Background:
Neurofilament light chain protein (NFL) and chitinase3-like1 (CHI3L1) have gained importance recently as prognostic biomarkers in multiple sclerosis (MS).
Objectives:
We aimed to ...investigate NFL and CHI3L1 cerebrospinal fluid (CSF) profiles in multiple sclerosis and the informative and prognostic potential of the individual and combined measures.
Methods:
CSF NFL and CHI3L1 levels were measured in a cross-sectional cohort of 157 MS patients 99 relapsing-remitting (RRMS), 35 secondary progressive (SPMS), and 23 primary progressive (PPMS). Clinical relapse and/or gadolinium-enhanced lesions (GEL) in MRI within 90 days from CSF collection by lumbar puncture (LP) were registered and considered as indicators of disease activity. Longitudinal treatment and disability data were evaluated during medical visits with a median follow-up of 50 months.
Results:
CSF levels of NFL and CHI3L1 were higher in MS patients compared to non-MS controls. In RRMS and SPMS patients, increased NFL levels were associated with clinical relapse, and gadolinium-enhanced lesions in MRI (
p
< 0.001), while high CHI3L1 levels were characteristic of progressive disease (
p
= 0.01). In RRMS patients, CSF NFL, and CHI3L1 levels correlated with each other (
r
= 0.58), and with IgM-oligoclonal bands (
p
= 0.02 and
p
= 0.004, respectively). In addition, CSF CHI3L1 concentration was a predictor for 1-point EDSS worsening {HR = 2.99 95% CI (1.27, 7.07)} and progression during follow-up {HR = 18 95% CI (2.31, 141.3)}. The pattern of combined measure of biomarkers was useful to discriminate MS phenotypes and to anticipate clinical progression: RRMS more frequently presented high NFL combined with low CHI3L1 levels, compared to SPMS (HR 0.41 0.18–0.82), and PPMS (HR 0.46 0.19–0.87), while elevation of both biomarkers preceded diagnosis of clinical progression in RRMS patients (log rank = 0.02).
Conclusions:
Individual measures of CSF NFL and CHI3L1 are biomarkers of disease activity and progression, respectively. The pattern of combined measure discriminates MS phenotypes. It also predicts the subset of RRMS patients that will progress clinically allowing early intervention.
In recent years new hydroelectric dam projects in Brazil have led to intense debate across society. A range of different social actors have been engaged in these controversies, all of them deploying ...different discourses to legitimise their postures. This paper addresses the study of the discourses emerging around this debate in the case of two hydroelectric projects in the Cuenca del Alto Paraná River, and examines the way the multiple arguments emanating from the social actors are grouped together. On the basis of a content analysis of qualitative interviews a factor analysis was carried out to identify the groups of arguments. One of the main outcomes of this analysis highlighted the discursive isolation of a single social group - the people affected by the construction of the dams - in contrast to the other actors, who shared arguments grounded in techno-economic rationales. As opposed to this, those affected by the dam projects used arguments based on their emotions, identities and daily experiences of place; their perspectives were absent from the discourses of other actors.
Objective
To determine baseline cerebrospinal fluid and magnetic resonance imaging (MRI) variables at the onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) that ...predict evolution to secondary progressive MS (SPMS).
Methods
276 CIS patients with a minimum follow-up of 10 years were studied. Baseline presence of oligoclonal IgG and IgM bands (OCGB and OCMB respectively); number of brain T2 lesions (B-T2L), brain gadolinium enhancement lesions (brain-GEL), cervical spinal cord T2 lesions (cSC-T2L); and fulfillment of 2017 McDonald criteria among other variables were collected.
Results
14 patients ended up with a non-MS condition. 138/276 CIS patients fulfilled 2017 McDonald criteria. Mean age was 32.4 years, 185 female. 227 received treatment, 95 as CIS. After a mean follow-up of 12 years, 36 patients developed SPMS. Conversion to SPMS was associated with OCGB (p = 0.02), OCMB (p = 0.0001); ≥ 9 B-T2L (p = 0.03), brain-GEL (p = 0.03), and cSC-T2L (p = 0.03). However, after adjusting for sex, age, BT2L, brain-GEL, SC-T2, and OCMB status, only OCMB (HR 4.4, 1.9–10.6) and cSC-T2L (HR 2.2, 1.0–6.2) suggested an independent association with risk of conversion to SPMS. Patients with both risk factors had a HR of 6.12 (2.8–12.9).
Discussion
OCMB and SC-T2 lesions are potential independent predictors of conversion to SPMS.
Rituximab (RTX) is an anti-CD20 monoclonal antibody that has been used in cases of refractory myasthenia gravis (MG). The aim of this work is to analyse the efficacy and safety of RTX in MG in real ...clinical practice in a tertiary hospital.
A retrospective study was conducted with patients with MG treated with RTX in our centre from March 2014 to September 2020. Demographic and serological data, together with information about previous immunomodulatory treatment, clinical response and adverse effects are collected.
Twenty patients with MG - 100% generalised: 70% late-onset MG (LOMG) and 30% early-onset MG (EOMG) - were given RTX (mean age: 66.8 years; 70% male). A total of 90% are seropositive, 16 of them with positive anti-acetylcholine receptor antibodies and two with positive muscle-specific tyrosine kinase (anti-MuSK) antibodies. All had failed previous treatments: 100% with steroids, 100% with intravenous immunoglobulins and/or plasmapheresis, 55% with other immunosuppressants (25% with one previous immunosuppressant, 10% with two, 15% with three and 5% with four) and 35% with thymectomy. After RTX, 75% of patients showed a clinical response (12 patients with complete remission and the possibility of steroid withdrawal without recurrence; and three patients with partial remission and the possible reduction of steroid dosage) and 25% therapeutic failure; in all these cases RTX was withdrawn. All the anti-MuSK+ patients (100%) and 92.8% of the LOMG patients responded to RTX, while 66% of EOMG patients failed. Only three patients reported adverse effects, all of which were mild and did not require RTX withdrawal.
In our experience, rituximab is a safe and effective treatment in aggressive generalised MG with anti-MuSK or late-onset MG (LOMG).
Introduction:
We have different treatment alternatives for relapsing-remitting multiple sclerosis–RRMS–within the so-called platform drugs. It would be desirable to know the ideal drug for each ...patient. Real clinical practice studies provide us with data on drug efficacy in the medium and long term, safety beyond clinical trials, and can help us to know the patient profile appropriate for each therapy.
Material and Methods:
An observational multicenter study of real clinical practice in patients with RRMS who were treated with teriflunomide in the Valencian Community, since teriflunomide was authorized in Spain. The database created for this study collects retrospectively patients followed prospectively in the MS clinics.
Objectives:
To analyze the efficacy and safety of teriflunomide treatment in patients with RRMS under the conditions of real clinical practice, and to identify a patient profile responding to the treatment.
Results:
We obtained data from 340 patients who received at least one dose of 14 mg teriflunomide. The patients were 69.4% female to 30.6% male, had a mean age of 46.4 years, and a mean time of progression of MS of 11.5 years. The mean pre-teriflunomide relapse rate was 0.4 years, the mean EDSS scorewas 1.98, IgG Oligoclonal bands were present in the CSF of 66.2% of the patients, IgM Oligoclonal bands were present in 46.9%, and the mean number of gadolinium-enhancing lesions was 1.07 lesions per patient at the beginning of treatment. The average number of treatments previously received was 1.04, and 28.53% were naïve. After a follow-up of up to 4 years, a reduction in the annualized and cumulative annualized relapse rate was observed in the first year, in the second year, and in the third year, compared to the pre-treatment year. The EDSS scores were stabilized throughout the follow-up. Likewise, there was a reduction in gadolinium-enhancing lesions in the 1st and 2nd years compared to the pre-treatment period. Applying different generalized multiple linear regression models, we identified a profile of a responding patient to teriflunomide as a male without IgM oligoclonal bands in the CSF, a previous EDSS score of <3, and more than 5 years duration of MS.
Since the nineties, interest in political and social environments has increased considerably. Several studies have found that the perception of people about their environment affects social cohesion, ...which has a significant impact on physical and mental health. The aim of this study is to verify the predictive role of satisfaction with the environment and perceptions of social problems on social cohesion in a sample of social housing tenants in Andalusia. A cross sectional study was conducted through questionnaires, with a final sample of 404 participants. The analysis of hierarchical and multiple linear regressions showed that the perception of context and satisfaction with social housing environment significantly predicted social cohesion, although differently for processes of attraction in the neighborhood, neighborhood perceptions and sense of community. The subjective experiences and perceptions of neighborhood residents appear to be important predictors of fundamental social processes such as social cohesion, which should be considered and studied with objective measures of the environment (e.g., unemployment levels or crime rates) in the study of social housing and the design of interventions aimed at social integration
Dysplasia epiphysialis hemimelica (DEH), also known as Trevor disease, is a very rare disease characterized by an overgrowth of the osteocartilaginous epiphyseal caused by unknown factors. The medial ...side of the epiphysis is affected twice as often as the lateral side and more than one epiphysis was affected in two-thirds of the cases. Only a few cases of DEH in the upper extremities have been published, as the lower limb is usually the most affected, especially in the bones of the ankle joint. The symptoms vary from little significant deformities to symptomatic cases, pain, and decreased function depending on the location and the size of the lesion. When surgery is indicated, the complete excision of the lesion is the procedure of choice. If this is not possible, because of the location or size of the lesion, a realignment osteotomy may be necessary. We report the case of a 12-year-old patient with a distal epiphysis DEH on the left radius, treated by wedge osteotomy realignment at the level of the lesion with Kirschner wires. The clinical outcome of realignment osteotomy of the radial epiphysis has been the correction of the deformity with a normal and painless function of the wrist and hand. The case reported was an extremely rare location in the distal radial epiphysis of DEH. We are aware of only one case published previously with involvement of the distal radius in children. The surgical treatment of realignment osteotomy without complete removal of the lesion has enabled anatomical and functional improvement of the joint as well as a reduction in lesion size. Level of EvidenceLevel IV case report.
A pulsed electrodeposition procedure has been developed to prepare macroporous films of the semiconducting mineral simonkolleite, Zn
5
(OH)
8
Cl
2
·H
2
O, on glass/FTO substrates. The morphology is ...characterized by the presence of smooth, micron-sized hexagonal platelets, and relatively thick films of 6
μ
m can be prepared in about 15 min. Simonkolleite can be transformed into crystalline, mesoporous ZnO using a relatively low temperature thermal treatment (250 °C). While the macrostructure of hexagonal platelets is maintained, they become mesoporous due to the removal of water and Cl
−
-containing reaction products. Dye-sensitized solar cells were fabricated with both simonkolleite and ZnO films, using the recently reported fully organic benzothiadiazole-based photosensitizer MG-207, and an electrolyte solution based on either the I
−
/I
3
−
or the Co(bpy)
3
2+/3+
redox couple. An efficiency of 1.74% has been obtained for ZnO/MG-207/Co(bpy)
3
2+/3+
solar cells, illustrating the promise of crystalline, mesoporous ZnO obtained via a low-temperature simonkolleite route for portable and lightweight devices based on flexible substrates.
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