Comparing a Single Clinician Versus a Multidisciplinary Consensus Conference Approach for Dementia Diagnostics.

BACKGROUND: Evidence-based recommendations on the optimal evaluation approach for dementia diagnostics are limited. This impedes a harmonized workup across clinics and nations. OBJECTIVE: To evaluate the diagnostic performance of a multidisciplinary consensus conference compared to a single clinician approach. METHODS: In this prospective study, we enrolled 457 patients with suspected cognitive decline, from two European memory clinics. A diagnostic evaluation was performed at baseline independently in two ways: 1) by a single clinician and 2) at a multidisciplinary consensus conference. A syndrome diagnosis and an etiological diagnosis was made. The confidence in the diagnosis was recorded using a visual analogue scale. An expert panel re-evaluation diagnosis served as reference for the baseline syndrome diagnosis and a 12-24-month follow-up diagnosis for the etiological diagnosis. RESULTS: 439 patients completed the study. We observed 12.5%discrepancy (k = 0.81) comparing the baseline syndrome diagnoses of the single clinician to the consensus conference, and 22.3%discrepancy (k = 0.68) for the baseline etiological diagnosis. The accuracy of the baseline etiological diagnosis was significantly higher at the consensus conference and was driven mainly by increased accuracy in the MCI group. Confidence in the etiological diagnosis at baseline was significantly higher at the consensus conference (p < 0.005), especially for the frontotemporal dementia diagnosis. CONCLUSION: The multidisciplinary consensus conference performed better on diagnostic accuracy of disease etiology and increased clinicians' confidence. This highlights the importance of a multidisciplinary diagnostic evaluation approach for dementia diagnostics, especially when evaluating patients in the MCI stage.

[Diagnosis and treatment of normal pressure hydrocephalus].

This review summarises the current knowledge of normal pressure hydrocephalus (NPH), which is considered to be a reversible cause of dementia. Early identification is important to select patients for surgical treatment with ventricular shunting. The symptoms of NPH are gait disturbance, cognitive dysfunction and urinary incontinence. NPH is diagnosed by a combination of the clinical presentation and neuroimaging and preferably supported by cerebrospinal fluid tests. The pathophysiology is not well described and a significant overlap with degenerative and small vessel brain diseases exist, making selection of patients for surgery difficult.

Expression and Localization of miR-21 and miR-126 in Mucosal Tissue from Patients with Inflammatory Bowel Disease.

BACKGROUND: microRNAs (miRNAs) are small noncoding RNAs that guide degradation of mRNA and regulate protein expression. miRNA based diagnostic biomarkers for ulcerative colitis (UC) and Crohn's disease (CD) are emerging but information about the cellular localization of many miRNAs is limited and more detailed histologic evaluation of miRNA expression patterns is needed to understand their immunobiological function. METHODS: Formalin-fixed paraffin-embedded colon biopsies from 10 patients with UC and 8 patients with CD together with 9 controls were examined by RT-qPCR and quantitative in situ hybridization (ISH). The cellular expression of miR-21 positive cells was further characterized using immunohistochemical cellular markers. RESULTS: Increased levels of miR-21 and miR-126 were found in UC compared with controls and increased levels of miR-21 were observed in UC compared with CD by both RT-qPCR and quantitative in situ hybridization. miR-126 was localized to endothelial cells and miR-21 to cells in the lamina propria. Multiplex immunohistochemical staining showed miR-21 expression in subsets of CD68 macrophages and CD3 T cells in UC, however, far the majority of the miR-21 positive cells could not be categorized among CD68, CD3, and CD19 cells. CONCLUSIONS: This study shows that miR-126 levels are increased in UC and expressed in endothelial cells. miR-21 is expressed in subsets of monocytes/macrophages and T cells and may work as a potential biomarker to distinguish UC from CD. Quantitative in situ hybridization may be a powerful tool for such analysis as it combines overall expression with validation of cellular origin. Studies in larger cohorts may confirm this for clinical diagnostics.

Auto-reactive T cells revised. Overestimation based on methodology?

Autoreactive T cells have been identified in most autoimmune diseases and recently even in healthy individuals. Similar, T cells that recognize either wild-type or tumorspecific tumor antigens have been increasingly reported to develop spontaneously in cancer patients. This insight has become possible mainly due to novel immunoassays which have revolutionized the discovery of rare antigen specific T cells. At present, the major dogma that explains this increasing number of reports of autoreactive T cells is that autoreactive T cells are counteracted by CD4+CD25+ regulatory T (Treg) cells in vivo, in particular in healthy individuals, whereas dysfunction in Tregs or Treg responsiveness may unmask the autoreactive T cell responses in patients with autoimmune diseases. However, studies that identify autoreactive T cells are usually performed by culturing T cells with antigen presenting cells loaded with E. coli produced recombinant protein or unmodified synthetic HLA binding peptides. Our concern is that this approach may ignore the presence of natural genetic variation and post-translational modifications such as e.g. the complex nature of N- and O-linked glycosylation of mammalian proteins. Thus, T cell antigen reactivities identified with unmodified antigens in vitro may in part represent in vitro T cell activation against neo-epitopes and not true in vivo autoreactivity as postulated. This methodological problem may have implications for the interpretation of the frequent reporting of autoreactive T cells in autoimmunity, T cell responses to wild-type tumor antigens in cancer patients and most important for the increasing reports on naïve T cells with specificity against self-antigens in healthy individuals. Here, we discuss and provide examples for the possibility that the experimental methodology applied to document T cell reactivity against unmodified protein or peptide may lead to overinterpretation of the reported frequencies of autoreactive CD4+ and CD8+ T cells.