937.8696.93161.1072.3543.297.54Filgotinib514/51 (7.84%)13.504.716.5415.8616.1411.965.142.57Upadacitinib300/30 (0%)n/an/an/an/an/an/an/an/aFigure 1.JAK inhibitor survival proportions.Of the 88 patients who discontinued a JAK inhibitor, 86% were female and 14% male. Median age was 60 years (IQR 53-70 years), and median duration of drug intake was 45.60 weeks (IQR 19.29-74.07). Of these 88 patients, 77% were Caucasian, 20% from the Indian subcontinent, and the remaining patients mixed race, Asian other, and not stated. Furthermore, 65.9% of patients were on concomitant DMARDs, 71.6% had received a previous biologic drug (median number of previous biologics was 1 [0-2]). Diagnosis was seropositive RA (rheumatoid arthritis) in 59.1%, seronegative RA in 27.3%, PsA (psoriatic arthritis) in 11.4%, and 2.2% in RA/PsA overlap.Of the 88 patients where the JAK inhibitor was discontinued, reasons included primary inefficacy 37.5%, toxic adverse events 35.23%, non-toxic reasons 17.05%, secondary inefficacy 5.68%, disease remission 1.14%, and not stated 3.41%. Adverse events of interest included viral infections 6.81%, non-viral infections 4.54%, malignancy 2.27%, and MHRA alerts 9.09%. In this multi-ethnic population, there were no discontinuations for venous thromboembolism, or major adverse cardiovascular events, although patients are screened for risk factors prior to commencement, and MHRA alerts led to discontinuation if risk factors developed during treatment.ConclusionIn this real-world population, tofacitinib followed by baricitinib had the highest discontinuation rates. While discontinuation rates for the 2nd generation JAK inhibitors appear more promising, patient numbers were lower. The most common reasons for discontinuation were primary inefficacy and toxic adverse events. Further real-world observational data is needed, particularly from multi-ethnic patient populations, to increase confidence levels in JAK inhibitor prescribing.Reference[1]Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023 Jan;82(1):3-18.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

PurposeTo evaluate whether there is an association between the chronological occurrence of pulmonary emboli, anatomical site, radiological extent and associated clinical risk factors.Materials and Methods1410 consecutive CTPA and VQ scans performed between December 2005 and October 2008 were retrospectively reviewed independently by 2 thoracic radiologists (kc=0.78). A third observer was used in equivocal cases. 270 cases of pulmonary emboli were identified. Records were available for 180 patients. 40 were excluded on the basis of incomplete presenting details. All diagnosed cases of pulmonary emboli were risk stratified according to the Wells score, underlying co-morbidities including diabetes, DVT, malignancy and cardiomyopathy. Morbidity, mortality and survival data were recorded. For 140 (Age 67 y SD ±17, 61 male), the occurrence of the pulmonary emboli based on onset of symptoms was defined by four time intervals. Each group was subdivided according to extent of clot. The average Wells score was calculated for each 6 h period.Results11% (n=16) patients presented between 00:00 and 06:00 h, 36% (n=50) between 06:00 and 12:00 hours, 30% (n=43) between 12:00 and 18:00, and 22% (n=31) between 18:00 and 24:00(χ2 =18.3, p<0.05). Average Wells Scores were 4 (SD±2), 6 (SD±1), 4 (SD±2) and 5 (SD±2) for the respective times. Patients with bilateral emboli affecting the main pulmonary arteries were distributed as follows: 00:00–06:00 (n=2), 06:00–12:00 (n=17), 12:00–18:00 (n=10), 18:00–24:00 (n=9) (χ2 =10.7, p<0.05). Patients with unilateral emboli affecting the main pulmonary arteries were found to present as follows: 00:00–06:00 (n=3), 06:00–12:00 (n=11), 12:00–18:00 (n=10), 18:00–24:00 (n=7) (χ2 =5.00, p=0.17). Patients with bilateral emboli affecting the segmental arteries presented at: 00:00–06:00 (n=4), 06:00–12:00 (n=12), 12:00–18:00 (n=8), 18:00–24:00 (n=3) (χ2 =7.52, p=0.05). Patients with unilateral emboli affecting the segmental arteries presented at: 00:00–06:00 (n=5), 06:00–12:00 (n=5), 12:00–18:00(n=8), 18:00–24:00 (n=5). (χ2 =1.17, p=0.76) In the 4 time intervals, patients with >2 symptoms of chest pain, dyspnoea, or haemoptysis were found to be distributed as: 00:00–06:00 (n=8), 06:00–12:00 (n=26), 12:00–18:00 (n=16), 18:00–24:00 (n=17) (χ2 =9.72, p<0.05).ConclusionPulmonary Emboli were most frequent between 06:00 and 12:00 h during which there was more extensive radiographical findings, associated with a higher Wells score, and more profound symptoms. This suggests a circadian pattern of the presentation of pulmonary emboli, correlating with the clinical and radiological severity of disease.

GATA binding protein 3 (GATA3) is a zinc-finger pioneer transcription factor involved in diverse processes. GATA3 regulates gene expression through binding nucleosomal DNA and facilitating chromatin remodelling. Post-translational modifications modulate its activity. During development, GATA3 plays a key role in cell differentiation. Mutations in GATA3 are linked to breast and bladder cancer. GATA3 expression is a feature of the luminal subtype of bladder cancer and has implications for immune status and therapeutic response. It also has clinical relevance in squamous cell carcinomas and soft tissue sarcomas. This paper reviews the structure and function of GATA3, its role in cancer and its use and pitfalls as an immunohistochemical marker.

Ureteroscopy and laser fragmentation of stones is a commonly used method to treat ureteric and renal calculi. We report the exceedingly rare finding of a renal pseudoaneurysm in an interpolar renal artery following ureteroscopy and laser stone fragmentation, which was successfully managed with angioembolisation.

Background Cocaine/Levamisole‐Associated Autoimmune Syndrome (CLAAS) encompasses a spectrum of autoimmune and vasculitic phenomena, which includes Cocaine‐Induced Midline Destructive Lesions (CIMDL), which can mimic ANCA‐associated vasculitis (AAV) due to overlapping clinical features and the potential for ANCA positivity. These similarities can lead to misdiagnosis and inappropriate immunosuppressive therapy. Methods This study highlights a case series of seven patients (from 2015 to 2024) with CLAAS with its subset of CIMDL, initially misdiagnosed as active AAV, in patients who were referred to various clinicians in the Rheumatology unit of a Tertiary Hospital in the United Kingdom. Results All patients presented with nasal symptoms, and they all exhibited additional systemic manifestations consistent with CLAAS. Five were ANCA‐positive at initial evaluation, leading to the initiation of immunosuppressive therapy; however, symptoms persisted. The diagnoses were then revised to CIMDL in all cases within the broader context of CLAAS following the identification of cocaine use after further patient inquiry and urine toxicology for drug of abuse (DOA) screening found cocaine metabolites. Conclusion A comprehensive drug history and urine toxicology screening are crucial in patients with suspected AAV, as ANCA positivity can occur in CLAAS as well as its subset of CIMDL, complicating the diagnosis. Differentiating between AAV and CIMDL related to CLAAS is essential to avoid unnecessary immunosuppression.

Up to 10% of Bladder Cancers may arise following occupational exposure to carcinogens. We hypothesised that different cancer phenotypes reflected different patterns of occupational exposure. Consecutive participants, with bladder cancer, self-completed a structured questionnaire detailing employment, tasks, exposures, smoking, lifestyle and family history. Our primary outcome was association between cancer phenotype and occupational details. We collected questionnaires from 536 patients, of whom 454 (85%) participants (352 men and 102 women) were included. Women were less likely to be smokers (68% vs. 81% Chi sq. p<0.001), but more likely than men to inhale environmental tobacco smoke at home (82% vs. 74% p = 0.08) and use hair dye (56% vs. 3%, p<0.001). Contact with potential carcinogens occurred in 282 (62%) participants (mean 3.1 per worker (range 0-14)). High-grade cancer was more common than low-grade disease in workers from the steel, foundry, metal, engineering and transport industries (p<0.05), and in workers exposed to crack detection dyes, chromium, coal/oil/gas by-products, diesel fumes/fuel/aircraft fuel and solvents (such as trichloroethylene). Higher staged cancers were frequent in workers exposed to Chromium, coal products and diesel exhaust fumes/fuel (p<0.05). Various workers (e.g. exposed to diesel fuels or fumes (Cox, HR 1.97 (95% CI 1.31-2.98) p = 0.001), employed in a garage (HR 2.19 (95% CI 1.31-3.63) p = 0.001), undertaking plumbing/gas fitting/ventilation (HR 2.15 (95% CI 1.15-4.01) p = 0.017), undertaking welding (HR 1.85 (95% CI 1.24-2.77) p = 0.003) and exposed to welding materials (HR 1.92 (95% CI 1.27-2.91) p = 0.002)) were more likely to have disease progression and receive radical treatment than others. Fewer than expected deaths were seen in healthcare workers (HR 0.17 (95% CI 0.04-0.70) p = 0.014). We identified multiple occupational tasks and contacts associated with bladder cancer. There were some associations with phenotype, although our study design precludes robust assessment.

Background Anti‐signal recognition particle (anti‐SRP) antibodies are myositis‐specific autoantibodies associated with immune‐mediated necrotizing myopathy. This study was undertaken to better understand how patients with anti‐SRP antibodies have been managed at our tertiary centre and to assess the spectrum of clinical features and outcomes in routine clinical practice. Methods We conducted a retrospective evaluation of 25 patients with anti‐SRP antibodies identified via line‐blot immunoassay at a tertiary care centre (2019–2024). Demographic, clinical, serological, and imaging data were reviewed. Results The group of patients had a mean age of 60.1 years, with a female‐to‐male ratio of 10:15. Eight patients (32%) were diagnosed with myositis, primarily presenting with proximal muscle weakness. Interstitial lung disease was observed in 53% of the group of patients, and 50% of the subset of patients with myositis. Coexisting myositis‐specific autoantibodies were present in 32%, and 48% had positive antinuclear antibody titres (≥ 1:400). Cardiac involvement was reported in two myositis patients. Corticosteroids, often combined with mycophenolate mofetil or other immunosuppressants, formed the basis of treatment. Conclusion Anti‐SRP antibodies are associated with a heterogeneous clinical spectrum, with many patients lacking myositis features. There was a high prevalence of coexisting autoantibodies. Further studies are needed to elucidate the pathogenic role of anti‐SRP and optimise management strategies.

Uroplakins are a family of membrane-spanning proteins highly specific to the urothelium. There are four uroplakin proteins in humans. These are encoded by the following UPK genes: UPK1A, UPK1B, UPK2 and UPK3. Uroplakin proteins span the apical membrane of umbrella cells of the urothelium, where they associate into urothelial plaques. This provides a barrier function to prevent passage of urine across the urothelium in the renal pelvis, ureters, and bladder. Uroplakins are also involved in developmental processes such as nephrogenesis. The specific localisation of uroplakins within the urothelium means that they are often expressed in primary and metastatic urothelial cell carcinoma and may be used as an immunohistochemical marker of urothelial malignancy.

We report the case of an 80-year-old Caucasian man with PL-12 antibody positive antisynthetase syndrome. He presented with progressive dyspnoea and weight loss, later developing dysphagia, mild proximal muscle weakness and mild sicca symptoms. Investigations revealed interstitial lung disease, inflammatory myopathy and an immunology profile consistent with PL-12 antisynthetase syndrome. Prednisolone and cyclophosphamide resulted in a significant improvement of all his symptoms.

IntroductionBaricitinib is an oral synthetic Janus Kinase inhibitor that inhibits JAK1 and JAK2, and the new kid on the block in the treatment of rheumatoid arthritis (RA). To date, there are no studies comparing the clinical benefit of baricitinib in RA between different ethnicities. Ethnicity plays a role in the effectiveness of therapeutic agents. Given the large multi-ethnic population of Leicestershire in the United Kingdom and the range of new therapeutics in RA, we reviewed our cohort of patients with RA to see whether there is any difference in baricitinib Disease Activity Score 28 (DAS28) response between the Asian and White cohorts.MethodsThis was a retrospective study. The patients included were those under the care of rheumatology at University Hospitals of Leicester (UHL) with a diagnosis of RA and either receiving baricitinib or had received it in the past. Data was collected using the UHL information technology systems, clinic letters and pharmacy records. In addition to ethnicity, we reviewed patient age, gender, concurrent disease-modifying anti-rheumatic drugs (DMARDs) used, previous biologics used, baseline and post-treatment DAS28, dropout from therapy, baseline biochemical assays (anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) status) and radiographic findings. An independent t-test was used to compare continuous data, and Pearson’s chi-squared test was used to compare categorical data.ResultsA total of 120 patients were included in the analysis, and data were analysed with Portable Format for Analytics (PFA). There was no statistically significant difference in the mean DAS28 at baseline (Asian: 5.17 versus White: 4.65; p-value = 0.107) and post-treatment (Asian: 2.8 versus White: 3.3; p-value = 0.404). Comparing both ethnicities, there was no statistically significant difference in previous biologics used, anti-CCP and RF titres, and radiographic findings of erosions.ConclusionThis is the first study of its kind, and it found no significant difference in baricitinib response between the Asian and White cohorts. Our study had certain limitations, and future studies will be needed to evaluate this subject further. Such data is important as it can contribute to a body of evidence that may in the future help inform clinical decision-making.