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1.
Artigo em Inglês | MEDLINE | ID: mdl-38844341

RESUMO

BACKGROUND: Cerebrospinal fluid myelin oligodendrocyte glycoprotein IgG (CSF MOG-IgG) are found in a proportion of patients with MOG antibody-associated disorder (MOGAD) and have been associated with severe disease presentations. However, most studies did not systematically investigate the role of MOG-IgG intrathecal synthesis (ITS). METHODS: We retrospectively studied 960 consecutive patients with paired serum and CSF samples screened for MOG-IgG using a live cell-based assays. MOG-IgG-specific antibody index (AIMOG) was systematically calculated using serum and CSF titres to assess MOG-IgG ITS, and clinical features were compared between MOG-IgG CSF+/CSF- and ITS+/ITS- patients. RESULTS: MOG-IgG were found in 55/960 patients (5.7%; serum+/CSF-: 58.2%, serum+/CSF+: 34.5%; serum-/CSF+: 7.3%). Serum/CSF MOG-IgG titres showed a moderate correlation in patients without ITS (ρ=0.47 (CI 0.18 to 0.68), p<0.001), but not in those with ITS (ρ=0.14 (CI -0.46 to -0.65), p=0.65). There were no clinical-paraclinical differences between MOG-IgG CSF+ vs CSF- patients. Conversely, patients with MOG-IgG ITS showed pyramidal symptoms (73% vs 32%, p=0.03), spinal cord involvement (82% vs 39%, p=0.02) and severe outcome at follow-up (36% vs 5%, p=0.02) more frequently than those without MOG-IgG ITS. A multivariate logistic regression model indicated that MOG-IgG ITS was an independent predictor of a poor outcome (OR: 14.93 (CI 1.40 to 19.1); p=0.03). AIMOG correlated with Expanded Disability Status Scale (EDSS) scores at disease nadir and at last follow-up (p=0.02 and p=0.01). CONCLUSIONS: Consistently with physiopathology, MOG-IgG ITS is a promising prognostic factor in MOGAD, and its calculation could enhance the clinical relevance of CSF MOG-IgG testing, making a case for its introduction in clinical practice.

2.
Curr Opin Oncol ; 35(1): 15-21, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36475458

RESUMO

PURPOSE OF REVIEW: Patients with slowly progressive and/or symptomatic oligometastatic radioactive iodine refractory (RAIR) differentiated thyroid carcinomas (DTCs) are candidates to receive locoregional treatment to delay the start of systemic therapy with multikinase inhibitors. Information provided by the recent literature has not been extensively reviewed in previous published works, thus we aim to bridge this gap. RECENT FINDINGS: We present for each metastatic site the different locoregional treatment options, contraindications and potential adverse events. Some techniques can be combined together, whereas others are discouraged in certain situations, requiring a high level of expertise and multidisciplinarity in the treatment algorithm. SUMMARY: Different techniques of radiation therapy and interventional radiology allow to control the metastatic spread. However, as no clinical trials are available to compare the treatment schemes in terms of safety and potential impact on the prognosis, the most appropriate option for each patient should be selected within a multidisciplinary decision making, taking into account the clinical conditions and the pattern/rapidity of metastatic disease.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/terapia , Radioisótopos do Iodo/uso terapêutico
3.
J Neurol Neurosurg Psychiatry ; 94(3): 201-210, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36460438

RESUMO

BACKGROUND: IgG antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) define a subset of associated disorders (myelin oligodendrocyte glycoprotein associated disorders (MOGAD)) that can have a relapsing course. However, information on relapse predictors is scarce. The utility of retesting MOG-IgG over time and measuring their titres is uncertain. We aimed to evaluate the clinical relevance of longitudinal MOG-IgG titre measurement to predict relapses in patients with MOGAD. METHODS: In this retrospective multicentre Italian cohort study, we recruited patients with MOGAD and available longitudinal samples (at least one >3 months after disease onset) and tested them with a live cell-based assay with endpoint titration (1:160 cut-off). Samples were classified as 'attack' (within 30 days since a disease attack (n=59, 17%)) and 'remission' (≥31 days after attack (n=295, 83%)). RESULTS: We included 102 patients with MOGAD (57% adult and 43% paediatric) with a total of 354 samples (83% from remission and 17% from attack). Median titres were higher during attacks (1:1280 vs 1:640, p=0.001). Median onset titres did not correlate with attack-related disability, age or relapses. Remission titres were higher in relapsing patients (p=0.02). When considering the first remission sample available for each patient, titres >1:2560 were predictors of relapsing course in survival (log rank, p<0.001) and multivariate analysis (p<0.001, HR: 10.9, 95% CI 3.4 to 35.2). MOG-IgG seroconversion to negative was associated with a 95% relapse incidence rate reduction (incidence rate ratio: 0.05, p<0.001). CONCLUSIONS: Persistent MOG-IgG positivity and high remission titres are associated with an increased relapse risk. Longitudinal MOG-IgG titres could be useful to stratify patients to be treated with long term immunosuppression.


Assuntos
Autoanticorpos , Imunoglobulina G , Humanos , Estudos Retrospectivos , Prognóstico , Glicoproteína Mielina-Oligodendrócito , Estudos de Coortes , Doença Crônica , Recidiva
4.
Int J Mol Sci ; 24(21)2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37958968

RESUMO

Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain during eye movements. Typical ON is associated with Multiple Sclerosis (MS) and is generally mild and steroid-responsive. Atypical forms are characterized by unusual features, such as prominent optic disc edema, poor treatment response, and bilateral involvement, and they are often associated with autoantibodies against aquaporin-4 (AQP4) or Myelin Oligodendrocyte Glycoprotein (MOG). However, in some cases, AQP4 and MOG antibodies will return as negative, plunging the clinician into a diagnostic conundrum. AQP4- and MOG-seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis are greatly different. The aim of this review is to describe the possible rarer etiologies of non-MS-related and AQP4- and MOG-IgG-seronegative inflammatory ON and discuss their diagnoses and treatments.


Assuntos
Esclerose Múltipla , Neurite Óptica , Humanos , Glicoproteína Mielina-Oligodendrócito , Estudos Retrospectivos , Neurite Óptica/diagnóstico , Neurite Óptica/etiologia , Aquaporina 4 , Autoanticorpos
5.
Muscle Nerve ; 64(2): 206-211, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34031902

RESUMO

INTRODUCTION/AIMS: Coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global pandemic. Patients with myasthenia gravis (MG), often treated with immunosuppressants, might be at higher risk of developing COVID-19 and of demonstrating a severe disease course. We aimed to study prevalence and describe features of COVID-19 in MG patients. METHODS: In May 2020, we conducted telephonic interviews with MG patients followed at our referral center. We collected structured data regarding MG and COVID-19, which was diagnosed as probable or confirmed according to the European Centre for Disease Prevention and Control case definition. We compared confirmed-COVID-19 prevalence calculated from the beginning of the pandemic in MG patients with that of the overall Pavia district. RESULTS: We interviewed 162 MG patients (median age, 66 y; interquartile range 41-77; males 59.9%), 88 from the Pavia district. Three patients had SARS-CoV-2-confirmed by polymerase chain reaction and eight had probable-COVID-19. In the Pavia district, the prevalence of confirmed-COVID-19 among MG patients (1/88, 1.14%) and overall population (4777/546 515, 0.87%) did not differ (P = .538). Higher Myasthenia Gravis Foundation of America clinicalclass and the need for recent rescue treatment, but not ongoing immunosuppressive treatments, were associated with COVID-19 risk. Of 11 MG patients with probable/confirmed-COVID-19, 3 required ventilator support, and 2 elderly patients died of COVID-19 respiratory insufficiency. Only 1 of11 patients experienced worsening MG symptoms, which improved after increasing their steroid dose. DISCUSSION: The risk of COVID-19 in MG patients seems to be no higher than that of the general population, regardless of immunosuppressive therapies. In our cohort, COVID-19 barely affected MG course.


Assuntos
COVID-19/diagnóstico , COVID-19/epidemiologia , Progressão da Doença , Miastenia Gravis/diagnóstico , Miastenia Gravis/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Teste de Ácido Nucleico para COVID-19/métodos , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/tratamento farmacológico
6.
Eur Spine J ; 29(2): 314-320, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31696335

RESUMO

PURPOSE: Related to the development and diffusion of ALIF and XLIF, it is possible to correct sagittal malalignment in selected cases of lumbar degenerative discopathy with a relatively low invasiveness. Still, the malposition or the inappropriate size of the implanted cages may lead to the subsidence of the vertebral endplates with loss of correction as well as a decrease in the potential to restore spinal biomechanics in the long run. The aim of this study is to evaluate safety, feasibility, and preliminary clinical and radiological results when using custom-made, trabecular titanium cages in ALIF and XLIF procedures. METHODS: We prospectively evaluated 18 consecutive patients who underwent either an ALIF or an XLIF procedure with the implant of a custom-made, trabecular titanium cage for lumbar degenerative disease with sagittal imbalance, with a minimum of 1-year clinical and radiological follow-up. RESULTS: After a mean follow-up of 14 months, the Oswestry score dropped to a mean of 13 from a preoperative value of 48 (p < 0.0001). Lumbar lordosis was significantly improved, especially in the lower lumbar segment L4-S1 (+ 11 ± 7°; p < 0.0001). No cases of subsidence were noted. CONCLUSIONS: Custom-made, trabecular titanium cages allowed a segmental, steady, durable sagittal correction via ALIF and XLIF approaches. The absence of cage subsidence at 1 year encourages further studies on a larger cohort with longer follow-up. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Fusão Vertebral , Titânio , Adulto , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
7.
J Neurol Neurosurg Psychiatry ; 90(11): 1201-1206, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31189614

RESUMO

OBJECTIVE: To study the effect of natural menopause on multiple sclerosis clinical course. METHODS: This was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status. RESULTS: 148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059). CONCLUSION: Natural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.


Assuntos
Menopausa , Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Progressão da Doença , Feminino , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
8.
Int J Mol Sci ; 20(24)2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31817248

RESUMO

Mycotoxins produced by Fusarium species on cereals represent a major concern for food safety worldwide. Fusarium toxins that are currently under regulation for their content in food include trichothecenes, fumonisins, and zearalenone. Biological control of Fusarium spp. has been widely explored with the aim of limiting disease occurrence, but few efforts have focused so far on limiting toxin accumulation in grains. The bacterial genus Streptomyces is responsible for the production of numerous drug molecules and represents a huge resource for the discovery of new molecules. Streptomyces spp. are also efficient plant colonizers and able to employ different mechanisms of control against toxigenic fungi on cereals. This review describes the outcomes of research using Streptomyces strains and/or their derived molecules to limit toxin production and/or contamination of Fusarium species in cereals. Both the scientific and patent literature were analyzed, starting from the year 2000, and we highlight promising results as well as the current pitfalls and limitations of this approach.


Assuntos
Agentes de Controle Biológico/farmacologia , Grão Comestível/microbiologia , Contaminação de Alimentos/prevenção & controle , Fusarium/efeitos dos fármacos , Streptomyces/química , Agentes de Controle Biológico/metabolismo , Bases de Dados Factuais , Fusarium/metabolismo , Micotoxinas/metabolismo , Patentes como Assunto , Streptomyces/metabolismo
9.
Eur Spine J ; 25(12): 4155-4163, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27220971

RESUMO

PURPOSE: XLIF ® is a widely used minimally invasive technique to treat different spine pathologies. The aim of this study was to quantify nerve distortion of lumbar plexus during XLIF ® approach and to correlate it with morphometric data. METHODS: Nine fresh frozen cadaveric specimens were used. All specimens were subjected to the same dissection procedure cored on a left XLIF® approach at L2/L3 and L4/L5 levels. Distortion of cutaneous superficial nerves, femoral nerve (FN) at L4/L5 and genitofemoral nerve (GN) at L2/L3 and L4/L5 while opening the retractor were assessed and analyzed with respect to psoas muscle features. RESULTS: Superficial nerves were slightly displaced but never stretched. FN, as well as GN at L4/L5 level, could be displaced and stretched by the blades. Statistically significant correlation between FN distortion and the amount of psoas fibers interposed between the posterior blade of the retractor and the nerve itself (TCK) was found. GN distortion was found to be related to its clock position on an axial section of psoas muscle seen from cranially at L4/L5. CONCLUSION: FN was in close connection with the deep psoas muscle fibers and it is subjected to anterior translation that correlates with TCK. This mechanism may partly explain the rate of femoral nerve palsy that occurs despite neuromonitoring and safe entry zones respect. The GN location at L4/L5 should be considered not only for its projection in Zone I, but also for its clock position on the psoas muscle surface, since it affects its distortion.


Assuntos
Dissecação/métodos , Vértebras Lombares/cirurgia , Plexo Lombossacral/patologia , Procedimentos Cirúrgicos Minimamente Invasivos , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Variação Anatômica , Cadáver , Dissecação/efeitos adversos , Feminino , Nervo Femoral/anatomia & histologia , Nervo Femoral/patologia , Humanos , Disco Intervertebral/cirurgia , Vértebras Lombares/anatomia & histologia , Plexo Lombossacral/anatomia & histologia , Plexo Lombossacral/cirurgia , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Músculos Psoas/anatomia & histologia , Músculos Psoas/cirurgia , Análise de Regressão
10.
J Neurovirol ; 21(6): 645-52, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25052191

RESUMO

The risk of developing progressive multifocal leukoencephalopathy (PML), as a consequence of infection/reactivation with JC virus (JCV), is consistent in natalizumab-treated multiple sclerosis (MS) patients, with 430 cases of PML reported so far. The risk of PML is higher in JCV seropositive patients, and it is recommended that only MS patients without JCV antibodies should be enrolled in the treatment postulating that they do not have JCV infection.We have studied forty-two natalizumab-treated MS patients, and urine and blood were collected monthly for up to 60 months. JCV and BK virus (BKV) DNA presence was verified using quantitative real-time PCR assays, and serum anti-JCV antibodies were measured with the Stratify and/or Stratify DxSelect tests.JCV and BKV DNA were not found in the blood samples, whereas they were found at least once in the urine of 21 of 42 (50 %) and of 25/42 (59.5 %) patients, respectively. JCV DNA urinary shedding increased up to month 24 of natalizumab treatment (45.2 %), and the effect of time was significant for JCV (p = 0.04), but not for BKV (p = 0.39). JCV viruria and seropositivity did not completely correlate, since three patients shedding JCV DNA in the urine were seronegative according to the serological tests.The results indicated that natalizumab therapy may increase the rate of JCV urinary shedding. Additionally, we confirmed that the identification of JCV carriers cannot solely rely on serological tests, but sensitive methods for viral DNA detection should be adopted to more precisely identify the truly JCV uninfected cases.


Assuntos
Anticorpos Antivirais/urina , DNA Viral/urina , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/virologia , Natalizumab/uso terapêutico , Adulto , Anticorpos Antivirais/sangue , DNA Viral/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Vírus JC/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/virologia , Reação em Cadeia da Polimerase em Tempo Real , Estudos Soroepidemiológicos , Eliminação de Partículas Virais/fisiologia , Adulto Jovem
12.
Acta Neurochir (Wien) ; 157(4): 711-20, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25646850

RESUMO

BACKGROUND: Spinal cord stimulation (SCS) is a technique used worldwide to treat several types of chronic neuropathic pain refractory to any conservative treatment. The aim of this data collection is to enforce evidence of SCS effectiveness on neuropathic chronic pain reported in the literature and to speculate on the usefulness of the trial period in determining the long-term efficacy. Moreover, the very low percentage of undesired side effects and complications reported in our case series suggests that all implants should be performed by similarly well-trained and experienced professionals. METHOD: A multicentric data collection on a common database from 11 Italian neurosurgical departments started 3 years ago. Two different types of electrodes (paddle or percutaneous leads) were used. Of 122 patients, 73 % (N = 89) were submitted to a trial period, while the remaining patients underwent the immediate permanent implant (N = 33). Statistical comparisons of continuous variables between groups were performed. RESULTS: Most of the patients (80 %) had predominant pain to their lower limbs, while only 17 % of patients had prevalent axial pain. Significant reduction in pain, as measured by variation in visual analogue scale (VAS) score, was observed at least 1 year after implantation in 63.8 % of the cases, 59.5 % of patients who underwent a test trial and 71.4 % of patients who underwent permanent implant at once. No statistical differences were found between the lower-limb pain group and the axial pain group. CONCLUSIONS: No relevant differences in long-term outcomes were observed in previously tested patients compared with patients implanted at once. Through this analysis we hope to recruit new centres, to give more scientific value to our results.


Assuntos
Espaço Epidural/fisiologia , Neuralgia/terapia , Estimulação da Medula Espinal/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Coleta de Dados , Espaço Epidural/cirurgia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Neuralgia/cirurgia , Estimulação da Medula Espinal/efeitos adversos , Estimulação da Medula Espinal/normas , Resultado do Tratamento
13.
Neurol Sci ; 35(2): 265-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23873521

RESUMO

Multiple sclerosis (MS) is the main cause of chronic disability in young people during their most productive years of life and therefore carries a high social and economic burden. The present study aimed to: (1) verify the capacity of an administrative data source to furnish data for constructing a model able to detect the occurrence of clinical relapses in MS patients and (2) validate the constructed theoretical model on a set of real-world data. Two MS experts identified some administrative variables as proxies of clinical relapses. Thereafter, the two MS experts analysed 889 events in 100 MS patients, considering only the administrative data relating to these patients, while a third neurologist independently analysed the real-world data (documented medical history) of the same patients in the same period. Absolute concordance between the theoretical model and the real-world data was found in 86 % of the events. The model we propose is easily and rapidly applicable, requiring the collection of just a few variables that are already present in local health authority administrative databases in Italy. It can be used to estimate, with a good level of reliability, the occurrence of relapses in various settings. Moreover, the model is also exportable to different and larger MS cohorts and could be useful for healthcare planning and for evaluating the efficacy of drugs in the real-world, thus favouring better resource allocation and management.


Assuntos
Modelos Neurológicos , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla/diagnóstico , Bases de Dados Factuais , Feminino , Humanos , Itália , Masculino , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Recidiva
14.
J Neurol ; 271(5): 2840-2843, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38280000

RESUMO

BACKGROUND: Live cell-based assay (LCBA) is the gold standard for MOG-IgG detection, and fixed CBA (FCBA) is a widely used commercial alternative. Recent criteria attributed a diagnostic value to MOG-IgG titration with both LCBA and FCBA, with low-titre samples requiring additional supporting features for MOGAD diagnosis. However, FCBA titration is not validated. We aimed to assess the impact of the criteria-based MOG-IgG testing in MOGAD diagnosis. METHODS: Thirty-eight serum samples of LCBA MOG-IgG1-positive MOGAD patients were titred on MOG-IgG LCBA and FCBA, and the presence of supporting features for MOGAD assessed. MOGAD criteria were evaluated in four testing scenarios: (a) FCBA without titration; (b) FCBA with titration; c) LCBA without titration; (d) LCBA with titration. RESULTS: FCBA without titration failed to reach MOGAD diagnosis in 11/38 patients (28.9%, negative results in 5, lack of supporting features in 6). Patients with unconfirmed diagnosis had optic neuritis (ON, n = 8), or transverse myelitis (TM, n = 3). FCBA with titration allowed MOGAD diagnosis in 4 additional patients. Correlation between LCBA and FCBA titres was moderate (Spearman's rho 0.6, p < 0.001). CONCLUSIONS: FCBA yields high rate of misdiagnosis mainly due a lower analytical sensitivity. FCBA titration provides a moderate diagnostic advantage in FCBA positive patients.


Assuntos
Doenças Autoimunes , Imunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Adulto , Feminino , Humanos , Masculino , Autoanticorpos/sangue , Imunoglobulina G/sangue , Glicoproteína Mielina-Oligodendrócito/imunologia , Mielite Transversa/diagnóstico , Mielite Transversa/sangue , Neurite Óptica/diagnóstico , Neurite Óptica/sangue , Neurite Óptica/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia
15.
J Neurol ; 271(6): 3496-3505, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38532143

RESUMO

BACKGROUND: Predicting disease progression in patients with the first clinical episode suggestive of multiple sclerosis (MS) is crucial for personalized therapeutic approaches. This study aimed to develop the EUMUS score for accurately estimating the risk of early evidence of disease activity and progression (EDA). METHODS: Retrospective analysis was conducted on data from 221 patients with a first clinical MS episode collected from four Italian MS centers. Various variables including socio-demographics, clinical features, cerebrospinal fluid analysis, evoked potentials, and brain MRI were considered. A prognostic multivariate regression model was identified to develop the EUMUS score. The optimal cutoff for predicting the transition from no evidence of disease activity (NEDA3) to EDA was determined. The accuracy of the prognostic model and score were tested in a separate UK MS cohort. RESULTS: After 12 months, 61.54% of patients experienced relapses and/or new MRI lesions. Younger age (OR 0.96, CI 0.93-0.99; p = 0.005), MRI infratentorial lesion(s) at baseline (OR 2.21, CI 1.27-3.87; p = 0.005), positive oligoclonal bands (OR 2.89, CI 1.47-5.69; p = 0.002), and abnormal lower limb somatosensory-evoked potentials (OR 2.77, CI 1.41-5.42; p = 0.003) were significantly associated with increased risk of EDA. The EUMUS score demonstrated good specificity (72%) and correctly classified 80% of patients with EDA in the independent UK cohort. CONCLUSIONS: The EUMUS score is a simple and useful tool for predicting MS evolution within 12 months of the first clinical episode. It has the potential to guide personalized therapeutic approaches and aid in clinical decision-making.


Assuntos
Progressão da Doença , Imageamento por Ressonância Magnética , Esclerose Múltipla , Humanos , Masculino , Feminino , Adulto , Estudos Retrospectivos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/fisiopatologia , Prognóstico , Pessoa de Meia-Idade , Adulto Jovem
16.
HardwareX ; 16: e00495, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38148970

RESUMO

The design of an open zero-gradient hardware is proposed in this work. The hardware is thought for characterizing single Polymer Electrolyte Membrane Fuel Cells (PEMFCs), specifically Membrane Electrode Assemblies (MEAs), with a focus on transport application. The objective of the proposed design is to minimize both operation and degradation heterogeneities over the cell active area in order to evaluate material properties only. It is indeed specifically intended to quantify the PEMFC materials performance without accounting for any interdependency between the layers of the MEA and the cell hardware design (e.g. heating/cooling system and flow field features). This is granted by combining high stoichiometry ratios of the gas reactants and limited pressure drops: they indeed keep uniform operating conditions (concentration in the gas phase, relative humidity, pressure and temperature), as verified by the electrochemical and operational characterization. With such characteristics, accurate information about both the performance and the degradation of the MEA materials can be provided. This tool is powerful for assessing the ranking in terms of performance and durability of different PEMFCs, as well as for application in the field of the materials local diagnostics.

17.
Sci Rep ; 13(1): 21960, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-38081859

RESUMO

Bowel dysfunctions (BD) in multiple sclerosis (MS) are under reported despite their clinical relevance. Scales usually applied do not thoroughly assess constipation and fecal incontinence. Instead, a proper qualitative and quantitative description of these symptoms might have relevant clinical and scientific consequences. The aim of this project is to study the prevalence of BD in a cohort of persons with MS (pwMS). Four-hundred and forty-seven pwMS (330 relapsing-remitting MS-RRMS and 117 progressive MS-PMS) were recruited. Three different questionnaires were administered: the neurogenic bowel dysfunction score (NBDS), the Wexner constipation scale (WexCon) and the Wexner incontinence scale (WexInc). All the scales were divided in subscores according to symptom severity. The prevalence of BD, considered as NBDS > 0, was 53.7%. Mean scores in pwMS group were as follows: NBDS 2.6 (SD 3.5), WexInc 1.1 (SD 2.4), WexCon 4.4 (SD 5.9). NBDS, WexCon and WexInc were significantly higher in PMS vs RRMS (p < 0.001), and significantly associated with disease duration, EDSS, multiple sclerosis severity score (p < 0.001), as well as with each other (p < 0.001). Our study confirms the presence of bowel dysfunctions in a large group of pwMS with a wide range of disability and their association with progressive disease phenotype and clinical disability.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Intestino Neurogênico , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/epidemiologia , Esclerose Múltipla Crônica Progressiva/complicações , Esclerose Múltipla Recidivante-Remitente/complicações , Constipação Intestinal , Intestino Neurogênico/complicações , Itália/epidemiologia
18.
Eur J Cancer ; 180: 146-154, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36599182

RESUMO

Anaplastic thyroid carcinoma (ATC) is a rare cancer accounting for 40% of thyroid cancer-specific deaths. In the last 5 years, improved insights into molecular pathways led the Food and Drug Administration to license BRAF/MEK inhibitors (B/Mi) in BRAFV600E-mutant ATC, and pembrolizumab in solid cancer with high tumour mutational burden (TMB-H) (≥10 mutations/megabase) (mut/Mb). In Europe, clinicians face challenges in prescribing novel treatments, as the European Medical Association (EMA) has not licensed B/Mi nor immunotherapy (IO) for ATC so far. Some patients manage to receive these drugs through alternative ways. We investigated the extent of this phenomenon launching an online survey from March 12th to 19th 2021 open to 239 Institutions in the EORTC Endocrine and Head & Neck Cancer Groups. Questions enquired about the number of ATC patients evaluated/year, feasibility of BRAF assessment, accessibility to B/Mi-IO, availability of clinical trials and interest in new studies. Colleagues from 94 Institutions (20 Countries) joined: 30 centres evaluated ≥5 ATC patients/year, with an overall incidence >200 patients/year. 80.8% tested BRAF status, 43.6% by next-generation sequencing. 62.7% and 70% of responders reported limitations in prescribing B/Mi and IO, respectively: either the impossibility of offering them, or drugs accessibility exclusively under certain conditions (e.g. health insurance, clinical trials, compassionate use, off-label). Only 13.8% had clinical trials ongoing while 91.5% of sites claimed ATC-dedicated trials. Disparities in access to novel treatments are diffuse. Access to cutting-edge therapies is an urgent issue in this setting, and clinical trials seem feasible within an appropriate network.


Assuntos
Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/patologia , Carcinoma Anaplásico da Tireoide/terapia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Europa (Continente) , Mutação
19.
Life (Basel) ; 13(6)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37374183

RESUMO

As life expectancy rises, more elderly people undergo spinal fusion surgery to treat lumbar degenerative diseases. The MIS-TLIF technique, which minimizes soft tissue manipulation, is a promising fusion technique for frailer patients. The aim of this study was to investigate if older age is a significant factor in the clinical outcome of single- or double-level MIS-TLIF. A cross-sectional study was conducted on 103 consecutive patients. Data were compared between younger (<65 y.o.) and older (≥65 y.o.) patients. We observed no significant differences between baseline characteristics of the two groups apart from the frequency of disk space treated, with a relative predominance of L3-L4 space treated in the elderly (10% vs. 28%, p = 0.01) and L5-S1 space in younger patients (36% vs. 5%, p = 0.006). There was no significant difference in complication rate, surgical satisfaction, EQ 5D-5L, or Oswestry Disability Index (ODI) global or specific scores, with the exception of the EQ 5D-5L "mobility" score, where older patients fared worse (1.8 ± 1.1 vs. 2.3 ± 1.4; p = 0.05). The minimal invasiveness of the surgical technique, age-related specific outcome expectations, and biomechanical issues are all potential factors influencing the lack of age group differences in outcome scores.

20.
Viruses ; 15(7)2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37515255

RESUMO

The recent SARS-CoV-2 pandemic and related vaccines have raised several issues. Among them, the potential role of the viral infection (COVID-19) or anti-SARS-CoV-2 vaccines as causal factors of dysimmune CNS disorders, as well as the safety and efficacy of vaccines in patients affected by such diseases and on immune-active treatments have been analyzed. The aim is to better understand the relationship between SARS-CoV-2 infection/vaccines with dysimmune CNS diseases by describing 12 cases of multiple sclerosis/myelitis onset or reactivation after exposure to SARS-CoV-2 infection/vaccines and reviewing all published case reports or case series in which MS onset or reactivation was temporally associated with either COVID-19 (8 case reports, 3 case series) or anti-SARS-CoV-2 vaccines (13 case reports, 6 case series). All the cases share a temporal association between viral/vaccine exposure and symptoms onset. This finding, together with direct or immune-based mechanisms described both during COVID-19 and MS, claims in favor of a role for SARS-CoV-2 infection/vaccines in unmasking dysimmune CNS disorders. The most common clinical presentations involve the optic nerve, brainstem and spinal cord. The preferential tropism of the virus together with the presence of some host-related genetic/immune factors might predispose to the involvement of specific CNS districts.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Esclerose Múltipla , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , Vacinas Virais
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