Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study.

BACKGROUND: Dupilumab has proven to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, real-world experience with dupilumab in a broader population is limited. METHODS: The study population comprised adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at 10 Italian teaching hospitals. We analyzed physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index [DLQI]), and serological markers (IgE and eosinophil count) after 16 weeks. RESULTS: We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median (IQR) change from baseline to 16 weeks of treatment in the EASI score was -87.5 (22.0) (P<.001). The EASI-50, EASI-75, and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4-point or higher improvement in DLQI from baseline. During treatment with dupilumab, 12.2% of the patients developed conjunctivitis, and total IgE decreased significantly (P<.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early onset of AD (OR, 2.25; 95%CI, 1.07-4.70; P=.03) and presence of eosinophilia (OR, 1.91; 95%CI, 1.05-3.39; P=.03). CONCLUSION: This is the broadest real-life study in AD patients treated with dupilumab to date. We observed more significant improvements induced by dupilumab in adult patients with moderate-to-severe AD than those reported in clinical trials.

Moderate-to-severe atopic dermatitis in adolescents treated with dupilumab: A multicentre Italian real-world experience.

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side-effects. Dupilumab was recently approved for treatment of adolescent AD. OBJECTIVES: A multicentre, prospective, real-world study on the effectiveness and safety of dupilumab in adolescents (aged from ≥12 to <18 years) with moderate-to-severe AD was conducted. The main AD clinical phenotypes were also examined. METHODS: Data of adolescents with moderate-to-severe AD treated with dupilumab at label dosage for 16 weeks were collected. Treatment outcome was assessed by EASI, NRS itch, NRS sleep loss and CDLQI scores at baseline and after 16 weeks of treatment. The clinical scores were also evaluated according to clinical phenotypes. RESULTS: One hundred and thirty-nine adolescents were enrolled in the study. Flexural eczema and head and neck eczema were the most frequent clinical phenotypes, followed by hand eczema and portrait-like dermatitis. Coexistence of more than 1 phenotype was documented in 126/139 (88.5%) adolescents. Three patients (2.1%) contracted asymptomatic SARS-CoV-2 infection and 1 of the discontinued dupilumab treatment before the target treatment period. A significant improvement in EASI, NRS itch, NRS sleep loss and CDLQI was observed after 16 weeks of treatment with dupilumab. This outcome was better than that observed in clinical trials. Dupilumab resulted effective in all AD phenotypes, especially in diffuse eczema. Twenty-eight (20.1%) patients reported adverse events, conjunctivitis and flushing being the most frequent. None of patients discontinued dupilumab due to adverse event. CONCLUSIONS: Dupilumab in adolescent AD showed excellent effectiveness at week 16 with consistent improvement of all clinical scores. Moreover, dupilumab showed a good safety profile also in this COVID-19 pandemic era.

Subclinical motor impairment assessed with an engineered glove correlates with magnetic resonance imaging tissue damage in radiologically isolated syndrome.

BACKGROUND: An engineered glove measuring finger motor performance previously showed ability to discriminate early-stage multiple sclerosis (MS) patients from healthy controls (HCs). Radiologically isolated syndrome (RIS) classifies asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities suggestive of multiple sclerosis. METHODS: Seventeen asymptomatic subjects with RIS and 17 HCs were assessed. They performed finger-to-thumb opposition sequences at their maximal velocity, metronome-paced bimanual movements and conventional and diffusion tensor MRI. RESULTS: Subjects with RIS showed lower (P = 0.005) maximal velocity and higher (P = 0.006) bimanual coordination impairment than HCs. In RIS, bimanual coordination correlated with T2-lesion volume, fractional anisotropy and radial diffusivity in the white matter. CONCLUSIONS: These findings point out the relevance of fine hand measures as a robust marker of subclinical disability.

Impairment in explicit visuomotor sequence learning is related to loss of microstructural integrity of the corpus callosum in multiple sclerosis patients with minimal disability.

Sequence learning can be investigated by serial reaction-time (SRT) paradigms. Explicit learning occurs when subjects have to recognize a test sequence and has been shown to activate the frontoparietal network in both contralateral and ipsilateral hemispheres. Thus, the left and right superior longitudinal fasciculi (SLF), connecting the intra-hemispheric frontoparietal circuits, could have a role in explicit unimanual visuomotor learning. Also, as both hemispheres are involved, we could hypothesize that the corpus callosum (CC) has a role in this process. Pathological damage in both SLF and CC has been detected in patients with Multiple Sclerosis (PwMS), and microstructural alterations can be quantified by Diffusion Tensor Imaging (DTI). In light of these findings, we inquired whether PwMS with minimal disability showed impairments in explicit visuomotor sequence learning and whether this could be due to loss of white matter integrity in these intra- and inter-hemispheric white matter pathways. Thus, we combined DTI analysis with a modified version of SRT task based on finger opposition movements in a group of PwMS with minimal disability. We found that the performance in explicit sequence learning was significantly reduced in these patients with respect to healthy subjects; the amount of sequence-specific learning was found to be more strongly correlated with fractional anisotropy (FA) in the CC (r=0.93) than in the left (r=0.28) and right SLF (r=0.27) (p for interaction=0.005 and 0.04 respectively). This finding suggests that an inter-hemispheric information exchange between the homologous areas is required to successfully accomplish the task and indirectly supports the role of the right (ipsilateral) hemisphere in explicit visuomotor learning. On the other hand, we found no significant correlation of the FA in the CC and in the SLFs with nonspecific learning (assessed when stimuli are randomly presented), supporting the hypothesis that inter-hemispheric integrity is specifically relevant for explicit sequence learning.

Magnetic resonance imaging as surrogate for clinical endpoints in multiple sclerosis: data on novel oral drugs.

Recent studies have provided evidence for using magnetic resonance imaging (MRI) active lesions as surrogate for relapses and disability progression in multiple sclerosis (MS). However, the validity of MRI metrics as surrogate endpoints in MS is controversial. Furthermore, the extrapolation of previous results to novel therapies is not warranted. We tested here the validity of MRI surrogacy in MS studies on recently published trials of oral drugs. The 92% of observed effects of oral drugs on clinical outcomes resulted close to those predicted by MRI active lesions. This further validates MRI surrogacy in MS, with important implications for future trials planning.

The patients' perspective on the perceived difficulties of dual-tasking: development and validation of the Dual-task Impact on Daily-living Activities Questionnaire (DIDA-Q).

BACKGROUND: Everyday-life activities often require performing dual tasks (DT), with consequent possible occurrence of motor-cognitive or motor-motor interference. This could reduce quality of life, in particular in people with neurological diseases. However, there is lack of validated tools to assess the patients' perspective on DT difficulties in this population. Therefore, we developed the Dual-task Impact on Daily-living Activities-Questionnaire (DIDA-Q) and tested its psychometric properties in people with multiple sclerosis (PwMS). METHODS: Items were generated based on existing scales, DT paradigms used in previous studies and the opinion of a multi-stakeholder group, including both experts and PwMS. Twenty DT constituted the preliminary version of the DIDA-Q which was administered to 230 PwMS. The psychometric properties of the scale were evaluated including internal consistency, validity and reliability. RESULTS: Nineteen items survived after exploratory factor analysis, showing a three-factor solution which identifies the components mostly contributing to DT perceived difficulty (i.e., balance and mobility, cognition and upper-limb ability). The DIDA-Q appropriately fits the graded response model, with first evaluations supporting internal consistency (Cronbach's alpha=0.95), validity (70% of the hypotheses for convergent and discriminant constructs confirmed) and reliability (intraclass correlation coefficients=0.95) of this tool. CONCLUSION: The DIDA-Q could be used in research and clinical settings to discriminate individuals with low vs. high cognitive-motor or motor-motor interference, and to develop and evaluate the efficacy of personalized DT rehabilitative treatments in PwMS.

White matter reduced streamline coherence in young men with autism and mental retardation.

BACKGROUND AND PURPOSE: It has been proposed that white matter alterations might play a role in autistic disorders; however, published data are mainly limited to high-functioning autism. The goal of this study was to apply diffusion tensor imaging (DTI) and fiber tractography (FT) to study white matter in low-functioning autism and the relationship between white matter and cognitive impairment. METHODS: Ten low-functioning males with autism (mean age: 19.7 +/- 2.83 years) and 10 age-matched healthy males (mean age: 19.9 +/- 2.64 years) underwent DTI-MRI scanning. fractional anisotropy (FA) maps were analyzed with whole brain voxel-wise and tract-of-interest statistics. Using FT algorithms, white matter tracts connecting the orbitofrontal cortex (OFC) with other brain regions were identified and compared between the two groups. FA mean values of the autistic group were correlated with intelligence quotient (IQ) scores. RESULTS: Low-functioning autistic subjects showed a reduced tract volume and lower mean FA values in the left OFC network compared with controls. In the autistic group, lower FA values were associated with lower IQ scores. CONCLUSIONS: We showed evidence of OFC white matter network abnormalities in low-functioning autistic individuals. Our results point to a relationship between the severity of the intellectual impairment and the extent of white matter alterations.

Autologous haematopoietic stem-cell transplantation in multiple sclerosis: benefits and risks.

Autologous haematopoietic stem-cell transplantation has been evaluated over the last years as a possible new therapeutic strategy in severe forms of multiple sclerosis unresponsive to the approved therapies. Up to now, more than 400 patients have been treated and numerous are the phase I and phase II studies which addressed the feasibility of this treatment, the efficacy, side effects and transplant-related mortality. The clinical response is strongly related to the intensity of the conditioning regimen utilized as well as to the phase of the disease course in which the therapy is carried out. Rapidly evolving multiple sclerosis with a relapsing-remitting clinical course and MRI signs of activity are the cases that can take more advantage. The risk of mortality, which dropped in the last years to 2-3%, is still the main problem of this powerful therapy.

White matter lesions in migraine and right-to-left shunt: a conventional and diffusion MRI study.

Subjects with migraine with aura (MA) have a high prevalence of white matter lesions (WMLs) on magnetic resonance imaging (MRI). Moreover, right-to-left shunt (RILES), mainly due to patent foramen ovale, is frequently associated with MA. The aim of this study was to clarify the relationship between RILES and WML in MA. We enrolled 87 consecutive subjects affected by MA. Patients were screened for migraine characteristics and cerebrovascular risk factors. Transcranial Doppler was used to diagnose RILES and MRI with T2-weighted and diffusion-weighted imaging (DWI) to evaluate presence, number and volume of WMLs. RILES was present in 45% of patients. We did not detect any DWI hyperintense lesion; WMLs were present in 61% of patients on T2-weighted images. Presence of WMLs did not correlate with any migraine clinical feature, whereas the presence, number and volume of WMLs increased with subjects' age. There was no significant difference in the total volume and number of WMLs in the group with and without RILES. In conclusion, RILES does not increase the likelihood of finding WMLs in migraineurs.

Functional magnetic resonance evidence of cortical alterations in a case of reversible congenital lymphedema of the lower limb: a pilot study.

We report the first application of brain functional Magnetic Resonance Imaging (fMRI) to congenital peripheral lymphedema patients before and after microsurgical treatment. Our aim was to evaluate the effects of limb shape change on cortical organization of the motor system and how the cortical sensorimotor network restructures after microsurgical therapy. We acquired fMRI during active motor and motor imagery tasks before surgery and six months after surgery in a patient with congenital lymphedema of the left leg. fMRI data revealed activation differences in primary and secondary motor areas between the two scanning sessions for both tasks and also between the patient's and a healthy volunteer's activations. We suggest that these alterations could be related to changes in body schema representation due to the congenital lymphedema.

The postural disorientation induced by neck muscle vibration subsides on lightly touching a stationary surface or aiming at it.

The aim of this study was to investigate whether the standing body spatial disorientation, induced by neck muscle vibration, and the related post-effects can be suppressed by light finger touch (LFT) of a stationary surface. Continuous (60 s) vibration of dorsal neck or sternocleidomastoid muscle was administered with eyes closed. The center of foot pressure (CFP) displacement, measured by a stabilometric platform, indicated the degree of vibration-induced body tilt. We also investigated whether sensory information from LFT itself was necessary or anticipation of a more secure posture was enough for reducing vibration effects. To this aim, we administered a vibration pulse (5 s) to dorsal neck or sternocleidomastoid muscle and during reaching to the stationary surface. CFP was recorded during both vibration and post-vibration condition and during the aiming task. Neck vibration induced significant CFP displacement in the direction opposite to vibration site. Post-vibration, CFP slowly returned to control values with ample oscillations. LFT during vibration reduced body tilt. LFT was more effective when fingertip contact was in the plane of the greatest tilt. LFT applied during either vibration or post-vibration period reduced post-vibration effects. Reaching toward the stationary surface was enough for reducing vibration-induced body tilt to values close to those observed during actual LFT. The novel conclusions of this study are: 1) LFT is able to relieve the effects of vibration-induced abnormal proprioceptive input from the neck, a segment central to postural control and orientation; 2) LFT during vibration also attenuates vibration post-effects, further suggesting that its action is not merely mechanical; 3) the intention to stabilize the body generates a new postural 'set' sufficient for diminishing body tilt.

The Rediscovery of Hydroxychloroquine in Allergic Diseases in the COVID-19 Era

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In vitro cortical neuronal networks as a new high-sensitive system for biosensing applications.

By taking advantages of the main features of the microelectrode array (MEA) technology (i.e. multisite recordings, stable and long-term coupling with the biological preparation), we analyzed the changes in activity patterns induced by applying specific substances to dissociated cortical neurons from rat-embryos (E18). Data were recorded simultaneously from 60 electrodes, and the electrophysiological behavior was investigated during the third week in vitro, both at the spike and burst level. The analysis of the electrophysiological activity modulation, by applying agonists of the ionotropic glutamate receptors at low (i.e. 0.2-1-5 microM) and high (i.e. 50-100 microM) concentrations, is presented. Preliminary results show that the dynamics of the in vitro cortical neurons is very sensitive to pharmacological manipulation of the glutamatergic transmission and the effects on the network behavior are strictly dependent from the drug concentration. In particular, the addition of a high-dose of agonist determined a global and irreversible depression of the network activity, while, in the low-concentration case, the electrophysiological behavior showed different results, depending on the type of receptor involved. From these observations, we are encouraged to think of a more engineered system, based on in vitro cortical neurons, as a novel sensitive system for drug (pre)-screening and neuropharmacological evaluations.

A multicenter study on the prevalence of clinical patterns and clinical phenotypes in adult atopic dermatitis

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