Background and Aims:
The National Multiple Sclerosis Society and other expert organizations recommended that all patients with multiple sclerosis (MS) should be vaccinated against COVID-19. However, ...the effect of disease-modifying therapies (DMTs) on the efficacy to mount an appropriate immune response is unknown. We aimed to characterize humoral immunity in mRNA-COVID-19 MS vaccinees treated with high-efficacy DMTs.
Methods:
We measured SARS-CoV-2 IgG response using anti-spike protein-based serology (EUROIMMUN) in 125 MS patients vaccinated with BNT162b2-COVID-19 vaccine 1 month after the second dose. Patients were either untreated or under treatment with fingolimod, cladribine, or ocrelizumab. A group of healthy subjects similarly vaccinated served as control. The percent of subjects that developed protective antibodies, the titer, and the time from the last dosing were evaluated.
Results:
Protective humoral immunity of 97.9%, 100%, 100%, 22.7%, and 3.8%, was observed in COVID-19 vaccinated healthy subjects (N = 47), untreated MS patients (N = 32), and MS patients treated with cladribine (N = 23), ocrelizumab (N = 44), and fingolimod (N = 26), respectively. SARS-CoV-2 IgG antibody titer was high in healthy subjects, untreated MS patients, and MS patients under cladribine treatment, within 29.5–55 days after the second vaccine dose. Only 22.7% of patients treated with ocrelizumab developed humoral IgG response irrespective to normal absolute lymphocyte count. Most fingolimod-treated MS patients had very low lymphocyte count and failed to develop SARS-COV-2 antibodies. Age, disease duration, and time from the last dosing did not affect humoral response to COVID-19 vaccination.
Conclusions:
Cladribine treatment does not impair humoral response to COVID-19 vaccination. We recommend postponing ocrelizumab treatment in MS patients willing to be vaccinated as a protective humoral response can be expected only in some. We do not recommend vaccinating MS patients treated with fingolimod as a protective humoral response is not expected.
Objective
Familial Mediterranean fever (FMF) is refractory to colchicine prophylaxis in 10–20% of patients. In a number of patient series, treatment with anakinra, an interleukin‐1–blocking agent, ...prevented FMF attacks in those with colchicine‐resistant FMF. This study was undertaken to evaluate the efficacy and safety of anakinra in the treatment of colchicine‐resistant FMF, using a randomized controlled trial.
Methods
Patients with colchicine‐resistant FMF receiving colchicine (dosage ≥1.5 to ≤3 mg/day) were recruited and randomly assigned to receive anakinra or placebo (vehicle). The treatment duration was 4 months. Primary efficacy outcomes were the number of attacks per month, and the number of patients with a mean of <1 attack per month. Quality of life was assessed using a 0–10‐grade visual analog scale (VAS), and safety was assessed according to the number and severity of adverse events.
Results
Twenty‐five patients with colchicine‐resistant FMF (14 women) were enrolled, of whom 12 were randomized to receive anakinra and 13 to receive placebo. The mean ± SD number of attacks per patient per month was 1.7 ± 1.7 in those receiving anakinra and 3.5 ± 1.9 in those receiving placebo (P = 0.037). Six patients in the anakinra group, compared to none in the placebo group, had <1 attack per month (P = 0.005). A beneficial effect of anakinra was noted in the number of attacks in the joints per month in patients receiving anakinra (mean ± SD 0.8 ± 1.6 versus 2.1 ± 1.1 in the placebo group; P = 0.019) and in quality of life (mean ± SD VAS score 7.7 ± 2.3 in the anakinra group versus 4.2 ± 2.9 in the placebo group; P = 0.045). The number of adverse events per patient per month was comparable between the anakinra group and the placebo group (mean ± SD 2.03 ± 1.75 versus 3.34 ± 2.5; P = 0.22). There were no severe adverse events.
Conclusion
In this randomized controlled trial, anakinra appears to be an effective and safe treatment for colchicine‐resistant FMF.
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.
Non–high-density lipoprotein cholesterol (non-HDL-C) may be equivalent or superior to low-density lipoprotein cholesterol (LDL-C) for prediction of cardiovascular disease (CVD) risk. However, studies ...comparing the predictive values of LDL-C and non-HDL-C for CVD and total mortality in a long-term follow-up yielded conflicting results. The Cardiovascular Occupational Risk Factor Determination in Israel Study (CORDIS) is a prospective cohort study of a young industrial population of workers with a long-term follow-up. The initial phase of the study was carried out in 1985–1999. Interviews and physical examinations were conducted, and fasting blood samples, including lipid panels, were undertaken. In 2007, after a 22-year follow-up period, the baseline data were merged with data on all-cause and CVD mortality obtained from the Israeli National Death Registry. A total of 4,832 men were included in the analysis with a mean age of 42.1 ± 12.1 years. Univariate analysis indicated a positive association between non-HDL-C and LDL-C levels and an increased risk for both all-cause and CVD mortality. Multiple regression analysis, following adjustment for potential confounders, resulted in attenuation of the association of both lipoproteins with total mortality. The adjusted association between non-HDL-C levels ≥190 mg/dl and CVD mortality remained significant (hazard ratio 1.80, 95% confidence interval 1.10 to 2.96), but the association of LDL-C with CVD mortality was attenuated (hazard ratio 1.53, 95% confidence interval 0.98 to 2.39). In conclusion, non-HDL-C may be a more potent predictor of CVD mortality than LDL-C levels.
AIM:To evaluate the effect of resistance training(RT)on non alcoholic liver disease(NAFLD)patients.METHODS:A randomized clinical trial enrolling NAFLD patients without secondary liver ...disease(e.g.,without hepatitis B virus,hepatitis C virus or excessive alcohol consumption).Patients were randomly allocated either to RT,three times weekly,for 3 mo or a control arm consisting of home stretching.The RT included leg press,chest press,seated rowing,latissimus pull down etc.with 8-12 repetitions,3 sets for each exercise,for a total duration of 40 min.Hepatic ultrasound,fasting blood tests,anthropometrics and body composition by dual energy X-ray absorptiometry were assessed.At baseline and follow-up,patients filled out a detailed semi-quantitative food frequency questionnaire reporting their habitual nutritional intake.Steatosis was quantified by the hepatorenal-ultrasound index(HRI)representing the ratio between the brightness level of the liver and the right kidney.The HRI has been previously demonstrated to be highly reproducible and was validated against liver biopsy and proton magnetic resonance spectroscopy.RESULTS:Eighty two patients with primary NAFLD were randomized to receive 3 mo of either RT or stretching.After dropout or exclusion from analysis because of protocol violation(weight change>3 kg),thirty three patients in the RT arm and 31 in the stretching arm completed the study per protocol.All baseline characteristics were similar for the two treatment groups with respect to demographics,anthropometrics and body composition,blood tests and liver steatosis on imaging.HRI score was reduced significantly in the RT arm as compared to the stretching arm(-0.25±0.37 vs-0.05±0.28,P=0.017).The RT arm had a significantly higher reduction in total,trunk and android fat with increase in lean body mass.There was no correlation between the reduction in HRI in the RT arm and weight change during the study,but it was positively correlated with the change in trunk fat(r=0.37,P=0.048).The RT arm had a significant reduction in serum ferritin and total cholesterol.There was no significant difference between arms in dietary changes and these did not correlate with HRI change.CONCLUSION:Three months RT improves hepatic fat content accompanied by favorable changes in body composition and ferritin.RT may serve as a complement to treatment of NAFLD.
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
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.
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.
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.
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.
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.
‘Malbec’ grapevines commonly have high yield, thus intermittently negatively affecting wine quality parameters. Here, we describe the use of late shoot pruning (LSP) practice applied for wine quality ...improvement. We examined the effect of timing of LSP on ‘Malbec’ vines grown in Mediterranean conditions during three consecutive seasons (2016–2018) in Israel. The timing of LSP treatment applications (applied one, two and three weeks after bud break) were compared with cluster-thinned, winter-pruned vines (WP + T) and standard winter pruning (WP). The LSP practice postponed bud break of target buds but did not have a temporal effect on the onset of veraison. Midday stem water potential was less negative and stomatal conductance and net CO2 assimilation rate were higher in the LSP vines. This practice led to a substantial reduction in the number of clusters and crop yield. Finally, wine quality was positively affected by applying LSP treatment. Performing the inexpensive LSP treatment at the precise timing after bud burst was found to save labor, decrease crop yield and improve grape and wine parameters. LSP application should be considered in adequate varieties as a significant tool for the enhanced effectiveness of vine growing in warm regions.
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.
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.
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
(Ca-SC) or calcium-carrying
(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.
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.
These findings suggest that calcium enriched in a
-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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