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Background and ObjectivesTo explore whether time to diagnosis, time to treatment initiation, and age to reach disability milestones have changed in patients with clinically isolated syndrome (CIS) according to different multiple sclerosis (MS) diagnostic criteria periods.MethodsThis retrospective study was based on data collected prospectively from the Barcelona-CIS cohort between 1994 and 2020. Patients were classified into 5 periods according to different MS criteria, and the times to MS diagnosis and treatment initiation were evaluated. The age at which patients with MS reached an Expanded Disability Status Scale (EDSS) score ≥3.0 was assessed by Cox regression analysis according to diagnostic criteria periods. Last, to remove the classic Will Rogers phenomenon by which the use of different MS criteria over time might result in a changes of prognosis, the 2017 McDonald criteria were applied, and age at EDSS score ≥3.0 was assessed by Cox regression.ResultsIn total, 1,174 patients were included. The median time from CIS to MS diagnosis and from CIS to treatment initiation showed a 77% and 82% reduction from the Poser to the McDonald 2017 diagnostic criteria periods, respectively. Patients of a given age diagnosed in more recent diagnostic criteria periods had a lower risk of reaching an EDSS score ≥3.0 than patients of the same age diagnosed in earlier diagnostic periods (reference category Poser period): adjusted hazard ratio (aHR) 0.47 (95% confidence interval 0.24–0.90) for McDonald 2001, aHR 0.25 (0.12–0.54) for McDonald 2005, aHR 0.30 (0.12–0.75) for McDonald 2010, and aHR 0.07 (0.01–0.45) for McDonald 2017. Patients in the early-treatment group displayed an aHR of 0.53 (0.33–0.85) of reaching age at EDSS score ≥3.0 compared to those in the late-treatment group. Changes in prognosis together with early-treatment effect were maintained after the exclusion of possible bias derived from the use of different diagnostic criteria over time (Will Rogers phenomenon).DiscussionA continuous decrease in the time to MS diagnosis and treatment initiation was observed across diagnostic criteria periods. Overall, patients diagnosed in more recent diagnostic criteria periods displayed a lower risk of reaching disability. The prognostic improvement is maintained after the Will Rogers phenomenon is discarded, and early treatment appears to be the most likely contributing factor.

Intrathecal production of kappa free light chains occurs in multiple sclerosis and can be measured using the kappa free light chain index. Kappa free light chain index values can be determined more easily than oligoclonal bands detection and seem more sensitive than the immunoglobulin (Ig)G index to diagnose multiple sclerosis. We assessed the value of oligoclonal bands, kappa free light chain index cut-offs 5.9, 6.6 and 10.61, and IgG index to diagnose multiple sclerosis with prospectively acquired data from a clinically isolated syndrome inception cohort. We selected patients with sufficient data to determine oligoclonal bands positivity, MRI dissemination in space and time, IgG index and sufficient quantities of paired CSF and blood samples to determine kappa free light chain indexes (n = 214). We used Kendall’s Tau coefficient to estimate concordance, calculated the number of additional diagnoses when adding each positive index to dissemination in space and positive oligoclonal bands, performed survival analyses for oligoclonal bands and each index with the outcomes second attack and 2017 MRI dissemination in space and time and estimated the diagnostic properties of oligoclonal bands and the different indexes for the previously mentioned outcomes at 5 years. Oligoclonal bands were positive in 138 patients (64.5%), kappa free light chain-5.9 in 136 (63.6%), kappa free light chain-6.6 in 135 (63.1%), kappa free light chain-10.61 in 126 (58.9%) and IgG index in 101 (47.2%). The highest concordance was between oligoclonal bands and kappa free light chain-6.6 (τ = 0.727) followed by oligoclonal bands and kappa free light chain-5.9 (τ = 0.716). Combining dissemination in space plus oligoclonal bands or kappa free light chain-5.9 increased the number of diagnosed patients by 11 (5.1%), with kappa free light chain-6.6 by 10 (4.7%), with kappa free light chain-10.61 by 9 (4.2%) and with IgG index by 3 (1.4%). Patients with positive oligoclonal bands or indexes reached second attack and MRI dissemination in space and time faster than patients with negative results (P < 0.0001 except IgG index in second attack: P = 0.016). In multivariable Cox models [adjusted hazard ratio (95% confidence interval)], the risk for second attack was very similar between kappa free light chain-5.9 [2.0 (0.9–4.3), P = 0.068] and kappa free light chain-6.6 [2.1 (1.1–4.2), P = 0.035]. The highest risk for MRI dissemination in space and time was demonstrated with kappa free light chain-5.9 [4.9 (2.5–9.6), P < 0.0001], followed by kappa free light chain-6.6 [3.4 (1.9–6.3), P < 0.0001]. Kappa free light chains-5.9 and -6.6 had a slightly higher diagnostic accuracy than oligoclonal bands for second attack (70.5, 71.1 and 67.8) and MRI dissemination in space and time (85.7, 85.1 and 81.0). Kappa free light chain indexes 5.9 and 6.6 performed slightly better than oligoclonal bands to assess multiple sclerosis risk and in terms of diagnostic accuracy. Given the concordance between oligoclonal bands and these indexes, we suggest using dissemination in space plus positive oligoclonal bands or positive kappa free light chain index as a modified criterion to diagnose multiple sclerosis.

To evaluate the diagnostic performance of texture analysis (TA) applied on non-contrast-enhanced susceptibility-weighted imaging (SWI) to differentiate acute (enhancing) from chronic (non-enhancing) multiple sclerosis (MS) lesions. We analyzed 175 lesions from 58 patients with relapsing-remitting MS imaged on a 3.0 T MRI scanner and applied TA on T2-w and SWI images to extract texture features. We evaluated the presence or absence of lesion enhancement on T1-w post-contrast images and performed a computational statistical analysis to assess if there was any significant correlation between the texture features and the presence of lesion activity. ROC curves and leave-one-out cross-validation were used to evaluate the performance of individual features and multiparametric models in the identification of active lesions. Multiple TA features obtained from SWI images showed a significantly different distribution in acute and chronic lesions (AUC, 0.617–0.720). Multiparametric predictive models based on logistic ridge regression and partial least squares regression yielded an AUC of 0.778 and 0.808, respectively. Results from T2-w images did not show any significant predictive ability of neither individual features nor multiparametric models. Texture analysis on SWI sequences may be useful to differentiate acute from chronic MS lesions. The good diagnostic performance could help to reduce the need of intravenous contrast agent administration in follow-up MRI studies. • Texture analysis applied on SWI sequences may be useful to differentiate acute from chronic multiple sclerosis lesions • The good diagnostic performance could help to minimize the need of intravenous contrast agent administration in follow-up MRI studies

CgA peptides in patients with TA stratified for therapy with steroids or immunosuppressive agents. (DOC 63 kb)

Four-way analysis of the variance (ANOVA) of the levels of CgA peptides and of the anti-angiogenic CgA potential. (DOC 44 kb)

CgA peptides in TA patients with and without arterial hypertension, stratified for therapy with PPIs. (DOC 49 kb)

OBJECTIVES: To compare the diagnostic performance of Magnetic Resonance (MR) and diffusion-weighted imaging (DWI), Multidetector Computed Tomography (MDCT), Endoscopic Ultrasonography (EUS) and 18F-FDG (Fluorodeoxyglucose) Positron Emission Tomography - Computed Tomography (PET-CT) in the preoperative loco-regional staging of oesophageal cancer. METHODS: Eighteen patients with oesophageal or Siewert I tumour (9 directly treated with surgery and 9 addressed to chemo/radiotherapy before) underwent 1.5 T MR and DWI, 64-channels MDCT, EUS and PET-CT before (n=18) and also after neoadjuvant treatment (n=9). All images were analysed and staged blindly by dedicated operators (7th TNM edition). Two radiologists calculated independently the Apparent Diffusion Coefficient (ADC) from the first scan. Results were compared with histopathological findings. After the population had been divided according to local invasion (T1-2 vs T3-4) and nodal involvement (N0 vs N+), sensitivity, specificity, accuracy, positive and negative predictive value were calculated and compared. Quantitative measurements from DWI and PET-CT were also analysed. RESULTS: For T staging, EUS showed the best sensitivity (100%) while MR showed the highest specificity (92%) and accuracy (83%). For N staging, MR and EUS showed the highest sensitivity (100%), but none of the techniques showed adequate results for specificity. Overall, MR showed the highest accuracy (66%) for N stage, even though this was not significantly different to the other modalities. ADC was different between surgery-only and chemo/radiotherapy groups (1.90 vs 1.30 x 10-3 mm2/s, respectively; p= 0.005) - optimal cut off for local invasion:1.33 x 10-3 mm2/s (p=0.05). Difference in SUV was also very close to conventional levels of statistical significance (8.81 vs 13.97 g/cc, respectively; p= 0.05) - optimal cut off: 7.97 g/cc (p=0.44). CONCLUSIONS: In this pilot study we have shown that MR with DWI could enrich the current preoperative workup for oesophageal cancer and could be used for T and N staging. However, larger studies will need to be carried out before introducing this technique in the standard diagnostic pathway, in order to understand if MR with DWI could change its management and replace more costly or invasive tests such as PET-CT or EUS. Advances in knowledge: This pilot study represents the first effort where the four techniques have been prospectively compared together for oesophageal cancer staging. The combination of MR and DWI could provide important, additional information for staging and initial treatment decision-making.