Patients with Chronic Obstructive Pulmonary Disease (COPD) periodically experience acute exacerbation (AECOPD). Carbocysteine represents a valid add on therapy in COPD by exerting antioxidant and ...anti-inflammatory activities. The in vivo effects of carbocysteine on inflammatory markers are not yet fully understood. The aims of this study were to assess: (i) miR-21, IL-8, soluble Receptor for Advanced Glycation End Products (sRAGE), and fluorescent Advanced Glycation End Products (fAGEs) in control subjects (
= 9), stable (
= 9), and AECOPD patients (
= 24); and (ii) whether carbocysteine modifies these markers and the functional parameters in mild AECOPD patients. Mild AECOPD patients received or not carbocysteine along with background inhalation therapy for 20 days. At the onset and at the end of the observation period, the following parameters were evaluated: FEV1, FEF25-75%, CAT questionnaire; miR-21 by Real Time PCR; IL-8 and sRAGE by ELISA; and fAGEs by spectro-fluorescence method. COPD patients showed higher levels of miR-21, IL-8, fAGEs and lower levels of sRAGE compared to that of controls. miR-21 inversely correlated with FEV1. IL-8 and fAGEs were significantly different in stable and exacerbated COPD patients. Carbocysteine improved symptoms, FEV1 and FEF25-75%, increased sRAGE, and reduced miR-21, IL-8, and fAGEs in mild AECOPD patients. The present study provides compelling evidence that carbocysteine may help to manage mild AECOPD by downregulating some parameters of systemic inflammation.
The main aim of the study is to evaluate the efficacy and safety profile of ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab (NTZ) exit strategies in ...relapsing–remitting multiple sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML). This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA from January 1st, 2019, to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity-score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs). Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. Patients from the 3 groups did not show differences for baseline characteristics, also after post hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpB
OCR
0.485, CI 95% 0.264–0.893,
p
= 0.020). This result was confirmed also for 12-month MRI activity (ExpB
OCR
0.248 CI 95% 0.065–0.948,
p
= 0.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile.
Machine Learning application on clinical data in order to support diagnosis and prognostic evaluation arouses growing interest in scientific community. However, choice of right algorithm to use was ...fundamental to perform reliable and robust classification. Our study aimed to explore if different kinds of Machine Learning technique could be effective to support early diagnosis of Multiple Sclerosis and which of them presented best performance in distinguishing Multiple Sclerosis patients from control subjects. We selected following algorithms: Random Forest, Support Vector Machine, Naïve-Bayes, K-nearest-neighbor and Artificial Neural Network. We applied the Independent Component Analysis to resting-state functional-MRI sequence to identify brain networks. We found 15 networks, from which we extracted the mean signals used into classification. We performed feature selection tasks in all algorithms to obtain the most important variables. We showed that best discriminant network between controls and early Multiple Sclerosis, was the sensori-motor I, according to early manifestation of motor/sensorial deficits in Multiple Sclerosis. Moreover, in classification performance, Random Forest and Support Vector Machine showed same 5-fold cross-validation accuracies (85.7%) using only this network, resulting to be best approaches. We believe that these findings could represent encouraging step toward the translation to clinical diagnosis and prognosis.
Background
Although the preventive efficacy of allergen immunotherapy (AIT) in the onset of new allergen sensitizations has been asserted by many reviews, position papers, and consensus conferences, ...the evidence available is from only 3 studies. The objective of this work was a systematic review to evaluate the preventive efficacy of AIT in the onset of new allergen sensitizations. The end‐point was the risk difference (RD) in the onset of new allergen sensitizations between patients treated with AIT and pharmacotherapy.
Methods
Computerized bibliographic searches of MEDLINE, EMBASE, and the Cochrane Library (until November 30th, 2016) were done. Random‐effects and fixed‐effects model meta‐analyses were performed. Randomized controlled trials or observational studies comparing children treated with AIT with house dust mite (HDM) to subjects who did not receive AIT, with a long‐term observation period (at least 3 years including treatment and follow‐up) have been included.
Results
Eight studies totaling 721 children (390 treated with AIT and 331 with pharmacotherapy) met the inclusion criteria. The risk of bias was high. Low evidence supports the conclusion that AIT prevents the onset of new allergen sensitizations, with 3 of 8 studies reporting a reduction in the onset of new sensitizations in patients treated with AIT vs pharmacotherapy. Our meta‐analysis found no difference between AIT and pharmacotherapy, with high heterogeneity (RD, −0.10; 95% confidence interval CI, −0.31 to 0.11; p = 0.32; I2 = 91.4%).
Conclusion
The data of this systematic review do not support a preventive effect in the onset of new allergen sensitizations, in children treated with AIT in comparison with those treated with pharmacotherapy.
Background Subcutaneous (SCIT) and sublingual (SLIT) immunotherapy are the 2 most prescribed routes for administering allergen-specific immunotherapy. They were shown to be effective in control of ...symptoms and in reducing rescue medication use in patients with allergic diseases, but their effectiveness has to be balanced against side effects. In recent years, SLIT has been increasingly prescribed, instead of SCIT, because of improved safety and easy administration. Objective We assessed which route is the most effective in the treatment of patients with seasonal allergic rhinitis to grass pollen. Methods An indirect meta-analysis–based comparison between SCIT and SLIT was performed. Treatment efficacy was determined as the standardized mean difference (SMD) in symptom and medication scores obtained with active treatment, SCIT or SLIT, compared with placebo. Studies were included if they were double-blind randomized controlled trials comparing SCIT or SLIT with placebo. Thirty-six randomized controlled trials (3014 patients; 2768 controls) were analyzed. Results The overall effect size of SCIT for symptom score (SMD, −0.92; 95%CI, −1.26 to −0.58) was significantly higher than SLIT, both administered via drops (SMD, −0.25; 95% CI, −0.45 to −0.05) and tablets (SMD, −0.40; 95%CI, −0.54 to −0.27). Similar results were reported for medication score (SCIT: SMD, −0.58; 95% CI, −0.86 to −0.30. SLIT drops: SMD, −0.37; 95% CI, −0.74 to −0.00. SLIT tablets SMD, −0.30; 95% CI, −0.44 to −0.16). Conclusions Our results provide indirect but solid evidence that SCIT is more effective than SLIT in controlling symptoms and in reducing the use of antiallergic medications in seasonal allergic rhinoconjuntivitis to grass pollen.
Food allergy is a common and increasing problem worldwide. The newly-found knowledge might provide novel experimental strategies, especially for laboratory diagnosis. Approximately 20% of the ...population alters their diet for a perceived adverse reaction to food, but the application of double-blind placebo-controlled oral food challenge, the ＂gold standard＂ for diagnosis of food allergy, shows that questionnaire-based studies overestimate the prevalence of food allergies. The clinical disorders determined by adverse reactions to food can be dassified on the basis of immunologic or nonimmunologic mechanisms and the organ system or systems affected. Diagnosis of food allergy is based on clinical history, skin prick tests, and laboratory tests to detect serum-food specific IgE, elimination diets and challenges. The primary therapy for food allergy is to avoid the responsible food. Antihistamines might partially relieve oral allergy syndrome and IgE-mediated skin symptoms, but they do not block systemic reactions. Systemic corticosteroids are generally effective in treating chronic IgE-mediated disorders. Epinephrine is the mainstay of treatment for anaphylaxis. Experimental therapies for IgE-mediated food allergy have been evaluated, such as humanized IgG anti-IgE antibodies and allergen specific immunotherapy.
Significant corpus callosum (CC) involvement has been found in relapsing-remitting multiple sclerosis (RRMS), even if conventional magnetic resonance imaging measures have shown poor correlation with ...clinical disability measures. In this work, we tested the potential of multimodal imaging of the entire CC to explain physical and cognitive disability in 47 patients with RRMS. Values of thickness, fractional anisotropy (FA) and mean diffusivity (MD) were extracted from 50 regions of interest (ROIs) sampled along the bundle. The relationships between clinical, neuropsychological and imaging variables were assessed by using Spearman's correlation. Multiple linear regression analysis was employed in order to identify the relative importance of imaging metrics in modeling different clinical variables. Regional fiber composition of the CC differentially explained the response variables (Expanded Disability Status Scale EDSS, cognitive impairment). Increases in EDSS were explained by reductions in CC thickness and MD. Cognitive impairment was mainly explained by FA reductions in the genu and splenium. Regional CC imaging properties differentially explained disability within RRMS patients revealing strong, distinct patterns of correlation with clinical and cognitive status of patients affected by this specific clinical phenotype.
Background The benefit of sublingual immunotherapy (SLIT) with grass allergens for seasonal allergic rhinitis has been extensively studied, but data on efficacy are still equivocal. Objective To ...assess the effectiveness of SLIT with grass allergens in the reduction of symptoms and medication in patients with seasonal allergic rhinitis to grass pollen. Methods Computerized bibliographic searches of MEDLINE (1995-2010) were supplemented by hand searches of reference lists. Studies were included if they were double-blind randomized controlled trials (RCTs) comparing SLIT to placebo and if they included patients with history of allergy to grass pollen treated with natural grass pollen extracts. Nineteen RCTs with 2971 patients were analyzed. The outcomes assessed were symptom and medication scores. Results Using a random-effects model, SLIT with grass allergens significantly reduces both symptoms (standardized mean difference, –0.32; 95% CI, –0.44 to –0.21) and medication use (standardized mean difference, –0.33; 95% CI, –0.50 to –0.16) compared with placebo. The treatment is more efficacious in adults than in children. Prolonging duration of preseasonal treatment for more than 12 weeks improves the treatment efficacy. Conclusion This meta-analysis found that SLIT with grass allergens is effective in patients with seasonal allergic rhinitis compared with placebo. The benefit is clinically modest, and criteria are needed to identify patients most likely to benefit from SLIT.
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