Publications by authors named "Benjamin Fisher"

Background: Interstitial lung disease (ILD) is a frequent manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. Clinical practice guidelines to standardise screening, diagnosis, treatment and follow-up for CTD-ILD are of high importance for optimised patient care.

Methods: A European Respiratory Society and European Alliance of Associations for Rheumatology task force committee, composed of pulmonologists, rheumatologists, pathologists, radiologists, methodologists and patient representatives, developed recommendations based on PICO (Patients, Intervention, Comparison, Outcomes) questions with grading of the evidence according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology and complementary narrative questions agreed on by both societies.

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Background: Interstitial lung disease (ILD) is a frequent manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. Clinical practice guidelines to standardise screening, diagnosis, treatment and follow-up for CTD-ILD are of high importance for optimised patient care.

Methods: A European Respiratory Society and European Alliance of Associations for Rheumatology task force committee, composed of pulmonologists, rheumatologists, pathologists, radiologists, methodologists and patient representatives, developed recommendations based on PICO (Patients, Intervention, Comparison, Outcomes) questions with grading of the evidence according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology and complementary narrative questions agreed on by both societies.

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Immune checkpoint inhibitors (ICI) used for the treatment of malignancy are associated with immune-related adverse events, which include inflammatory arthritis. ICI-induced inflammatory arthritis (ICI-IA) is a new clinical entity that may lead to functional impairment and may be persistent even after ICI cessation. We discuss the clinical features, investigation and differential diagnosis.

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Ectopic lymphoid structures (ELS) are aggregates of lymphoid cells that often form within inflamed tissues in patients with autoimmune diseases, cancer, infectious diseases and cardiovascular conditions. These structures drive B cell maturation into memory B cells and plasma cells through B cell and T cell co-stimulation, and their role in pathogenesis is increasingly recognized. Understanding how ELS develop and persist in inflamed tissues is essential for elucidating the pathogenesis and treatment responses in diseases in which they have a prominent role.

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Introduction: Management of diabetes mellitus in very young children presents challenges due to variable insulin sensitivity, unpredictable carbohydrate intake, and low insulin requirements. An automated insulin delivery (AID) system addresses some of these challenges and can be used with diluted insulin where indicated.

Methods: Retrospective case series of children aged <6 years with diabetes starting CamAPS FX AID with standard (U100) or diluted (U5 or U10) insulin at a single UK clinical centre between October 2020 and April 2022.

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Primary Sjögren's disease (pSjD) is an autoimmune rheumatic disease involving exocrine glands and associated with high symptom burden (dryness, fatigue, pain), systemic features and salivary gland dysfunction. B-cell hyperactivity is common, with an increased risk of mucosa-associated lymphoid tissue lymphoma. This review describes the unmet need, scientific validity of outcome measures, optimisation of clinical trial design, therapeutic advances and how clinical improvement relates to health-related quality of life, additional quality-adjusted life years and economic benefit in pSjD.

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Nomenclature for the disease widely known as Sjögren syndrome has proven unsatisfactory. Patients have perceived 'syndrome' as indicative of a vague collection of symptoms, prompting the Sjögren's Foundation to abandon the term. Furthermore, the traditional distinction between 'primary' and 'secondary' forms fails to account for the complex interplay between overlapping autoimmune diseases.

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Parasitic infections are a major worldwide health burden, yet most studies of CD8 T cell differentiation focus on acute viral and bacterial infections. To understand effector and memory CD8 T cell responses during erythrocytic malaria infection in mice, we utilized transgenic OT-I T cells and compared CD8 T cell responses between infection with OVA-expressing strains of Listeria monocytogenes (Lm) and Plasmodium berghei ANKA (PbA). We find that CD8 T cells expand vigorously during both infections.

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Introduction: Following endovascular treatment (EVT) or microsurgical treatment (MT) of intracranial aneurysms (IA), radiological follow-up is performed to assess for recurrence and to determine the need for re-treatment. There is a paucity of evidence describing the long-term results of EVT and MT for IA and therefore data to inform the design of follow-up protocols are lacking. The overarching aim of the META study is to determine the clinically relevant long-term outcomes of EVT and MT for IA, and use this data to create evidence based radiological and clinical follow-up protocols for these aneurysms.

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Objectives: Although disparities exist in aspirin administration for chest pain and ST elevation myocardial infarctions (STEMI), little is known about community-based disparities in aspirin administration for prehospital patients. We evaluated disparities in prehospital aspirin using a national prehospital database.

Methods: We conducted a retrospective analysis of the 2018-2021 NEMSIS database linked to census data, including adult prehospital encounters.

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Objectives: Minor salivary gland (MSG) biopsy has an important role in Sjögren's disease diagnosis and research. MSGs show within-patient variation in number of lymphocytic foci per unit area, but the optimal number of MSGs required to balance reproducibility and clinical acceptability has not been determined.

Methods: Monte Carlo simulations were performed to investigate impact of MSG number on (i) diagnosis based on focus score (FS) ≥1; (ii) reproducibility, defined as the extent to which 2 FS measurements obtained from 2 within-patient biopsies are the same, assuming no systematic differences have occurred in between biopsies; and (iii) smallest sample size required to detect a clinically meaningful difference in FS.

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Purpose: To determine predictors of high pain in open globe injury (OGI) cases treated and transported by Emergency Medical Services.

Methods: The National Emergency Medical Services Information System database was queried for activations of OGI between 2017 and 2021. Demographic, location, medication, and date and time information was collected.

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Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures.

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Background: School shooting events and lockdowns have increased in the United States, raising concerns about their impact on youth mental health.

Method: This study assessed the association between school lockdowns and changes in youth mental health in 10,049 children who participated in the Adolescent Brain and Cognitive Development study. The exposure was school lockdowns related to violence and shooting incidents, and the outcomes were Child Behavior Checklist scores on five mental health disorders.

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Background And Aims: High-throughput in vitro pharmacological toxicity testing is essential for drug discovery. Precision-cut liver slices (PCLS) provide a robust system for screening that is more representative of the complex 3D structure of the whole liver than isolated hepatocytes. However, PCLS are not available as off-the-shelf products, significantly limiting their translational potential.

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Objectives: Salivary gland ultrasound (SGUS) has an interest in primary Sjögren's disease (pSD) for diagnosis, but the evolution of parenchymal lesions over time is unknown. The objective of this study was to assess the severity of ultrasound abnormalities in relation to pSD duration from the time of buccal dryness onset.

Methods: In this cross-sectional international multicentre study, patients with pSD according to the 2002 or 2016 ACR/EULAR classification criteria were included.

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Unlike other autoimmune diseases, little is known about the environmental risk factors for Sjögren's disease (SjD). Smoking is an important risk factor for rheumatoid arthritis but the relationship between smoking and SjD is more complex to understand. Current smoking seems to be negatively linked to SjD, whereas there is mixed data on past smoking.

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Objective: The objective of this study was to report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD).

Methods: Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks until week 24 (treatment period [TP]1). At week 24, patients on 300 mg were rerandomized to continue 300 mg or receive placebo until week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, and patients on 5 and 50 mg directly entered posttreatment safety follow-up.

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Article Synopsis
  • Social determinants of health (SDOH), like community race, income, and education, significantly affect outcomes in pediatric out-of-hospital cardiac arrest (POHCA).
  • Analysis of data from over 27,000 POHCAs revealed that communities with lower minority populations, higher wealth, and better education had notably better rates of bystander CPR, AED use, and return of spontaneous circulation (ROSC).
  • The findings highlight the opportunity for public health interventions aimed at reducing health disparities linked to community SDOH to improve POHCA outcomes.
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Article Synopsis
  • Several existing COA tools for assessing Sjögren's disease symptoms lack a comprehensive evaluation of health-related quality of life (HRQoL); this study aimed to create a new patient-reported outcome (PRO) instrument for better assessment in clinical settings and trials.
  • The development of the Sjögren's Related Quality of Life (SRQoL) included qualitative interviews with patients to capture their experiences and establish the content validity of the tool and associated severity assessment items (PGI-S and PGI-C).
  • After interviewing 20 participants, eight domains of HRQoL impact were identified, including emotional well-being, sleep, daily activities, cognition, physical functioning, social/family dynamics, work, and sexual functioning, signaling the SRQo
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Background: Sjögren's disease is a chronic autoimmune disease with an unmet need for targeted therapies. The aim of the TWINSS study is to evaluate the safety and efficacy of iscalimab, a monoclonal antibody against CD40, in patients with active Sjögren's disease.

Methods: This randomised, double-blind, placebo-controlled, phase 2b study, conducted at 71 sites in 23 countries, enrolled patients aged 18 years or older fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) 2016 criteria.

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Inflammatory rheumatic diseases are different pathologic conditions associated with a deregulated immune response, codified along a spectrum of disorders, with autoinflammatory and autoimmune diseases as two-end phenotypes of this continuum. Despite pathogenic differences, inflammatory rheumatic diseases are commonly managed with a limited number of immunosuppressive drugs, sometimes with partial evidence or transferring physicians' knowledge in different patients. In addition, several randomized clinical trials, enrolling these patients, did not meet the primary pre-established outcomes and these findings could be linked to the underlying molecular diversities along the spectrum of inflammatory rheumatic disorders.

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