Lupus remains a disease with a low prioritisation in the national agendas of many countries in Latin America, the Middle East, and Asia-Pacific, where there is a dearth of rheumatologists and limited access to new or even standard lupus treatments. There is thus an important need for education, advocacy, and outreach to prioritise lupus in these regions to ensure that patients receive the care they need. This article reviews some of the specific challenges facing the care and management of people with lupus in these regions and suggests strategies for improving patient outcomes. Specifically, we review and discuss (with a focus on the aforementioned regions) the epidemiology of lupus; economic costs, disease burden, and effects on quality of life; barriers to care related to disease assessment; barriers to effective treatment, including limitations of standard treatments, high glucocorticoid use, inadequate access to new treatments, and low adherence to medications; and strategies to improve lupus management and patient outcomes. We hope that this represents a call to action to come together and act now for the lupus community, policymakers, health authorities, and healthcare professionals to improve lupus management and patient outcomes in Latin America, the Middle East, and Asia-Pacific.

BACKGROUND: Existing therapies of systemic lupus erythematosus (SLE) are efficacious only in certain patients. Developing new treatment methods is urgent. This meta-analysis aimed to evaluate the efficacy and safety of low-dose IL-2 (LD-IL-2).
METHODS: According to published data from PubMed, Web of Science, Embase, ClinicalTrials.gov, MEDLINE, MEDLINE, Web of Knowledge, Cochrane Library, and FDA.gov, eight trials were included.
RESULTS: After the LD-IL-2 treatment, 54.8% of patients had distinct clinical remission. The SRI-4 response rates were 0.819 (95% confidence interval [CI]: 0.745-0.894), and the SELENA-SLEDAI scores were significantly decreased (SMD = -2.109, 95% CI: [-3.271, -0.947], p < .001). Besides, the proportions of CD4+ T (SMD = 0.614, 95% CI: [0.250, 0.979], p = .001) and Treg cells (SMD = 1.096, 95% CI: [0.544, 1.649], p < .001) were increased dramatically after LD-IL-2 treatment, while there were no statistical differences in the proportions of CD8+ T cells, Th1 cells, Th2 cells, and Th17 cells (p > .05). Besides, the proportions of Th17 (SMD = 1.121, 95% CI: [0.709, 1.533], p < .001) and Treg (SMD = 0.655, 95% CI: [0.273, 1.038], p = .001) were significantly increased after receiving subcutaneously 0.5 million IU of LD-IL-2 treatment per day for 5 days, but there were no statistical differences in the proportions of Treg after receiving 1 million IU every other day subcutaneously of LD-IL-2 treatment. Injection site reaction and fever were common side effects of IL-2, which occurred in 33.1% and 14.4% of patients. No serious adverse events were reported.
CONCLUSIONS: LD-IL-2 was promising and well-tolerated in treating SLE, which could promote Treg\'s proliferation and functional recovery. Injecting 0.5 million IU of IL-2 daily can better induce the differentiation of Treg cells and maintain immune homeostasis than injecting 1 million IU every other day.

OBJECTIVE: We initially explored the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T (Treg) cells by detecting the lncRNA expression profiles in patients with systemic lupus erythematosus (SLE), then analyzed the correlation between Treg-related lncRNAs and the clinical features of SLE patients, predicting the mechanism by which lncRNAs regulate the differentiation and development of Treg cells, and provided new ideas for the treatment of SLE.
METHODS: Peripheral blood of 9 active SLE patients were collected and mononuclear cells (PBMCs) were extracted; the lncRNA expression profiles of PBMCs were analyzed by whole transcriptome sequencing. Nine healthy people were used as controls to screen the differentially expressed lncRNAs, to analyze the correlation between lncRNAs and Treg cell number. Pearson test was used to analyze the correlation between lncRNAs and the number of Treg cell, and the correlation between Treg-associated lncRNA and SLEDAI score, ESR, C3, and C4 in SLE patients. The targeted genes of Treg-associated lncRNAs were predicted with miRcode and Targetscan databases and coexpression network.
RESULTS: There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs (p < 0.05) and 106 lowly expressed lncRNAs (p < 0.05). The expression of ANKRD44-AS1 (r = 0.7417, p = 0.0222), LINC00200 (r = 0.6960, p = 0.0373), AP001363.2 (r = 0.7766, p = 0.0138), and LINC02824 (r = 0.7893, p = 0.0114) were positively correlated with the number of Treg cell, and the expression of AP000640.1 (r = - 0.7225, p = 0.0279), AC124248.1 (r = - 0.7653, p = 0.0163), LINC00482 (r = - 0.8317, p = 0.0054), and MIR503HG (r = - 0.7617, p < 0.05) were negatively correlated with the number of Treg cell. Among these Treg-associated lncRNAs, the expression of LINC00482 (r = - 0.7348, p < 0.05) and MIR503 HG (r = - 0.7617, p < 0.05) were negatively correlated with C3. LINC00200, ANKRD44 - AS1, and AP000640.1 related to Treg cells regulate the expression of signal transducer and activator of transcription 5 (STAT5), phospholipase D1 (PLD1), homeodomain-only protein X (HOPX), and runt-related transcription factor 3 (RUNX3) through competitive binding of miRNA or trans-regulatory mechanism, thereby regulating the differentiation and development of Treg cell.
CONCLUSIONS: The lncRNA expression profiles were changed in SLE patients, the differentially expressed lncRNAs were associated with abnormal number and function of Treg cells in SLE, and Treg-associated lncRNAs were associated with SLE-disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Treg cell function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism. Key points • Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and systems. lncRNAs may affect Treg cells function by regulating genes expression, which may be an important pathogenesis of SLE. • This study, taking SLE as an example, preliminarily analyzed the correlation between lncRNA and Treg cells in SLE patients, analyzed the correlation between Treg-related lncRNA and the clinical characteristics of SLE, and speculated that lncRNA could regulate the differentiation and development of Treg cells through competitive combination with miRNA or trans-regulatory mechanisms. • It is possible to target epigenetic therapy for SLE.

UNASSIGNED: Inflammatory burden index (IBI) is a systemic inflammation indicator that reflects the inflammatory status. We aimed to investigate the prognostic value of IBI after endovascular thrombectomy (EVT) in patients with acute ischemic stroke.
UNASSIGNED: We enrolled patients treated with EVT from a multicenter cohort between June 2020 and December 2021. The IBI was calculated as C-reaction protein × neutrophil / lymphocyte count. The primary outcome was the unfavorable functional outcome (90-day modified Rankin scale score 3-6). C-statistics and net reclassification indexes were used to assess the predictive accuracy. Multivariable logistic regression models were used to investigate the association between IBI and unfavorable outcome.
UNASSIGNED: A total of 295 patients (mean age, 64.0 ± 12.8 years; male, 63.7%) were enrolled in this study. In multivariable models, higher IBI levels were associated with an increased risk of 90-day unfavorable outcome after EVT (per 1-SD: odds ratio, 1.754; 95% confidence interval, 1.241-2.587; P = 0.002). Restricted cubic spline curve displayed a linear relationship between the IBI level and 90-day unfavorable outcome (P for nonlinearity = 0.410). Besides, IBI was a more accurate biomarker for predicting unfavorable outcomes with the highest predictive accuracy and reclassification indexes.
UNASSIGNED: This study demonstrated that higher IBI was associated with an increased risk of 90-day unfavorable outcome in acute ischemic stroke treated with EVT.

UNASSIGNED: To explore the lessons learned from the misdiagnosis of systemic lupus erythematosus (SLE) combined with urinary tuberculosis leading to tuberculous meningitis (TBM) and the diagnosis and treatment of TBM through case reports and review of the literature.
UNASSIGNED: We report a case of an SLE patient presenting with urinary tuberculosis infection misdiagnosed as interstitial cystitis and complex urinary tract infection, who developed neurological infection after a cystocentesis biopsy and was eventually diagnosed with TBM. In addition, all cases of SLE combined with TBM from January 1975 to February 2022 were summarised and reviewed to compare current diagnostic and treatment strategies for the disease.
UNASSIGNED: The patient suddenly developed neurological symptoms after cystocentesis biopsy, and we detected Mycobacterium tuberculosis in the macrogenomic next-generation sequence (mNGS) of the cerebrospinal fluid. We therefore excluded interstitial cystitis and neuropsychiatric lupus to confirm the diagnosis of Mycobacterium tuberculosis infection leading to urinary tract tuberculosis and TBM.
UNASSIGNED: SLE is complicated by urological tuberculosis, surgery triggering hematogenous dissemination leading to tuberculous meningitis. At the same time, the lack of specificity in the clinical presentation of patients makes it easy to misdiagnose neuropsychiatric lupus and delay treatment, so timely and accurate diagnosis and effective anti-tuberculosis treatment are essential.

Neuropsychiatric involvement is one of the major concerns in systemic lupus erythematosus (SLE). The therapeutic effect of intrathecal treatment of methotrexate and dexamethasone has been investigated in some exploratory studies, but its influence on the long-term prognosis of neuropsychiatric SLE (NPSLE) remains unknown.
This was a propensity score-matched retrospective study. Outcomes at discharge and time free from NPSLE relapse or death were evaluated by multivariate logistic regression, survival analysis, and Cox regression as appropriate.
Among 386 hospitalized patients with NPSLE, the median [IQR] age was 30.0 [23.0-40.0] years, and 342 patients (88.4%) were female. Of those, 194 patients received intrathecal treatment. Patients in the intrathecal treatment group had higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores (median 17 vs. 14 points, IQR 12-22 vs. 10-19 points, P <0 .001) and were more likely to receive methylprednisolone pulse therapy (71.6% vs. 49.5%, P < 0.001) than those who did not receive intrathecal therapy. Intrathecal treatment was associated with a higher probability of survival and being free from NPSLE relapse than control treatment among the 386 unmatched patients (P =0.042 by log-rank test) and within 147 propensity score-matched pairs (P =0.032 by log-rank test). In the subgroup of NPSLE patients with increased levels of protein in cerebrospinal fluid, intrathecal treatment had a positive influence on their prognosis (P < 0.001).
Intrathecal treatment of methotrexate and dexamethasone was associated with a more favorable prognosis of NPSLE and may serve as a valuable additional therapy for NPSLE patients, especially for those with elevated levels of protein in cerebrospinal fluid.

BACKGROUND: We describe a case of relentless placoid chorioretinitis (RPC) that progressed despite administration of peribulbar and systemic corticosteroids, and was resolved by systemic combined with intravitreal methotrexate.
METHODS: A 16-year-old male reported painless blurred vision and a temporal scotoma in his right eye for one week. Due to widespread distribution and continuous enlargement, multimodal imaging of the lesions led to the diagnosis of RPC. Lesions in the right eye extended despite peribulbar injection of triamcinolone acetonide, but the progression was immediately terminated by a single dose of intravitreal methotrexate. A new fresh lesion occurred in the contralateral eye despite systemic prednisolone but was resolved by oral methotrexate.
CONCLUSIONS: Systemic immunosuppressants should be given upon RPC diagnosis. Intravitreal methotrexate immediately halted progression and may be considered for sight-threatening cases as part of the initial therapy.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that represents a prodigious challenge of diagnosis and treatment. In 2019, under the leadership of the Chinese Rheumatology Association, a multidisciplinary guideline development group was established to develop an evidence-based diagnosis and treatment guideline for patients with SLE in PR China. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence and the strength of recommendations. The guideline was reported following the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. In this guideline, we provided recommendations for SLE classification criteria, disease activity monitoring and assessment, medication administration and considerations for SLE patients with organs and systems involved, and management of special populations such as SLE patients in the setting of pregnancy. This guideline serves as an evidence-based tool for Chinese clinicians to diagnose and treat patients with SLE.

OBJECTIVE: The aim of the study was to construct and validate a risk nomogram for clinically significant macular edema (CSME) prediction in diabetes mellitus (DM) patients using systemic variables.
METHODS: In this retrospective study, DM inpatients who underwent routine diabetic retinopathy screening were recruited and divided into training and validation sets according to their admission date. Ninety-three demographic and systemic variables were collected. The least absolute shrinkage and selection operator was used to select the predictive variables from the training set. The selected variables were used to construct the CSME prediction nomogram. Internal and external validations were performed. The C-index, calibration curve and decision curve analysis (DCA) were reported.
RESULTS: A total of 349 patients were divided into the training set (240, 68.77%) and the validation set (109, 31.23%). The presence of diabetic peripheral neuropathy (DPN) symptoms, uric acid, use of insulin only or not for treatment, insulin dosage, urinary protein grade and disease duration were chosen for the nomogram. The C-index of the prediction nomogram was 0.896, 0.878 and 0.837 in the training set, internal validation and external validation, respectively. The calibration curves of the nomogram showed good agreement between the predicted and actual outcomes. DCA demonstrated that the nomogram was clinically useful.
CONCLUSIONS: A nomogram with good performance for predicting CSME using systemic variables was developed. It suggested that DPN symptoms and renal function may be crucial risk factors for CSME. Moreover, this nomogram may be a convenient tool for non-ophthalmic specialists to rapidly recognize CSME in patients and to transfer them to ophthalmologists for early diagnosis and treatment.

To reveal the characteristics of and risk factors for systemic lupus erythematosus (SLE) patients with frequent readmission aiming at intervening early and improve the quality of care during initial hospitalizations. This was a single-center, retrospective case-control study involving 521 hospitalized patients with SLE from January 2014 to December 2016 in the Affiliated Hospital of Guangdong Medical University. A total of 521 patients were enrolled, including 400 patients who were hospitalized once and 121 patients who were hospitalized repeatedly, and 23.2% of the patients were readmitted within 1 year. The results showed that the age of SLE onset (odds ratio [OR] 1.022, 95% confidence interval [CI] 1.007-1.036), serum albumin (OR 0.965, 95% CI 0.942-0.989), and cystatin C (OR 1.404, 95% CI 1.180-1.670) were closely related to readmission. The most common causes of readmission were infections (52 cases, 28.4%), especially respiratory tract infections, and lupus activity or recurrence (45 cases, 24.6%). Special attention should be paid to SLE patients with older age of onset, low serum albumin levels, and high cystatin C levels to avoid infection and recurrence with the aim of reducing the hospital readmission rate.