Performance optimization of water cycle algorithm for multilevel lupus nephritis image segmentation

Lupus nephritis (LN) is one of the most common and serious clinical manifestations of systemic lupus erythe-matosus (SLE), which causes serious damage to the kidneys of patients. To effectively assist the pathological diagnosis of LN, many researchers utilize a scheme combining multi-threshold image segmentation (MIS) with metaheuristic algorithms (MAs) to classify LN. However, traditional MAs-based MIS methods tend to fall into local optima in the segmentation process and find it difficult to obtain the optimal threshold set. Aiming at this problem, this paper proposes an improved water cycle algorithm (SCWCA) and applies it to the MIS method to generate an SCWCA-based MIS method. Besides, this MIS method uses a non-local means 2D histogram to represent the image information and utilizes Renyi's entropy as the fitness function. First, SCWCA adds a sine initialization mechanism (SS) in the initial stage of the original WCA to generate the initial solution to improve the population quality. Second, the covariance matrix adaptation evolution strategy (CMA-ES) is applied in the population location update stage of WCA to mine high-quality population information. To validate the excellent performance of the SCWCA-based MIS method, the comparative experiment between some peers and SCWCA was carried out first. The experimental results show that the solution of SCWCA was closer to the global optimal solution and can effectively deal with the local optimal problems. In addition, the segmentation experiments of the SCWCA-based MIS method and other equivalent methods on LN images showed that the former can obtain higher-quality segmented LN images.

Immunological and translational key challenges in systemic lupus erythematosus: A symposium update.

The first LBMR-Tim (Toulouse Referral Medical Laboratory of Immunology) symposium convened on December 16, 2022 in Toulouse, France to address challenging questions in systemic lupus erythematosus (SLE). Special focus was put on (i) the role played by genes, sex, TLR7, and platelets on SLE pathophysiology; (ii) autoantibodies, urinary proteins, and thrombocytopenia contribution at the time of diagnosis and during follow-up; (iii) neuropsychiatric involvement, vaccine response in the COVID-19 era, and lupus nephritis management at the clinical frontline; and (iv) therapeutic perspectives in patients with lupus nephritis and the unexpected adventure of the Lupuzor/P140 peptide. The multidisciplinary panel of experts further supports the concept that a global approach including basic sciences, translational research, clinical expertise, and therapeutic development have to be prioritized in order to better understand and then improve the management of this complex syndrome.

Systemic lupus erythematosus flare during SARS-CoV-2 infection: Report of 3 cases presented during the fourth wave of the pandemic in Colombia.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has become a worldwide pandemic since first discovered in 2019. Systemic lupus erythematosus (SLE) flare has been reported in the post-infectious period. In Colombia, the fourth pandemic wave started at the beginning of 2022 when we observed flare of 3 SLE patients during active infection. CASE PRESENTATION: We describe 3 patients with inactive SLE, who presented coronavirus disease 2019 and severe flare in early 2022, 2 patients with nephritis and 1 with severe thrombocytopenia. All patients had increase of antinuclear and anti-DNA antibody titers and complement consumption. CONCLUSIONS: Three cases with SLE flare concomitant with active SARS-CoV-2 infection were different from others reported earlier in the pandemic with post-infectious flare.

Presentation of SLE after COVID vaccination in a pediatric patient.

BACKGROUND: The outbreak of severe acute respiratory syndrome coronavirus 2 has had an enormous impact on global health. Vaccination remains one of the most effective interventions for disease prevention. Clinically significant vaccine side effects are uncommon, though autoimmune-mediated disease occurs in a small percentage of vaccine recipients. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that is associated with significant morbidity and mortality. Childhood-onset SLE tends to have more severe disease manifestations than adult-onset SLE. In adults, there are a few reported cases of SLE developing soon after coronavirus disease 2019 (COVID-19) mRNA vaccination. CASE PRESENTATION: A 14-year-old previously healthy male developed laboratory and clinical evidence of SLE, including maculopapular malar rash, arthritis, pleuritic chest pain, and class V (membranous) lupus nephritis, 2 days after his third dose of the Pfizer-BioNTech COVID-19 vaccine. The patient's symptoms improved after initiation of prednisone and mycophenolate mofetil. We also summarize eleven prior case reports describing SLE after COVID-19 vaccine in adults. CONCLUSION: To our knowledge, this is the first reported pediatric patient with new onset SLE following COVID-19 mRNA vaccination. While potential mechanistic links exist between COVID-19 vaccination and SLE development, additional studies are necessary to elucidate the exact nature of this relationship.

Oral Abstract Presentation Abstracts

In abortion patients, we found number of Treg cells ( I P i = 0.008) was decreased as compared to no abortion patients, leading to significantly imbalance of effector T and Treg cells (Figure 1C). A >=50% reduction from baseline in UPCR was achieved by all voclosporin-treated patients and 25 (83.3%) control-treated patients;the median time to this endpoint was significantly shorter in the voclosporin arm (1.0 vs 1.9 months, respectively, [HR 1.98, I P i < 0.021]). CDK is associated with the progression of SLE and COVID-19, which may be the potential therapeutic drug for SLE patients with COVID-19 infection. RA decreased in pEMT-Singscorehigh patients compared with pEMT-Singscorelow patients. [Extracted from the article]

[Relapse of lupus nephritis in temporal association with anti SARS-CoV-2 vaccination]

During the past two years we have witness a tremendous worldwide health crisis imposed by the coronavirus disease (COVID-19). This situation led to the urgent development and implementation of vaccines in an attempt to decrease not only the SARS-CoV-2 transmissibility but also the severe forms of COVID-19. Although these vaccines were approved based on an adequate benefit-risk ratio, at the moment of their implementation in 2021 we did not have sub-studies in special populations;patients with systemic lupus erythematosus (SLE) among them. We describe two cases of lupus nephritis flare following the immunization against SARS-CoV-2 with the first component of Sputnik V and Sinopharm. Both patients were in complete remission on maintenance therapy with mycophenolate and without glucocorticoids. The flare presented with an increased protein/creatinine ratio in urine and positive anti-DNA antibodies without other relevant accompanying findings. After treatment with prednisone (20 y 10 mg/day in case 1 and 2, respectively) and an increased dose of mycophenolate (from 1.5 g/day to 2.0 g/dayand 1.08 to 1.44 g/dia of sodic mycophenolate in case 1 y 2, respectively) both patients regained renal remission. These cases are of relevance as they introduce a possible association between the different anti-SARS-CoV-2 vaccine platforms and SLE flares;at the same time to suggest the need for close control in the post vaccination period in this population of patients.

Psychological Implications to the Therapy of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic and multi-systemic autoimmune disease, which has a deleterious impact on patients' psychological well-being. This paper aims to review the existing literature on empirical research on psychological outcomes of SLE and psychological interventions to improve well-being in SLE patients. A search of significant English language articles was conducted in PubMed, Medline, ScienceDirect, Scopus, and ResearchGate databases. Titles and abstracts were screened for the relevant terms, including "systemic lupus erythematosus", "childhood-onset systemic lupus erythematosus", "juvenile systemic lupus erythematosus", "lupus nephritis", and their respective synonyms along with "depression", "anxiety", "fatigue", "medical adherence", "health-related quality of life", "self-management" or "intervention". The articles were evaluated by independent reviewers and the lists of eligible publications were compared whilst disagreements were settled by discussion. Of the 59 publications sought for retrieval, 35 papers were shortlisted based on predefined inclusion/exclusion criteria. They were classified according to their content and the methodology applied. Research topics including "anxiety and depression in SLE" and "self-management interventions for SLE patients" were identified and are presented in this review. As the prognosis and life expectancy of SLE patients are improving, further research on the psychological outcomes of SLE and the evidence-based psychological interventions to improve patients' well-being are justified.

Characteristics of SARS-CoV-2 Infection in an Actively Monitored Cohort of Patients with Lupus Nephritis.

(1) Background: We sought to investigate the impact of the COVID-19 pandemic in patients with lupus nephritis (LN); (2) Methods: A total of 95 patients with LN actively monitored in our department between 26 February 2020, when the first case of COVID-19 was diagnosed in Romania, and 1 May 2021, were included in the study. Multivariate logistic regression analysis was performed to identify the independent risk factors for SARS-CoV-2 infection; (3) Results: A total of 15 patients (15.8%) had a confirmed SARS-CoV-2 infection during a total follow-up time of 105.9 patient-years (unadjusted incidence rate: 14.28 SARS-CoV-2 infections per 100 patient-years). Median time to SARS-CoV-2 infection was 9.3 months (IQR: 7.2-11.3). The majority of patients had a mild form of SARS-CoV-2 infection (73.3%), while the remaining had moderate forms. None of the patients had a severe infection or a SARS-CoV-2-related death. The most frequent symptom was fatigue (73.3%), followed by loss of taste/smell (53.3%) and fever (46.7%). Forty percent of those with SARS-CoV-2 infection were hospitalized for a median 11.5 days (IQR:3.75-14). In the multivariate logistic regression analysis, a current oral corticosteroid dose ≥ 15 mg/day was associated with a 7.69-fold higher risk (OR, 7.69; 95%, 1.3-45.46), while the use of hydroxychloroquine was associated with a 91% lower risk for a SARS-CoV-2 infection (OR, 0.09; 95%CI, 0.01-0.59). (4) Conclusions: Our study confirms that the SARS-CoV-2 infection-associated morbidity might only be moderately increased in patients with LN. The current oral corticosteroid dose was the only independent predictor of infection occurrence, while use of hydroxychloroquine was associated with a protective effect.

Urine Soluble CD163 Is a Promising Biomarker for the Diagnosis and Evaluation of Lupus Nephritis.

Introduction: Urine-soluble CD163 (usCD163) is released from alternatively activated macrophages involved in the resolution of inflammation in glomeruli and plays an important role in glomerulonephritis. This study explored the role of usCD163 in patients with systemic lupus erythematosus (SLE). Materials and Methods: usCD163 concentrations were measured cross-sectionally in 261 SLE patients in Taiwan. Clinical and laboratory data were collected, and SLE disease activity scores were calculated to assess the correlation with usCD163. Results: SLE patients with high usCD163 levels tended to be younger, with a higher hospital admission rate, higher prednisolone dose, lower estimated glomerular filtration rate, higher urine protein creatinine ratio (UPCR), more pyuria and hematuria, higher levels of inflammatory markers, higher rates of anemia, neutropenia, and lymphopenia, lower complement 3 (C3) levels, higher anti-double-stranded DNA antibody (anti-dsDNA Ab) levels, and higher disease activity scores (p < 0.05). usCD163 levels were significantly higher in patients with active lupus nephritis (LN) than in those with extrarenal or inactive SLE and correlated with UPCR, disease activity, and anti-dsDNA Ab levels. SLE patients with high usCD163 levels tended to have a higher chronic kidney disease stage. Discussion and conclusion: The usCD163 level correlates with the severity of LN and disease activity in renal SLE.

New-onset lupus nephritis associated with COVID-19 infection.

A dysregulated immune response plays a critical role in systemic lupus erythematosus (SLE) pathogenesis. Environmental factors such as viruses, including coronavirus 2 (COVID-19), have been described to play a role in SLE presentation and exacerbation. These viruses trigger a host's humoral and cellular immunities typically essential in elimination of the viral infection. We present a case of a Hispanic male who developed new-onset lupus nephritis class II after a COVID-19 infection.

Hydroxychloroquine in systemic lupus erythematosus: overview of current knowledge.

The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ's effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.

Glomerular Disease in Temporal Association with SARS-CoV-2 Vaccination: A Series of 29 Cases.

Background: Immune responses to vaccination are a known trigger for a new onset of glomerular disease or disease flare in susceptible individuals. Mass immunization against SARS-CoV-2 in the COVID-19 pandemic provides a unique opportunity to study vaccination-associated autoimmune kidney diseases. In the recent literature, there are several patient reports demonstrating a temporal association of SARS-CoV-2 immunization and kidney diseases. Methods: Here, we present a series of 29 cases of biopsy-proven glomerular disease in patients recently vaccinated against SARS-CoV-2 and identified patients who developed a new onset of IgA nephropathy, minimal change disease, membranous nephropathy, ANCA-associated GN, collapsing glomerulopathy, or diffuse lupus nephritis diagnosed on kidney biopsies postimmunization, as well as recurrent ANCA-associated GN. This included 28 cases of de novo GN within native kidney biopsies and one disease flare in an allograft. Results: The patients with collapsing glomerulopathy were of Black descent and had two APOL1 genomic risk alleles. A brief literature review of patient reports and small series is also provided to include all reported cases to date (n=52). The incidence of induction of glomerular disease in response to SARS-CoV-2 immunization is unknown; however, there was no overall increase in incidence of glomerular disease when compared with the 2 years prior to the COVID-19 pandemic diagnosed on kidney biopsies in our practice. Conclusions: Glomerular disease to vaccination is rare, although it should be monitored as a potential adverse event.

A glimpse into the future of systemic lupus erythematosus.

This viewpoint article on a forecast of clinically meaningful changes in the management of systemic lupus erythematosus (SLE) in the next 10 years is based on a review of the current state of the art. The groundwork has been laid by a robust series of classification criteria and treatment recommendations that have all been published since 2019. Building on this strong foundation, SLE management predictably will take significant steps forward. Assessment for lupus arthritis will presumably include musculoskeletal sonography. Large-scale polyomics studies are likely to unravel more of the central immune mechanisms of the disease. Biomarkers predictive of therapeutic success may enter the field; the type I interferon signature, as a companion for use of anifrolumab, an antibody against the common type I interferon receptor, is one serious candidate. Besides anifrolumab for nonrenal SLE and the new calcineurin inhibitor voclosporin in lupus nephritis, both of which are already approved in the United States and likely to become available in the European Union in 2022, several other approaches are in advanced clinical trials. These include advanced B cell depletion, inhibition of costimulation via CD40 and CD40 ligand (CD40L), and Janus kinase 1 (Jak1) and Tyrosine kinase 2 (Tyk2) inhibition. At the same time, essentially all of our conventional therapeutic armamentarium will continue to be used. The ability of patients to have successful SLE pregnancies, which has become much better in the last decades, should further improve, with approaches including tumor necrosis factor blockade and self-monitoring of fetal heart rates. While we hope that the COVID-19 pandemic will soon be controlled, it has highlighted the risk of severe viral infections in SLE, with increased risk tied to certain therapies. Although there are some data that a cure might be achievable, this likely will remain a challenge beyond 10 years from now.

Use of telemedicine for follow-up of lupus nephritis in the COVID-19 outbreak: The 6-month results of a randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the short-term patient satisfaction, compliance, disease control, and infection risk of telemedicine (TM) compared with standard in-person follow-up (FU) for patients with lupus nephritis (LN) during the COVID-19 pandemic. METHOD: This was a single-center open-label randomized controlled study. Consecutive patients followed at the LN clinic were randomized to either TM or standard FU (SF) group in a 1:1 ratio. Patients in the TM group received FU via videoconferencing. SF group patients continued conventional in-person outpatient care. The 6-month data were compared and presented. RESULTS: From June to December 2020, 122 patients were randomized (TM: 60, SF: 62) and had at least 2 FUs. There were no baseline differences, including SLEDAI-2k and proportion of patients in lupus low disease activity state (LLDAS), between the two groups except a higher physician global assessment score (PGA) in the TM group. After a mean FU of 19.8 ± 4.5 weeks, the overall patient satisfaction score was higher in the TM group. More patients in the TM group had hospitalization (15/60, 25.0% vs 7/62, 11.3%; p = .049) with higher baseline PGA (OR = 1.17; 95% CI, 1.08-1.26) being the independent predictor. The proportions of patients remained in LLDAS were similar in the two groups (TM: 75.0% vs SF: 74.2%, p = .919). None of the patients had COVID-19. CONCLUSIONS: TM FU resulted in better patient satisfaction and similar short-term disease control in patients with LN compared to standard care. However, it was associated with more hospitalizations and might need to be complemented by in-person visits especially in patients with higher PGA.

Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis.

BACKGROUND: Hydroxychloroquine (HCQ) has been recommended as a basic treatment for lupus nephritis (LN) during this decade based on its ability to improve LN-related renal immune-mediated inflammatory lesions. As a classical lysosomal inhibitor, HCQ may inhibit lysosomal degradation and disrupt protective autophagy in proximal tubular epithelial cells (PTECs). Therefore, the final renal effects of HCQ on LN need to be clarified. METHOD: HCQ was administered on spontaneous female MRL/lpr LN mice with severe proteinuria daily for 4 weeks. Moreover, the MRL/lpr mice with proteinuric LN were subjected to cisplatin-induced or unilateral ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) after 2 weeks of HCQ preadministration. RESULTS: As expected, HCQ treatment increased the survival ratio and downregulated the levels of serum creatinine in the mice with LN, ameliorated renal lesions, and inhibited renal interstitial inflammation. Unexpectedly, HCQ preadministration significantly increased susceptibility to and delayed the recovery of AKI complicated by LN, as demonstrated by an increase in PTEC apoptosis and expression of the tubular injury marker KIM-1 as well as the retardation of PTEC replenishment. HCQ preadministration suppressed the proliferation of PTECs by arresting cells in G1/S phase and upregulated the expression of cell cycle inhibitors. Furthermore, HCQ preadministration disrupted the PTEC autophagy-lysosomal pathway and accelerated PTEC senescence. CONCLUSION: HCQ treatment may increase susceptibility and delay the recovery of AKI complicated by LN despite its ability to improve LN-related renal immune-mediated inflammatory lesions. The probable mechanism involves accelerated apoptosis and inhibited proliferation of PTECs via autophagy-lysosomal pathway disruption and senescence promotion.

Belimumab in Lupus Nephritis: A Systematic Review and Meta-Analysis.

Belimumab is a recombinant human IgG-1λ monoclonal antibody. It inhibits the B-cell activating factor (BAFF) and is approved for patients with systemic lupus erythematosus (SLE) older than five years with positive autoantibody. We aimed to evaluate the role of belimumab in the maintenance phase of treatment for lupus nephritis (LN). PubMed, PubMed Central (PMC), Cochrane Library, and Embase were searched using appropriate keywords. The screening of title and abstract was done in Covidence, followed by data extraction of the relevant studies based on inclusion criteria. Review manager (RevMan 5.4) was used for data analysis with random or fixed effects model based on heterogeneities. Two randomized controlled trials were included in the quantitative analysis. There were 1.71 times higher odds of complete renal response in the belimumab group than in the control group (odds ratio (OR), 1.71; 95% confidence interval (CI), 1.12-2.60; I-square (I2) ​​​​= 0%). Similarly, there was 34% lower odds for having no response among the belimumab group (OR, 0.66; 95% CI, 0.45-0.96; I2 = 0%). No significant differences between the two groups were observed for the occurrence of treatment-related adverse events (TRAEs) (OR, 1.07; 95% CI, 0.74-1.56; I2 = 0%), treatment-related serious adverse events (OR, 0.54; 95% CI, 0.15-1.96; I2 = 68%), and treatment-related infections (OR, 0.65; 95% CI, 0.27-1.55; I2 = 21%).Therefore, belimumab and standard treatment were instrumental for beneficial renal response in patients with lupus nephritis and were not associated with increased odds of adverse effect compared with the standard treatment alone.

When and How Is It Possible to Stop Therapy in Patients with Lupus Nephritis: A Narrative Review.

Glucocorticoids and other immunosuppressants still represent the cornerstone drugs for the management of SLE and lupus nephritis. The refined use of these drugs over the years has allowed us to obtain stable disease remission and improvement of long-term kidney and patient survival. Nevertheless, a prolonged use of immunosuppressive agents may be accompanied by severe and even life-threatening side effects. Theoretically, a transient or even definitive withdrawal of immunosuppression could be useful to prevent iatrogenic morbidities. For many years, however, the risk of SLE reactivation has held clinicians back from trying to interrupt therapy. In this review, we report the results of the attempts to interrupt glucocorticoids and other immunosuppressive agents in lupus nephritis and in SLE. The available data suggest that therapy withdrawal is feasible at least in patients enjoying a complete clinical remission after a prolonged therapy. A slow and gradual reduction of treatment under medical surveillance is needed to prevent flares of activity. After therapy withdrawal, around one-quarter of patients may have kidney or systemic flares. However, most flares may respond to therapy if rapidly diagnosed. The other patients can enter stable remission for even 20 years or more. The use of antimalarials can help in maintaining the remission after the withdrawal of the immunosuppressive therapy. A repeated kidney biopsy could be of help in deciding to stop therapy, but given the few available data, it cannot be considered essential.

Factors Associated With Use of Telemedicine for Follow-Up of SLE in the COVID-19 Outbreak.

Objective: To investigate the factors associated with telemedicine (TM) use for follow-up of Systemic Lupus Erythematous (SLE) patients in the COVID-19 pandemic. Methods: This was a single-centered cross-sectional study conducted in Hong Kong. Consecutive patients followed up at the lupus nephritis clinic were contacted for their preference in changing the coming consultation to TM in the form of videoconferencing. The demographic, socioeconomic, and disease data of the first 140 patients opted for TM and 140 control patients preferred to continue standard in-person follow-up were compared. Results: The mean age of all the participants was 45.6 ± 11.8 years, and the disease duration was 15.0 ± 9.2 years. The majority of them were on prednisolone (90.0%) and immunosuppressants (67.1%). The mean SLEDAI-2k was 3.4 ± 2.4, physician global assessment (PGA) was 0.46 ± 0.62 and Systemic Lupus International Collaborating Clinics (SLICC) damage index was 0.97 ± 1.23. A significant proportion of the patients (72.1%) had 1 or more comorbidities. It was found that patients with higher mean PGA (TM: 0.54 ± 0.63 vs. control: 0.38 ± 0.59, p = 0.025) and family monthly income > USD 3,800 (TM: 36.4% vs. control: 23.6%; p = 0.028) preferred TM, while full-time employees (TM: 40.0% vs. control: 50.7%; p = 0.041) preferred in-person follow-up. These predictors remained significant in the multivariate analysis after adjusting for age and gender. No other clinical factors were found to be associated with the preference of TM follow-up. Conclusion: When choosing the mode of care delivery between TM and physical clinic visit for patients with SLE, the physician-assessed disease activity and patient's socio-economic status appeared to be important.