Explore the vast range of titles available.

BackgroundBioelectrical impedance analysis (BIA) is a validated method to assess body composition in persons with fluid homeostasis and reliable body weight. This is not the case during critical illness. The raw BIA markers resistance, reactance, phase angle, and vector length are body weight independent. Phase angle reflects cellular health and has prognostic significance. We aimed to assess the course of phase angle and vector length during intensive care unit (ICU) admission, and determine the relation between their changes (Δ) and changes in body hydration.MethodsA prospective, dual-center observational study of adult ICU patients was conducted. Univariate and multivariable regression analyses were performed, including reactance as a marker of cellular mass and integrity and total body water according to the Biasioli equation (TBWBiasioli) and fluid balance as body weight independent markers of hydration.ResultsOne hundred and fifty-six ICU patients (mean ± SD age 62.5 ± 14.5 years, 67% male) were included. Between days 1 and 3, there was a significant decrease in reactance/m (−2.6 ± 6.0 Ω), phase angle (−0.4 ± 1.1°), and vector length (−12.2 ± 44.3 Ω/m). Markers of hydration significantly increased. Δphase angle and Δvector length were both positively related to Δreactance/m (r2 = 0.55, p < 0.01; r2 = 0.38, p < 0.01). Adding ΔTBWBiasioli as explaining factor strongly improved the association between Δphase angle and Δreactance/m (r2 = 0.73, p < 0.01), and Δvector length and Δreactance/m (r2 = 0.77, p < 0.01).ConclusionsOur results show that during critical illness, changes in phase angle and vector length partially reflect changes in hydration.

Background Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is difficult to manage due to the heterogeneous disease course. There is a high need for new biomarkers to identify patients at high risk for ILD progression. Fibroblast activation protein (FAP) has gained interest as a biomarker to reflect fibrotic activity. As circulating FAP (cFAP) can be measured in blood, we aimed to investigate the value of cFAP in SSc-ILD. Methods cFAP concentrations were determined in plasma samples of 210 patients with systemic sclerosis (SSc) using an enzyme-linked immunosorbent assay. We compared cFAP in baseline and repeated longitudinal samples between SSc patients with ( n  = 63) and without ILD ( n  = 147). Furthermore, we investigated the correlation between cFAP and ILD progression at follow-up. In an exploratory analysis, we also investigated if cFAP was associated with other disease-related clinical features and all-cause mortality. Results cFAP levels were not different between SSc patients with- and without ILD, both at baseline (median 91.5 and 97.7 ng/mL respectively; p  = 0.80) or during follow-up. Furthermore, we found no association between cFAP at baseline and ILD progression at 1, 2 and 5 years of follow-up. Notably, cFAP levels were elevated at baseline in patients with higher skin scores (mRSS ≥ 10 compared to mRSS < 10; p  = 0.01). Finally, we did not find an association between cFAP and all-cause mortality at 5 and 10 years of follow-up. Conclusion In conclusion, cFAP does not seem useful as a biomarker in SSc-ILD. However, the association between cFAP and skin score deserves further investigation.

Background This study aimed to assess the quantitative uptake of 18 F-FDG PET-CT in the lungs of patients with early severe diffuse cutaneous systemic sclerosis (SSc) with and without interstitial lung disease (ILD), compared to controls. In patients with SSc-ILD, 18 F-FDG uptake was correlated to high-resolution computed tomography (HRCT) and pulmonary function test (PFT) parameters. Methods A prospective, cross-sectional study was conducted, involving 15 patients with SSc-ILD, 5 patients with SSc without ILD, and 7 controls without SSc. 18 F-FDG PET-CT scans were performed following standardized protocols, and quantitative analysis of tracer uptake was conducted in predefined lung regions. In addition, HRCT scans were evaluated for ILD-related radiologic abnormalities. Between-group differences were compared with non-parametric tests, while correlations with PFT parameters were analyzed using Spearman correlation coefficients. Results 18 F-FDG uptake was mainly increased in the dorsobasal lung fields of patients with SSc-ILD compared to SSc without ILD and controls ( p  = 0.03 and p  < 0.001, respectively). 18 F-FDG uptake was higher in SSc patients with extensive ILD (≥ 20% vs < 20%, p  = 0.04) and correlated with lower DLCO% ( R  = -0.59, p  = 0.02). Ground-glass opacities, with or without reticulation, corresponded to increased 18 F-FDG uptake. Conclusions 18 F-FDG PET-CT can detect metabolic activity in the lungs of patients with early severe diffuse cutaneous SSc and ILD, correlating with higher ILD extent (≥ 20%) and lower DLCO%. These results suggest the potential utility of 18 F-FDG PET-CT in the early detection of ILD (progression) and aiding in risk stratification.

Background The clinical management of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is challenging due to its heterogeneous progression. While recent studies have shown that pulmonary uptake of 18 F-FDG and 68 Ga-FAPI on positron emission tomography (PET) may indicate ILD activity, the spatial distribution of their molecular targets—GLUT1, GLUT3, and FAPα—in SSc-ILD lung tissue is largely unexplored. Here, we investigate the expression patterns of these markers across varying fibrosis stages in lung tissue of SSc-ILD patients and controls to improve PET interpretation. Methods Immunohistochemistry for GLUT1, GLUT3, and FAPα was performed on lung tissue from SSc-ILD patients ( n  = 9) and controls ( n  = 8). Fibrosis stage and cell-type-specific expression of these markers were analyzed by 2 experienced ILD pathologists, and quantitative staining was assessed using QuPath software. Marker expression was analyzed in and compared between areas with varying fibrosis stages. Results GLUT1 positive cells were primarily erythrocytes, GLUT3 positive cells were mainly myeloid cells and FAPα positive cells were predominantly fibroblasts, endothelial cells, epithelial cells, and macrophages. All cells positive for these markers were more present in SSc-ILD compared to controls, with GLUT1 and FAPα positive cells showing highest prevalence in areas with early signs of fibrosis. Conclusions The prevalence of cells expressing GLUT1 and FAPα is increased in areas with early signs of fibrosis and the expression of GLUT1, GLUT3 and FAPα is observed in different cell types suggesting that 18 F-FDG and 68 Ga-FAPI PET each may be useful to visualize different aspects of ILD activity.

Positron emission tomography (PET) is a promising technique to improve the assessment of systemic sclerosis associated interstitial lung disease (SSc-ILD). This technique could be of particular value in patients with severe diffuse cutaneous SSc (dcSSc) that are possibly eligible for autologous hematopoietic stem cell transplantation (aHSCT). aHSCT is a potentially effective therapy for patients with severe dcSSc and ILD, leading to stabilization or improvement of lung function. However, there is a high need to improve patient selection, which includes (1) the selection of patients with rapidly progressive ILD for early rather than last-resort aHSCT (2) the prediction of treatment response on ILD and (3) the understanding of the mechanism(s) of action of aHSCT in the lungs. As previous studies with 18 F-FDG PET in SSc-ILD and other forms of ILD have demonstrated its potential value in predicting disease progression and reactivity to anti-inflammatory treatment, we discuss the potential benefit of using this technique in patients with early severe dcSSc and ILD in the context of aHSCT. In addition, we discuss the potential value of other PET tracers in the assessment of ILD and understanding the mechanisms of action of aHSCT in the lung. Finally, we provide several suggestions for future research.

Background The clinical management of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is challenging due to its heterogeneous progression. While recent studies have shown that pulmonary uptake of .sup.18F-FDG and .sup.68Ga-FAPI on positron emission tomography (PET) may indicate ILD activity, the spatial distribution of their molecular targets–GLUT1, GLUT3, and FAP[alpha]–in SSc-ILD lung tissue is largely unexplored. Here, we investigate the expression patterns of these markers across varying fibrosis stages in lung tissue of SSc-ILD patients and controls to improve PET interpretation. Methods Immunohistochemistry for GLUT1, GLUT3, and FAP[alpha] was performed on lung tissue from SSc-ILD patients (n = 9) and controls (n = 8). Fibrosis stage and cell-type-specific expression of these markers were analyzed by 2 experienced ILD pathologists, and quantitative staining was assessed using QuPath software. Marker expression was analyzed in and compared between areas with varying fibrosis stages. Results GLUT1 positive cells were primarily erythrocytes, GLUT3 positive cells were mainly myeloid cells and FAP[alpha] positive cells were predominantly fibroblasts, endothelial cells, epithelial cells, and macrophages. All cells positive for these markers were more present in SSc-ILD compared to controls, with GLUT1 and FAP[alpha] positive cells showing highest prevalence in areas with early signs of fibrosis. Conclusions The prevalence of cells expressing GLUT1 and FAP[alpha] is increased in areas with early signs of fibrosis and the expression of GLUT1, GLUT3 and FAP[alpha] is observed in different cell types suggesting that .sup.18F-FDG and .sup.68Ga-FAPI PET each may be useful to visualize different aspects of ILD activity. Keywords: Systemic sclerosis, Interstitial lung disease, Immunohistochemistry, Glucose transporters, Fibroblast activation protein alpha

ObjectivesTo compare the cumulative incidence and disease severity of reported SARS-CoV-2 omicron breakthrough infections between patients with immune-mediated inflammatory diseases (IMID) on immunosuppressants and controls, and to investigate determinants for breakthrough infections.MethodsData were used from an ongoing national prospective multicentre cohort study on SARS-CoV-2 vaccination responses in patients with IMID in the Netherlands (Target-to-B! (T2B!) study). Patients wih IMID on immunosuppressants and controls (patients with IMID not on immunosuppressants and healthy controls) who completed primary immunisation were included. The observation period was between 1 January 2022 and 1 April 2022, during which the SARS-CoV-2 omicron (BA.1 and BA.2 subvariant) was dominant. A SARS-CoV-2 breakthrough infection was defined as a reported positive PCR and/or antigen test at least 14 days after primary immunisation. A multivariate logistic regression model was used to investigate determinants.Results1593 patients with IMID on immunosuppressants and 579 controls were included. The cumulative incidence of breakthrough infections was 472/1593 (29.6%; 95% CI 27% to 32%) in patients with IMID on immunosuppressants and 181/579 (31.3%; 95% CI 28% to 35%) in controls (p=0.42). Three (0.5%) participants had severe disease. Seroconversion after primary immunisation (relative risk, RR 0.71; 95% CI 0.52 to 0.96), additional vaccinations (RR 0.61; 95% CI 0.49 to 0.76) and a prior SARS-CoV-2 infection (RR 0.60; 95% CI 0.48 to 0.75) were associated with decreased risk of breakthrough infection.ConclusionsThe cumulative incidence of reported SARS-CoV-2 omicron breakthrough infections was high, but similar between patients with IMID on immunosuppressants and controls, and disease severity was mostly mild. Additional vaccinations and prior SARS-CoV-2 infections may reduce the incidence of breakthrough infections.

Background Studies have suggested incremental short-term adverse events (AE) after repeated vaccination. In this report, we assessed occurrence and risk factors for short-term AEs following repeated SARS-CoV-2 vaccination in patients with various immune-mediated inflammatory diseases (IMIDs). Methods Self-reported daily questionnaires on AEs during the first 7 days after vaccination were obtained of 2259 individuals (2081 patients and 178 controls) participating in an ongoing prospective multicenter cohort study on SARS-CoV-2 vaccination in patients with various IMIDs in the Netherlands (T2B-COVID). Relative risks were calculated for potential risk factors associated with clinically relevant AE (rAE), defined as AE lasting longer than 2 days or impacting daily life. Results In total, 5454 vaccinations were recorded (1737 first, 1992 second and 1478 third vaccinations). Multiple sclerosis, Crohn’s disease and rheumatoid arthritis were the largest disease groups. rAEs were reported by 57.3% (95% CI 54.8–59.8) of patients after the first vaccination, 61.5% (95% CI 59.2–63.7) after the second vaccination and 58% (95% CI 55.3–60.6) after the third vaccination. At day 7 after the first, second and third vaccination, respectively, 7.6% (95% CI 6.3–9.1), 7.4% (95% CI 6.2–8.7) and 6.8% (95% CI 5.4–8.3) of patients still reported AEs impacting daily life. Hospital admissions and allergic reactions were uncommon (<0.7%). Female sex (aRR 1.43, 95% CI 1.32–1.56), age below 50 (aRR 1.14, 95% CI 1.06–1.23), a preceding SARS-CoV-2 infection (aRR 1.14, 95% CI 1.01–1.29) and having an IMID (aRR 1.16, 95% CI 1.01–1.34) were associated with increased risk of rAEs following a vaccination. Compared to the second vaccination, the first vaccination was associated with a lower risk of rAEs (aRR 0.92, 95% CI 0.84–0.99) while a third vaccination was not associated with increased risk on rAEs (aRR 0.93, 95% CI 0.84–1.02). BNT162b2 vaccines were associated with lower risk on rAEs compared to CX-024414 (aRR 0.86, 95% CI 0.80–0.93). Conclusions A third SARS-CoV-2 vaccination was not associated with increased risk of rAEs in IMID patients compared to the second vaccination. Patients with an IMID have a modestly increased risk of rAEs after vaccination when compared to controls. Most AEs are resolved within 7 days; hospital admissions and allergic reactions were uncommon. Trial registration NL74974.018.20 , Trial ID: NL8900. Registered on 9 September 2020.

Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs. Methods IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies. Results In total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls ( p  < 0.001). Seropositivity rates were lowest in patients on anti-CD20 (40.0%) and anti-tumor necrosis factor (TNF) agents (60.5%), as compared to other ISPs ( p  < 0.001 and p  < 0.001, respectively). Increased disease activity after infection was reported by 68 of 260 patients (26.2%; 95% CI 21.2–31.8%), leading to ISP intensification in 6 out of these 68 patients (8.8%). Conclusion IMID patients using ISPs showed reduced long-term humoral immune responses after primary SARS-CoV-2 infection, which was mainly attributed to treatment with anti-CD20 and anti-TNF agents. Increased disease activity after SARS-CoV-2 infection was reported commonly, but was mostly mild. Trial registration NL74974.018.20, Trial ID: NL8900. Registered on 9 September 2020.