The treatment outcomes in IgG4-related disease.

INTRODUCTION: IgG4-related disease (IgG4-RD) is an emerging systemic inflammatory disease involving nearly all organs eventually leading to fibrosis. Prompt and adequate treatment to prevent irreversible organ damage is therefore pivotal. To evaluate the treatment outcomes, we studied a well-defined cohort of patients with IgG4-RD. METHOD: 32 patients with histologically confirmed IgG4-RD diagnosed between 1999 and April 2017 were included and reviewed for demographic and clinical characteristics. The response to treatment with glucocorticoids, disease modifying antirheumatic drugs, rituximab and other therapeutic interventions were evaluated. RESULTS: Glucocorticoids as well as rituximab appeared successful therapeutic drugs leading to clinical remission (complete or partial remission) in all patients. Recurrences, however, were frequently seen (62% versus 100%, respectively). Diseases modifying antirheumatic drugs (DMARDs), including azathioprine, methotrexate and mycophenolate mofetil were effective in less than half of the cases. A minority of patients was treated with alternative treatments including hydroxychloroquine, thalidomide and infliximab which all appeared effective. Surgical intervention and radiotherapy in local disease seemed to induce clinical remission and were associated with low recurrence rates. CONCLUSION: Glucocorticoids and rituximab induce substantial responses as well as primary surgical intervention and radiotherapy, while the efficacy of DMARDs is limited. Based on the few data available, hydroxychloroquine, infliximab and thalidomide may be promising treatment options for second or third line strategies.

Results on patient flow of implementing an Acute Medical Unit.

BACKGROUND: There is an increased influx of patients needing admission. Introducing an acute medical unit (AMU) may increase the admission capacity without increasing the total number of beds. METHODS: Data collected during the first four years after implementation of an AMU in an academic tertiary care center in Amsterdam were analyzed. RESULTS: A 24 bed unit was realized. The total number of admissions increased in the first year with 977 (16%), with an additional 4.1% increase after 2 years with stabilization thereafter. The length of stay decreased, the absolute number of refusals declined, the number of readmissions remained unchanged. CONCLUSION: Introduction of AMUs in overcrowded services could be beneficial in improving the strain on the acute healthcare systems.

Exploring the preventable causes of unplanned readmissions using root cause analysis: Coordination of care is the weakest link.

IMPORTANCE: Unplanned readmissions within 30days are a common phenomenon in everyday practice and lead to increasing costs. Although many studies aiming to analyze the probable causes leading to unplanned readmissions have been performed, an in depth-study analyzing the human (healthcare worker)-, organizational-, technical-, disease- and patient-related causes leading to readmission is still missing. OBJECTIVE: The primary objective of this study was to identify human-, organizational-, technical-, disease- and patient-related causes which contribute to acute readmission within 30days after discharge using a Root-Cause Analysis Tool called PRISMA-medical. The secondary objective was to evaluate how many of these readmissions were deemed potentially preventable, and to assess which factors contributed to these preventable readmissions in comparison to non-preventable readmissions. DESIGN: Cross-sectional retrospective record study. SETTING: An academic medical center in Amsterdam, The Netherlands. PARTICIPANTS: Fifty patients aged 18years and older discharged from an internal medicine department and acutely readmitted within 30days after discharge. MAIN OUTCOME MEASURES: Root causes of preventable and unpreventable readmissions. RESULTS: Most root causes for readmission were disease-related (46%), followed by human (healthcare worker)- (33%) and patient- (15%) related root causes. Half of the readmissions studied were considered to be potentially preventable. Preventable readmissions predominantly had human-related (coordination) failures. CONCLUSION AND RELEVANCE: Our study suggests that improving human-related (coordinating) factors contributing to a readmission can potentially decrease the number of preventable readmissions.

Plasma globotriaosylsphingosine: diagnostic value and relation to clinical manifestations of Fabry disease.

Fabry disease is an X-linked lysosomal storage disorder due to deficiency of alpha-Galactosidase A, causing accumulation of globotriaosylceramide and elevated plasma globotriaosylsphingosine (lysoGb3). The diagnostic value and clinical relevance of plasma lysoGb3 concentration was investigated. All male and adult female patients with classical Fabry disease could be discerned by an elevated plasma lysoGb3. In young pre-symptomatic Fabry heterozygotes, lysoGb3 levels can be normal. Individuals carrying the R112H and P60L mutations, without classical Fabry symptoms, showed no elevated plasma lysoGb3. Multiple regression analysis showed that there is no correlation of plasma lysoGb3 concentration with total disease severity score in Fabry males. However, plasma lysoGb3 concentration did correlate with white matter lesions (odds ratio: 6.1 per 100 nM lysoGb3 increase (95% CI: 1.4-25.9, p=0.015). In females, plasma lysoGb3 concentration correlated with overall disease severity. Furthermore, plasma lysoGb3 level was related to left ventricular mass (19.5+/-5.5 g increase per 10 nM lysoGb3 increase; p=0.001). In addition, it was assessed whether lifetime exposure to lysoGb3 correlates with disease manifestations. Male Fabry patients with a high lysoGb3 exposure (>10,000 U), were moderately or severely affected, only one mildly. Female patients with a low exposure (<1000 U) were asymptomatic or mildly affected. A large proportion of the females with an exposure >1000 U showed disease complications. Plasma lysoGb3 is useful for the diagnosis of Fabry disease. LysoGb3 is an independent risk factor for development of cerebrovascular white matter lesions in male patients and left ventricular hypertrophy in females. Disease severity correlates with exposure to plasma lysoGb3.

Vasculopathy in patients with Fabry disease: current controversies and research directions.

Fabry disease is an X-linked lysosomal storage disorder due to deficiency of the enzyme alpha-galactosidase A. The principal clinical manifestations of Fabry disease consist of cardiovascular complications including cerebrovascular, renal and cardiac disease but the pathophysiology of this specific vasculopathy is unclear. With the development of targeted treatment for Fabry disease, i.e. enzyme replacement therapy, it has become apparent that the removal of stored glycosphingolipid from the endothelial cells does not prevent progression of vascular disease in many patients. The aim of this study is to review the current available literature on vascular function tests, imaging and pathology studies and propose a hypothesis on the evolution of arterial complications in Fabry disease. Clearly, although premature atherosclerosis is suggested to occur, most studies describe absence of characteristic plaque formation. Smooth muscle cell hypertrophy, is probably the earliest feature of a complex vasculopathy, as in females and atypical cardiac variants, who have residual enzyme activity, no endothelial storage of significance is found. Subsequently, processes occur as observed in neo intima formation however with formation of more fibrotic structures. In the presence of a hyperdynamic circulation in combination with a less compliant vascular wall, it is hypothesized that upregulation of local renin angiotensine systems may occur. Angiotensin II is known to increase adhesion molecules, cytokines and chemokines and exerts a pro-inflammatory effect on leucocytes, endothelial cells and vascular smooth muscle cells. This enhances release of pro-thrombotic factors and opposes actions mediated through angiotensin 2 (AT2) receptor, including the release of nitric oxide (NO). A combination of reduced vascular compliance and activation of pro-thrombotic factors can lead to vascular complications in Fabry disease.