Introduction: Rheumatoid arthritis (RA) improves during pregnancy and flares after delivery. It has been hypothesized that high levels of the complement factor mannose-binding lectin (MBL) are... Show moreIntroduction: Rheumatoid arthritis (RA) improves during pregnancy and flares after delivery. It has been hypothesized that high levels of the complement factor mannose-binding lectin (MBL) are associated with a favourable disease course of RA by facilitating the clearance of pathogenic immunoglobulin G (IgG) lacking galactose sugar moieties. During pregnancy, increased galactosylation of IgG and simultaneously increased MBL levels can be observed, with the latter being strictly related to maternal MBL genotypes. Therefore, increased MBL levels in concert with increased IgG galactosylation may be associated with pregnancy-induced improvement of RA. The objective of this study was to investigate whether MBL genotypes are associated with changes in RA disease activity and with changes in IgG galactosylation during pregnancy and in the postpartum period. We also studied the association between MBL genotypes and pregnancy outcomes in RA. Methods: Serum from 216 patients with RA and 31 healthy controls participating in the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) Study was collected before, during and after pregnancy. IgG galactosylation was determined by performing matrix-assisted laser desorption/ionization time of flight mass spectrometry. Disease activity was determined using the internationally recognized Disease Activity Score 28 (DAS28). MBL genotypes were determined. The pregnancy outcome measures studied were gestational age, birth weight, miscarriage and hypertensive disorders. Results: No association was found between the MBL genotype groups and changes in RA disease activity (P = 0.89) or changes in IgG galactosylation (patients, P = 0.75, and controls, P = 0.54) during pregnancy and in the postpartum period. Furthermore, MBL genotype groups were not related to the studied pregnancy outcome measures. Conclusions: This study does not provide evidence for a role for MBL in the improvement of RA during pregnancy or for a role for MBL in pregnancy outcome. Show less
Groot, R.I. de; Dekkers, O.M.; Herold, I.H.F.; Jonge, E. de; Arbous, M.S. 2011
Introduction: A semi-upright position in ventilated patients is recommended to prevent ventilator-associated pneumonia (VAP) and is one of the components in the Ventilator Bundle of the Institute... Show moreIntroduction: A semi-upright position in ventilated patients is recommended to prevent ventilator-associated pneumonia (VAP) and is one of the components in the Ventilator Bundle of the Institute for Health Care Improvement. This recommendation, however, is not an evidence-based one. Methods: A systematic review on the benefits and disadvantages of semi-upright position in ventilated patients was done according to PRISMA guidelines. Then a European expert panel developed a recommendation based on the results of the systematic review and considerations beyond the scientific evidence in a three-round electronic Delphi procedure. Results: Three trials (337 patients) were included in the review. The results showed that it was uncertain whether a 45 degrees bed head elevation was effective or harmful with regard to the occurrence of clinically suspected VAP, microbiologically confirmed VAP, decubitus and mortality, and that it was unknown whether 45 degrees elevation for 24 hours a day increased the risk for thromboembolism or hemodynamic instability. A group of 22 experts recommended elevating the head of the bed of mechanically ventilated patients to a 20 to 45 degrees position and preferably to a >= 30 degrees position as long as it does not pose risks or conflicts with other nursing tasks, medical interventions or patients' wishes. Conclusions: Although the review failed to prove clinical benefits of bed head elevation, experts prefer this position in ventilated patients. They made clear that the position of a ventilated patient in bed depended on many determinants. Therefore, given the scientific uncertainty about the benefits and harms of a semi-upright position, this position could only be recommended as the preferred position with the necessary restrictions. Show less
Leenen, C.H.M.; Geurts-Giele, W.R.R.; Dubbink, H.J.; Reddingius, R.; Ouweland, A.M. van den; Tops, C.M.J.; ... ; Wagner, A. 2011
Background. Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are... Show moreBackground. Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical characteristics of patients, to get better insight on behavior and prognosis of these diseases. Method. A retrospective study was conducted using clinical data of 144 Ollier and 17 Maffucci patients from 13 European centers and one national databank supplied by members of the European Musculoskeletal Oncology Society. Results. Patients had multiple enchondromas in the hands and feet only (group I, 18%), in long bones including scapula and pelvis only (group II, 39%), and in both small and long/flat bones (group III, 43%), respectively. The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4 patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in group II and 26 patients (46%) in group III, respectively. The risk of developing chondrosarcoma is increased when enchondromas are located in the pelvis (odds ratio, 3.8; p = 0.00l). Conclusions. Overall incidence of development of chondrosarcoma is 40%, but may, due to age-dependency, increase when considered as a lifelong risk. Patients with enchondromas located in long bones or axial skeleton, especially the pelvis, have a seriously increased risk of developing chondrosarcoma, and are identified as the population that needs regular screening on early detection of malignant transformation. Show less
Jonge, A. de; Rijnders, M.; Agyemang, C.; Stouwe, R. van der; Otter, J. den; Muijsenbergh, M.E.T.C. van den; Buitendijk, S. 2011
Objective: Mixed results have been reported of matrix metalloproteinases (MMP) and their association with restenosis after percutaneous coronary intervention (PCI). The current study examines... Show moreObjective: Mixed results have been reported of matrix metalloproteinases (MMP) and their association with restenosis after percutaneous coronary intervention (PCI). The current study examines whether multiple single nucleotide polymorphisms (SNPs), covering the full genomic region of MMP2 and MMP3, were associated with restenosis in the GENDER study population. Methods and results: The GENetic DEterminants of Restenosis (GENDER) study enrolled 3104 consecutive patients after successful PCI. The primary endpoint was clinical restenosis, defined as target vessel revascularization (TVR), occurring in 9.8% of the patients. From the Hapmap database, 19 polymorphisms of MMP2 and 11 of MMP3 were selected. Furthermore, in a subpopulation, a genome-wide association analysis (GWA) was performed. No significant association was found with any of the investigated SNPs, including the previously reported 5A/6A polymorphism (rs3025058), with regard to TVR using single SNP analysis or haplotype analysis. Conclusion: We found no significant association of MMP2 or MMP3 with TVR with this SNP-broad gene approach. Although we did not test all the known polymorphisms of these genes, using tagging analyses we examined those SNPs covering all known haplotypes of MMP2 and MMP3 to conclude that these genes do not correlate with a genetic risk of coronary restenosis after successful PCI. Show less
