Five-Factor Score Research Articles

B-Cell-Depleting Therapy Improves Myocarditis in Seronegative Eosinophilic Granulomatosis with Polyangiitis.

Cardiac involvement is a major mortality cause in eosinophilic granulomatosis with polyangiitis (EGPA), requiring novel therapeutics to spare the use of cyclophosphamide with known cardiotoxicity. Despite the observed efficacy of B-cell-depleting therapy in myocarditis of seropositive microscopic polyangiitis, it remains to be elucidated in seronegative EGPA. A retrospective study was performed in 21 hospitalized active patients aged 20 to 70 years with five-factor score 1 or 2, eosinophil counts 10,034 ± 6641/μL and vasculitis scores 27 ± 6. Overt myocarditis was identified in 10 cases, at disease onset in 6 and relapse in 4, with endomyocarditis in 4 and myopericarditis in 4. Five seronegative and one seropositive patient received rituximab with an induction regimen 375 mg/m2 weekly × 4 for refractory or relapse disease, and the same regimen for annual maintenance therapy. All cases had lower eosinophil counts, improved cardiac dysfunction and clinical remission with a relapse-free follow-up, 48 ± 15 months after the induction treatment. One seronegative endomyocarditis patient had eosinophilia and disease relapse with asthma attack and worsening cardiac insufficiency 24 months after induction, achieving clinical remission under anti-IL-5 therapy. Our findings suggest the suppression of IL-5-mediated eosinophilia as an action mechanism of B-cell-depleting therapy in seronegative EGPA myocarditis.

Nutrition Risk Index Score at Diagnosis Can Effectively Predict Poor Prognosis in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

This study investigated whether the nutritional risk index (NRI) score at diagnosis might be useful for anticipating poorprognosis, in particular, all-cause mortality and end-stage renal disease (ESRD) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The medical records of 242 immunosuppressive drug-naïve patients with AAV were retrospectively reviewed. Data at diagnosis and poor prognosis and medications during follow-up were assessed. The NRI score was calculated by 1.519 × serum albumin (g/L)+41.7 × present (kg)/ideal body weight (kg). The median age at diagnosis of patients with AAV (131 microscopic polyangiitis, 62 granulomatosis with polyangiitis, and 49 eosinophilic granulomatosis with polyangiitis) was 60years (85 male). During follow-up, twenty-nine patients (12.0%) died after a period of 35.9months, and 42 patients (17.4%) had ESRD for a period of 30.0months. Using the receiver operator characteristic curve, the cutoffs of the NRI scores for all-cause mortality and ESRD were calculated as NRI≤101.95 (sensitivity, 46.5%; specificity, 89.7%) and NRI≤99.85 (sensitivity, 57.0%; specificity, 83.3%). In the multivariable Cox hazard model analyses, age (hazard ratio [HR], 1.035), five-factor score (HR, 1.623), and the NRI score≤101.95 (HR, 4.262) were independent predictors of all-cause mortality, whereas, five-factor score (HR, 1.516), hypertension (HR, 1.906), and the NRI score≤99.85 (HR, 3.623) were independent predictors of ESRD occurrence during follow-up in patients with AAV. The NRI score at diagnosis may be a useful index to anticipate all-cause mortality and ESRD occurrence during follow-up in patients with AAV.

Serum adipokine profiles in patients with microscopic polyangiitis and granulomatosis with polyangiitis: An exploratory analysis.

ObjectivesPrevious studies have shown that adipokines may serve as potential biomarkers reflecting disease activity in various autoimmune diseases. Here, we investigated the relationship between four adipokines and clinical/laboratory findings in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).MethodsSera from 63 patients with MPA and GPA who were registered in a prospective cohort were used to detect serum levels of adiponectin, chemerin, resistin, and vaspin using commercial enzyme-linked immunosorbent assay kits. Associations between adipokines and clinical and laboratory data was assessed using Pearson’s correlation analysis.ResultsThe median age was 65.0 years, 24 patients were male, and 42 patients were diagnosed with MPA. The median levels of adiponectin, chemerin, resistin, and vaspin in patient sera were 13.9 ng/mL, 9.2 ng/mL, 23.7 ng/mL, and 0.1 ng/mL, respectively. A significant correlation between chemerin level and five-factor score (FFS) was found (r = 0.320, p = 0.011), and resistin was correlated with both Birmingham vasculitis activity score and FFS (r = 0.256, p = 0.043 and r = 0.320, p = 0.011). Regarding laboratory data, adiponectin level was associated with creatinine, and chemerin level was associated with creatinine, albumin, and erythrocyte sedimentation rate (ESR). On the other hand, resistin was found to be associated with white blood cell count, creatinine, ESR, and C-reactive protein. Age did not have a significant impact on the levels of adipokines.ConclusionsThe expression of adipokines in the sera of patients with MPA and GPA differs depending on clinical and laboratory features, and serum resistin may be suggested as a potential biomarker reflecting disease activity.

Predictors of renal and patient outcomes in anti-neutrophil cytoplasmic antibody-associated vasculitis: Our single-center, tertiary care experience.

Objectives This study aims to assess the different predictors of renal and patient prognosis in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients with and without renal involvement.Patients and methods A total of 79 patients (51 males, 28 females; mean age: 57.3±14.2 years; range, 18 to 71 years) with AAV between January 2006 and November 2019 were retrospectively analyzed. Demographic and laboratory data including the complement 3 (C3) serum levels and renal biopsy findings were extracted from the electronic and printed medical records of the hospital registry. Survival, renal survival, remission, and relapse outcomes were analyzed.Results A total of 35% of the patients with renal involvement progressed to end-stage renal disease (ESRD). The dialysis requirement at the time of admission (hazard ratio [HR]: 21.95 [2.93-164.22]; p=0.003), estimated glomerular filtration rate (eGFR) (HR: 0.97 [0.94-0.99]; p=0.024) and Five-Factor Score (FFS) ≥2 at the time of diagnosis (HR: 3.59 [1.08-11.94]; p=0.037) were the predictors of ESRD. The five-year patient survival rate was 87.1%. The only predictor of mortality was age (HR: 1.07 [1.01-1.14]; p=0.024). The patients with hypocomplementemia (22%) had a lower remission rate (p=0.049), FFS ≥2 at the time of diagnosis (p=0.026), and higher levels of hematuria (p=0.004) and proteinuria (p=0.037). The FFS ≥2 at the time of diagnosis was an independent predictor of relapse (HR: 8.9 [1.02-77.36]; p=0.047).Conclusion Our study suggests that the baseline renal function and FFS ≥2 at the time of diagnosis are the major prognostic factors for progression to ESRD in AAV patients. In addition, AAV patients with hypocomplementemia may have a lower remission rate.

Clinical features of central nervous system involvement in patients with eosinophilic granulomatosis with polyangiitis: a retrospective cohort study in China

BackgroundCentral nervous system (CNS) involvement is extremely rare in eosinophilic granulomatosis with polyangiitis (EGPA), but is associated with a poor prognosis in the five-factor score. This study aims to elucidate the clinical features and independently associated factors of EGPA with CNS involvement.ResultsCNS involvement was observed in 17.3% (19/110) of EGPA patients from Peking Union Medical College Hospital between 2007 and 2019. We retrospectively reviewed their clinical data and analyzed the independently associated factors. Their mean age was 51.7 ± 11.56 years with no male/female predominance. Ischemic lesions were the most common manifestations, accounting for 63.2% of the 19 cases, followed by posterior reversible encephalopathy syndrome (36.8%), spinal cord involvement (15.8%), medulla oblongata involvement (15.8%), and intracranial hemorrhages (15.8%). Compared to the control group, patients with CNS involvement were of older age (51.7 ± 11.56 vs. 43.7 ± 13.78 years, p = 0.019) and had a higher ratio in the digestive tract involvement (52.6% vs. 28.6%, p = 0.042). Further multivariate analysis revealed that age, disease duration, and fever were the potential independent risk factors for CNS involvement of EGPA. Glucocorticoids combined with cyclophosphamide were the strategic therapy (94.7%). Intrathecal injections of dexamethasone and methotrexate were administered to 21.1% of the patients. Although seven patients relapsed during glucocorticoid reduction, seventeen patients finally achieved clinical remission. One patient died of acute intracerebral hemorrhage within one month, and another died of gastrointestinal perforation. Outcomes and cumulative survival show no significant differences between the two groups.ConclusionsCNS involvement is uncommon in EGPA with various manifestations, and ischemic lesions are the most frequent. Age, disease duration, and fever are independent factors associated with CNS involvement in EGPA. The therapy of glucocorticoids combined with cyclophosphamide and intrathecal injections yields favorable responses. Acute intracranial hemorrhage and gastrointestinal perforation may be the principal causes of death.

Serum chitinase-3-like 1 protein is a useful biomarker to assess disease activity in ANCA-associated vasculitis: an observational study

BackgroundTo investigate whether serum chitinase-3-like 1 protein (YKL-40) is associated with disease activity in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).MethodsELISA was performed in serum samples from AAV patients who were enrolled in our prospective observational cohort to estimate levels of YKL-40. Birmingham vasculitis activity score (BVAS) (version 3), five factor score (FFS), and short form-36 (SF-36), as well as clinical and laboratory data were collected. Kidney expression of YKL-40 was assessed by immunohistochemical staining using renal biopsy tissues from ANCA-associated glomerulonephritis patients (AAGN). Severe AAV and FFS were defined as BVAS ≥ 12 and FFS ≥ 2, and the correlations between laboratory variables, BVAS, FFS, and SF-36 score were assessed using linear regression analysis. The optimal cut-off of serum YKL-40 for severe AAV and high FFS was calculated using the receiver operator characteristic curve analysis.ResultsOf the included 60 patients, 32 (53.3%), 17 (28.3%), and 11 (18.3%) were classified as microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis. The median BVAS and FFS were 7.0 and 1.0, whereas the mean SF-36 physical and mental component scores were 50.5 and 58.3. Serum YKL-40 level was higher in patients with severe AAV and high FFS compared to those without (p = 0.007 and p < 0.001); multivariable linear regression analysis revealed that serum YKL-40 was independently associated with BVAS, FFS, and SF-36 scores. On kidney tissues obtained from AAGN patients, strong cytoplasmic staining of YKL-40 was found in cells present in inflammatory lesions. In addition, AAV patients had higher levels of serum YKL-40 compared to those with systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, and healthy control. The proportion of patients having severe AAV and high FFS was significantly higher in those with serum YKL-40 > 221.3 ng/mL and > 227.1 ng/mL than those without (relative risk 2.852 and 7.000). In 12 patients with serial YKL-40 testing, 11 patients (91.7%) exhibited a reduction in serum YKL-40 levels following a decrease in disease activity (p < 0.001).ConclusionOur findings suggest that serum YKL-40 may be a clinically useful biomarker to assess AAV disease activity.Trial registrationRetrospectively registered.

Clinical Characteristics and Outcomes of Mexican Patients With Polyarteritis Nodosa: A Single-Center Study Over 40 Years.

We conducted a medical records review study (1975-2018) that included patients with childhood- and adult-onset PAN. Demographics, organ involvement, phenotype, treatment, and outcomes were assessed and compared against previously published cohorts. Thirty-one patients were included, 20 (64.5%) female, with a median age at diagnosis of 28 years (interquartile range [IQR], 16-42). Seven (23%) were classified as cutaneous; 23 (74%), systemic; and 1 (3%), progressive systemic phenotype. Eleven patients (35%) had childhood-onset PAN. Most common manifestations were musculoskeletal (71%), cutaneous (68%), constitutional (61%), peripheral neuropathy (39%), and gastrointestinal (29%). The median Birmingham Vasculitis Activity Score and Five-Factor Score at diagnosis were 9 (IQR, 4-13) and 1 (IQR, 0-1), respectively. Most patients were treated with glucocorticoids (94%). Twenty-four (80%) achieved complete and 6 (20%) partial remission at a median follow-up time of 30 months (8-192 months). The median Vasculitis Damage Index at last follow-up was 1 (IQR, 0-1). Nineteen (66%) experienced relapses. Patients with childhood-onset PAN more frequently had central nervous system and gastrointestinal involvement (36% vs 5%, p = 0.04 and 64% vs 10%, p = 0.003, respectively), microaneurysms (100% vs 38%, p = 0.02), and lower levels of C-reactive protein (0.3 vs 15.4 mg/dL, p = 0.03), compared with adult-onset PAN patients. Our cohort of PAN patients showed predominantly a systemic phenotype. Outcomes were generally good, with most patients achieving complete remission. Childhood-onset differed from adult-onset PAN in terms of clinical and serological characteristics, whereas clinical manifestations and outcomes may be different than the ones reported in other cohorts.

Male Sex Is a Significant Predictor of All-cause Mortality in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

BackgroundWe investigated and compared the initial clinical features at diagnosis and the poor outcomes during follow-up in Korean patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on sex.MethodsThe medical records of 223 immunosuppressive drug-naïve patients with AAV were reviewed. Age, body mass index (BMI), smoking history, AAV subtypes, ANCA positivity, clinical manifestations, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at diagnosis were collected. All-cause mortality, end-stage renal disease (ESRD), cerebrovascular accident (CVA) and cardiovascular disease (CVD) were assessed as the poor outcomes of AAV during follow-up.ResultsThe median age was 59.0 years and 74 of 223 AAV patients (33.2%) were men. Among variables at diagnosis, male patients exhibited higher BMI than female. However, there were no differences in other demographic data, AAV subtypes, ANCA positivity, BVAS, FFS, ESR and CRP between the two groups. Male patients received cyclophosphamide more frequently, but there were no significant differences in the frequencies of the poor outcomes of AAV between the two groups. Male patients exhibited a significantly lower cumulative patients' survival rate than female patients during the follow-up period based on all-cause mortality (P = 0.037). In the multivariable analysis, both male sex (hazard ratio [HR], 2.378) and FFS (HR, 1.693) at diagnosis were significantly and independently associated with all-cause mortality during follow-up.ConclusionMale sex is a significant and independent predictor of all-cause mortality in AAV patients.

Serum Clusterin Level Could Reflect the Current Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

PurposeWe investigated whether serum clusterin levels could reflect the current antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-specific indices.Materials and MethodsFifty-seven patients with AAV and 40 healthy controls were included in this study. AAV-specific indices included the Short-Form 36-Item Health Survey Physical and Mental Component Summaries (SF-36 PCS and MCS) scores, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and vasculitis damage index. Clinical and laboratory data and AAV-specific indices were obtained at blood collection. The highest tertile of BVAS (≥16) was defined as high activity of AAV.ResultsThe median age of AAV patients was 64.0 years and 19 patients were male. SF-36 PCS score (r=0.328), SF-36 MCS score (r=0.289), BVAS (r=−0.404), erythrocyte sedimentation rate (r=−0.336), and C-reactive protein levels (r=−0.421) were significantly correlated with serum clusterin levels. In the multivariable linear regression analysis using AAV-specific indices and serum clusterin levels, both FFS (β=0.412) and serum clusterin levels (β=−0.250) were significantly associated with BVAS. When the optimal serum clusterin cut-off level for high activity of AAV was identified as 130.45 µg/mL, patients with serum clusterin level ≤130.45 µg/mL had a significantly higher risk for high activity of AAV than did those without (relative risk 7.194). Patients with AAV exhibited significantly lower serum clusterin levels than did healthy controls (168.2 µg/mL vs. 230.5 µg/mL).ConclusionSerum clusterin levels could reflect the current disease activity in patients with AAV.

Association Between Serum Alarmin Levels and Disease-specific Indices in Patients With Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis.

We evaluated the relationship between serum alarmin levels and disease-specific indices in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Sera and data from 79 patients were utilized. For AAV-specific indices, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and vasculitis damage index (VDI) were collected and serum levels of four alarmins (hepatoma-derived growth factor, high mobility group box protein 1, S100A9, and S100A12) were measured using enzyme-linked immunosorbent assay. Associations between alarmin levels, AAV-specific indices, and inflammatory laboratory markers were assessed. S100A9 levels were significantly correlated with C-reactive protein levels (r=0.316, p=0.005) and S100A12 levels correlated with VDI (r=0.232, p=0.040), which was consistent in a subgroup of patients with myeloperoxidase (perinuclear)-ANCA positivity. No other associations were found between alarmin levels and BVAS, FFS, and VDI. The serum S100A12 level was associated with organ damage in AAV, especially in myeloperoxidase (perinuclear)-ANCA-positive patients.

Serological Biomarkers and Indices for the Current Activity and Prognosis of ANCA-Associated Vasculitis: Experience in a Single Centre in Korea

Small vessel vasculitis is composed of two types of vasculitis based on immune-complex deposits, immune-complex vasculitis and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) according to the 2012 Chapel Hill Consensus Conferences Nomenclature of Vasculitis. In general, the current disease-states are assessed in three ways in real clinical practice such as activity, damage and functional status. Birmingham vasculitis activity score (BVAS, version 3) and five-factor score were calculated for assessing the cross-sectional activity and for predicting the prognosis of AAV, respectively. Since BVAS includes a wide spectrum of nine systemic items with differently weighted scores based on new-onset/worsening or persistent each symptom, it has been considered as the most reliable tool to assess AAV activity to date. However, since BVAS represents both cross-sectional and chronic clinical features, it has a limitation in flexibly reflecting the cross-sectional activity or severity of AAV. In addition, the heterogeneous items of BVAS are difficult to reflect the close correlation between BVAS and AAV pathogenesis. It is practically difficult to discover new biomarkers or indices that exceed the reliability of AAV-specific indices or acute-phase reactants established by long clinical experience. However, efforts to discover and develop new biomarkers or indices are expected to complement the clinical unmet need of existing AAV-specific indices and acute-phase reactants. In this review, we reviewed the serological biomarkers and indices that have been reported to date and introduced studies that investigated serological biomarkers and indices in Korean patients with AAV.

Prognostic value of the baseline circulating T cell receptor β chain diversity in advanced lung cancer

ABSTRACT An indicator for systemic evaluation of the adaptive immune status is lacking. Peripheral blood is important in antitumour immunity, and the T-cell receptor (TCR) repertoire diversity is key for effective immunity. This study aimed to investigate changes in the circulating T cell receptor β chain (TCRB) diversity during the first few (1 ~ 4) treatment cycles and its clinical value in patients with advanced lung cancer. TCRB-enriched sequencing data combined with transcriptomic RNA sequencing data of peripheral blood leukocytes were obtained from 72 patients with advanced lung cancer before and after targeted therapy or chemotherapy. Changes in the circulating TCRB diversity during treatment and the relationship of the baseline circulating TCRB diversity with prognosis and therapeutic effects were evaluated. We found that targeted therapy or chemotherapy did not significantly affect the T lymphocyte composition or circulating TCRB diversity (3.83 vs 3.74, T-test, p = .16) in patients with advanced lung adenocarcinoma (LUAD) during the first few treatment cycles. The higher circulating TCRB diversity was linked to improved therapeutic effects (T-test, p = .00083) in LUAD patients receiving targeted therapy. Higher baseline circulating TCRB diversity was associated with better prognosis. In addition, a five-factor prognostic risk score model was built for more accurate prognosis prediction for LUAD patients. The chemotherapeutic agents for advanced lung cancer do not significantly affect adaptive immune function over the first few treatment cycles. The circulating TCRB diversity reflects the adaptive immunological repertoire and might be a convenient indicator for evaluating the adaptive immune status and prognosis.

Proton Pump Inhibitor Utilization in Veteran Patients on Combined Antithrombotic Therapy and Validation of Simplified Bleeding Risk Score.

Concomitant use of anticoagulant and antiplatelet agents can increase the risk of gastrointestinal bleed (GIB). Use of proton pump inhibitors (PPIs) has been proposed to decrease the risk of GIB in patients on combined antithrombotic therapy (CAT). To describe the current utilization of PPIs in veteran patients on CAT and associated clinical predictors of GIB. This retrospective study included patients on CAT receiving PPIs, with at least one of the CAT agents initiated between January 1, 2018 and October 30, 2018. Data were extracted from the computerized patient record system. Primary end point included estimating proportion of patients on CAT receiving PPI co-therapy, describing patient characteristics, and identifying clinical predictors of GIB. Secondary outcomes included reporting GIB events and all-cause mortality. Additional outcome was to validate the five-factor risk score (FFRS) for GIB in patients on CAT and compare its overall predictive performance to HAS-BLED score. This study reports an overall rate of PPI co-therapy in patients on CAT of 40.9% (484/1181), with only 22.3% of patients on CAT receiving PPI for GIB prophylaxis. There was no difference in the mean follow up duration of PPI users and PPI co-therapy (264.01 vs 271.92days; p=0.3761). Current alcohol use (p=0.005), current smokers (p=0.022), chronic kidney disease (p=0.004), peptic ulcer disease (p<0.001), and non-steroidal anti-inflammatory drug use (p=0.048) were significant predictors of GIB in multivariate analyses of our study cohort. We further provide exploratory validation that use of a simplified FFRS to predict GIB showed a trend towards better overall predictive performance as compared to HAS-BLED score (C-statistic: 0.738; 95% CI 0.684-0.787 for FFRS vs C-statistic: 0.596; 95% CI 0.538-0.653 for HAS-BLED; p=0.0094). This study reports lower rate of PPI co-therapy in veteran patients on CAT per currently available guidance. Further we explore utilization of simplified FFRS model to predict GIB in patients on CAT with long-term PPI co-therapy.

Development and validation of a five-factor score for prediction of pathologic pneumatosis.

The significance of pneumatosis intestinalis (PI) remains challenging. While certain clinical scenarios are predictive of transmural ischemia, risk models to assess the presence of pathologic PI are needed. The aim of this study was to determine what patient factors at the time of radiographic diagnosis of PI predict the risk for pathologic PI. We conducted a retrospective cohort study examining patients with PI from 2010 to 2016 at a multicenter hospital network. Multivariate logistic regression was used to develop a predictive model for pathologic PI in a derivation cohort. Using regression-coefficient-based methods, the final multivariate model was converted into a five-factor-based score. Calibration and discrimination of the score were then assessed in a validation cohort. Of 305 patients analyzed, 102 (33.4%) had pathologic PI. We identified five factors associated with pathologic PI at the time of radiographic diagnosis: small bowel PI, age 70 years or older, heart rate 110 bpm or greater, lactate of 2 mmol/L or greater, and neutrophil-lymphocyte ratio 10 or greater. Using this model, patients in the validation cohort were assigned risk scores ranging from 0 to 11. Low-risk patients were categorized when scores are 0 to 4; intermediate, score of 5 to 6; high, score of 7 to 8; and very high risk, 9+. In the validation cohort, very high-risk patients (n = 17; 18.1%) had predicted rates of pathologic pneumatosis of 88.9% and an observed rate of 82.4%. In contrast, patients labeled as low risk (n = 37; 39.4%) had expected rates of pathologic pneumatosis of 1.3% and an observed rate of 0%. The model showed excellent discrimination (area under the curve, 0.90) and good calibration (Hosmer-Lemeshow goodness-of-fit, p = 0.37). Our score accurately stratifies patient risk of pathologic pneumatosis. This score has the potential to target high-risk individuals for expedient operation and spare low-risk individuals invasive interventions. Prognostic Study, Level III.

Survival in ANCA-Associated Vasculitides in a Peruvian Center: 28 Years of Experience.

The aim of this study was to identify demographic and clinical risk factors for mortality in patients with antineutrophil cytoplasmic antibodies-associated vasculitides (AAVs) in a Peruvian tertiary referral hospital. Medical records of patients with AAV according to classification criteria or diagnosed by an experienced rheumatologist, covering the period between January 1990 and December 2018, were reviewed. Granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited vasculitis were included. Potential predictors of mortality were demographic factors, clinical manifestations, antineutrophil cytoplasmic antibodies status, diagnosis, disease categorization, the 2009 Five Factor Score (FFS), and treatment. Cox regression models were used to determine the risk factors for mortality. Univariable and multivariable analyses using a backward selection method were performed. One hundred ninety-six patients were included; female-to-male ratio was 2:1. The median (interquartile range) age at diagnosis and follow-up were 60.0 (51.0-68.0) and 4.8 (1.3-11.6) years, respectively. One hundred forty-eight patients (75.5%) had microscopic polyangiitis, 37 (18.9%) granulomatosis with polyangiitis, 5 (2.6%) eosinophilic granulomatosis with polyangiitis, and 6 (3.0%) renal-limited vasculitis. Overall survival rates at 1, 5, and 10 years were 83.4%, 68.2%, and 51.7%, respectively. Ocular involvement was protective (hazards ratio [HR], 0.36; 95% confidence interval [CI], 0.17-0.74; p = 0.006), whereas renal (HR, 2.09; 95% CI, 1.33-3.28; p = 0.001) and lung involvement (HR, 2.07; 95% CI, 1.31-3.28; p = 0.002) and the 2009 FFSs were predictive of mortality (2009 FFS = 1: HR, 2.46; 95% CI, 1.50-4.04; p < 0.001; 2009 FFS = 2: HR, 3.07; 95% CI, 1.54-6.10; p = 0.001; 2009 FFS = 3: HR, 13.29; 95% CI, 3.69-47.88; p < 0.001). Ocular involvement was protective, whereas 2009 FFS ≥ 1 and renal and lung involvement were predictive factors of mortality in Peruvian AAV patients.

Evaluation of body composition using computed tomography in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Background/AimsMeasures of body composition, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA), are considered important prognostic factors in chronic diseases. The association of these measures with auto-inflammatory disorders, such as anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), remains unclear. We investigated the clinical significance of VAT, SAT, and SMA in patients with AAV.MethodsPatients with AAV subjected to chest computed tomography (CT), abdominal CT, or positron emission tomography-CT on diagnosis of AAV were evaluated. Quantitative assessment of VAT, SAT, and SMA was performed at the third lumbar vertebral level and computed by summing the pixel attenuation for tissue-specific Hounsfield units in the corresponding region. Associations of VAT, SAT, and SMA with clinical and laboratory data and clinical outcome measures were evaluated.ResultsOf the 117 patients, 61 (52.1%) were classified as having microscopic polyangiitis, 28 (23.9%) as granulomatosis with polyangiitis, and 28 (23.9%) as eosinophilic granulomatosis with polyangiitis. VAT significantly correlated with age, weight, body mass index (BMI), and Birmingham Vasculitis Activity Score, whereas SAT correlated with weight, BMI, and creatinine levels. A significant association was found between SMA and age, height, weight, BMI, and the Five-Factor Score. Cox proportional hazards analysis showed that creatinine levels (odds ratio [OR], 1.346; 95% confidence interval [CI], 1.034 to 1.753; p = 0.027) and high VAT (OR, 7.137; 95% CI, 1.343–37.946; p = 0.021) were independently associated with all-cause mortality during follow-up.ConclusionsEvaluation of VAT using CT is useful for estimating disease activity and all-cause mortality in patients with AAV.

Serum interleukin-16 significantly correlates with the Vasculitis Damage Index in antineutrophil cytoplasmic antibody-associated vasculitis

BackgroundInterleukin (IL)-16 is a T cell chemoattractant produced by peripheral mononuclear cells. We investigated whether IL-16 plays a pro- or an anti-inflammatory role in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Furthermore, we investigated whether the level of IL-16 could predict the activity and extent of organ damage in AAV based on AAV-specific indices.MethodsSeventy-eight patients with AAV from a prospective observational cohort were included in this analysis. Blood sampling and clinical assessments, including the Birmingham Vasculitis Activity Score (BVAS), Five-Factor Score (FFS), Short Form 36-item Health Survey (SF-36), and Vasculitis Damage Index (VDI), were performed, and laboratory data were collected. Serum IL-16 was measured from stored sera.ResultsThe median age was 62.0 years, and 27 patients were male. The median serum IL-16 concentration was 84.1 pg/dL, and the median BVAS, FFS, VDI, and SF-36 scores were 7.0, 1.0, 3.0, and 48.0, respectively. Among the AAV-related indices, the serum IL-16 concentration was correlated with VDI (R2 = 0.306, P = 0.006), but not with BVAS (R2 = 0.024, P = 0.834), FFS (R2 = − 0.069, P = 0.550), or SF-36 (R2 = − 0.015, P = 0.898). The serum IL-16 concentration also did not correlate with either the erythrocyte sedimentation rate or the C-reactive protein concentration. Per our analysis based on organ involvement, only patients with ear, nose, and throat manifestations had higher serum IL-16 concentrations relative to those with other conditions (P = 0.030).ConclusionsThis was the first study to elucidate the clinical implication of serum IL-16 in patients with AAV. We found that the serum IL-16 level may reflect the cross-sectional VDI scores among AAV-specific indices. Future studies with larger numbers of patients and serial measurements could provide more reliable data on the clinical implications of serum IL-16 in AAV.

Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Is Inversely Correlated with the Activity of ANCA-Associated Vasculitis.

Lectin-like oxidized low-density lipoprotein (LDL) receptor 1 (LOX1) binds to oxidized LDL, which is associated with inflammation in various vascular disorders. Here, we aimed to investigate the potential of soluble LOX1 (sLOX1) as an indicator of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) activity. Serum levels of sLOX1 in frozen samples from patients with AAV enrolled in a prospective observational cohort study at the Severance Hospital were measured using enzyme-linked immunosorbent assay. Clinical and laboratory data were collected on the date when the blood sampling was performed. The association between sLOX1 and clinical and laboratory data was assessed using Pearson's correlation analysis. The median age of the recruited 79 patients was 62.0 years, and 27 (34.2%) patients were men. The median Birmingham vasculitis activity score (BVAS), five-factor score, vasculitis damage index, and sLOX1 level were 6, 1, 3, and 911.9 pg/mL, respectively. Correlation analysis based on BVAS revealed that sLOX1 and total cholesterol were significantly inversely correlated with BVAS (r=−0.224, p=0.047 and r=−0.424, p<0.001, respectively). No significant correlations were observed between continuous variables and sLOX1 except for BVAS, although total cholesterol tended to correlate with sLOX1 (r=0.190, p=0.093). Additionally, sLOX1 was not influenced by sex, hypertension, diabetes mellitus, or the presence of pulmonary, cardiovascular, and renal involvement of AAV. In summary, sLOX1 was inversely correlated with BVAS in AAV patients, which is different from other vascular diseases or inflammatory diseases.

Reliability and construct validity of the Personality Inventory for ICD-11 (PiCD) in Italian adult participants.

To assess the psychometric properties of the Personality Inventory for ICD-11 (PiCD, where ICD-11 is the International Classification of Diseases, 11th Revision), a sample of Italian community-dwelling adult participants (N = 1,122) was administered the PiCD, the Five-Factor Model Rating Form, the Big Five Inventory, the Personality Inventory for DSM-5 Short Form (where DSM-5 is the Diagnostic and Statistical Manual of Mental Disorders, fifth edition), and the Measure of Disordered Personality Functioning. Our findings supported the unidimensionality hypothesis for the PiCD Negative Affectivity, Detachment, and Dissocial scale items, whereas adequate fit indices were observed for the bifactor model of the PiCD Disinhibition and Anankastic item joint polychoric correlation matrix. The PiCD scales showed adequate internal consistency, test-retest reliability (n = 262), and meaningful relationships with five-factor model domains and their maladaptive variants. A four-factor model of the joint correlation matrix of the PiCD, Personality Inventory for DSM-5 Short Form, and the five-factor model composite score was provided with adequate fit. All PiCD scales were significantly associated with the impairment in personality functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Double positivity for antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody could predict end-stage renal disease in ANCA-associated vasculitis: a monocentric pilot study.

To investigate the detection rate of double positivity for antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody at diagnosis and its clinical implication during follow-up in Korean patients with ANCA-associated vasculitis (AAV). We retrospectively reviewed the medical records of 96 Korean AAV patients. We obtained data at diagnosis and assessed the poor outcomes of AAV such as all-cause mortality, relapse and end-stage renal disease (ESRD). Comparison of cumulative survivals were analysed by the Kaplan-Meier survival analysis, and hazard ratios (HRs) were obtained by the multivariable Cox hazard model. Seven of 96 AAV patients (7.3%) had double positivity for ANCA and anti-GBM. Among variables at diagnosis, there were no significant differences between patients with double positivity for ANCA and anti-GBM and those without. In the cumulative survival analysis, AAV patient with double positivity for ANCA and anti-GBM at diagnosis exhibited the lower cumulative ESRD-free survival rate than those without (P = 0.044) and furthermore, than those with positive for only ANCA and those with double negativity (P = 0.022). Myeloperoxidase (MPO)-ANCA, renal manifestation and five-factor score at diagnosis were also associated with ESRD occurrence in AAV patients. In the multivariable Cox hazards model using these 4 variables, only double positivity for ANCA and anti-GBM exhibited the significant association with ESRD occurrence during follow-up (HR 3.831). Double positivity for ANCA and anti-GBM at diagnosis were observed in 7.3% of AAV patients, and it could predict ESRD occurrence during follow-up in Korean patients with AAV.Key Points• 7.3% of AAV patients had double positivity for ANCA and anti-GBM at diagnosis (total n = 96)• Double positivity for ANCA and anti-GBM could predict ESRD occurrence during follow-up (HR 9.021, P = 0.004)• AAV patients with double positivity for ANCA and anti-GBM exhibited the lower cumulative ESRD-free survival rate compared with those without (P = 0.044).