Buikpijn en koorts na consumptie van waterkers in turkije: Fascioliasis

A 52-year-old woman presented several months after returning from a visit to Turkey with stomach-ache and fever. Laboratory results showed leucocytosis with marked eosinophilia. Furthermore, serum liver enzyme activities were slightly elevated. A CT scan of the abdomen showed several spots which, on a later scan, had migrated. Serologic tests confirmed the clinical diagnosis of fascioliasis. The patient was successfully treated with triclabendazole. Infection presumably occurred after eating watercress which the patient had bought on a market in Turkey

The relation between C-reactive protein and serum amyloid A in patients with autoinflammatory diseases

Background: Autoinflammatory diseases are rare disorders of the innate immune system characterized by fever and other signs of inflammation. A feared complication of autoinflammatory diseases is the development of AA amyloidosis. AA amyloidosis is caused by extracellular deposition of soluble serum amyloid A (SAA) proteins as insoluble amyloid fibrils leading to organ damage. Prolonged high levels of SAA are a prerequisite to develop AA amyloidosis. Since measurement of SAA is relatively expensive and sometimes unavailable, C-reactive protein (CRP) is often used as a surrogacy marker to test for inflammation. Objective: The aim of this research is to evaluate the possible relation between CRP and SAA. Methods: A retrospective cohort of patients with autoinflammatory diseases (n = 99) where SAA and CRP blood testing was performed in the period between 2015 and 2021 in the University Medical Centre in Groningen was used to investigate the correlation between CRP and SAA. Results: CRP and SAA have a high correlation (rho = 0.755, p < 0.001). A CRP value below 0.45 mg/L results in 100% sensitivity for SAA below 4 mg/L. CRP below 5 mg/L is a good predictor of SAA below 4 mg/L with 85.4% sensitivity and 83.6% specificity. Only prednisone and erythrocyte sedimentation rate (ESR) significantly influence the relation between CRP and log10SAA. Conclusion: There was a significant correlation between CRP and SAA in our retrospective cohort. CRP levels below 5 mg/L proved to be highly predictive of SAA levels below 4 mg/L. This may not be true for patients on steroids

The relation between C-reactive protein and serum amyloid A in patients with autoinflammatory diseases

Background: Autoinflammatory diseases are rare disorders of the innate immune system characterized by fever and other signs of inflammation. A feared complication of autoinflammatory diseases is the development of AA amyloidosis. AA amyloidosis is caused by extracellular deposition of soluble serum amyloid A (SAA) proteins as insoluble amyloid fibrils leading to organ damage. Prolonged high levels of SAA are a prerequisite to develop AA amyloidosis. Since measurement of SAA is relatively expensive and sometimes unavailable, C-reactive protein (CRP) is often used as a surrogacy marker to test for inflammation. Objective: The aim of this research is to evaluate the possible relation between CRP and SAA. Methods: A retrospective cohort of patients with autoinflammatory diseases (n = 99) where SAA and CRP blood testing was performed in the period between 2015 and 2021 in the University Medical Centre in Groningen was used to investigate the correlation between CRP and SAA. Results: CRP and SAA have a high correlation (rho = 0.755, p < 0.001). A CRP value below 0.45 mg/L results in 100% sensitivity for SAA below 4 mg/L. CRP below 5 mg/L is a good predictor of SAA below 4 mg/L with 85.4% sensitivity and 83.6% specificity. Only prednisone and erythrocyte sedimentation rate (ESR) significantly influence the relation between CRP and log10SAA. Conclusion: There was a significant correlation between CRP and SAA in our retrospective cohort. CRP levels below 5 mg/L proved to be highly predictive of SAA levels below 4 mg/L. This may not be true for patients on steroids

Age‐associated changes in ultrasound measurements of the calcaneus in men and women:The rotterdam study

Broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the os calcis were measured in a sample of 1405 persons (628 men), aged 55–93 years, from the cohort of the Rotterdam Study, a population‐based study of diseases in the elderly. We studied the effect of age, body mass index, age at menopause, current use of thiazides, loop diuretics, and estrogens, smoking, and disability on SOS and BUA. Comparisons were made between ultrasound measurements and bone mineral density (BMD) measurements of the lumbar spine and proximal femur using DXA. We found a significant decline with age in SOS and BUA in men (‐0.4 and −0.1 %/year, respectively) and women (‐1.3 and −0.4%/year, respectively), which persisted after adjustment for body mass index. Age at menopause was not associated with SOS or BUA. Pack‐years of smoking was negatively related to SOS in both sexes and to BUA in men. Severe disability was associated with lower SOS and BUA in men, but not in women. Despite the small number of exposed persons, current corticosteroid use was associated with lower BUA in men. The other risk factors examined did not affect the ultrasound measurements. We observed modest correlations between SOS or BUA, on the one hand, and BMD of the lumbar spine, on the other hand (r = 0.32–0.42). Similar correlations were found between ultrasound measurements and BMD measurements of the proximal femur. We conclude that in persons 55 years or over (1) there is a significant age‐related decline of BUA and SOS, which is about three times higher in women compared with men, and (2) ultrasound measurements are not able to predict low BMD in hip or spine.</p

A pilot study into bosentan (Tracleer®) as an immunomodulating agent in patients with Behçet's disease

BACKGROUND: Behçet's disease (BD) is an auto-inflammatory vasculitis characterized by aphthous oro-genital ulcers, inflammatory skin changes and uveitis. Treatment is mainly immunosuppressive. Interestingly, elevated endotheline-1 (ET-1) levels suggest a possible beneficial effect of treatment with an ET-1 receptor antagonist. OBJECTIVE: The aim of our study was to investigate the possible beneficial effect of the ET-1 inhibitor bosentan. METHODS: We performed a prospective double-blind placebo controlled pilot study into the effect and safety of bosentan in BD patients. Disease activity was measured using the Behçet Disease Current Activity Form. The primary objective of the study was to determine whether bosentan is therapeutically effective in patients with BD. Secondary endpoints were safety, tapering of medication and the effect of bosentan on possible disease activity markers such as ET-1, circulating endothelial cells (CECs), soluble interleukin-2 receptor (sIL2R) and cytokine levels. RESULTS: Ten patients were randomized to either bosentan or placebo. Overall, no effect on disease activity was observed, although one patient responded clinically and continued treatment after the study period. Despite one SAE, bosentan seems safe to use. No effect on tapering of medication, CECs, sIL2R and cytokine levels was found. In the bosentan group, ET-1 levels were elevated during the treatment period, with no correlation with disease activity. CONCLUSIONS: Although this is a small pilot study, bosentan appears to be safe in BD patients. One patient had a durable and significant clinical response. Our observations should be confirmed and extended in a larger patient cohort to be of significant impact in the treatment options for BD

Long-Term Follow-up of Patients With Uveitis Treated With Adalimumab: Response Rates and Reasons for Discontinuation of Therapy

PURPOSE: To evaluate the effectiveness and reasons for discontinuation including the side effect profiles of adalimumab in a real-world setting. DESIGN: Retrospective clinical cohort study. METHODS: A medical chart review of clinical practice in 2 tertiary eye care services in Rotterdam, the Netherlands, was performed Data were collected from May 1, 2004, through September 1, 2020. Patients with noninfectious uveitis treated with adalimumab (n = 341; 633 affected eyes) were included. The primary outcome was the effectiveness of adalimumab, measured by the number of patients achieving inactive disease, remission, and relapse-free survival. The secondary outcomes were the reasons for discontinuation, including side effects, and the number of patients who developed antibodies. RESULTS: In total, 341 patients were treated with adalimumab between May 2004 and September 2020. The uveitis recurrence-free survival interval was 3.4 years (range, 0-13 years). Adalimumab had an acceptable side effect profile. A total of 178 patients achieved inactive disease while continuing adalimumab, and 51 patients maintained remission after discontinuing adalimumab. Reasons for discontinuation of adalimumab were no response, relapse, or reasons unrelated to the effectiveness of treatment. Adalimumab antibodies were present in 40 of 115 patients (35%). Antibodies were associated with lower adalimumab levels, and antibodies were observed more often in patients on adalimumab monotherapy (P < .01). CONCLUSIONS: Adalimumab is effective for patients with noninfectious uveitis, with an acceptable side effect profile. Although relapses can occur, the majority of the patients achieved inactive disease or remission after cessation of adalimumab, without other systemic immunosuppressive medication

Altered leukocyte subsets and immune proteome indicate proinflammatory mechanisms in mastocytosis

Background: Indolent systemic mastocytosis (ISM) is characterized by pathologic accumulation of mast cells. The mechanism behind its phenotypic heterogeneity is not well understood. Interaction of mast cells with other immune cells might cause systemic inflammation and thereby associated symptoms. Objective: We investigated peripheral leukocyte compartments and serum immune proteome in ISM. Methods: Peripheral blood leukocyte phenotyping using flow cytometry in a cohort of 18 adults with ISM and 12 healthy controls. Targeted proteomics was performed to measure 169 proteins associated with inflammation on serum of another 20 ISM patients and 20 healthy controls. Results: Proportions of plasmacytoid dendritic cells and monocytes were significantly decreased while TH2 cells were increased in peripheral blood of ISM patients. Furthermore, a shift from naive to memory T cells was observed. Hierarchical clustering of the serum proteome revealed 2 distinct subgroups within ISM patients. In subgroup A (n = 8), 62 proteins were significantly overexpressed, whereas those of subgroup B (n = 12) were comparable to healthy controls. Patients in subgroup A displayed upregulated signaling pathways downstream of Toll-like receptor 4, TNF-α, and IFN-γ. Fatigue was more often present in subgroup A compared to B (75% vs 33% respectively, P = .06). Conclusions: Altered distribution of leukocyte subsets and a proinflammatory proteome were observed in subsequent 2 cohorts of ISM patients. We hypothesize that neoplastic mast cells recruit and activate plasmacytoid dendritic cells, monocytes, and T cells, leading to a vicious cycle of inflammation

The association between age and bone mineral density in men and women aged 55 years and over: The Rotterdam Study

In this cross-sectional study, bone mineral density (BMD) measurements were performed in 1762 ambulatory subjects (678 men and 1084 women) aged 55 years and over from the Rotterdam Study, a population based study of diseases in the elderly. BMD measurements of the proximal femur and lumbar spine were performed using dual energy X-ray absorptiometry. No age-related decline in BMD could be observed in the lumbar spine. Yearly percentage BMD reduction in women and men was −0.6% and −0.3% in the femoral neck, −0.8% and −0.5% in the Ward's triangle, and −0.4% and −0.3% in the trochanter, respectively. Late menopause was associated with high BMD in Ward's triangle and lumbar spine. We conclude that: (1) accurate assessment of age-related bone reduction in the spine is impossible from cross-sectional studies since BMD measurements in the elderly may be influenced by spinal osteoarthritis; and (2) the rate of age-related bone reduction in the femoral neck appears to be approximately two times higher in women than in men

Hyperresponsive cytosolic DNA-sensing pathway in monocytes from primary Sjögren's syndrome

OBJECTIVES: Cytosolic DNA-sensing pathway stimulation prompts type I IFN (IFN-I) production, but its role in systemic IFN-I pathway activation in primary SS (pSS) is poorly studied. Here we investigate the responsiveness of pSS monocytes and plasmacytoid dendritic cells (pDCs) to stimulator of interferon genes (STING) activation in relation to systemic IFN-I pathway activation and compare this with SLE. METHODS: Expression of DNA-sensing receptors cGAS, IFI16, ZBP-1 and DDX41, signalling molecules STING, TBK1 and IRF3, positive and negative STING regulators, and IFN-I-stimulated genes MxA, IFI44, IFI44L, IFIT1 and IFIT3 was analysed in whole blood, CD14+ monocytes, pDCs, and salivary glands by RT-PCR, monocyte RNA sequencing data, flow cytometry and immunohistochemical staining. Peripheral blood mononuclear cells (PBMCs) from pSS, SLE and healthy controls (HCs) were stimulated with STING agonist 2'3'-cGAMP. STING phosphorylation (pSTING) and intracellular IFNα were evaluated using flow cytometry. RESULTS: STING activation induced a significantly higher proportion of IFNα-producing monocytes, but not pDCs, in both IFN-low and IFN-high pSS compared with HC PBMCs. Additionally, a trend towards more pSTING+ monocytes was observed in pSS and SLE, most pronounced in IFN-high patients. Positive STING regulators TRIM38, TRIM56, USP18 and SENP7 were significantly higher expression in pSS than HC monocytes, while the dual-function STING regulator RNF26 was downregulated in pSS monocytes. STING was expressed in mononuclear infiltrates and ductal epithelium in pSS salivary glands. STING stimulation induced pSTING and IFNα in pSS and SLE pDCs. CONCLUSION: pSS monocytes and pDCs are hyperresponsive to stimulation of the STING pathway, which was not restricted to patients with IFN-I pathway activation