Table_1_Comparison of Aspergillus-specific antibody cut-offs for the diagnosis of aspergillosis.DOCX

BackgroundAspergillus diseases are frequently encountered in patients who are immunocompromised. Without a prompt diagnosis, the clinical consequences may be lethal. Aspergillus-specific antibodies have been widely used to facilitate the diagnosis of Aspergillus diseases. To date, universally standardized cut-off values have not been established. This study aimed to investigate the cut-off values of Aspergillus-specific antibodies and perform a narrative review to depict the geographic differences in the Taiwanese population.MethodsWe analyzed enrolled 118 healthy controls, 29 patients with invasive aspergillosis (IA), chronic pulmonary aspergillosis (CPA), and allergic bronchopulmonary aspergillosis (ABPA) and 99 with disease control, who were tested for Aspergillus fumigatus and Aspergillus niger-specific IgG and IgE using ImmunoCAP. 99 participants not fulfilling the diagnosis of IA, CPA, and ABPA were enrolled in the disease control group. The duration of retrieval of medical records from June 2018 to September 2021. Optimal cut-offs and association were determined using receiver operating characteristic curve (ROC) analysis.ResultsWe found that patients with CPA had the highest A. fumigatus-specific IgG levels while patients with ABPA had the highest A. fumigatus-specific IgE, and A. niger-specific IgG and IgE levels. In patients with CPA and ABPA, the optimal cut-offs of A. fumigatus-specific IgG and A. niger-specific IgG levels were 41.6, 40.8, 38.1, and 69.9 mgA/l, respectively. Geographic differences in the cut-off values of A. fumigatus-specific IgG were also noted. Specifically, the levels were different in eco-climatic zones.ConclusionWe identified the optimal cut-offs of Aspergillus-specific antibodies to facilitate a precise diagnosis of aspergillosis. The observed geographic differences of the antibody levels suggest that an eco-climatic-specific reference is needed to facilitate a prompt and accurate diagnosis of aspergillosis.</p

Additional file 1 of Multidisciplinary-derived clinical score for accurate prediction of long-term mortality in fibrotic lung disease patients

Additional file 1. Table S1. The AUC and cutoff for different predictors. DLCO (% predicted) was the most accurate variable for predicting outcomes, with an Area Under the Curve (AUC) of 0.88, followed by mMRC Dyspnea Score (AUC = 0.82), 6MWT distance (AUC = 0.80), and GAP score (AUC = 0.77). The respective cutoffs for these variables were 63% for DLCO, 1 for mMRC Dyspnea Score, 392 meters for 6MWT distance, and 2 for GAP score

Tocilizumab potentially prevents bone loss in patients with anticitrullinated protein antibody-positive rheumatoid arthritis

<div><p>Rheumatoid arthritis (RA) is associated with a high risk of osteoporosis and fracture. Interleukin (IL)-6 inhibitors may suppress osteoclast activation. Anticitrullinated protein antibody (ACPA) titers are inversely associated with bone mineral density (BMD). However, the differential effect of ACPA on bone turnover marker (BTM) and BMD changes after IL-6 inhibition remains unclear. This prospective study recruited patients with active RA with inadequate response to methotrexate or biologics. BMD was measured before and after 2-year tocilizumab (TCZ) treatment. Serum osteocalcin, N-terminal propeptide of type I collagen (P1NP), and C-terminal cross-linking telopeptide of type I collagen (CTX) levels were assessed at the baseline and after treatment. We enrolled 76 patients with RA (89.5% women, age: 57.2 ± 13.3 years) receiving TCZ. The 28-joint disease activity score was negatively correlated with BMD and T-scores of the lumbar spine and bilateral femoral neck. ACPA-positive patients had lower lumbar spine and femoral neck T-scores. After 2-year TCZ treatment, CTX levels significantly decreased (0.32 ± 0.21 vs. 0.26 ± 0.17, <i>p</i> = 0.038). Femoral neck BMD increased significantly (0.71 ± 0.22 vs. 0.69 ± 0.55, <i>p</i> = 0.008). Decreased CTX levels and improved BMD were observed only in ACPA-positive patients. After treatment, femoral neck BMD significantly increased only in patients receiving a glucocorticoid dose of ≥5 mg/day. Two-year TCZ treatment reduced bone resorption and increased femoral BMD in ACPA-positive patients. The net effects of glucocorticoids and IL-6 inhibition on BMD imply that strict inflammation control might affect bone metabolism.</p></div

Comparison of BTM and BMD between patients with RA receiving a daily glucocorticoid dose of ≥5 mg and those receiving a daily glucocorticoid dose of <5 mg before and after tocilizumab treatment.

<p>(A) osteocalcin, (B) P1NP, (C) CTX, (D) lumbar spine BMD, (E) right femoral neck BMD, and (F) left femoral neck BMD. Error bars: mean ± standard error, *: <i>p</i> value < 0.05 by Wilcoxon signed rank test. BMD: bone mineral density; BTM: bone turnover markers; CTX: C-terminal cross-linking telopeptide of type I collagen; GC: glucocorticoid; P1NP: N-terminal propeptide of type I collagen; RA: rheumatoid arthritis.</p

Comparison of BTM and BMD between patients with ACPA-positive RA and those with ACPA-negative RA before and after tocilizumab treatment.

<p>(A) osteocalcin, (B) P1NP, (C) CTX, (D) lumbar spine BMD, (E) right femoral neck BMD, and (F) left femoral neck BMD Error bars: mean ± standard error, *: <i>p</i> value < 0.05 by the Wilcoxon signed rank test. ACPA: anticitrullinated protein antibody; BMD: bone mineral density; BTM: bone turnover markers; CTX: C-terminal cross-linking telopeptide of type I collagen; P1NP: N-terminal propeptide of type I collagen; RA: rheumatoid arthritis.</p

Comparison of demographic data, bone turnover markers, and bone mineral density between patients with ACPA-positive RA and those with ACPA-negative RA.

<p>Comparison of demographic data, bone turnover markers, and bone mineral density between patients with ACPA-positive RA and those with ACPA-negative RA.</p

Bone turnover markers and bone mineral density before and after tocilizumab treatment.

<p>Bone turnover markers and bone mineral density before and after tocilizumab treatment.</p

Comparison of bone turnover markers and bone mineral density between patients receiving a daily glucocorticoid dose of ≥5 mg versus those receiving a daily glucocorticoid dose of <5 mg after tocilizumab treatment.

<p>Comparison of bone turnover markers and bone mineral density between patients receiving a daily glucocorticoid dose of ≥5 mg versus those receiving a daily glucocorticoid dose of <5 mg after tocilizumab treatment.</p

Comparison of bone turnover markers and bone mineral density between patients with ACPA-positive RA and those with ACPA-negative RA after tocilizumab treatment.

<p>Comparison of bone turnover markers and bone mineral density between patients with ACPA-positive RA and those with ACPA-negative RA after tocilizumab treatment.</p

The risk of tuberculosis disease in rheumatoid arthritis patients on biologics and targeted therapy: A 15-year real world experience in Taiwan

<div><p>The objective of this study is to determine the risk of tuberculosis (TB) disease in biologics users among rheumatoid arthritis (RA) patients in Taiwan from 2000 to 2015. This retrospective cohort study enrolled adult RA patients initiated on first biologics at Taichung Veterans General Hospital. TB risks were determined as hazard ratio (HR) with 95% confidence interval (CI) using cox regression. A total of 951 patients were recruited; etanercept (n = 443), adalimumab (n = 332), abatacept (n = 74), golimumab (n = 60), tocilizumab (n = 31) and tofacitinib (n = 11). Twenty-four TB cases were identified; 13 in etanercept and 11 in adalimumab group with the TB incidence rate of 889.3/ 100,000 and 1055.6/ 100,000 patient-years respectively. There was no significant difference in TB risk between adalimumab and etanercept users with an incidence rate ratio of 1.27 (<i>p</i> = 0.556 by Poisson model). Significant 2-year TB risk factors included elderly patient >65 year-old (HR: 2.72, 95% CI: 1.06–6.99, <i>p</i> = 0.037), history of TB (HR: 6.24, 95% CI: 1.77–22.00, <i>p</i> = 0.004) and daily glucocorticoid use ≥5mg (HR:5.01, 95% CI: 1.46–17.21, <i>p</i> = 0.010). Sulfasalazine treatment appeared to be protective (HR: 0.32, 95% CI: 0.11–0.97, <i>p</i> = 0.043). Risk management plan (RMP) for TB before initiation of biologics commenced in 2012. The 2-year TB risks after RMP was compared with that before 2012 (HR:0.67, 95% CI: 0.30–1.49, <i>p</i> = 0.323). Elderly RA patients with a history of previous TB infection and concomitant moderate dose glucocorticoid were at higher risk of TB disease. Concurrent sulfasalazine treatment appeared to be a protective factor against TB disease.</p></div