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Type 2 (T2)-low severe asthma (SA) presents a distinct subpopulation for which, in lack of a consistent classification system, epidemiological and clinical outcome data remain unclear and therapeutic needs remain largely unmet. The aim of the PHOLLOW real-world study is to assess the prevalence and predictors of T2-low SA, and depict the patient profile, clinical features, treatment patterns and disease burden using clinical and patient-reported outcomes (PROs) in routine settings in Greece. This is a cross-sectional and retrospective chart review 2-part study that will enroll 600 adult outpatients with SA over a 1-year period by 20-30 asthma specialists. A new SA phenotype classification system and two different definitions proposed herein will be used to categorize patients into definite or possible T2-low (unlikely or least likely T2-high) SA, and definite/most likely or possible/likely T2-high SA, based on a composite measure of airway inflammation markers (blood eosinophil counts, fractional exhaled nitric oxide), allergic/atopic status and age-of-onset phenotype, taking into consideration the current receipt of biologic and/or maintenance oral corticosteroid treatment and response to it. Part A will collect top-level data for all participants to assess T2-low SA prevalence and predictors. T2-low SA patients will proceed to part B, where further data and PROs assessing asthma symptom control, quality of life, anxiety, depression, work productivity and activity impairment will be collected. In view of anticipated new treatments for SA, evidence generated by PHOLLOW will provide insight into T2-low SA prevalence and disease burden, using a well-defined classification scheme, which can inform healthcare decisionmaking. [ABSTRACT FROM AUTHOR]

Severe eosinophilic asthma (SEA) is associated with poor disease control and compromised health-related quality of life (HRQoL), leading to a substantial psychosocial and economic disease burden. Benralizumab, an interleukin-5-alpha receptor monoclonal antibody, is approved as an add-on maintenance treatment for SEA, yet real-world evidence of its effectiveness is limited. EMPOWAIR is a non-interventional, multicenter, 48-week prospective cohort study aiming to evaluate the clinical effectiveness and the patient-perceived impact of benralizumab on HRQoL, sleep quality, depression, anxiety, work productivity and activity impairment among SEA patients treated in routine care settings in Greece. The study will also engage advanced remote patient monitoring technologies using portable spirometers and wearable activity trackers to collect data on lung function parameters and physical activity. The study plans to consecutively enroll 150 adult patients treated by lung specialists practicing in various healthcare settings across the country over an 18-month recruitment period. Eligible patients must be newly prescribed benralizumab per the approved label. Primary data will be collected at enrollment and 4, 8, 16, 32, and 48 weeks after treatment initiation through routine clinic visits or telephone contacts as per the standard clinical practice. The primary objective is to assess the change from baseline in HRQoL, as measured by the St. George's Respiratory Questionnaire (SGRQ), and to estimate the proportion of patients achieving a minimum clinically important improvement in respiratory health status, defined as ≥ 4-point reduction from baseline in SGRQ total score, after 16 weeks of benralizumab treatment. The study rationale, design and protocol, are described herein. [ABSTRACT FROM AUTHOR]

Abstract: We applied static and dynamic light scattering (DLS) to probe the structural and physicochemical determinants of the interaction between the gp120 V3 domain of the human immunodeficiency virus HIV-1 and the amino terminal of the chemokine receptor CCR5 (CCR5-Nt). CCR5-Nt is a co-receptor that infectious HIV strains utilize to gain entry into target cells. Preventing HIV from interacting with these co-receptors prevents viral entry. In this study, we present the first systematic investigation of the size, shape, dynamics, and interactions of self-associating peptide complexes formed by a 13-residue peptide, V3 (from the strain MN), in dilute aqueous solution, using DLS. Nuclear magnetic resonance (NMR) spectra indicate that the free V3 and CCR5-Nt peptides as well as the V3-CCR5-Nt mixture are somehow structured in solution. Also, NMR spectra in combination with peptide titration suggest a weak interaction between the V3 domain and CCR5-Nt. Finally, the NMR data suggest monomeric or self-associating complexes amenable to NMR studies without significant spectral line broadening, for V3, CCR5-Nt, and the V3–CCR5-Nt complex. The monomers or self-associating complexes observed by NMR are not expected to be in exchange with the self-associating complexes observed by dynamic light scattering. Light scattering on exactly the same NMR samples confirms the presence of the complexes that were observed at lower concentrations. [Copyright &y& Elsevier]

Systemic lupus erythematosus (SLE) has a spectrum of phenotypes. Its management should target remission or low disease activity, prevention of relapses and organ damage, minimisation of drug-related harms, and optimisation of health-related quality of life. Advances in our understanding of the disease pathophysiology have expanded the treatment armamentarium with targeted biologics that demonstrate superiority over conventional drugs in controlling activity, reducing flares and glucocorticoid exposure, and improving patient-related outcomes. In view of this, there is a critical need for real-world evidence providing insight into the spectrum of activity, the treatment landscape, and unmet needs among SLE patients. Such information can support regulatory and reimbursement decision-making. The primary objective of the NYMERIA multicentre study is to generate real-world evidence on the activity state of SLE patients treated in routine care settings in Greece. The overarching aim is to capture the disease burden based on both clinical aspects and the patient perspective., Competing Interests: GB reports honoraria and/or consulting fees from Lilly, Aenorasis, Novartis, Otsuka, AstraZeneca, GSK, SOBI, Pfizer, participation in advisory boards from Novartis. AF reports honoraria and/or consulting fees from Lilly, Boehringer, Novartis, AbbVie, AstraZeneca, GSK, MSD, Pfizer, UCB, Amgen, Aenorasis, support for attending meetings from UCB. MB and PG are AstraZeneca employees. DTB reports unrestricted investigational grants from GSK, honoraria and/or consulting fees from GSK, AstraZeneca, Pfizer., (© 2024 The Mediterranean Journal of Rheumatology (MJR).)

Infection of target host cells by the human immunodeficiency virus-1 (HIV-1) is a multi-step process involving a series of conformational changes in the viral gp120 and gp41 proteins. Gp120 binding to the main cell receptor, CD4, on the surface of cells expressing this molecule, and interaction with the cell chemokine receptors CCR5 and CXCR4, are among the key events for HIV-1 infection. These steps are crucial for the virus and offer potential therapeutic targets. For this reason, understanding the structure and the physicochemical characteristics of the gp120 in relation to these interactions has drawn much attention. This review article focuses on the biologically important V3 region of the gp120 and summarizes the functional role, the sequence variation and the conformational features of V3 peptides, which are important for co-receptor selectivity, specificity and interaction. Synthetic V3 peptides have been extensively studied by NMR spectroscopy and X-ray crystallography, in solution or in solid state, in their free or bound form, and valuable information was generated with the aim to be exploited in the design of new, effective inhibitors of HIV-1 infection. The features of the potential gp120 interacting sites on the two chemokine co-receptors, CCR5 and CXCR4, are also discussed, and co-receptor blocking molecules under clinical trial are also reported.