Mortality In Systemic Lupus Erythematosus Patients Research Articles

A deeper look into the functions of right ventricle using three-dimensional echocardiography: the forgotten ventricle in children with systemic lupus erythematosus

Studies on the right ventricular dysfunction (RV) in systemic lupus erythematosus (SLE) patients are limited, particularly in the pediatric age group. The study aimed to identify subclinical RV alterations in childhood-onset SLE (c-SLE) using conventional and three-dimensional echocardiography (3DE). Forty SLE pediatric patients and 40 healthy controls were included. Disease activity and chronicity were evaluated by SLE disease activity index (SLEDAI) score and SLE damage index (SDI). Participants underwent detailed RV echocardiographic examination with conventional and 3DE assessment using 3D auto RV software. Patients included 35/40 (87.5%) females with mean age of 15.6 ± 1.7 years. Using conventional pulmonary artery systolic pressure echocardiography-derived measurement, none of the c-SLE patients had pulmonary hypertension. By 3DE, RV end-systolic and end-diastolic volumes (p = < 0.001, 0.02, respectively) were greater, whereas 3D-derived RV ejection fraction (p < 0.001), septal, and lateral longitudinal strain (both p < 0.001) were lower in SLE. SDI displayed a significant correlation with 3D auto RV ejection fraction (EF), tricuspid annular plane systolic excursion (TAPSE), fractional area change, and RV longitudinal strain (RVLS)-free wall (p = 0.01, 0.003, 0.007, and < 0.001, respectively). Cumulative SLEDAI score also showed a significant correlation with RV EF, TAPSE, FAC, and RVLS-free wall (p = 0.03, 0.007, 0.002, and < 0.001, respectively). By multivariate regression analysis, SDI remained an independent predictor of RVLS-free wall (ß coefficient − 0.4, p = 0.03) and TAPSE (ß − 0.5, p = 0.02). Conclusion: Subtle right ventricular myocardial dysfunction could be detected in childhood-onset SLE patients, especially via 3D-derived auto RV echocardiographic parameters, despite the absence of evident pulmonary hypertension. These parameters correlate with the SLE disease activity and chronicity scores.What is Known:•Diseases of the cardiovascular system are one of the most common causes of morbidity and mortality in SLE patients.•RV labeled the forgotten ventricle in many diseases, was also forgotten in SLE patients and has been rarely addressed in adults, with scarce research in pediatrics.What is New:•Right ventricular functions are affected in children with SLE in comparison to healthy controls, especially three-dimensional echocardiography-derived parameters, which is an aspect that has not been investigated in previous research in the pediatric age group.•Some of the detected myocardial dysfunctions of the right ventricle correlated with SLE disease activity and chronicity-related scores.

308 Machine learning to predict genetic variation and cardiovascular risk in Hispanic patients with Systemic lupus erythematosus

OBJECTIVES/GOALS: Cardiovascular disease (CVD) is the most common cause of death in systemic lupus erythematosus (SLE). Genome-wide association studies have identified single nucleotide polymorphisms linked with CVD risk, but the association with SLE is not well established. We aimed to determine associations using machine learning in a multi-ethnic lupus cohort. METHODS/STUDY POPULATION: We will use data from the established SLE cohort study named Genetic Profile Predicting the Phenotype (PROFILE). PROFILE was constituted in 1998 by combining existing cohorts at multiple sites which are also of defined ethnicity (Hispanics of Mexican ancestry and Puerto Rico, African American, and Caucasian). The cohort consists of 3,118 individuals and the database contains socioeconomic–demographic, clinical, laboratory, and genetic variables. Genetic data consist of 196,524 single nucleotide polymorphisms. To detect risk genes and predict an individual’s SLE risk will design a random forest classifier using SNP genotype data. Logistic regression models will be performed with CVD as the outcome, adjusted for age, sex, ethnicity, disease duration, and traditional and nontraditional risk factors for CVD. RESULTS/ANTICIPATED RESULTS: We expect to find several established and new susceptibility genes associated with CVD. DISCUSSION/SIGNIFICANCE: This approach offers an opportunity to characterize distinct genetic risk factors and the relationship of CVD with SLE. These data may be important in the identification of patients at high risk for such events and may allow the design of preventive strategies which may beneficially have an impact on the morbidity and mortality of SLE patients.

Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by the involvement of multiple organs. Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in SLE patients. Hence, designing effective drugs is pivotal for treating individuals with LN. Fisetin plays a senolytic role by specifically eliminating senescent cells, inhibiting cell proliferation, and exerting anti-inflammatory, anti-oxidant, and anti-tumorigenic effects. However, limited research has been conducted on the utility and therapeutic mechanisms of fisetin in chronic inflammation. Similarly, whether the effects of fisetin depend on cell type remains unclear. In this study, we found that LN-prone MRL/lpr mice demonstrated accumulation of Ki-67-positive myofibroblasts and p15INK4B-positive senescent tubular epithelial cells (TECs) that highly expressed transforming growth factor β (TGF-β). TGF-β stimulation induced senescence of NRK-52E renal TECs and proliferation of NRK-49F renal fibroblasts, suggesting that TGF-β promotes senescence and proliferation in a cell type-dependent manner, which is inhibited by fisetin treatment in vitro. Furthermore, fisetin treatment in vivo reduced the number of senescent TECs and myofibroblasts, which attenuated kidney fibrosis, reduced senescence-associated secretory phenotype (SASP) expression, and increased TEC proliferation. These data suggest that the effects of fisetin vary depending on the cell type and may have therapeutic effects in complex and diverse LN pathologies.

Hydroxychloroquine use reduces mortality risk in systemic lupus erythematosus: A systematic review and meta-analysis of cohort studies.

Hydroxychloroquine (HCQ) is widely used in patients with systemic lupus erythematosus (SLE), but its effects on the mortality have not reached a definite conclusion. In this systematic review and meta-analysis, we aimed to assess whether HCQ use could reduce the risk of mortality in SLE patients. PubMed, Embase, Web of Science, and Cochrane database were searched from inception to April 17, 2022 without language restrictions to explore the relationship between HCQ use and SLE mortality. The relative risk (HR) was pooled using the STATA software. A total of 21 studies with a pooled patient population of 26,037 were included in the study, including 14 studies on the association between HCQ alone and mortality risk and seven studies on the association between HCQ/chloroquine (CQ) and mortality risk. The pooled findings suggested that HCQ significantly reduced the overall mortality risk of SLE (pooled HR 0.46, 95% CI 0.38-0.57, p < 0.001). In subgroup analysis of SLE complications, HCQ use also decreased the risk of death in SLE patients with renal (HR=0.43, 95% CI 0.26-0.70, p = 0.001) and cardiopulmonary involvement (HR=0.37, 95% CI= 0.25-0.54, p < 0.001). In addition, HCQ use was also protective against the risk of mortality in SLE patients in different regions, such as Asia (HR=0.46, 95% CI=0.33-0.64, p < 0.001), Europe (HR= 0.40, 95% CI = 0.22-0.71, p = 0.002), and America (HR=0.52, 95% CI= 0.42-0.64, p < 0.001). Our data suggested that HCQ use was associated with a reduced risk of mortality in patients with SLE.

S702 Effects of Gastrointestinal Comorbidities on Mortality in Patients Admitted for Systemic Lupus Erythematosus

Introduction: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune inflammatory disease with multi-organ involvement. Gastrointestinal manifestations typically arise as a result of adverse reactions, therapeutic agents or infections. However, SLE gastrointestinal involvement is important to identify because undertreatment can lead to life threatening complications such as lupus mesenteric vasculitis, protein losing enteropathy, and acute pancreatitis. Our project aims to look at the effects of gastrointestinal comorbidities on the mortality of patients admitted for SLE. Methods: A retrospective analysis of the largest inpatient database, the National Inpatient Sample, was performed from 2001-2013. Primary diagnosis of SLE and comorbidities including gastrointestinal bleeding (GIB), dysphagia, gastroesophageal reflux disease (GERD), Celiac disease, Crohn’s disease, Ulcerative colitis, serositis, pancreatitis, malabsorption was extracted using International Classification of Diseases, Ninth Revision (ICD-9) codes. A propensity-matched multivariable logistic regression analysis was performed to analyze the correlation of patients against their healthy counterparts and the effect on mortality. Propensity matching was performed to adjust for baseline patient and hospital demographics. All significance levels of p< 0.01. Results: After adjusting for age, race, median income, insurance status, hospital region, and Charlson Comorbidity Severity, it was found that GIB was significantly associated with mortality. Patients with GIB admitted for SLE were 3.85 times more likely to die compared to those without GIB. GERD, dysphagia, Celiac disease, Crohn’s disease, Ulcerative colitis, serositis, pancreatitis, and malabsorption were not significantly associated with mortality in SLE patients. (Figure) Conclusion: SLE patients who present with GIB are more likely to die compared to those without SLE. This may be due to SLE patients having prolonged bleeding times. Additionally, many SLE patients have renal involvement and chronic kidney disease which may further exacerbate coagulation and hemostasis problems. SLE patients are also at risk for lupus mesenteric vasculitis, a potential life threatening cause for bleeding. Accurate diagnosis and early treatment of GIB in SLE patients is necessary to reduce mortality risk. Future studies should investigate factors that increase GIB risk in SLE patients.Figure 1.: Predictors of mortality in patient with SLE and concurrent GI diseases.

Risks of Hemorrhage and Poor Clinical Outcome in SLE with Thrombocytopenia at Dr. Sardjito Hospital

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects various body organs and causes chronic inflammation. Thrombocytopenia is common in SLE, and there is a risk of causing bleeding, which can result in death. This study aimed to analyze the relationship of thrombocytopenia with bleeding and poor clinical outcomes in SLE patients at Dr. Sardjito Hospital. The design of this study was retrospective observational analytic. The research subjects were patients diagnosed with SLE at Dr. Sardjito Hospital from January 2016-December 2019 who conducted ANA and anti-dsDNA examinations. Statistical analysis using MedCalc version 13.0. Receiver operating characteristic curve analysis to determine the cut-off value of the platelet count for the occurrence of bleeding. Chi-Square for trend test to determine the relationship between the degree of thrombocytopenia and the degree of bleeding. Kaplan-Meier test to determine the six months survival analysis for SLE patients. There were 61 SLE patients at Dr. Sardjito Hospital. Thirty-two patients (52.5%) had thrombocytopenia. The AUC of the platelet count for the occurrence of hemorrhage was 0.988 (95% CI=0.918-1, p &lt; 0.0001), the cut-off value was 146x103/L, sensitivity 100%, specificity 90.6%, and LR+ 10.33. The AUC of the platelet count for grade 3 hemorrhage was 0.929 (95% CI=0.833-0.979, p &lt; 0.0001), cut-off value 91x103/L, sensitivity 100%, specificity 89.3%, and LR+ 9.33. Hemorrhage was seen in 29 subjects with thrombocytopenia. Five subjects (8.2%) died, with a significant difference in the mortality of SLE patients with and without thrombocytopenia in the six months survival analysis (p=0.028). The risk of hemorrhage and poor clinical outcome (death) were significantly higher in SLE patients with thrombocytopenia and increased with the thrombocytopenia grade.

A Histology-Guided Approach to the Management of Patients with Lupus Nephritis: Are We There Yet?

Renal involvement is a frequent complication of systemic lupus erythematosus (SLE). It occurs in up to two-thirds of patients, often early during the disease course, and is the most important predictor of the morbidity and mortality of SLE patients. Despite tremendous improvements in the approach of the lupus nephritis (LN) therapy, including the recent approval of two new disease-modifying therapies, up to 50% of patients do not obtain a renal response and up to 25% will eventually progress to end-stage renal disease (ESRD) within 10 years of diagnosis. Given the lack of correlation between clinical features and histological lesions, there is an increasing need for a histology-guided approach to the management of patients with LN. Apart from the initial diagnosis of type and severity of renal injury in SLE, the concept of a repeat kidney biopsy (either in a for-cause or a per-protocol scenario) has begun to gain increasing popularity in the nephrology community. Herein, we will provide a comprehensive overview of the most important areas of utility of the kidney biopsy in patients with LN.

Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice.

Systemic lupus erythematosus (SLE) is an autoimmune disorder with no known cure and is characterized by persistent inflammation in many organs, including the kidneys. Under such circumstances, the kidney loses its ability to clean waste from the blood and regulate salt and fluid concentrations, eventually leading to renal failure. Women, particularly those of childbearing age, are diagnosed nine times more often than men. Kidney disease is the leading cause of mortality in SLE patients. The present protocol describes a quick and simple method to measure excreted protein levels in collected urine, tracking lupus progression over time. In addition, an approach to isolate kidney mononuclear cells is provided based on size and density selection to investigate renal infiltration of leukocytes. Furthermore, an immunohistochemical method has been developed to characterize protein deposition in the glomeruli and leukocyte infiltration in the tubulointerstitial space. Together, these methods can help investigate the progression of chronic inflammation associated with the kidneys of lupus-prone MRL/lpr mice.

Prognostic factors of systemic lupus erythematosus patients with pulmonary embolism: An 11-year cohort study.

Systemic lupus erythematosus (SLE) patients have a higher risk of pulmonary embolism (PE) which is life-threatening, but there has been no research focusing on the prognosis of SLE patients with PE. This study was conducted to explore the prognostic factors of mortality in SLE patients with PE. In this observational cohort study, SLE inpatients with PE treated at Peking Union Medical College Hospital between January 2010 and December 2020 were included and age, gender, smoking history, the onset of SLE and PE, organ involvement, SLE disease activity index-2000 (SLEDAI-2K), severity of PE, and treatment regimen were collected. Kaplan-Meier survival curve and univariate and multivariate COX regression analysis were used to explore the prognostic factors of SLE patients with PE. A total of 86 SLE patients with PE were enrolled, with the age of 37.72±15.79 years old and the average lupus duration of 46.5 months. 17 patients (19.77%) died. 1- and 3-year survival rates were 83.40% and 79.40%. Thrombocytopenia (log-rank p = 0.004) and lymphocytopenia (log-rank p = 0.030) were predictors of mortality, and effective anticoagulation (log-rank p = 0.032), hydroxychloroquine (HCQ) (log-rank p = 0.021) were protective factors of mortality in SLE patients with PE. Effective anticoagulation was an independent protective factor of mortality in SLE patients with PE (HR = 0.14, p = 0.006). Patients with thrombocytopenia and lymphocytopenia are more likely to develop a poor prognosis. Effective anticoagulation and HCQ could improve the prognosis.

MBL2 gene polymorphisms and its relation to infection in Brazilian systemic lupus erythematosus patients: A 10-years follow-up study.

Systemic lupus erythematosus (SLE) is a multifactorial disease and MBL2 genetic variants, which are associated to differential peripheral MBL levels, potentially affect its etiology and increase infection risk in this population. To evaluate the potential association of MBL2 polymorphisms of the coding and promoter gene region and haplotypes on hospitalization, number of admission and days of admission for major infection causes in Brazilian SLE patients. Methods: 325 SLE patients from a southern Brazilian outpatient SLE clinic were genotyped in 2006 for MBL2 gene polymorphisms from coding and promoter region (rs1800450, rs1800451, rs5030737, rs11003125, and rs7096206) and followed until 2016. Clinical and laboratory data from each patient were obtained and information regarding the need for hospitalization, the number of admissions and number of days admitted for infection treatment were compiled and compared with MBL2 gene polymorphisms and haplotypes. A linear regression analysis was constructed considering the variables of bivariate which demonstrated an association (p<0.05) and variables which had a theoretical basement. No difference was found in polymorphism prevalence when comparing the group that was admitted for infection treatment and the group who did not. Allele C, and haplotypes LY and HY correlated with more infection hospitalizations [wild-type homozygosis for C: 2 (IQR 1-3), heterozygosis for C: 3 (IQR 2-6) p=0.038; LY 2 (IQR 1-3) p=0.049; HY 2 (IQR 1-3) p=0.005] and haplotype HY carriers stayed fewer days in hospital for infection treatment: 18 (IQR 10-38) p=0.041. When linear regression was applied HY associated with shorter admission time for infections (-18.11days, p=0.021) and HY (-1.52 admission, p 0.001) carriers with older age at diagnosis had less admissions for infection (HY regression model: -0.42, p=0.006; LY regression model -0.04, p=0.010; -0.04, p=0.013). The presence of the HY promoter haplotype associated to fewer in hospital care for infection treatment probably due to higher MBL plasma levels. Also, HY haplotype and older age at SLE diagnosis is related to less admissions for infection. This factor should be taken into consideration, since infection is a very import cause of mortality in SLE patients being also related to aggressive immunosuppressive treatment.

Erythropoietin in Lupus: Unanticipated Immune Modulating Effects of a Kidney Hormone.

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease with variable clinical presentation, typically characterized by a relapsing-remitting course. SLE has a multifactorial pathogenesis including genetic, environmental, and hormonal factors that lead to loss of tolerance against self-antigens and autoantibody production. Mortality in SLE patients remains significantly higher than in the general population, in part because of the limited efficacy of available treatments and the associated toxicities. Therefore, novel targeted therapies are urgently needed to improve the outcomes of affected individuals. Erythropoietin (EPO), a kidney-produced hormone that promotes red blood cell production in response to hypoxia, has lately been shown to also possess non-erythropoietic properties, including immunomodulatory effects. In various models of autoimmune diseases, EPO limits cell apoptosis and favors cell clearance, while reducing proinflammatory cytokines and promoting the induction of regulatory T cells. Notably, EPO has been shown to reduce autoimmune response and decrease disease severity in mouse models of SLE. Herein, we review EPO's non-erythropoietic effects, with a special focus on immune modulating effects in SLE and its potential clinical utility.

Lupus Nephritis; Pathogenesis and Treatment Update Review

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). LN is a leading cause of morbidity and mortality in SLE patients. LN presents with various symptoms and signs, ranging from asymptomatic renal involvement to End-Stage Renal Failure (ESRD). The pathogenesis of LN is not clearly understood, however, there are extra and intra-renal underlying factors that have been postulated in LN pathogenesis. Renal biopsy is crucial to stage LN and to rule out other causes. Histopathological studies have shown six different types of LN. Knowing the histopathological lesion, chronicity and the disease activity are essential to plan the LN treatment and to predict the outcome. There are different regimens for treating LN. In this review, LN pathogenesis and new advances in treatment will be briefly reviewed.

Pulmonary arterial hypertension associated with systemic lupus erythematosus

Pulmonary arterial hypertension (PAH) associated with connective tissue diseases is the most common cause of pulmonary hypertension. Systemic lupus Erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. The prevalence of PAH in SLE is less than 4% when the PAH diagnosis is based on the gold standard, namely right heart catheterization. The aim of this study was to describe the clinical and biological presentation of PAH in SLE. The study population consisted of 238 Tunisian patients with SLE who fulfilled the revised criteria of the American Rheumatism Association and were admitted to the internal medicine and rheumatology department in Fattouma Bourguiba University Hospital between 2010 and 2020. All patients underwent Doppler echocardiography study. PAH was hemodynamically defined by increased systolic pulmonary artery pressure (SPAP) at rest ≥ 25 mmHg. Of the 238 patients, 12 women presented PAH (5%). Mean age were 38, 2 years. SPAP ranged from 25 to 36 mmHg. Two patients had associated systemic scleroses. Comparison of patients with and without PAH found out that patients with PAH had significantly higher frequency of Reynaud's phenomenon (41,7% VS 13,4%; P = 0.023) and serositis (50% VS 21%; P = 0.046). Immunological variables associated with PAH include anti-SSA ( P = 0.003), anti-SSB ( P = 0.023) and anticardiolipine antibodies IgM/IgG ( P = 0.029). No significant differences between the two groups regarding cardiac involvement, thrombosis, anti-DNA and anti-SM antibodies were found. On follow up, the PAH was associated with an increased risk of mortality (OR = 7, 23; 95% CI = 1.294–40.447). PAH is a rare complication of SLE. Other studies are needed to confirm whether the presence of PAH is a risk factor for mortality in SLE patients.

Abstract 15263: Co-existing Systemic Lupus Erythematosus Does Not Negatively Impact Outcomes of Patients Admitted for Acute Coronary Syndrome: Analysis of the National Inpatient Sample

Introduction: Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease with effects on multiple organ systems and a wide range of clinical manifestations. Cardiovascular diseases from accelerated atherosclerosis are one of the major causes of mortality in SLE patients. This study aims to compare the outcomes of patients primarily admitted for Acute Coronary Syndrome (ACS) with and without a secondary diagnosis of SLE. Methods: Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 Database. This database is the largest collection of inpatient hospitalization data in the United States (U.S). The NIS was searched for hospitalizations for adult patients with ACS as principal diagnosis with and without SLE as secondary diagnosis using ICD 10 codes. The primary outcome was inpatient mortality. Secondary outcomes of interest are showed in Table 1. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used to analyze the data. Results: There were over 71 million discharges included in the combined 2016 and 2017 NIS database. Out of 1.3 million patients with ACS, 5,485 (0.42%) had SLE. The adjusted odds ratio (AOR) for inpatient mortality for ACS with co-existing SLE compared to those without SLE was 1.16 (95% CI 0.86-1.56, P=0.333). Hospitalizations for ACS with co-existing SLE had a decrease in adjusted mean total hospital charge of $5,164 compared to those without SLE (95% CI - {10,202-126}, P=0.045). Conclusions: Patients admitted primarily for ACS with a secondary diagnosis of SLE had less total hospital charges, but similar inpatient mortality, LOS, revascularization strategies, rates of IABP and PEAD placement compared to those without SLE. Though SLE is known to increase the risk of cardiovascular diseases, SLE does not negatively impact outcomes in patients primarily admitted for ACS based on U.S. national hospital billing data.

Laboratory-confirmed bloodstream infection in systemic lupus erythematosus: Risk profiling and short-term mortality.

To delineate laboratory-confirmed bloodstream infection (LCBI), analyze risk factors for its occurrence and predictors for its short-term mortality in systemic lupus erythematosus (SLE) patients.Methods A single center, retrospective, case-controlled study was performed in 159 SLE patients (2013-2019) to identify risk factors of LCBI by comparing patients with LCBI (n = 39) to those without infection (n = 120). The predictors associated with 30-day mortality in LCBI patients were also analyzed. Altogether 40 bacteria strains were isolated in 39 LCBI patients with a predominance of the gram-negative bacilli (24 strains, 60.0%). Escherichia coli and Staphylococcus aureus were the leading Gram-negative and Gram-positive microorganisms, respectively. Occurrence of LCBI was independently predicted by: SLE disease duration >4 years, SLEDAI score >4 points, glucocorticoids dose >7.5 mg/d and the previous or concomitant occurrence of autoimmune hemolytic anemia (AIHA) or thrombotic microangiopathy (TMA). Based on the identified risk factors, we developed a matrix model for the risk of future LCBI. The 30-day mortality (39 cases) was 23.1% and healthcare-associated LCBI was a predictor for 30-day mortality in SLE patients compared with community-acquired LCBI. Longer duration, higher disease activity and glucocorticoids dose, and occurrence of AIHA or TMA were risk factors of LCBI in SLE and its poor short-term prognosis may attribute to healthcare-associated LCBI.

Efficacy and Safety of Vaccinations in Systemic Lupus Erythematosus

Patients with rheumatological or immunological conditions, such as systemic lupus erythematosus (SLE), are particularly vulnerable to infections either due to the underlying immunological aberrations of the disease itself or treatment-related/iatrogenic immunosuppression. Infections remain the leading cause of morbidity and mortality in SLE patients and appropriate vaccination is of paramount importance. Despite clear guidance for the most common vaccinations, the greatest barrier to appropriate vaccinations likely remains with physician awareness or willingness for recommendation. To address this, we review the current evidence regarding the impact of the most commonly recommended vaccinations on SLE.

Difference in thrombotic microangiopathy between concurrently and previously diagnosed systemic lupus erythematosus.

Thrombotic microangiopathy (TMA) syndromes are potentially life-threatening complications and are defined as integrated syndromes of microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect various organs, including the hematopoietic system. SLE can complicate with TMA and can be categorized into two distinct groups by chronological association: TMA occurring as the initial presentation and leading to a diagnosis of SLE concurrently (TMA-cSLE) or TMA developing in patients previously diagnosed as having SLE (TMA-pSLE). We examined the differences in clinical characteristics, treatment responses, and clinical outcomes between these groups. We reviewed data of patients diagnosed as having TMA and SLE at Taipei Veterans General Hospital between 2002 and 2013. We included 29 patients: 8 and 21 in TMA-cSLE and TMA-pSLE groups, respectively. All underwent plasma exchange. Patients' demographic and clinical characteristics, disease activity, and treatment modality were summarized. Overall survival (OS) from SLE or TMA diagnosis was poor for the TMA-cSLE group. Median OS from SLE diagnosis was 2.9 months in the TMA-cSLE group and 103.5 months in the TMA-pSLE group (p < 0.001). Median OS from TMA diagnosis was 2.9 months in the TMA-cSLE group and 10.7 months in the TMA-pSLE group (p = 0.58). Time to TMA remission after treatment appeared longer in the TMA-cSLE group (38.00 vs 10.76 days). Multivariate Cox analysis revealed TMA-cSLE and anti-RNP positivity were independent risk factors for mortality in SLE patients with TMA. The occurrence of TMA with SLE is rare, and its vigorous course results in high mortality and morbidity rates. In patients without a history of autoimmune disease, early suspicion of TMA and working-up for SLE under this condition are vital. Early recognition of TMA-cSLE and prompt plasma exchange with upfront immunosuppressive therapies for TMA-cSLE patients or anti-RNP-positive patients may improve their prognosis.

Effect of Candida albicans bronchial colonization on hospital-acquired bacterial pneumonia in patients with systemic lupus erythematosus.

To investigate the effect of Candida albicans airway colonization on hospital-acquired bacterial pneumonia (HABP) in patients with systemic lupus erythematosus (SLE). SLE patients with HAP were enrolled in this retrospective cohort study from January 2015 to December 2018. According to the culture results of respiratory tract secretions and antifungal treatment, patients were divided into non-C. albicans colonization group (NCG), C. albicans colonization with antifungal treatment group (CTG) and C. albicans colonization without antifungal treatment group (CNTG). Twenty-eight days of all-cause mortality after the onset of HABP of each group was assessed, total duration of antibiotic treatment, changes of inflammatory cytokines and markers of immune status were documented. A total of 269 SLE patients with HABP were finally included in the study. Among them, 69.1% (186/269) were found C. albicans airway colonization, and 36.1% (97/269) received antifungal treatment. No difference of 28 days of all-cause mortality after HABP onset was found among the three groups (10.8% vs. 13.4% vs. 15.7%, P>0.05). Duration of antibiotic treatment of HABP due to Acinetobacter baumannii was shorter in CTG (11.21±2.45 days) than that in CNTG (12.89±3.87 days) as well as HABP due to Pseudomonas aeruginosa (10.57±2.66 vs. 12.56±3.04 days) (P<0.05, respectively). Antifungal treatment could decrease the level of interleukin-1β, interleukin-6, tumor necrosis factor-α and interferon-γ in CTG than in CNTG (P<0.05, respectively). In addition, it could regulate immune function by decrease the concentration of interleukin-17 and elevate the counts of CD4+Th lymphocyte as well (P<0.05, respectively). C. albicans airway colonization was not associated with HABP mortality in SLE patients. Antifungal therapy in these patients might shorten the duration of antibiotics in treating HABP due to A. baumannii and P. aeruginosa.

Role of Cardiologists in the Management of Systemic Lupus Erythematosus: First Reported Case of Three-vessel Disease in a Young Woman in Pakistan

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disorder with predilection towards young women. SLE is associated with increased risk of incidence of cardiac diseases which include atherosclerosis and coronary artery disease (CAD) that can present clinically as angina or myocardial infarction (MI) or be clinically silent in the initial stages. Furthermore, the use of corticosteroids for the treatment of SLE exacerbates the risk of thrombosis, possibly resulting in adverse cardiovascular events in such patients. Antiphospholipid syndrome (APS) is another autoimmune condition which can occur in the setting of SLE, also resulting in hypercoagulability and thrombosis. This goes on to show how important a role cardiologists play in anticipating and managing the cardiac manifestations of SLE, which can significantly reduce the morbidity and mortality of SLE patients. Here we present a case of a young woman with SLE having three-vessel disease, presenting in the cardiac emergency department of Civil Hospital, Karachi with typical chest pain. This case is the first of its kind to be reported in Pakistan, to the best of our knowledge.

Mortality prediction in systemic lupus erythematosus patients with pulmonary infection.

The impact of pulmonary infection (PI) on mortality of patients with systemic lupus erythematosus (SLE) has been established. Nevertheless, the effect of risk factors in mortality remains controversial. The objective of this study is to determine the risk factors of short-term mortality among SLE patients with PI. The clinical data of 54 SLE patients with 59 episodes of PI who were hospitalized from January 2013 to May 2018 was retrospectively analyzed. Demographic data, clinical features, and outcomes were collected. Logistic regression analysis was carried out to determine the independent predictors of 60-day mortality during hospitalization. We used receiver operating characteristics (ROC) curves to verify the indices as mortality predictors in the study patients. There were a total of 54 patients with 59 episodes of PI. There were 12 deaths during hospitalization. In multivariate analysis, 24-hour urinary protein (24h-PRO) (odds ratio [OR]: 2.713, 95% CI: 1.234-5.965, P=0.013), peripheral lymphocyte count (OR: 0.066, 95% CI: 0.005-0.887, P=0.040), and serum complement 3 level (C3) (OR: 0.097, 95% CI: 0.010-0.954, P=0.045) were associated with mortality among our cohort of SLE patients with PI. ROC curve values were 0.818 for lymphocyte count (95% CI: 0.696-0.907, P=0.001), 0.894 for 24h-PRO (95% CI: 0.786-0.959, P<0.001) and 0.825 for C3 (95% CI: 0.704-0.912, P=0.001). The cut-off value of lymphocytes, 24h-PRO and C3 were 0.53 × 109 /L, 0.92g and 0.52g/L, respectively. The presence of albuminuria, lymphopenia and low complement C3 levels were independent prognostic predictors of short-term mortality in SLE patients with PI.