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INTRODUCTION: MRI activity is less frequent among secondary progressive multiple sclerosis (SPMS) patients. In the current study, we aimed to identify SPMS patients with higher radiological disease activity (RDA) and determine their clinical characteristics. METHODS: We evaluated the occurrence of RDA in SPMS patients followed at the Sheba Multiple Sclerosis Center between January 1, 2015, and December 31, 2020. All patients underwent brain and spinal cord MRI examinations as a routine follow-up unrelated to clinical disease activity. Patients were subdivided into RDA and non-RDA MRI groups based on the presence of active gadolinium-enhancing T1 lesions and/or new/enlarging T2 lesions. Demographic variables and disease-related data were compared. RESULTS: One hundred consecutive SPMS patients, 74 females, median age of 50 years, disease duration of 19.5 years, and neurological disability by the Expanded Disability Status Scale (EDSS) score of 6.0, were included in the study. The RDA group comprised 35 patients (35%), of them 65.7% (n = 23) exhibited only brain MRI activity, 22.8% (n = 8) only spinal cord MRI activity, and 11.4% (n = 4) had both. Patients in the RDA group were diagnosed at a younger mean (SD) age of 28.2 (8.9) versus 33.7 (10.1) years and were younger with a mean (SD) age of 47.8 (9.9) versus 53.4 (10.1) years, as compared with the non-RDA group. No significant differences were found in relation to disease duration, EDSS, exposure to immunomodulatory treatments, and duration of immunomodulatory treatments. CONCLUSIONS: RDA unrelated to clinical symptomatology was more frequent in a subgroup of young SPMS patients.
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Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Femenino , Humanos , Persona de Mediana Edad , Adulto , Esclerosis Múltiple/patología , Imagen por Resonancia Magnética , Médula Espinal , Encéfalo/patología , Progresión de la EnfermedadRESUMEN
BACKGROUND: Prevention of cognitive decline in Multiple Sclerosis (MS) is of major importance. We explored the effect of a 6 months computerized game training program on cognitive performance in MS patients with mild cognitive impairment. METHODS: This was a single-center, randomized prospective study. We enrolled in this study 100 eligible MS patients treated with Interferon-beta-1a (Rebif). All had mild cognitive impairment in either executive function or information processing speed. Patients were randomized 1:1 to either use the cognitive games platform by HappyNeuron (HN) or receive no intervention. Executive function and information processing speed scores were measured at 3 and 6 months from baseline to evaluate the effect of game training on cognitive scores. RESULTS: In both executive function and information processing speed, the game Training group showed significant improvement after 3 and 6 months. The Non-Training group showed mild deterioration in both domains at 3 months, and further deterioration that became significant at 6 months in executive function. Furthermore, at 6 months, the percent of patients in the Training group that improved or remained stable in both cognitive domains was significantly higher compared to the Non-Training group. CONCLUSIONS: Our findings suggest that cognitive game training has a beneficial effect on cognitive performance in MS patients suffering from mild cognitive impairment. While further evaluation is required to assess the longevity of that effect, we nonetheless recommend to MS patients to be engaged in cognitive gaming practice as part of a holistic approach to treating their condition.
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Disfunción Cognitiva , Esclerosis Múltiple , Cognición/fisiología , Disfunción Cognitiva/etiología , Humanos , Interferón beta , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/psicología , Pruebas Neuropsicológicas , Estudios ProspectivosRESUMEN
Coronavirus disease 2019 (COVID19) is a life-threatening infection with uncertain progression and outcome. Assessing the severity of the disease for worsening patients is of importance in making decisions related to supportive mechanical ventilation and aggressive treatments. This was a prospective, non-randomized study that included hospitalized patients diagnosed with COVID19. Pro-inflammatory cytokines were assessed during hospitalization, and we calculated a prediction paradigm for 30-day mortality based on the serum levels of interleukin1ß (IL1ß), interleukin6 (IL6), interleukin8 (IL8), and tumor necrosis factor alpha (TNFα) measured by next-generation ELISA. Data of 71 COVID19 patients, mean age 62 years, SD13.8, 50 males, 21 females, were analyzed. Twelve (16.9%) patients died within 7-39 days of their first COVID19 positive nasopharyngeal test. Levels of IL6 and TNFα were significantly higher in patients that did not survive. IL6 predicted mortality at the cut-off value of 163.4 pg/ml, with a sensitivity of 91.7% and specificity of 57.6%. Our findings demonstrate that IL6 expression is significant for the prediction of 30-day mortality in hospitalized COVID19 patients and, therefore, may assist in treatment decisions.
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Infecciones por Coronavirus/mortalidad , Interleucina-1beta/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Neumonía Viral/mortalidad , Factor de Necrosis Tumoral alfa/sangre , Betacoronavirus/inmunología , COVID-19 , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/mortalidad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/inmunología , Pronóstico , Estudios Prospectivos , SARS-CoV-2RESUMEN
BACKGROUND: The rate of post-relapse residual disability in patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease-modifying drugs (DMD) has not been studied. OBJECTIVE: To assess relapse residual disability in DMD-treated RRMS patients. METHODS: We followed DMD-treated RRMS patients presenting with acute relapse who received high-dose steroids. Increases in Expanded Disability Status Scale (EDSS) of at least 2.0, 1.0-1.5 or 0.5 were defined as severe, moderate or mild relapses, respectively. The proportions of patients with post-relapse residual disability defined as the failure to regain pre-relapse neurological status at 1, 4 and 12 months were evaluated. RESULTS: Out of 1672 relapses in DMD-treated RRMS patients, 17% were severe. In patients who presented with a severe relapse, we observed post-relapse residual disability of at least 1.0 EDSS point in 60.1%, 55.9% and 48.2% of patients at 1, 2 and 12 months of follow-up, respectively. Post-relapse residual disability of at least 2.0 EDSS points was observed in 37.4%, 30.7% and 20.7% of patients after 1, 2 and 12 months, respectively. CONCLUSION: A high rate of incomplete recovery was seen 12 months following severe relapse among RRMS patients and may contribute to the accumulation of long-term disability.
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Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Recuperación de la Función , Adulto , Evaluación de la Discapacidad , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Masculino , RecurrenciaRESUMEN
We examined the performance of the Framingham Heart Study (FHS) and the European Systematic Coronary Risk Evaluation (SCORE) models for cardiovascular disease (CVD) mortality prediction in Israeli industrial workers, and developed and validated new risk prediction models for CVD mortality incidence in the same population. Our database was a longitudinal Israeli industrial cohort (CORDIS cohort) of 4809 adult males followed-up for 22years. Performance of the FHS and the SCORE prediction models was analyzed by insertion of the CORDIS cohort measurements to each model separately. The standard prognostic variables and results obtained from the new refined Cox regression analyses were used to construct two new 10- and 20-year CVD mortality risk scoring systems: a modified FHS model (FHS/Cox) and an omnibus model with Cox regression (Omnibus/Cox). The SCORE model of high-risk and low-risk charts yielded 10-year mortality mean risks of 1.12% and 0.64%, respectively, for male subjects aged>30years. The new FHS/Cox and Omnibus/Cox models generated a mean predictive 10-year risk of 1.12% and 1.50%, respectively. The mean 20-year risk predicted by the new FHS/Cox and the Omnibus/Cox models was 2.66% and 3.75%, respectively. Internal validation of both models demonstrated a high and stable area under the receiver operating characteristic curve>0.85. No significant differences were found between the two models. In conclusion, the CVD mortality risk prediction scoring systems tailored for the Israeli workers population demonstrated good performance. Additional studies to externally validate these algorithms will indicate which of these quantitative risk estimation platforms should be used in specific settings.
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Algoritmos , Enfermedades Cardiovasculares/epidemiología , Medición de Riesgo/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Humanos , Incidencia , Israel , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Salud Laboral , Factores de Tiempo , Población BlancaRESUMEN
OBJECTIVES: Leisure-time physical activity (LTPA) is a well-established protective factor for all-cause mortality and cardiovascular mortality while occupational physical activity (OPA) has shown contradictory results. We examined the association between OPA and all-cause and coronary heart disease (CHD) mortality, and tested its combined effect with LTPA. METHODS: The CORDIS Study (Cardiovascular Occupational Risk Factor Determination in Israel Study) is a prospective cohort study of industrial workers examined during 1985-1989 and followed-up for 22â years. Data on self-reported OPA and LTPA among 4819 males (20-70â years old) were merged with data on all-cause and CHD mortality obtained from the National Death Registry. RESULTS: A higher incidence rate of all-cause mortality and CHD mortality was observed among men who performed moderate-hard OPA compared with those who performed none-mild OPA. Multiple regression analysis based on the Cox proportional hazards model showed that moderate-hard OPA was associated with increased risk of all-cause mortality (HR=1.42, 95% CI 1.16 to 1.74, p<0.001), while LTPA (30â min at least twice a week vs less or none) was associated with reduced risk for all-cause mortality (HR=0.61, 95% CI 0.48 to 0.79, p<0.001), after adjusting for potential confounders, including sociodemographic variables, body mass index, comorbidity and lifestyle habits. Employees who performed moderate-hard OPA and no LTPA had the greatest risk for all-cause mortality and employees who performed none-light OPA and LTPA had the lowest risk. Similar but non-significant trends were observed for the association with CHD mortality. CONCLUSIONS: Moderate-hard OPA among industrial male workers may be deleterious to health and should not be a substitute to LTPA.
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Enfermedad Coronaria/mortalidad , Ejercicio Físico , Actividades Recreativas , Estilo de Vida , Ocupaciones , Trabajo , Adulto , Causas de Muerte , Encuestas Epidemiológicas , Humanos , Israel/epidemiología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Statistic significance, also known as p-value, and CI (Confidence Interval) are common statistics measures and are essential for the statistical analysis of studies in medicine and life sciences. These measures provide complementary information about the statistical probability and conclusions regarding the clinical significance of study findings. This article is intended to describe the methodologies, compare between the methods, assert their suitability for the different needs of study results analysis and to explain situations in which each method should be used.
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Intervalos de Confianza , Interpretación Estadística de Datos , Proyectos de Investigación , Humanos , ProbabilidadRESUMEN
Confidence interval calculation is a common statistics measure, which is frequently used in the statistical analysis of studies in medicine and life sciences. A confidence interval specifies a range of values within which the unknown population parameter may lie. In most situations, especially those involving normally-distributed data or large samples of data from other distributions, the normal approximation may be used to calculate the confidence interval. But, if the number of observed cases is small or zero, we recommend that the confidence interval be calculated in more appropriate ways. In such cases, for example, in clinical trials where the number of observed adverse events is small, the criterion for approximate normality is calculated. Confidence intervals are calculated with the use of the approximated normal distribution if this criterion is met, and with the use of the exact binomial distribution if not. This article, accompanied by examples, describes the criteria in which the common and known method cannot be used as well as the stages and methods required to calculate confidence intervals in studies with a small number of observations.
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Intervalos de Confianza , Tamaño de la Muestra , Investigación Biomédica/métodos , Investigación Biomédica/normas , Biometría/métodos , Interpretación Estadística de Datos , HumanosRESUMEN
Anabolic treatment is indicated for high and very-high risk patients with osteoporosis, but acceptance is limited because current anabolic medications require subcutaneous injections. The purpose of this study was to assess the effects of a novel orally administered PTH tablet on serum markers of bone formation (PINP and osteocalcin), bone resorption (crosslinked C-telopeptide [CTX]), BMD, and safety in postmenopausal women with low BMD or osteoporosis. In this 6-mo, double-blind, placebo-controlled study, 161 patients were randomized to oral PTH tablets containing 0.5, 1.0, 1.5, or 2.5 mg or placebo daily. Biochemical markers were assessed at 1, 2, 3, and 6 mo and BMD of LS, TH, and FN was measured at 6 mo. Biochemical marker changes were dose dependent with minimal or no effect at the 2 lowest doses. At the highest dose (2.5 mg once daily), serum PINP and OC levels increased 30% within 1 mo after oral PTH initiation (P < .0001), remained elevated through 3 mo, and were back to baseline at 6 mo. In contrast, serum CTX levels declined 16% and 21% below baseline at 3 and 6 mo, respectively (both P ≤ .02). At 6 mo, 2.5 mg tablets increased mean BMD vs placebo of the LS by 2.7%, TH by 1.8%, and FN by 2.8% (all P ≤ .01). There were no drug-related serious adverse events. The most common adverse events were headache, nausea, and dizziness. In contrast to subcutaneous PTH, the oral PTH tablet appears to increase BMD rapidly by the dual mechanism of stimulating formation and inhibiting bone resorption. This might be the first effective oral anabolic alternative to subcutaneous administration for the treatment of low BMD or osteoporosis.
Despite the superior benefits of bone-building (anabolic) agents and guidelines supporting their use, these medications are used in a minority of patients for whom they are appropriate, in part because they require daily or monthly injections, which limit patient acceptance. An oral anabolic tablet has potential to address this substantial treatment gap. In this double-blind, placebo controlled, dose-finding randomized study, 161 postmenopausal women with low BMD or osteoporosis were treated with varying doses of the active part of PTH(1-34) or placebo given in daily oral tablets for 6 mo. The highest oral PTH tablet dose (2.5 mg) produced an increase in markers of bone formation while simultaneously decreasing the markers of bone breakdown. Significant gains in BMD of the spine and hip were observed at the end of the 6-mo study and there were no significant safety concerns. The 2.5 mg oral PTH tablet dose was well tolerated when patients were instructed to titrate up to the full dose. We conclude that this PTH tablet might be the first effective orally administered bone building medication and should be studied further in treatment of women with osteoporosis.
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Densidad Ósea , Humanos , Femenino , Administración Oral , Persona de Mediana Edad , Anciano , Densidad Ósea/efectos de los fármacos , Biomarcadores/sangre , Comprimidos , Posmenopausia/efectos de los fármacos , Posmenopausia/sangre , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/sangre , Método Doble Ciego , Hormona Paratiroidea/sangre , Placebos , Teriparatido/administración & dosificación , Teriparatido/farmacología , Fragmentos de Péptidos/sangreRESUMEN
Although the causes of multiple sclerosis are largely unknown, genetic and environmental components play an important role. Geographic distribution, varying with latitude, reflects both genetic and environmental influences. We conducted a retrospective exploratory observational study to characterize the disability progression of 2396 Jewish patients with relapsing-remitting multiple sclerosis, followed at the Sheba Multiple Sclerosis Center, Tel-Aviv, Israel; 188 patients who originated in Iraq and 2207 patients who originated in northern Europe. Peripheral blood microarray gene expression analysis was performed in a subgroup of patients to identify molecular pathways associated with faster disability progression. During a follow-up period of 18.8 and 19.8 years, respectively, 51.6% of patients with an Iraqi origin progressed to moderate disability defined as expanded disability status scale (EDSS) score of 3.0 to 5.5, compared to 44.2% of patients with a northern European origin (odds ratio 1.347, 95% CI 1.0-1.815, p = 0.049). An Iraqi origin was associated with increased risk of progression to moderate disability adjusted for sex, disease duration, age at onset, and treatment with immunomodulatory drugs (hazard ratio 1.323; 95% CI, 1.049-1.668, p = 0.02), but not to severe disability defined as EDSS score > = 6.0 (i.e., walking aids are required for a distance of 100 meters, (hazard ratio 1.311; 95% CI, 0.918-1.874, p = 0.136). Gene expression analysis disclosed 98 differentially expressed genes (79 over-expressed and 19 under-expressed) between relapsing-remitting multiple sclerosis patients of Iraqi origin (N = 17) and northern European (N = 34) origin. Interestingly, this gene expression was enriched with genes related to neuronal pathways associated with morphology of axons, branching of neurites, proliferation of neocortical neurons, and formation of myelin sheath, suggesting an augmented process of neurodegeneration in relapsing-remitting multiple sclerosis patients with an Iraqi origin. The study results suggest that relapsing-remitting multiple sclerosis patients with an Iraqi origin progress faster to disability possibly due to an enhanced process of neurodegeneration.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Estudios Retrospectivos , Etnicidad , Neuronas , Progresión de la Enfermedad , Evaluación de la DiscapacidadRESUMEN
Chronological age prediction from DNA methylation sheds light on human aging, health, and lifespan. Current clocks are mostly based on linear models and rely upon hundreds of sites across the genome. Here, we present GP-age, an epigenetic non-linear cohort-based clock for blood, based upon 11,910 methylomes. Using 30 CpG sites alone, GP-age outperforms state-of-the-art models, with a median accuracy of â¼2 years on held-out blood samples, for both array and sequencing-based data. We show that aging-related changes occur at multiple neighboring CpGs, with implications for using fragment-level analysis of sequencing data in aging research. By training three independent clocks, we show enrichment of donors with consistent deviation between predicted and actual age, suggesting individual rates of biological aging. Overall, we provide a compact yet accurate alternative to array-based clocks for blood, with applications in longitudinal aging research, forensic profiling, and monitoring epigenetic processes in transplantation medicine and cancer.
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Envejecimiento , Metilación de ADN , Humanos , Preescolar , Metilación de ADN/genética , Envejecimiento/genética , Algoritmos , Secuencia de Bases , Epigénesis GenéticaRESUMEN
Continually increasing global temperature could severely affect grape berry metabolite accumulation and ultimately wine polyphenol concentration and color intensity. To explore the effect of late shoot pruning on grape berry and wine metabolite composition, field trials were carried out on Vitis vinifera cv. Malbec and cv. Syrah grafted on 110 Richter rootstock. Fifty-one metabolites were detected and unequivocally annotated employing UPLC-MS based metabolite profiling. Integrating the data using hierarchical clustering showed a significant effect of late pruning treatments on must and wine metabolites. Syrah metabolite profiles were characterized by a general trend of higher metabolite content in the late shoot pruning treatments, while Malbec profiles did not show a consistent trend. In summary, late shoot pruning exerts a significant effect, though varietal specific, on must and wine quality-related metabolites, possibly related to enhanced photosynthetic efficiency, which should be taken into consideration when planning mitigating strategies in warm climates.
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Background: Relapsing-remitting multiple sclerosis (RRMS) affects predominantly young women within reproductive years. As an increased risk of relapses is known to occur during the post-partum period, it is important to consider treatment options. Aim: Evaluate the effects of intravenous immunoglobulins (IVIg) to prevent post-partum relapses. Methods: We prospectively followed 198 pregnant female RRMS patients, 67 treated with IVIg during pregnancy and the three months post-partum, and 131 untreated patients that served as controls. Results: During the pre-gestation year, 41.4% were treated with immunomodulatory drugs, and 28.3% experienced a relapse. During pregnancy and the post-partum period, the number of relapsing patients significantly decreased in the IVIg group (37.3%, 10.4%, 8.9%, respectively, p = 0.0003), while no significant change was observed in the untreated group (23.7%, 17.6%, and 22.1%). During the three-month post-partum period, there were only mild and moderate relapses in the IVIg group, while in the untreated group, there were also severe relapses. Stepwise logistic regression that assessed the relation between three-month post-partum relapse and explanatory variables demonstrated that untreated patients had increased risk for post-partum relapse (odds ratio = 4.6, 95% CI [1.69, 12.78], p = 0.033). Conclusions: IVIg treatment proved efficient to reduce the rate and severity of relapses during pregnancy and the three-month post-partum.
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Introduction: Bioavailability of calcium is an important consideration when designing supplements for achieving adequate calcium intake, mainly in high-risk, and aged populations. Alternative supplementation strategies may be able to circumvent absorption issues commonly seen with calcium supplements. The objective of this study was to assess the bioavailability of a single serving of two calcium formulations vs. comparator product in healthy postmenopausal women. Methods: A total of 24 participants between 45 and 65 years were enrolled in a randomized, double-blind, three-phase, crossover study, with a 7-day washout period between phases. The bioavailability of calcium from calcium-carrying Saccharomyces cerevisiae (Ca-SC) or calcium-carrying Lactobacillus (Ca-LAB) in the form of postbiotic products versus calcium citrate, a conventional salt-based calcium supplement, was determined. Each product provided 630 mg of calcium and 400 IU of vitamin D3. After a 14-h (overnight) fast followed by a single dose of product with a standard low-calcium breakfast, both serum and urine calcium concentrations were assessed for up to 8 and 24 h, respectively. Results: Ca-LAB resulted in greater calcium bioavailability, demonstrated by significantly higher area under the curve and peak concentration both in blood and urine, and total calcium mass excreted in urine. The bioavailability of calcium was similar for Ca-SC and calcium citrate except for the peak concentration value that was significantly higher for calcium citrate. Both Ca-LAB and Ca-SC were well tolerated with no significant difference in adverse events between the products during the study. Discussion: These findings suggest that calcium enriched in a Lactobacillus-based postbiotic system is associated with higher levels of bioavailability as compared to calcium citrate, while a calcium-enriched yeast-based postbiotic does not influence calcium absorption.
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BACKGROUND: The impact of disease-modifying therapies on the efficacy to mount appropriate immune responses to COVID-19 vaccination in patients with multiple sclerosis (MS) is currently under investigation. OBJECTIVE: To characterize long-term humoral and cellular immunity in mRNA-COVID-19 MS vaccinees treated with teriflunomide or alemtuzumab. METHODS: We prospectively measured SARS-COV-2 IgG, memory B-cells specific for SARS-CoV-2 RBD, and memory T-cells secreting IFN-γ and/or IL-2, in MS patients vaccinated with BNT162b2-COVID-19 vaccine before, 1, 3 and 6 months after the second vaccine dose, and 3-6 months following vaccine booster. RESULTS: Patients were either untreated (N = 31, 21 females), under treatment with teriflunomide (N = 30, 23 females, median treatment duration 3.7 years, range 1.5-7.0 years), or under treatment with alemtuzumab (N = 12, 9 females, median time from last dosing 15.9 months, range 1.8-28.7 months). None of the patients had clinical SARS-CoV-2 or immune evidence for prior infection. Spike IgG titers were similar between untreated, teriflunomide and alemtuzumab treated MS patients both at 1 month (median 1320.7, 25-75 IQR 850.9-3152.8 vs. median 901.7, 25-75 IQR 618.5-1495.8, vs. median 1291.9, 25-75 IQR 590.8-2950.9, BAU/ml, respectively), at 3 months (median 1388.8, 25-75 1064.6-2347.6 vs. median 1164.3 25-75 IQR 726.4-1399.6, vs. median 837.2, 25-75 IQR 739.4-1868.5 BAU/ml, respectively), and at 6 months (median 437.0, 25-75 206.1-1161.3 vs. median 494.3, 25-75 IQR 214.6-716.5, vs. median 176.3, 25-75 IQR 72.3-328.8 BAU/ml, respectively) after the second vaccine dose. Specific SARS-CoV-2 memory B cells were detected in 41.9%, 40.0% and 41.7% of subjects at 1 month, in 32.3%, 43.3% and 25% at 3 months, and in 32.3%, 40.0%, 33.3% at 6 months following vaccination in untreated, teriflunomide treated and alemtuzumab treated MS patients, respectively. Specific SARS-CoV-2 memory T cells were found in 48.4%, 46.7% and 41.7 at 1 month, in 41.9%, 56.7% and 41.7% at 3 months, and in 38.7%, 50.0%, and 41.7% at 6 months, of untreated, teriflunomide-treated and alemtuzumab -treated MS patients, respectively. Administration of a third vaccine booster significantly increased both humoral and cellular responses in all patients. CONCLUSIONS: MS patients treated with teriflunomide or alemtuzumab achieved effective humoral and cellular immune responses up to 6 months following second COVID-19 vaccination. Immune responses were reinforced following the third vaccine booster.
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COVID-19 , Esclerosis Múltiple , Femenino , Humanos , ARN , Alemtuzumab/uso terapéutico , Vacunas contra la COVID-19 , Vacuna BNT162 , Esclerosis Múltiple/tratamiento farmacológico , COVID-19/prevención & control , SARS-CoV-2 , Vacunación , Inmunidad Celular , Anticuerpos AntiviralesRESUMEN
INTRODUCTION: Cladribine is an effective immunomodulatory treatment used for relapsing forms of multiple sclerosis (MS). OBJECTIVES: To describe the clinical outcomes and rates of no evidence of disease activity (NEDA) in patients with highly-active disease treated with 2 years cumulative dose of cladribine, for years 3 and 4. METHODS: We used the Sheba Multiple Sclerosis computerized data registry to retrospectively evaluate year-3 and year-4 clinical outcomes and NEDA-2 rates in highly active RRMS patients who completed the 2-dose 2-year cladribine treatment protocol (3.5 mg/kg cumulative dose over 2 years). The first week of treatment in year 1 was considered as baseline. Data analyses were performed using Python (version 3.0) and SAS® (version 9.4 SAS Institute, Cary, NC). RESULTS: Among 128 patients with highly-active MS that received cladribine treatment, 61 patients, 43 females, were studied for year-3 clinical outcomes, and 35 patients, 23 females, also for year-4. At the initiation of cladribine treatment, the mean ± SD age was 39.6 ± 10.74 years (45.9% of the patients were between 18 and 40 years), disease duration 12.7 ± 9.08 years, Expanded Disability Status Scale (EDSS) 3.7 ± 1.86 (54% had EDSS score > 3.0), and the annual relapse rate was 1.6 ± 0.9. The annual relapse rate decreased to 0.36 in year-3 and was 0.17 in year-4; 68.9% (42/61) of the patients were relapse-free in year-3, and 82.9% (29/35) were relapse-free in year-4. Disability at year-3 was 3.1 ± 2.07; 83.6% (51/61) of the patients remained neurologically stable (33, 54.1%) or improved (18, 29.5%). In year-4, EDSS was 3.2 ± 1.91, and 85.7% (30/35) of the patients remained stable (20, 57.1%) or improved (10, 28.6%). NEDA-2 was achieved for 59.0% (36/61) of patients in year-3, and for 74.3% (26/35) in year-4 of cladribine treatment. CONCLUSIONS: In the real-world cladribine proved to be clinically effective in year-3 and year-4 of treatment in the majority of highly active RRMS patients.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Cladribina/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The majority of multiple sclerosis [MS] patients treated with fingolimod fail to develop a protective level of IgG humoral and adaptive cellular immune responses following full BNT162b2 SARS-CoV-2 vaccination. OBJECTIVE: To compare the efficacy of the third COVID-19 vaccine dose in vaccine non-responders fingolimod-treated MS patients. STUDY DESIGN: This is a prospective 3-month, single-center, randomized clinical trial. METHODS: Twenty relapsing MS patients who had been on fingolimod therapy ≥ 12 months and failed to develop humoral IgG immune response to 2-dose Pfizer BNT162b2 COVID-19 vaccination were randomized into two groups: fingolimod-continuation group and fingolimod-discontinuation group. Humoral and memory cellular immune responses were assessed within 1 and 3 months following the third Pfizer BNT162b2 vaccine dose and compared between the groups. RESULTS: A higher rate of patients in the fingolimod-discontinuation group [n = 8/10] compared to fingolimod-continuation group [n = 2/10] developed positive SARS-COV-2 IgG. Median IgG titer 1 month following the third dose was 202.3 BAU/ml vs. 26.4 BAU/ml, respectively, p = 0.022. The development of IgG humoral response correlated with absolute lymphocyte count. Specific SARS-COV-2 memory B cell and T cell immune responses were not detected in both groups, either at 1 month or 3 months following the third COVID-19 vaccine dose. CONCLUSIONS: Short period of fingolimod treatment discontinuation was associated with the development of humoral protection but not with adaptive cellular immunity.
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COVID-19 , Esclerosis Múltiple , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Clorhidrato de Fingolimod/uso terapéutico , Humanos , Inmunidad , Inmunoglobulina G , Recuento de Linfocitos , Esclerosis Múltiple/tratamiento farmacológico , Estudios Prospectivos , SARS-CoV-2RESUMEN
Multiple sclerosis (MS) is a chronic disease marked by progressive disability and decreased mobility over time. We studied whether individuals with MS of higher disability levels will be more overweight/obese as a result of their immobility and/or recurrent steroid treatments. In a prospective study, 130 individuals with MS and significant disability were classified according to the Expanded Disability Status Scale (EDSS) score as belonging to four groups: EDSS 3.0-4.0 (n = 31, 24%), EDSS 4.5-5.5 (n = 24, 18%), EDSS = 6.0 (n = 44, 34%) and EDSS ≥ 6.5 (n = 31, 24%). Medical history, body mass index (BMI), waist circumference and the level of engagement in physical activity were obtained. The mean ± standard error age was 55.8 ± 0.5 years, disease duration 18.2 ± 1.0 years and EDSS score 5.5 ± 0.1. Disease duration, the number of steroid courses per disease duration, weight, BMI and physical activity did not differ according to the four disability groups. The mean waist circumference increased significantly with increased severity of EDSS, p = 0.03. Increased disability in individuals with MS was not correlated with disease duration, lifestyle habits or overweight/obesity. However, increased disability was associated with central obesity.
RESUMEN
Multiple sclerosis (MS) itself and first-line disease modifying therapies do not increase the risk of contracting COVID-19. However, home isolation is likely to result in a significant decrease in participation in leisure time physical activities and an increase in sedentary behavior. Therefore, using an online cross-sectional survey we examined the impact of the COVID-19 epidemic on physical activity (PA) behavior and fitness level in an Israeli cohort of people with multiple sclerosis (PwMS). The survey PA questionnaire included 10 questions. Specifically, participants reported on whether, and to what extent, the pandemic conditions had altered their PA behavior. One hundred and twenty PwMS filled out the online survey, 78 were females with a mean age of 43.0 (S.D.=12.9) years. PA behavior during the pandemic demonstrated that 17.5% who were engaged in PA before the COVID-19 pandemic, ceased PA, 33.3% reduced their PA, 20.0% continued their PA as before, 18.3% increased their PA during the pandemic, and 10.8% did not perform any PA in the past and did not so during the pandemic. As for the patient's self-reported fitness level, 31.7% reported that their fitness level had decreased during the pandemic, 60.0% felt no change, and 8.3% reported an improvement. Our findings serve as a call of action for all professionals involved in MS management to address physical activity behavior in PwMS during the COVID-19 epidemic.
Asunto(s)
COVID-19 , Ejercicio Físico , Esclerosis Múltiple , Adulto , Femenino , Humanos , Israel , Masculino , Persona de Mediana Edad , Sistemas en Línea , Distanciamiento Físico , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Appropriate immune response following COVID-19 vaccination is important in the context of disease-modifying treatments (DMTs). In a prospective cross-sectional study, we determined SARS-COV-2 IgG response up to 6 months following PfizerBNT162b2 vaccination in 414 multiple sclerosis (MS) patients and 89 healthy subjects. Protective response was demonstrated in untreated MS patients (N = 76, 100%), treated with Cladribine (N = 48, 100%), Dimethyl fumarate (N = 35, 100%), Natalizumab (N = 32, 100%), and Teriflunomide (N = 39, 100%), similarly to healthy subjects (N = 89, 97.8%). Response was decreased in Fingolimod (N = 42, 9.5%), Ocrelizumab (N = 114, 22.8%) and Alemtuzumab (N = 22, 86.4%) treated patients. IgG response can help tailor adequate vaccine guidelines for MS patients under various DMTs.