Impact of amyloid-PET in daily clinical management of patients with cognitive impairment fulfilling appropriate use criteria

To evaluate the use of amyloid-positron emission tomography (PET) in routine clinical practice, in a selected population with cognitive impairment that meets appropriate use criteria (AUC). A multicenter, observational, prospective case-series study of 211patients from 2 level-3 hospitals who fulfilled clinical AUC for amyloid-PET scan in a naturalistic setting. Certainty degree was evaluated using a 5-point Likert scale: 0 (very low probability); 1 (low probability); 2 (intermediate probability); 3 (high probability); and 4 (practically sure), before and after amyloid PET. The treatment plan was considered as cognition-specific or noncognition-specific. Amyloid-PET was positive in 118 patients (55.9%) and negative in 93 patients (44.1%). Diagnostic prescan confidence according amyloid-PET results showed that in both, negative and positive-PET subgroup, the most frequent category was intermediate probability (45.7% and 55.1%, respectively). After the amyloid-PET, the diagnostic confidence showed a very different distribution, that was, in the negative-PET group the most frequent categories are very unlikely (70.7%) and unlikely (29.3%), while in the positive- PET group were very probable (57.6%) and practically sure (39%). Only in 14/211 patients (6.6%) the result of the amyloid-PET did not influence the diagnostic confidence, while in 194 patients (93.4%), the diagnostic confidence improved significantly after amyloid- PET results. The therapeutic intention was modified in 93 patients (44.1%). Specific treatment for Alzheimer disease was started, before amyloid-PET, in 80 patients (37.9%). This naturalistic study provides evidence that the implementation of amyloid-PET is associated with a significant improvement in diagnostic confidence and has a high impact on the therapeutic management of patients with mild cognitive impairment fulfilled clinical AUC

Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients

Educafarma 10.0

Memoria ID-030. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2021-2022

O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

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IGF-1 and ADMA levels are inversely correlated in nondiabetic ankylosing spondylitis patients undergoing anti-TNF-alpha therapy

Like rheumatoid arthritis, ankylosing spondylitis (AS) is also an inflammatory disease associated with accelerated atherosclerosis and the presence of metabolic syndrome (MeS) features. AS patients often display osteoporosis as well as new bone formation. Insulin-like growth factor 1 (IGF-1) is a protein involved in both inflammation and bone metabolism. In the present study we assessed whether disease activity, systemic inflammation, MeS features, adipokines, and biomarkers of endothelial activation were associated with IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels in a series of 30 nondiabetic AS patients without CV disease undergoing TNF-α antagonist-infliximab therapy. All determinations were made in the fasting state, immediately before an infliximab infusion. Although no association of IGF-1 and IGFBP-3 levels with angiopoietin-2 or osteopontin was found, an inverse correlation between IGF-1 levels and asymmetric dimethylarginine (ADMA), an endogenous endothelial nitric oxide synthase inhibitor that impairs nitric oxide production and secretion promoting endothelial dysfunction, was found (r=-0.397; P=0.04). However, no significant association was found between IGF-1 and IGFBP-3 levels and disease activity, systemic inflammation, metabolic syndrome features, or adipokines. In conclusion, in nondiabetic patients with AS undergoing periodic anti-TNF-α therapy, IGF-1 and ADMA are inversely correlated

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C : A prospective observational study

Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with ≥2 clinical signs/symptoms of NP-C were considered 'suspected NP-C' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI ≥70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 [4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores ≥70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis