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Summary: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder whose pathology involves multiple immune cell types, including B and T lymphocytes as well as myeloid cells. While it is clear that autoantibody‐producing B cells, as well as CD4+ T cell help, are key contributors to disease, little is known regarding the role of innate lymphoid cells such as natural killer (NK) cells in the pathogenesis of SLE. We have characterized the phenotype of NK cells by multi‐color flow cytometry in a large cohort of SLE patients. While the overall percentage of NK cells was similar or slightly decreased compared to healthy controls, a subset of patients displayed a high frequency of NK cells expressing the proliferation marker, Ki67, which was not found in healthy donors. Although expression of Ki67 on NK cells correlated with Ki67 on other immune cell subsets, the frequency of Ki67 on NK cells was considerably higher. Increased frequencies of Ki67+ NK cells correlated strongly with clinical severity and active nephritis and was also related to low NK cell numbers, but not overall leukopenia. Proteomic and functional data indicate that the cytokine interleukin‐15 promotes the induction of Ki67 on NK cells. These results suggest a role for NK cells in regulating the immune‐mediated pathology of SLE as well as reveal a possible target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

In recent decades, the global environmental balance has been disrupted due to new environmental conditions and increasing anthropogenic pressure. In this context, the increase in frequency and magnitude of jellyfish proliferation in the Mediterranean Sea can be examined as an indicator closely associated with potential impacts of global changes. Despite their importance in ecosystem function and services, current knowledge of jellyfish diversity and phenology is largely lacking in the southern Mediterranean Sea, particularly along the Moroccan Mediterranean coast. Rhizostoma pulmo is a large scyphozoan jellyfish endemic to the Mediterranean. It is the second dominant scyphozoan species in the jellyfish community of Al Hoceima Bay. In this article, we explore the seasonal dynamics of the jellyfish R. pulmo between the estuaries of Oued Ghis and Nekkour at Souani Beach. Due to the disparity between the visual abundance of jellyfish and their rare beaching along the shores of Al Hoceima Bay, we implemented a specific method for collecting R. pulmo. This approach involves the use of a coastal trawl, a fishing net 200 meters long with a mesh size of 5 cm, deployed 80 meters from the shore and pulled from both sides by fishermen. Sampling missions conducted throughout the year 2022 revealed that R. pulmo reaches its maximum abundance in summer. The results indicate a maximum abundance of 0.28 ind/m2 in July 2022, with a maximum umbrella diameter reaching 26 cm in August 2022. Under the jellyfish umbrellas, fry of two fish species and one crustacean species were observed, adding an ecological dimension to this study.

Cissus quadrangularis (Vitaceae) is a common perennial succulent climber plant belonging to the Vitaceae family. The plant has a strong pharmacological profile with a variety of phytoconstituents and is geographically distributed throughout tropical and subtropical regions of the world. It is prominently found in India, Pakistan, and Bangladesh. The plant is found all over India, but its presence is dominantly observed in states such as Assam, Kerala, Odisha, Madhya Pradesh, Tamil Nadu, and Uttar Pradesh. The plant in India is popularly called ‘Hadjod’ or ‘Asthisamharaka’ and is very well established as a medicine related to the management of bone, muscles, and ligament issues. Traditionally, almost all aerial and underground parts have medicinal value, but the stem is most commonly used. Phytochemicals studies performed on the plant revealed the presence of a variety of constituents, viz., tannins, proteins, carbohydrates, phenol flavonoids, triterpenoids, phytosterols, glycosides, saponins, vitamin C, and alkaloids. In addition, these plants are also a rich source of calcium. The systematic review also established the pharmacological role of the plant as a bone setter and fractured bone healer; its antimicrobial, anti-diabetic, anti-inflammatory, anti-obesity, and anti-oxidant effects; bone turnover; cardiovascular and hepatoprotective properties; and many more. The current review article carried out a detailed discussion of its phytochemical and pharmacological potential.

Clinical research advances medical knowledge and improves healthcare outcomes. However, disparities in research participation hinder progress. The Unmet Research Needs in Spondyloarthritis Conference IV highlighted critical insights and strategies to enhance equity in clinical research. Talks focused on engaging underrepresented communities and addressing disparities in rheumatic diseases, particularly spondyloarthritis (SpA), to ensure research results are generalizable and inclusive. Disparities in SpA management, such as greater back pain severity among Black and Hispanic Americans and sex-based differences in pain management, emphasize the need for equitable research. Dr. Elizabeth Ferucci discussed the racial disparities in rheumatologic care, highlighting the importance of early access to rheumatologists and culturally informed primary care to improve outcomes. Dr. Hani El-Gabalawy's talk on engaging Indigenous communities stressed the importance of community consent and reciprocal benefits. Dr. Sarfaraz Hasni's presentation on mitigating disparities in research participation underscored the need for inclusive practices and strategies to promote diverse representation. Finally, Dr. Edith Williams emphasized institutional approaches to fostering equity, including diverse recruitment practices and institutional review board alignment with diversity priorities. Strategies to enhance equity in clinical research include community engagement, addressing logistical barriers to participation, and ensuring diverse research teams. These approaches can dismantle barriers for underrepresented communities, making research more accessible and reflective of the broader population. The SpA research community must commit to creating structures that foster inclusivity, ensuring medical advancements benefit all populations, especially historically underrepresented groups. The principles and strategies proposed serve as a roadmap for achieving equity in SpA research., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome characterized by autoreactive responses to nucleic acids, dysregulation of the type I interferon (IFN-I) pathway, and accelerated atherosclerosis. The stimulator of IFN genes (STING), a cytosolic DNA sensor, has pathogenic implications in various inflammatory diseases. However, its specific role in SLE pathogenesis, particularly in tissue damage, remains unclear. This study aimed to elucidate the role of STING in murine models of Toll-like receptor 7 (TLR7)-driven lupus and atherosclerosis., Methods: A TLR7-driven lupus model was induced using imiquimod (IMQ) in wild-type (WT) and STING knockout (Sting1 -/- ) mice on a B6 background. Mice were assessed for organ involvement, serum autoantibodies, and innate and adaptive immune responses. Additionally, Sting1 -/- mice were backcrossed to apolipoprotein E knockout (Apoe -/- ) mice, and both Apoe -/- and Apoe -/- Sting1 -/- mice were fed a high-fat chow diet to induce atherosclerosis. Phenotypic assessments were conducted., Results: Compared with IMQ-treated WT mice, Sting1 -/- mice exhibited reduced disease severity in the lupus-like phenotype, characterized by decreased splenomegaly, lower renal immune complex deposition and renal damage, diminished expansion of myeloid cells, and reduced activation of T and B lymphocytes. IMQ-induced DNA release associated with IFN-β production and subsequent IFN-induced responses were attenuated in Sting1 -/- mice. DNase I treatment mitigated IMQ-induced proinflammatory responses in WT mice but had no effect in Sting1 -/- mice. Furthermore, STING deficiency conferred protection against vascular damage and reduced atherosclerosis burden, accompanied by decreased IFN-I production. Human monocyte-derived macrophages treated with IFN-I significantly internalized more acetylated low-density lipoprotein when compared with untreated cells, whereas an association between oxidized nucleic acids and disease activity and vascular damage was found in human SLE., Conclusion: These findings highlight a pathogenic role of STING and downstream IFN responses in TLR7-driven autoimmunity, vascular damage and atherosclerosis, supporting a therapeutic potential for STING inhibition in SLE treatment. Further research is warranted to elucidate the mechanisms underlying STING's involvement in these processes and to explore the feasibility of targeting STING as a therapeutic strategy in SLE and related autoimmune disorders., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objectives: An important pathogenic role for neutrophils in systemic lupus erythematosus (SLE) has been proposed. Neutrophils that lack brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 ( Bmal1 ), one of the clock genes, are defective in aging and proinflammatory responses. We assessed the role of Bmal1 in clinical and immunologic manifestations of murine lupus and in human SLE neutrophils., Methods: Myeloid-conditional Bmal1 knockout mice ( Bmal1 Mye-/- ) and wild type (WT) were treated with epicutaneous TLR7/8 agonist (imiquimod; IMQ) for 6 weeks to induce a lupus phenotype. Upon euthanasia, immune responses, autoantibodies and renal manifestations were evaluated. NET formation and gene expression of bone marrow (BM)-derived murine neutrophils were evaluated. BMAL1 expression was quantified in SLE neutrophils and compared with clinical disease., Results: IMQ-treated Bmal1 Mye-/- and WT displayed comparable systemic inflammation. While renal function did not differ, serum anti-dsDNA levels and renal immune complex deposition were significantly increased in Bmal1 Mye-/- . While no differences were observed in NET formation, expression levels of April in BM neutrophils were significantly higher in Bmal1 Mye-/- . Bulk RNA-sequence data showed that BM neutrophils in IMQ-treated Bmal1 Mye-/- were relatively immature when compared with IMQ-treated WT. BM showed an enhanced April protein expression in Bmal1 Mye-/- mice. BMAL1 levels in human SLE peripheral blood neutrophils correlated positively with serum C3 and negatively with serum anti-dsDNA levels., Conclusion: Bmal1 is associated with lower disease activity in SLE. These results indicate that perturbation in the circadian rhythm of neutrophils can have pathogenic consequences in SLE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nakabo, Sandoval-Heglund, Hanata, Brooks, Hoffmann, Zhang, Ambler, Manna, Poncio, Hasni, Islam, Dell’Orso and Kaplan.)

The Krebs cycle enzyme aconitate decarboxylase 1 (ACOD1) mediates itaconate synthesis in monocytes and macrophages. Previously, we reported that administration of 4-octyl itaconate to lupus-prone mice abrogated immune dysregulation and clinical features. In this study, we explore the role of the endogenous ACOD1/itaconate pathway in the development of TLR7-induced lupus (imiquimod [IMQ] model). We found that, in vitro, ACOD1 was induced in mouse bone marrow-derived macrophages and human monocyte-derived macrophages following TLR7 stimulation. This induction was partially dependent on type I IFN receptor signaling and on specific intracellular pathways. In the IMQ-induced mouse model of lupus, ACOD1 knockout (Acod1-/-) displayed disruptions of the splenic architecture, increased serum levels of anti-dsDNA and proinflammatory cytokines, and enhanced kidney immune complex deposition and proteinuria, when compared with the IMQ-treated wild-type mice. Consistent with these results, Acod1-/- bone marrow-derived macrophages treated in vitro with IMQ showed higher proinflammatory features. Furthermore, itaconate serum levels in systemic lupus erythematosus patients were decreased compared with healthy individuals, in association with disease activity and specific perturbed cardiometabolic parameters. These findings suggest that the ACOD1/itaconate pathway plays important immunomodulatory and vasculoprotective roles in systemic lupus erythematosus, supporting the potential therapeutic role of itaconate analogs in autoimmune diseases.

Objectives: Inflammatory cytokines that signal through the Janus kinases-signal transducer and activator of transcription (JAK-STAT) pathway, especially interferons (IFNs), are implicated in Sjögren's disease (SjD). Although inhibition of JAKs is effective in other autoimmune diseases, a systematic investigation of IFN-JAK-STAT signalling and the effect of JAK inhibitor (JAKi) therapy in SjD-affected human tissues has not been fully investigated., Methods: Human minor salivary glands (MSGs) and peripheral blood mononuclear cells (PBMCs) were investigated using bulk or single-cell (sc) RNA sequencing (RNAseq), immunofluorescence (IF) microscopy and flow cytometry. Ex vivo culture assays on PBMCs and primary salivary gland epithelial cell (pSGEC) lines were performed to model changes in target tissues before and after JAKi., Results: RNAseq and IF showed activated JAK-STAT pathway in SjD MSGs. Elevated IFN-stimulated gene (ISGs) expression associated with clinical variables (eg, focus scores, anti-SSA positivity). scRNAseq of MSGs exhibited cell type-specific upregulation of JAK-STAT and ISGs; PBMCs showed similar trends, including markedly upregulated ISGs in monocytes. Ex vivo studies showed elevated basal pSTAT levels in SjD MSGs and PBMCs that were corrected with JAKi. SjD-derived pSGECs exhibited higher basal ISG expressions and exaggerated responses to IFN-β, which were normalised by JAKi without cytotoxicity., Conclusions: SjD patients' tissues exhibit increased expression of ISGs and activation of the JAK-STAT pathway in a cell type-dependent manner. JAKi normalises this aberrant signalling at the tissue level and in PBMCs, suggesting a putative viable therapy for SjD, targeting both glandular and extraglandular symptoms. Predicated on these data, a phase Ib/IIa randomised controlled trial to treat SjD with tofacitinib was initiated., Competing Interests: Competing interests: BMW has Cooperative Research Award and Development Agreements (CRADA) from Pfizer and Mitobridge (a subsidiary of Astellas Pharma). NIAMS has CRADAs with AstraZeneca and Bristol Myers Squibb. These CRADA did not financially support the experimental results presented herein., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In Africa, Morocco is the 10th largest producer of plastic. The severity of this plastic has attracted increasing amounts of attention in the Moroccan Atlantic and Mediterranean in recent years. However, at the national level, there is limited knowledge of plastic pollution. To obtain an exhaustive and comprehensive evaluation of plastic pollution levels in Morocco, large-scale monitoring is needed on all the coasts of the country. In this context, this paper examined the composition, abundance, distribution, source and quality of beaches on two Moroccan coasts using four beach quality indices along 29 beaches. During two seasons, a total of 72,105 items were counted. The mean litter abundance was 0.31 items/m 2, and the Mediterranean beaches were more dense than the Atlantic beaches. In particular, litter density was greater in spring (0.35 items/m 2 ) than in summer (0.29 items/m 2 ). The data indicate considerable differences in the density of marine debris according to the seasonality, beach typology and presence of rivers. Hazardous litter items were collected along both Moroccan coasts, constituting 8.41 % of the total collected items, with a mean of 0.026 items/m 2 . The use of environmental indices allowed us to classify Moroccan beaches as "moderate cleanliness", "moderate abundance" of plastics, "moderately safe" presence of hazardous litter and "mediocre" environmental status. The findings of the present study indicate that the sources of litter on both Moroccan coasts come mainly from recreational activities and dumping. The waste management practices recommended for Moroccan beaches include reducing sources, mitigating mitigation measures and changing littering behavior., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

BACKGROUND Idiopathic giant cell myocarditis (IGCM) is an uncommon and frequently fatal type of myocarditis. It primarily affects young individuals and has the potential to result in heart failure and life-threatening arrhythmias. IGCM seems to be dependent on activation of CD4-positive T lymphocytes and can show improvement with treatment aimed at reducing T-cell function. We present a case of a 65-year-old patient who presented with features of acute heart failure refractory to guideline-directed medical therapy (GDMT), due to IGCM. A review of the natural history and treatment of IGCM is also presented. CASE REPORT A 65-year-old woman with multiple comorbidities was admitted to our hospital for ventricular tachycardia in the setting of progressive non-ischemic heart failure, unresponsive to GDMT. This led to further investigation, including an endomyocardial biopsy, which revealed inflammatory infiltration, with multinucleated giant cells and lymphocytes in the absence of granuloma formation, prompting a diagnosis of IGCM. An implantable cardioverter-defibrillator (ICD) was placed for secondary prevention of sudden cardiac death and the patient was initiated on combined immunosuppressive therapy. Owing to numerous comorbidities, she was determined to be unsuitable for a heart transplant. Unfortunately, she eventually died from complications secondary to the disease. CONCLUSIONS IGCM remains a challenging clinical diagnosis with a poor long-term outcome without heart transplantation. This case highlights the importance of considering atypical causes of heart failure in patients who do not respond to conventional therapies. Early recognition and appropriate management, involving medical and interventional approaches, are crucial in improving outcomes for patients with IGCM.

Objectives: Late-onset SLE is usually milder and associated with lower frequency of LN and neuropsychiatric manifestations. The diagnosis of NPSLE is especially challenging in older patients because of increased incidence of neurological comorbidities. We performed a systematic review and meta-analysis to evaluate the differences in NPSLE manifestations in early-onset (<50-year-old) vs late-onset (≥50-year-old) SLE patients., Methods: A literature search was performed using the PubMed, Web of Science and Cochrane Library databases. Studies available in English (1959-2022) including a late-onset SLE comparison group and evaluating the frequency of NPSLE were eligible. A forest plot was used to compare odds ratios (95% CI) of incidence and manifestations of NPSLE by age groups. Study heterogeneity was assessed using I2 statistics., Results: A total of 44 studies, including 17 865 early-onset and 2970 late-onset SLE patients, fulfilled our eligibility criteria. CNS involvement was reported in 3326 patients. Cumulative NPSLE frequency was higher in the early-onset group than in the late-onset group (OR: 1.41, 95% CI: 1.24, 1.59, P < 0.0001). In early-onset SLE patients, seizures (OR: 1.68, 95% CI: 1.27, 2.22) and psychosis (OR: 1.72, 95% CI: 1.23, 2.41) were more common than in late-onset SLE patients (P values, 0.0003 and 0.0014, respectively). Peripheral neuropathy was more commonly reported in the late-onset SLE group than in the early-onset SLE group (OR: 0.64, 95% CI: 0.47, 0.86, P = 0.004)., Conclusion: Our meta-analysis revealed that the frequencies of overall NPSLE, seizures, and psychosis were less common in late-onset SLE patients than in early-onset SLE patients. In contrast, peripheral neuropathy was more common in the late-onset SLE group., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Childhood-onset systemic lupus erythematosus (cSLE) patients are unique, with hallmarks of Mendelian disorders (early-onset and severe disease) and thus are an ideal population for genetic investigation of SLE. In this study, we use the transmission disequilibrium test (TDT), a family-based genetic association analysis that employs robust methodology, to analyze whole genome sequencing data. We aim to identify novel genetic associations in an ancestrally diverse, international cSLE cohort. Forty-two cSLE patients and 84 unaffected parents from 3 countries underwent whole genome sequencing. First, we performed TDT with single nucleotide variant (SNV)-based (common variants) using PLINK 1.9, and gene-based (rare variants) analyses using Efficient and Parallelizable Association Container Toolbox (EPACTS) and rare variant TDT (rvTDT), which applies multiple gene-based burden tests adapted for TDT, including the burden of rare variants test. Applying the GWAS standard threshold (5.0 × 10 -8 ) to common variants, our SNV-based analysis did not return any genome-wide significant SNVs. The rare variant gene-based TDT analysis identified many novel genes significantly enriched in cSLE patients, including HNRNPUL2, a DNA repair protein, and DNAH11, a ciliary movement protein, among others. Our approach identifies several novel SLE susceptibility genes in an ancestrally diverse childhood-onset lupus cohort., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Recent population-based cohort studies suggest that the incidence of systemic lupus erythematosus (SLE) is increased in patients with immune thrombocytopenic purpura (ITP). We performed a systematic review and meta-analysis to evaluate the development of SLE in patients with ITP., Methods: Literature search was performed in PubMed, Web of Science and Cochrane Library for studies published prior to October 2022. Studies were included that reported development of SLE in ITP patients. Forest plot was used to detect overall SLE frequency in ITP and compare risk ratios for SLE development in different ITP subgroups. Study heterogeneity was assessed by using I 2 statistics., Results: 26 eligible studies comprising 14867 ITP patients were included in analysis. 311 ITP patients developed SLE during the follow-up period (range: 1.1-14 years) (2.09%, 95%CI: 1.87-2.33). Relative risk (RR) for developing SLE was significantly higher in female ITP patients (RR: 4.23, 95%CI: 2.52-7.12, p < 0.0001). Anti-nuclear antibody (ANA) was reported in 23 studies, there were 766/4377 ANA positive patients with ITP (17.5%). The risk of SLE development in ANA positive ITP patients was significant (RR: 26.29, 95%CI: 14.45-47.81, p < 0.0001)., Conclusions: Our study suggests ITP patients are at high risk of developing SLE in future. Pooled data revealed that females and patients with a positive ANA titer are at a significantly high risk of developing SLE., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sarfaraz Hasni reports a relationship with National Institute of Arthritis and Musculoskeletal and Skin Diseases that includes: employment., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Few studies were dedicated to characterizing the dromedary milk (DM) as consumed by Bedouins, mixed with a small amount of dromedary urine (DU). Therefore, this work aimed to reveal some physical and biochemical characteristics of the DM alone, and incorporated with DU at two different concentrations. pH, colour, Brix, fats, and minerals were evaluated with proteins and sugar content using FTIR; in addition to protein oxidation. The results showed that DM counts as a rich source of the nutritional element yet its proprieties were affected by the addition of DU. An important increase in colour, sugar, fat, and protein concentration with a remarkable augmentation in the pH, mineral content, and protein oxidation where the more urine is added the more milk proteins are oxidated as demonstrated by the characteristics showed in the two mixtures which will negatively affect DM therapeutical proprieties, especially the one related to proteins., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive skin fibrosis. It has 2 main clinical subtypes-diffuse cutaneous scleroderma and limited cutaneous scleroderma. Non-cirrhotic portal hypertension (NCPH) is defined as presence of elevated portal vein pressures without cirrhosis. It is often a manifestation of an underlying systemic disease. On histopathology, NCPH may be found to be secondary to multiple abnormalities such as nodular regenerative hyperplasia (NRH) and obliterative portal venopathy. There have been reports of NCPH in patients with both subtypes of SSc secondary to NRH. However, simultaneous presence of obliterative portal venopathy has not been reported. We present a case of NCPH due to NRH and obliterative portal venopathy as a presenting sign of limited cutaneous scleroderma. The patient was initially found to have pancytopenia and splenomegaly and was erroneously labeled as cirrhosis. She underwent workup to rule out leukemia, which was negative. She was referred to our clinic and diagnosed with NCPH. Due to pancytopenia, she could not be started on immunosuppressive therapy for her SSc. Our case describes the presence of these unique pathological findings in the liver and highlights the importance of an aggressive search for an underlying condition in all patients diagnosed with NCPH.

Purpose: Patients with systemic lupus erythematosus (SLE) experience excessive, debilitating fatigue with previously reported evidence of etiologically mediated cardiorespiratory impairments. Performance fatigability provides a precise characterization of fatigue as it can be quantified objectively as a function of time, frequency, and/or duration. Nevertheless, little consideration has been given to understanding performance fatigability and its physiological determinants in those with SLE. The purpose of this study was to characterize performance fatigability in patients with SLE, utilizing measures surrounding the anaerobic threshold, with emphasis on cardiorespiratory impairment as a potential mediating factor., Methods: This was a case-control study design. 44 physically inactive women, 26 with SLE and 18 controls, completed a treadmill cardiopulmonary exercise test to volitional exhaustion., Results: There were no significant differences in age (SLE 34.8(9.0) vs Control 36.9(7.3) yrs; p=0.422) between groups. BMI (SLE 27.1(5.4) vs Control 23.8(5.2) kg/m 2 ; p=0.045) was significantly higher in the SLE vs Control group. Resting heart rate (SLE 68(16) vs Control 78(15) bpm; p=0.040) was significantly lower in the SLE compared to the Control group. The VO 2 corresponding to the anaerobic threshold (AT-VO 2 ), used to identify the onset of exercise-induced fatigue, was significantly lower in women with SLE than in controls (SLE 12.4(3.1) vs Control 16.4(2.2) ml/kg/min; p<0.001), as was AT-stage (SLE 2.5(0.90) vs Control 3.4(0.78); p=0.002). Additionally, Fatigue Severity Score (FSS) was highly and inversely correlated with AT-VO 2 (rho=-0.615; p<0.001) and FSS was highly correlated with Functional Aerobic Impairment Index (FAI; rho=0.663; p<0.001)., Conclusion: This study underscores severe performance fatigability in patients with SLE and its link to cardiorespiratory insufficiency. Physiological presentation of performance fatigability was observed during very low intensities of exercise, emphasizing the negative impact it may have on physical function in this population., Competing Interests: Conflicts of Interest: There are no conflicts of interest for any of the authors.

Background: Cyclophosphamide (CYC) has known cytotoxic effects on ovarian reserve and has been linked to premature ovarian failure (POF) in systemic lupus erythematosus (SLE). The concurrent use of gonadotropin-releasing hormone agonists (GnRHas) is postulated to preserve ovarian function by reducing the number of follicles exposed to CYC, but there is paucity of data to establish its efficacy. We conducted a meta-analysis to summarize the effect of concurrent GnRHa use in persevering ovarian function and pregnancy., Methods: English language databases of PubMed, Embase, and Cochrane were searched to include studies published between 2000 and 2021. Studies in females with rheumatic diseases receiving concurrent GnRHa and CYC therapy to evaluate ovarian preservation as defined by amenorrhea, follicle stimulating hormone (FSH), anti-mullerian hormone (AMH), or estradiol levels or successful pregnancy were included. We used a fixed effect, exact, Mantel-Haenszel approach to estimate the overall odds ratio (OR) and associated 95% confidence intervals (95% CIs)., Results: Seven studies with 218 female patients were included. The ovarian function was preserved in 125/132 (94.6%) of women who received GnRHa concurrently with CYC compared to 50/86 (58%) of women who did not receive GnRHa (OR = 10.3, CI = 4.83-36.29). The OR for pregnancy with GnRHa use = 2.94 (CI = 1.04-9.89)., Conclusion: Our results based on limited published studies suggest that concurrent GnRHa use preserves ovarian function and increase odds of pregnancy. It can be considered for premenopausal SLE females receiving CYC . Long-term follow-up studies are needed to establish the efficacy and safety of GnRHa use for ovarian preservation.