Fiber based mode converters and mode splitters are important elements in the FMF mux./demux. Long Period Gratings (LPGs) have been investigated and results presented together with a potential technique for real time mode monitoring during manufacture.
Inflammatory rheumatic and musculoskeletal diseases (iRMDs) have a predilection for women of childbearing age. Active disease increases the risk of adverse pregnancy outcomes, whilst passage of Ro antibodies may lead to congenital heart block (CHB). Pregnancy may be poorly tolerated by women with established organ damage and counselling is complicated by the limited evidence available to guide prescribing. The Obstetric Rheumatology clinic was established at University College London Hospital (UCLH) in 2007 to provide pre-pregnancy, pregnancy and post-partum care for women with iRMDs. Our local catchment area is ethnically diverse and UCLH itself delivers a range of highly specialist services resulting in referrals from across the United Kingdom. The UCLH Obstetric unit also acts as the central site for the North Central London Maternal Medicine Network.
Objectives:
To describe pregnancy outcomes in patients attending the Obstetric Rheumatology clinic at UCLH.
Methods:
We conducted a retrospective review of pregnancy outcomes for all patients attending the clinic between January 2013-May 2023. Selected information was extracted from the electronic patient record and inputted to Excel. A single encounter was recorded for each patient within the database for each pregnancy. For patients attending for pre-pregnancy counselling (PPC) – the appointment was coded as part of the pregnancy encounter if they subsequently conceived within 2 years of PPC or separately if no conception took place within this time or prior to the end of data collection for those seen late 2021 onwards.
Results:
Mean age was 32.9 years old (range 17—52 years old). 55.2% were white, 10.1% black, 15% Asian, 4.6% of mixed heritage, 9.8% listed as other, and ethnicity undocumented in 5.3%. Accounting for some patients having more than one iRMD, diseases included 176 rheumatoid arthritis, 167 systemic lupus erythematosus, 126 juvenile inflammatory arthritis, 61 inflammatory spondyloarthritis, 57 Sjogren's syndrome, 44 seronegative arthritis, 40 undifferentiated connective tissue disease, 42 psoriatic arthritis, 14 vasculitis, 15 inflammatory myositis, 12 adult onset still's disease, 9 scleroderma and 112 miscellaneous conditions including hypermobility and fibromyalgia. 852 unique pregnancy or pre-pregnancy encounters were recorded in 753 women. 185 of these encounters were for PPC only. Of the 667 encounters with a current or subsequent pregnancy within 2 years (or within the period of data collection ending for those seen after 2021) there were 600 encounters resulting in livebirth (587 singleton infants, 13 sets of twins of whom 25 were liveborn), 4 stillbirths (1 of whom was a twin), 34 miscarriages, 1 ectopic pregnancy and 4 terminations. In 5 the pregnancy is ongoing at the time of writing. In 20 the pregnancy outcome is unknown. Not all pregnancies had complete outcome data. Among the 612 live borns, there were 3 neonatal deaths (including 1 twin) and 8 congenital defects. Among 600 encounters resulting in livebirths – 282 delivered via c-section, 268 delivered vaginally, and in 50 it wasn't recorded. Among 603 encounters resulting in livebirths and/or stillbirths, 12 were recorded as having gestational hypertension, 22 pre-eclampsia, 58 gestational diabetes and 10 obstetric cholestasis. 103 of these encounters were in women known to be anti-Ro positive (including 4 women with twins); 2 cases of CHB occurred (ratio 1:51.5). Both CHB cases were born to mothers with previously affected infants; 1 of the mothers could not take hydroxychloroquine due to retinopathy. Of singleton livebirths with sufficient documentation to calculate, 109/468 (23.3%) were small for gestational age (SGA; birthweight below 10th centile; rate in general UCLH population 15%), and 56/508 (11%) were born pre-term (<37 weeks; UK-wide 7.6% of babies born preterm). There were no maternal deaths within a year of pregnancy.
Conclusion:
We report the longest and largest Obstetric Rheumatology clinic experience in the literature to date. Multidisciplinary specialist care of women with iRMD achieves good pregnancy outcomes but with an ongoing risk of CHB, SGA and prematurity.
REFERENCES:
NIL.
Acknowledgements:
Dr Bethan Goulden and Dr George Woodward contributed equally to this abstract and are co-main authors on this study.
Disclosure of Interests:
Bethan Goulden: None declared, George Woodward: None declared, Siddharth Jain: None declared, Sophie Leiner: None declared, Trini Mitra: None declared, Hanh Nguyen: None declared, Diane Nzelu: None declared, David Williams: None declared, Ian Giles Speaker fees for UCB, honoraria as a co-author on an educational review article in 2020 for MGP, Payment for advisory board for UCB (manufacturer of cimzia), Unrestricted research grant for clinical PhD fellowship.
depression status on objectively and subjectively measured physical health outcomes over a 2-year follow-up period.Methods: A secondary data analysis of a clinical trial (CARDERA) was performed.CARDERA was a 2-year randomized double-blind factorial trial in 467 patients with RA within 2 years of diagnosis.Patients were recruited from 42 centres across England and Wales and randomized into 1 of 4 factors: MTX monotherapy; MTX and ciclosporin; MTX and prednisolone; and Triple Therapy.Depression was measured using the EQ-5D, and data for 9 physical health outcomes were available: Larsen score; tender joint count (TJC); swollen joint count (SJC); ESR; assessor and patient global assessments (AGA/PGA); HAQ; pain; and DAS-28.Multi-level regression models were created for each outcome in 3 stages: unadjusted; adjusted for demographics (data not shown); additionally adjusted for clinical variables, including treatment group.Results: Data were available for 379 patients.Patients' mean age was 54.1 (12.3), and 68.3% of the sample were female.In total, 44.9% had no depression symptoms, 48.7% had some depressive symptoms and 6.5% had severe depression symptoms.Before adjusting for any covariates, in comparison with patients with no depression at baseline, patients with some level of depression showed significantly higher follow-up AGA (d ¼ 0.25, P ¼ 0.02), HAQ (d ¼ 0.44, P < 0.001), PGA (d ¼ 0.37, P < 0.001), Pain (d ¼ 0.33, P < 0.001) and DAS-28 (d ¼ 0.34, P < 0.01) scores.Patients with severe depression had significantly higher DAS-28 (d ¼ 0.86, P < 0.001), SJC (0.70, P < 0.01), AGA (d ¼ 0.56, P ¼ 0.01), PGA (d ¼ 0.87, P < 0.001)and pain levels (d ¼ 0. 86, P < 0.001), in comparison with patients with no depression.After controlling for all demographic and clinical variables, depression status remained a significant predictor of DAS-28 (d ¼ 0.47, P < 0.05) and TJC (d ¼ 0.44, P < 0.05) outcomes, and a medium non-significant effect size was also seen in PGA (d ¼ 0.39, P ¼ 0.06) and HAQ outcomes (d ¼ 0.28, P ¼ 0.09).Conclusion: Depression is a significant predictor of several crucial subjective and objective physical health outcomes, over and above physical and medication variables.Of particular note is the impact of depression on the DAS-28, a clinical tool often used for medical and treatment decision-making.These results have key implications for the development of mental health interventions to improve physical health in RA.
Synovial fluid analysis is an indispensable investigation to attain a diagnosis in a patient with acute hot swollen joint(s), septic arthritis in particular. A delay in appropriate early management results in serious undesired consequences.We evaluated clinical practice at two teaching hospitals including 81 patients. We analysed medical records, laboratory pathology results and discharge summaries with regard to documentation of joint aspiration, blood cultures, antibiotic treatment and specialist referral. We then conducted a survey of 140 medical trainees to evaluate their self-reported competence at managing the acute hot swollen joint.We found that synovial aspiration and blood cultures were performed in only 42(52%) and 30(37%) patients, respectively, not in accord with current guidelines. Given trainee doctors are responsible for the early management of acute hot swollen joint(s), our survey reveal low self-reported levels of competence and confidence at managing acute hot swollen joint(s) in 72(52%) and 37(27%) respondents, respectively. Furthermore, 101(75%) trainees indicated a need for more training in joint aspiration. We also report that 13 of 15 hospitals surveyed in London and South East UK do not provide specific training on the management of the hot swollen joint and joint aspiration as part of their induction programme.Early management of patients with hot swollen joint(s) to perform synovial fluid aspiration and blood cultures are not being done in accordance with guidelines. We suggest that the medical trainee curricula should incorporate joint aspiration skills as an 'essential procedure', to improve the trainee doctor's confidence and competence at managing acute hot swollen joint(s) to improve adherence to guidelines, and consequently, patient outcomes.
Rheumatoid arthritis (RA) is an autoimmune rheumatic disease (ARD) characterised by circulating autoantibodies, including anti-citrullinated protein antibodies (ACPA). Many RA patients have extra-articular disease, including ∼10% with interstitial lung disease (ILD). Risk factors for RA-ILD include: male sex; age; smoking history and ACPA positivity.
Hypothesis
We propose that RA-IgG, including ACPA, modulate neutrophil functions including: generation of reactive oxygen species (ROS), neutrophil adhesion and generation of neutrophil extracellular traps (NETs) that may contribute to joint and extra-articular tissue damage, including ILD.
Methods
Neutrophils and IgG were isolated from RA patients or healthy controls (HC). Bronchoalveolar lavage (BAL) was performed on ILD patients and controls underdoing bronchoscopy for other reasons. ROS production was measured using an enzymatic assay to assess hydrogen peroxide (H2O2) generation. Neutrophil integrins were quantified by flow cytometry. Effects of purified IgG upon neutrophil adhesion to immobilised fibrinogen (Mac-1/aMß2-dependent) and fibronectin (VLA-4/a4ß1-dependent) were determined using a fluorescent adhesion assay. NETosis was measured using a novel capture ELISA.
Results
We demonstrated increased NETs in the BAL of patients with active ILD (n = 3; ARD-ILD) compared to those with inactive disease (n = 2; IPF and ARD-ILD) or controls (n = 1; CLL). In addition, we showed binding of RA-IgG to control neutrophils, which increased with neutrophil activation. Stimulation of HC (n = 12) and RA (n = 7) neutrophils with PMA produced similar rates of H2O2 generation (p = 0.9939). Exposure of HC neutrophils to RA-IgG (n = 9) however, increased H2O2 production compared to HC-IgG (n = 9) (p < 0.0001), which was not blocked by FcR blockade. RA-IgG also enhanced PMA-stimulated adhesion of HC neutrophils to fibrinogen (p = 0.0028) and fibronectin (p = 0.0024), which was inhibited by aMß2 or ß1 integrin blockade respectively. RA-IgG increased both spontaneous (p = 0.0248) and PMA-induced (p = 0.0200) NETosis of HC neutrophils compared to HC-IgG. Immunofluorescence studies demonstrate that aMß2 activation induces NETosis. Further examination found that NETosis could be suppressed by p38 MAPK inhibition (p = 0.0034).
Conclusion
We have shown that RA-IgG modulates several aspects of neutrophil activation and function. In addition, we found increased neutrophil activation in the lungs of patients with active ARD-ILD. Further work is underway to evaluate the contribution of these processes to the pathogenesis of RA-ILD.
Suppression of the polarization drift of optical fiber ring resonators is investigated both theoretically and experimentally by employing anisotropy in a polarization maintaining fiber ring. A general analytic expression for the transmission of the device is derived allowing the fiber modes to exhibit any combination of polarization crosstalk, differential loss or differential coupling. The analysis shows that a moderate level of ring anisotropy, such as that of 10 dB in line polarizer or polarization selective coupler, is sufficient to greatly suppress the drift of the eigenstates of polarization (ESOPs), finesse and resonant point, restoring the device's suitability for most practical applications. An inevitable consequence of introducing ring anisotropy is the loss of orthogonality of the ESOPs. This effect limits the anticipated benefit in high sensitivity applications. A practical anisotropic PMRR is demonstrated by inserting a thin film of nematic liquid crystal between the two halves of the polished coupler of the ring. This resonator demonstrates a polarization response immune to environmental perturbations.
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