Does remission in systemic lupus erythematosus according to the 2021 DORIS definition match the treating rheumatologist's judgement?

OBJECTIVES: To assess agreement between the 2021 Definition Of Remission In SLE (DORIS) and physician-judged lupus activity. METHODS: A cross-sectional analysis was conducted of data from a Spanish prospective multicentre study of SLE patients. We applied the 2021 DORIS criteria and assessed whether remission status based on this definition agreed with remission as per physician clinical judgement and reasons for disagreement between them. RESULTS: Out of 508 patients [92% women; mean age (s.d.): 50.4 years (13.7)] studied, 267 (54.4%) met the criteria for 2021 DORIS remission. Based on physicians' judgement, 277 (55.9%) patients were classified as in remission or serologically active clinically quiescent (SACQ). The overall rate of agreement between these assessments was 81.2% (95% CI: 79.9, 82.9%) with a Cohen's kappa of 0.62 (0.55-0.69). Overall, 46 (9.1%) patients were classified as in remission/SACQ by rheumatologists but did not meet the 2021 DORIS criteria for remission. The main reasons for discrepancies were a clinical SLE Disease Activity Index (cSLEDAI) score >0 in 39 patients, a Physician Global Assessment score >0.5 in five patients, and prednisone >5 mg/day in another five patients. CONCLUSIONS: The 2021 DORIS remission is an achievable target in clinical practice. There is substantial agreement between the DORIS definition and physician-judged remission. The discordance was mainly due to physicians classifying some patients with ongoing mild disease activity as in remission. Thus, the standardized DORIS definition should be used to define the target in a treat-to-target strategy for the management of SLE.

Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients.

OBJECTIVES: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. METHODS: A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. RESULTS: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. CONCLUSION: Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

Does expert opinion match the definition of lupus low disease activity state? Prospective analysis of 500 patients from a Spanish multicentre cohort.

OBJECTIVES: To apply the lupus low disease activity state (LLDAS) definition within a large cohort of patients and to assess the agreement between the LLDAS and the physician's subjective evaluation of lupus activity. METHODS: We conducted a cross-sectional analysis of a prospective multicentre study of SLE patients. We applied the LLDAS and assessed whether there was agreement with the clinical status according to the physician's opinion. RESULTS: A total of 508 patients [92% women; mean age 50.4 years (s.d. 3.7)] were recruited and 304 (62.7%) patients were in the LLDAS. According to physician assessment, 430 (86.1%) patients were classified as remission or low activity. Overall agreement between both evaluations was 71.4% (95% CI: 70.1, 70.5) with a Cohen's κ of 0.3 [interquartile range (IQR) 0.22-0.37]. Most cases (96.1%) in the LLDAS were classified as remission or low activity by the expert. Of the patients who did not fulfil the LLDAS, 126 (70.4%) were classified as having remission/low disease activity. The main reasons for these discrepancies were the presence of new manifestations compared with the previous visit and a SLEDAI 2K score >4, mainly based on serological activity. CONCLUSIONS: Almost two-thirds of SLE patients were in the LLDAS. There was a fair correlation between the LLDAS and the physician's evaluation. This agreement improves for patients fulfilling the LLDAS criteria. The discordance between both at defining lupus low activity, the demonstrated association of the LLDAS with better outcomes and the fact that the LLDAS is more stringent than the physician's opinion imply that we should use the LLDAS as a treat-to-target goal.

2022 Systemic lupus erythematosus remission in clinical practice. Message for Polish rheumatologists.

Systemic lupus erythematosus (SLE) is a complicated multiorgan disease and can lead to organ damage and increased risk of morbidity and mortality. The strategy of management while avoiding complications, especially caused by chronic glucocorticoid therapy, improves outcomes. Different definitions of the treatment goal in different configurations of lupus activity indexes have appeared over the years. In 2021 the definition of remission and recommendations for its achievement were published and it become a way to implement a treat-to-target strategy. The main goal of treatment has become DORIS (definition of remission in SLE) remission and the alternative LLDAS (low lupus disease activity state). Prolonging remission with clinical and immunological lupus activity restrictions and minimizing or stopping steroid doses reduced flares and damage accrual. The analysis and neutralization of poor prognosis predictive factors in lupus could be the most beneficial for less morbidity and mortality and better quality of life.

Remission in SLE-do DORIS criteria match the treating physician's judgment? A cross-sectional study to assess reasons for discordance.

OBJECTIVES: The definition of an accurate target for a treat-to-target approach in SLE has been challenging over past years, and recently the DORIS definitions of remission were presented by the international DORIS task force. It was our aim to assess the frequency of DORIS remission and LLDAS in our SLE cohort and their agreement with the treating physician's (DORIS-) independent remission judgement. Patient characteristics leading to lack of agreement and incoherence ought to be identified. METHODS: In this monocentric cross-sectional study, patients with SLE were enrolled and assessed between September 2016 and December 2017. DORIS remission definitions were applied and after the clinical consultation, the treating physicians gave his/her opinion on whether the patient was in remission. Regression analyses were performed to identify parameters influencing physician remission. RESULTS: A total of 233 patients were included (87.6% female); 99 (42.5%) patients fulfilled any of the four DORIS remission definitions, while 126 patients were in remission according to their physician's judgement. We observed discordance in the assessment of remission in 53 patients (22.7%). Physician remission was influenced by disease activity [odds ratio (OR) 0.76, 95% CI: 0.63, 0.90], disease and/or treatment-related damage (OR 0.78, 95% CI: 0.62, 0.98) and the presence of ds-DNA antibodies (OR 2.47, 95% CI: 1.06, 6.04). CONCLUSIONS: DORIS remission proved an achievable target in our outpatient clinic. Still we found discordance regarding DORIS remission and the treating physician's judgement with a greater number of patients considered in remission by their physicians.

Analysis of 25 Years of Polar Motion Derived from the DORIS Space Geodetic Technique Using FFT and SSA Methods.

Polar motion (PM) has a close relation to the Earth's structure and composition, seasonal changes of the atmosphere and oceans, storage of waters, etc. As one of the four major space geodetic techniques, doppler orbitography and radiopositioning integrated by satellite (DORIS) is a mature technique that can monitor PM through precise ground station positioning. There are few articles that have analyzed the PM series derived by the DORIS solution in detail. The aim of this research was to assess the PM time-series based on the DORIS solution, to better capture the time-series. In this paper, Fourier fast transform (FFT) and singular spectrum analysis (SSA) were applied to analyze the 25 years of PM time-series solved by DORIS observation from January 1993 to January 2018, then accurately separate the trend terms and periodic signals, and finally precisely reconstruct the main components. To evaluate the PM time-series derived from DORIS, they were compared with those obtained from EOP 14 C04 (IAU2000). The results showed that the RMSs of the differences in PM between them were 1.594 mas and 1.465 mas in the X and Y directions, respectively. Spectrum analysis using FFT showed that the period of annual wobble was 0.998 years and that of the Chandler wobble was 1.181 years. During the SSA process, after singular value decomposition (SVD), the time-series was reconstructed using the eigenvalues and corresponding eigenvectors, and the results indicated that the trend term, annual wobble, and Chandler wobble components were accurately decomposed and reconstructed, and the component reconstruction results had a precision of 3.858 and 2.387 mas in the X and Y directions, respectively. In addition, the tests also gave reasonable explanations of the phenomena of peaks of differences between the PM parameters derived from DORIS and EOP 14 C04, trend terms, the Chandler wobble, and other signals detected by the SSA and FFT. This research will help the assessment and explanation of PM time-series and will offer a good method for the prediction of pole shifts.

[Treat to target in systemic lupus erythematosus]. / Treat-to-Target beim systemischen Lupus erythematodes.

BACKGROUND: For the first time, the European League Against Rheumatism (EULAR) recommendations for the management of systemic lupus erythematosus (SLE) include a treat to target (T2T) strategy, naming remission as the main target. The aim is to improve the long-term survival, prevent damage and optimize the health-related quality of life. Compared to rheumatoid arthritis (RA) for which the T2T approach is already widely used, establishing T2T in SLE remains challenging due to its heterogeneity and limited treatment options. OBJECTIVE: The aim of this article is to outline the current status of the T2T concept for SLE and to identify challenges and particularities. A special focus is placed on the use of activity scores and the importance of steroids in targeted treatment of SLE. RESULTS AND CONCLUSION: The use of T2T for SLE remains a challenge. With the definitions of the lupus low disease activity states (LLDAS) and the definitions of remission in SLE (DORIS) a big step forward has been taken on the road towards the ideal treatment target; however, many aspects of the "treat" remain unclear. As an example, due to a lack of data there are no explicit strategies for steroid reduction although it is often mandatory to achieve the targets. The T2T also includes much more than only immunosuppressive treatment and antimalarial agents, as disease damage which has already occurred and damage due to drugs, concomitant phenomena (such as depression) and comorbidities as well as measures for secondary prophylaxis must also be included.

Use of belimumab in treating patients with systemic lupus erythematosus: a single-center, real-world retrospective study.

OBJECTIVE: To investigate the efficacy and safety of belimumab in the treatment of systemic lupus erythematosus (SLE) in a real-world setting and provide a valuable reference for clinical treatment. METHODS: In this retrospective study, 101 patients with SLE who came to our hospital from March 2020 to September 2022, 56 of whom with lupus nephritis (LN), were selected. All patients received belimumab in combination with standard of care(SoC)therapy regimen for more than 52 weeks and their clinical/laboratory data, assessment of disease activity, glucocorticoids dosage and occurrence of adverse events were recorded. Lupus Low Disease Activity State (LLDAS) and DORIS remission as a primary goal in the treatment of SLE. The groups were classified according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K): SLEDAI-2 K < 6 was categorized as the mild group (mild activity) and SLEDAI-2 K ≥ 6 was categorized as the active group (moderate-severe activity). The disease of the two groups mentioned above were assessed using the SELENA-SLEDAI Flare Index (SFI) and the SLE Responder Index-4 (SRI-4), respectively. Furthermore, we used complete remission (CR) and partial remission (PR) in the kidney as the standard for efficacy evaluation for LN patients. RESULTS: After 52 weeks of treatment with belimumab, patients' complement levels increased significantly (p < 0.05); Other indicators such as 24-hour urine protein quantification and daily glucocorticoids dose decreased compared to pretreatment (p < 0.05). At 52 weeks, (i) after evaluation, the whole group of patients showed significant improvement in their condition; (ii) 55.4% of patients achieved LLDAS and 23.8% achieved DORIS remission; (iii) 73.2% of patients with LN achieved CR, 16.1% achieved PR. Adverse reactions were observed in 15 patients (14.9%), all of which normalized after symptomatic treatment. CONCLUSIONS: In general, during treatment with belimumab, immunological and biochemical indices improved in SLE patients, urinary protein levels were reduced in LN patients, and the rate of renal function remission was effectively increased; At the same time, the use of belimumab is associated with a low frequency of side effects, good overall tolerability and a favorable safety profile.

Targeting DORIS Remission and LLDAS in SLE: A Review.

Remission is the established therapeutic goal for patients with systemic lupus erythematosus (SLE) and is currently defined by the widely adopted Definition Of Remission In SLE (DORIS) criteria. Attainment of remission is rare in the clinical setting, thus an alternative, pragmatic treatment target of low disease activity, as defined by the Lupus Low Disease Activity State (LLDAS), provides a less stringent and more attainable treatment goal for a wider proportion of patients compared with DORIS remission. Randomized controlled trials and real-world analyses have confirmed the positive clinical benefits of achieving either DORIS remission or LLDAS. The treat-to-target (T2T) approach utilizes practical clinical targets to proactively tailor individual treatment regimens. Studies in other chronic inflammatory diseases using the T2T approach demonstrated significantly improved clinical outcomes and quality-of-life measures compared with established standard of care. However, such trials have not yet been performed in patients with SLE. Here we review the evolution of DORIS remission and LLDAS definitions and the evidence supporting the positive clinical outcomes following DORIS remission or LLDAS attainment, before discussing considerations for implementation of these outcome measures as potential T2T objectives. Adoption of DORIS remission and LLDAS treatment goals may result in favorable patient outcomes compared with established standard of care for patients with SLE.

Systemic lupus erythematosus (SLE) is a complex disease that can affect many organs. It can lead to life-threatening complications and poor quality of life. As SLE is very different in each person, it can be challenging to measure disease activity. Doctors are encouraged to set clinical targets to tailor treatment for each patient. Clinical targets include scoring systems that measure disease improvement. Remission is an established clinical target. When a patient is in remission, disease activity is controlled, and the patient does not experience any symptoms. As remission is difficult to achieve, experts developed a more realistic yet still favorable state. This is the lupus low disease activity state, when lupus symptoms are minimal on stable therapy. Doctors use remission and low disease activity in clinical trials to compare existing SLE drugs with new treatments, including biologic drugs. Biologics target key parts of the immune system to help suppress SLE. In this review, we looked at recent clinical trials and found that biologic drugs can help patients achieve remission or low disease activity. Patients who achieved these clinical targets had slower disease progression and improved quality of life. Clinical trials in SLE should continue to use remission and low disease activity targets to help compare treatments. Doctors are encouraged to use them in their routine clinics as treatment targets to measure SLE disease control. Low disease activity state may be particularly helpful as an initial target for patients who are not yet in remission.

Moments of realization: extending Homeworld in British-African Novelist Doris Lessing's Four-Gated City.

For Husserl, the homeworld is the tacit, taken-for-granted sphere of experiences, understanding, and situations marking out a world that is comfortable, usual, and "the way things are and should be." Always, according to Husserl, the homeworld is in some mode of lived mutuality with an alienworld-a world as seen as a realm of difference, atypicality, and otherness. In this article, I draw on British-African novelist Doris Lessing's 1969 novel, The Four-Gated City, to consider the shifting homeworld of protagonist Martha Quest, a young white African woman emigrating to battle-scarred London immediately after World War II. Throughout the novel, Quest finds herself in unfamiliar or challenging situations where the world she takes for granted is called into question. Lessing draws on these life-testing experiences to portray Quest's shifting understandings of other individuals' homeworlds that at first she sees as atypical, abnormal, or unreal.

Establishing the places of care for the old people in The Diaries of Jane Somers by Doris Lessing.

The Nobel-prize winner Doris Lessing brings forward the significance of caring for the old and dying people in her novel The Diaries of Jane Somers, which reveals that human flourishing is based on responsibility, interdependency, and trust between the carer and cared for. In this novel, Lessing mainly emphasizes the significance of caring for both close relatives and distant others who suffer from old age and sickness via the protagonist Jane Somers, who develops unconditional care for a ninety-year-old woman, Maudie Fowler. By depicting Jane's transformation into a caring and interdependent character, contrary to her earlier indifference and autonomy, Lessing proposes that the claims of the old, the sick, and the dying people could be responded to by sharing their experiences and feelings, especially in their personal places. In this respect, this study aims to explore the relationship between literature and care ethics within the scope of ageing studies. This study will embrace the claims of care ethicists and analyse how they are reflected in a literary work. Thus, the aim is to create awareness through literature about caring for older, sick, and dying people by establishing or sharing the places of care, such as older people's homes, rooms, beds, bathrooms, and even deathbeds.

Modernizing and Expanding the NASA Space Geodesy Network to Meet Future Geodetic Requirements.

NASA maintains and operates a global network of Very Long Baseline Interferometry (VLBI), Satellite Laser Ranging (SLR), and Global Navigation Satellite System (GNSS) ground stations as part of the NASA Space Geodesy Program. The NASA Space Geodesy Network (NSGN) provides the geodetic products that support Earth observations and the related science requirements as outlined by the US National Research Council (NRC 2010, 2018). The Global Geodetic Observing System (GGOS) and the NRC have set an ambitious goal of improving the Terrestrial Reference Frame (TRF) to have an accuracy of 1 millimeter and stability of 0.1 millimeters per year, an order of magnitude beyond current capabilities. NASA and its partners within GGOS are addressing this challenge by planning and implementing modern geodetic stations co-located at existing and new sites around the world. In 2013, NASA demonstrated the performance of its next-generation systems at the prototype next-generation core site at NASA's Goddard Geophysical and Astronomical Observatory in Greenbelt, Maryland. Implementation of a new broadband VLBI station in Hawaii was completed in 2016. NASA is currently implementing new VLBI and SLR stations in Texas and is planning the replacement of its other aging domestic and international legacy stations. In this article, we describe critical gaps in the current global network and discuss how the new NSGN will expand the global geodetic coverage and ultimately improve the geodetic products. We also describe the characteristics of a modern NSGN site and the capabilities of the next-generation NASA SLR and VLBI systems. Finally, we outline the plans for efficiently operating the NSGN by centralizing and automating the operations of the new geodetic stations.

Differential transcriptional analysis between red and white skeletal muscle of Chinese Meishan pigs.

In order to better understand and elucidate the major determinants of red and white muscle phenotypic properties, the global gene expression profiling was performed in white (longissimus doris) and red (soleus) skeletal muscle of Chinese Meishan pigs using the Affymetrix Porcine Genechip. 550 transcripts at least 1.5-fold difference were identified at p < 0.05 level, with 323 showing increased expression and 227 decreased expression in red muscle. Quantitative real-time PCR validated the differential expression of eleven genes (alpha-Actin, ART3, GATA-6, HMOX1, HSP, MYBPH, OCA2, SLC12A4, TGFB1, TGFB3 and TNX). Twenty eight signaling pathways including ECM-receptor interaction, focal adhesion, TGF-beta signaling pathway, MAPK signaling pathway, Wnt signaling pathway, mTOR signaling pathway, insulin signaling pathway and cell cycle, were identified using KEGG pathway database. Our findings demonstrate previously unrecognized changes in gene transcription between red and white muscle, and some potential cascades identified in the study merit further investigation.

Application of modified latissimus dorsi flap for repairing huge skin and soft tissue defects in lower limbs / 中华显微外科杂志

Objective To explore the feasibility and clinic outcome of the modified latissimus dorsi flap when it is used to repair huge soft tissue defects in lower limbs.Methods The latissimus dorsi muscle is rich blood supply and available for harvest huge areas.According to these characteristics the modified latissimus dorsi flap was designed:a limited latissimus dorsi skin flap with a large area of latissimus dorsi muscle flap,skin graft area was transferred from donor-site to recipient-site.From April 2009 to August 2011,ten patients with large soft tissue defects in lower limbs were treated with modified latissimus dorsi flap.The size of skin and soft tissue defects range from 19 cm × 10 cm to 32 cm × 16 cm.Ten modified latissimus dorsi flaps had been used for coverage of these wounds,which were amplified 1-2 cm compared with the corresponding wounds.The size of skin flap was 20 cm × 6 cm-33 cm × 10 cm which was allowable to get direct closure of donor-site wounds.Results All the flaps and skin graft survived completely with no complication.Donor-site and recipient-site were primary closed and healing in all patients.All of the patients had got follow-up from 6 months to 36 months.All flaps survived with excellent color and quality,and no extremely fat contour.The results in donor site were satisfying and only left liner scar.It has no effect in the shoulder function.Conclusion The modified latissimus doris flap can provide with a huge amount of skin and soft tissue and be designed in various ways.It is a safe and reliable way to reconstruct huge skin and soft tissue defect in lower limbs.