Correction to: Impact of smoking habit on adult-onset Still’s disease prognosis,findings from a multicentre observational study

Clinical Rheumatology -     

Serum neurofilaments increase at progressive multifocal leukoencephalopathy onset in natalizumab‐treated multiple sclerosis patients

This study analyzed serum neurofilament light chains (NfL) in 2 European cohorts of 312 multiple sclerosis (MS) patients to investigate whether NfL are biomarkers of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment. The cohort comprised 25 PML, 136 natalizumab‐treated, and 151 untreated MS patients. Patients subsequently developing PML had similar NfL to other natalizumab‐treated MS patients. At PML onset, NfL were 10‐fold higher than in the pre‐PML condition and in natalizumab‐treated or untreated MS patients, and NfL continued to increase until onset of immune reconstitution inflammatory syndrome. The results suggest that in natalizumab‐treated patients, NfL may represent an early and accessible marker of PML. Ann Neurol 2019;85:606–610     

Vulnerability of multiple large‐scale brain networks in dementia with Lewy bodies

Aberrations of large‐scale brain networks are found in the majority of neurodegenerative disorders. The brain connectivity alterations underlying dementia with Lewy bodies (DLB) remain, however, still elusive, with contrasting results possibly due to the pathological and clinical heterogeneity characterizing this disorder. Here, we provide a molecular assessment of brain network alterations, based on cerebral metabolic measurements as proxies of synaptic activity and density, in a large cohort of DLB patients (N = 72). We applied a seed‐based interregional correlation analysis approach (p < .01, false discovery rate corrected) to evaluate large‐scale resting‐state networks' integrity and their interactions. We found both local and long‐distance metabolic connectivity alterations, affecting the posterior cortical networks, that is, primary visual and the posterior default mode network, as well as the limbic and attention networks, suggesting a widespread derangement of the brain connectome. Notably, patients with the lowest visual and attention cognitive scores showed the most severe connectivity derangement in regions of the primary visual network. In addition, network‐level alterations were differentially associated with the core clinical manifestations, namely, hallucinations with more severe metabolic dysfunction of the attention and visual networks, and rapid eye movement sleep behavior disorder with alterations of connectivity of attention and subcortical networks. These multiple network‐level vulnerabilities may modulate the core clinical and cognitive features of DLB and suggest that DLB should be considered as a complex multinetwork disorder.     

Core-Shell Arginine-Containing Chitosan Microparticles for Enhanced Transcorneal Permeation of Drugs

Chitosan oligosaccharide (C) was functionalized with l-arginine (A) and short hydrocarbon chains (C₈) to design an amphiphilic copolymer, henceforth CAC₈, leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). l-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC₈ MPs (CAC₈-MPs) were studied, showing that CAC₈-MPs can strongly interact with mucin, and thus gradually release their payload in situ to potentially improve the bioavailability of the drug after topical administration. In vitro transcorneal studies also showed that CAC₈-MPs are endowed with effective permeation enhancer ability combined with negligible toxicity.     

Incidence of dementia after age 90 in a multiracial cohort

Introduction

Little is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence.

New drugs in early-stage clinical trials for allergic rhinitis

Introduction: Allergic rhinitis (AR) is the most common allergic disease, and it has a relevant impact on the quality of life of the patient. Treatment of AR includes a combination of strategies of proven efficacy and effectiveness; however, a relevant proportion of patients remain uncontrolled.

Areas covered: This review article summarizes emerging therapeutic approaches to AR; these approaches include nasal sprays, oral drugs, alternative allergen immunotherapy administration routes, and biologic agents.

Expert opinion: The agents discussed require further clinical trials to prove their efficacy in the treatment of AR. Some of these agents, in particular, allergen immunotherapies and biologics, have the potential to form crucial precision medicine approaches to AR. Those that prove their efficacy in clinical trials must also be evaluated from a pharmacoeconomic perspective, possibly in real-life studies; this will define which therapeutic strategies achieve the most convenient and cost-effective ratio, thus yielding a novel opportunity for the most severe and previously treatment-resistant allergic patients.