Search

Current COVID-19 mRNA vaccines delivered intramuscularly (IM) induce effective systemic immunity, but with suboptimal immunity at mucosal sites, limiting their ability to impart sterilizing immunity. There is strong interest in rerouting immune responses induced in the periphery by parenteral vaccination to the portal entry site of respiratory viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by mucosal vaccination. We previously demonstrated the combination adjuvant, NE/IVT, consisting of a nanoemulsion (NE) and an RNA-based RIG-I agonist (IVT) induces potent systemic and mucosal immune responses in protein-based SARS-CoV-2 vaccines administered intranasally (IN). Herein, we demonstrate priming IM with mRNA followed by heterologous IN boosting with NE/IVT adjuvanted recombinant antigen induces strong mucosal and systemic antibody responses and enhances antigen-specific T cell responses in mucosa-draining lymph nodes compared to IM/IM and IN/IN prime/boost regimens. While all regimens induced cross-neutralizing antibodies against divergent variants and sterilizing immunity in the lungs of challenged mice, mucosal vaccination, either as homologous prime/boost or heterologous IN boost after IM mRNA prime, was required to impart sterilizing immunity in the upper respiratory tract. Our data demonstrate the benefit of hybrid regimens whereby strong immune responses primed via IM vaccination are rerouted by IN vaccination to mucosal sites to provide optimal protection against SARS-CoV-2., Competing Interests: Declaration of interests P.T.W., M.S., J.R.B., and A.G.-S. are co-inventors on a patent for NE/IVT. The A.G.-S laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck, outside of the reported work. A.G.-S. has consulting agreements with the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer and Prosetta, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and Astrazeneca. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York. The M.S. laboratory received unrelated research support as sponsored research agreements from ArgenX BV, Phio Pharmaceuticals, 7Hills Pharma LLC and Moderna., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction/objectives: Controversy exists regarding the concordance of patient-reported outcome measures (PROMs) with other assessment parameters in systemic sclerosis-associated interstitial lung disease (SSc-ILD). This study aims to explore the association between the St. George's Respiratory Questionnaire (SGRQ) and various outcome measures in patients with SSc-ILD within a real-world cross-sectional setting., Method: Patients with SSc-ILD were consecutively recruited from our SSc cohort. Simultaneous administration of SGRQ, scleroderma Health Assessment Questionnaire (sHAQ), respiratory visual analog scale (R-VAS), pulmonary function tests (PFTs), and the 6-min walking test (6-MWT) was conducted. The total extent of lung fibrosis was quantified using high-resolution computed tomography (HRCT) images. Relationships between SGRQ and functional, radiographic, and other patient-reported outcome measures were analyzed., Results: The total SGRQ score demonstrated correlations with forced vital capacity (FVC) and R-VAS (r =  - 0.397, p = 0.016 and r = 0.418, p = 0.027, respectively). Symptom score correlated with ILD-extension (r = 0.430, p = 0.005); activity score correlated with FVC and R-VAS (r =  - 0.502, p = 0.002 and r = 0.395, p = 0.038, respectively); impact score correlated with R-VAS (r = 0.386, p = 0.043). In patients with fibrosis extent exceeding 20%, total SGRQ score was associated with sHAQ and R-VAS (r = 0.398, p = 0.049; r = 0.524, p = 0.021, respectively), activity score with R-VAS (r = 0.478, p = 0.038), and impact score with 6-MWT-D and R-VAS (r =  - 0.489, p = 0.034; r = 0.545, p = 0.016, respectively). The symptom score and activity score demonstrated optimal performance in identifying patients with interstitial lung disease (ILD) extent exceeding 20% and forced vital capacity (FVC) less than 70% (area under the curve [AUC] 0.799, p = 0.002, and AUC 0.792, p = 0.03, respectively)., Conclusions: Our study reveals varying degrees of correlation between SGRQ and distinct outcome measures. Given the incomplete alignment of SGRQ with other outcome measures, an integrative approach utilizing existing criteria as complementary tools is recommended. Key Points • Patient-reported outcome measures (PROMs) derive from patients' subjective evaluations of the impact of the disease on their daily activities, social interactions, and psychological well-being. • PROMs frequently serve as outcome measures in randomized controlled trials, yet conflicting findings have emerged in relation to primary outcomes. • This study aims to assess the appropriateness and interrelation of PROMs with both radiological and functional outcome measures, providing insight into the current state of our patients in a real-life context. The investigation delves into the compatibility of these measures with each other., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: This retrospective study aimed to conduct a comprehensive analysis of Turkish Systemic Lupus Erythematosus (SLE) patients of Caucasian ethnicity, focusing on their clinical, immunological, and therapeutic characteristics, damage accural and mortality., Patients and Methods: We carried out a retrospective assessment of 300 SLE patients diagnosed between 2001 and 2017 at Kocaeli University Rheumatology Clinic. Demographic data, clinical manifestations, immunological profiles, treatment approaches, disease-related damage, and survival information were collected., Results: The study population had a significant female predominance (89%) with a mean age of disease onset of 35.4 (SD:13.3) years. Hematological (72.6%) and mucocutaneous (72%) manifestations were the most common clinical findings, followed by arthritis (66.3%). Females had higher frequency of photosensitivity (p = 0.019), malar rash (p < 0.001), and alopecia (p = 0.014). Anti-dsDNA antibodies were detected in 61.6% of patients, while 57% of patients had hypocomplementemia. Secondary antiphospholipid syndrome was observed in 15.3% of patients; the most common manifestations included deep venous thrombosis (32.6%) and cerebrovascular accidents (30.4%). Lupus Nephritis (LN) affected 40.3% of the cohort. The most common pathologic finding was Class IV LN (30.5%). Eventually, 13 (4.3%) patients developed chronic kidney disease (CKD) and 4 had renal replacement therapies. Patients with LN had higher usage of pulse steroids, azathioprin, mycophenolate mofetil, cyclophosphamide, and rituximab (p < 0.001 for each).  In the juvenile-onset group (n = 31, 10.3%), an increased occurrence of malar rash (p = 0.009), nephritis (p = 0.034), hypocomplementemia (p = 0.001), positive anti-dsDNA (p = 0.007), anti-Sm (p = 0.046), anti-rib-P (p = 0.014) antibodies were observed. At least one damage parameter was observed in 32.6% patients with musculoskeletal manifestations being the most common. Thirteen patients were diagnosed with various malignancies, with cervical cancer being the most common (4 cases). The total 5 and 10-year survival rates were 92.5% and 86.7%, respectively. However, patients with CKD, had lower survival rates; 75% at 3 years and 60% at 15 years. Regression analysis demonstrated an association of CKD and  history of infections with decreased survival (p = 0.02, each)., Conclusion: Ethnicity and geography influence the clinical diversity of SLE. Recognizing these disparities is crucial for tailoring patient care. Future inception cohort studies in Turkish SLE patients are necessary to address the limitations of retrospective research., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Sjögren's syndrome (SS) is an autoimmune systemic disease affecting many organs and systems, such as genital system., Aim: This study aimed to present the gynecological symptoms of patients who were followed up in an outpatient clinic because of primary Sjögren's syndrome (pSS) and secondary Sjögren's syndrome (sSS) and to show how the disease affected sexuality., Methods: This study is a cross-sectional study conducted between 2019 and 2020. The study sample consisted of 60 pSS patients, 42 sSS patients, and 52 healthy control subjects., Outcomes: All the participants were questioned about sexuality, and completed the 36-item Short Form Survey, Hospital Anxiety and Depression Scale, Health Assessment Questionnaire, and Modified Hill questionnaire., Results: The patients had a mean age of 55.6 ± 11.85 years in pSS, 59.39 ± 11.18 years in sSS, and 56.1 ± 10.46 years in healthy control subjects. Vaginal and vulvar dryness and dyspareunia were present at a significantly higher rate in SS, especially in pSS, compared with the control subjects. The Health Assessment Questionnaire score was significantly lower in the pSS group than in the sSS group. Arthralgia, myalgia, and fatigue were prominent in all SS patients., Clinical Implications: Gynecological symptoms, sexual ability, and the effects of the disease on sexuality should be questioned in all SS patients., Strengths and Limitations: It is very important that we evaluate the gynecological symptoms of both pSS and sSS patients and the effect of the disease on these symptoms. The small number of patients and healthy control subjects is a limitation., Conclusion: The gynecological and musculoskeletal symptoms negatively affected sexuality in patients with pSS and sSS, and the negative effect of the disease on sexuality was more pronounced in the pSS group., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Radiological alterations in psoriatic arthritis (PsA) are an established phenomenon frequently observed throughout the disease course. Our goal was to investigate the changes in the bone structure of PsA patients by conventional radiography., Methods: This study designed as a retrospective cohort study and cross-sectional evaluation for disease activity. The disease activity and the severity of skin and nail involvement were assessed. The Simplified Psoriatic Arthritis Radiographic Score (SPARS) was used to investigate the radiological progression. Logistic regression analysis was used to determine the predictors of radiological changes., Results: Joint space narrowing and bone proliferation in hands (p = 0.001 and p = 0.001, respectively) and joint space narrowing in feet (p = 0.047) were more common at the final evaluation than at the baseline assessment. Total scores of joint space narrowing and bone proliferation in hands and feet were higher at the last visit than at the initial assessment (p < 0.001). Male gender (p = 0.030, OR 4.32 (95%CI 1.15-16.15)], older age (for joint space narrowing [p = 0.026 OR 1.08 (95%CI 1.01-1.56)] and for proliferation [p = 0.025 OR 1.08 (95%CI 1.01-1.44)]), high Disease Activity index for Psoriatic Arthritis (DAPSA) scores at baseline [p = 0.032 OR 6.21 (95%CI 1.17-32.92)], and symmetrical polyarticular involvement at baseline [p = 0.025 OR 5.3 (95% CI 1.23-22.4)] were found as predictors of structural changes., Conclusion: By the end of the decade, joint space narrowing and proliferation were observed to be more common than erosion. Male gender, older age, higher initial DAPSA scores, and initial polyarticular involvement were identified as predictors of radiological damage. Key Points • The radiological changes of Psoriatic arthritis are a well-known entity. However, studies investigating the progression of joint involvement over time are scarce. • This study reveals that joint space narrowing and proliferation are the most prominent radiological alterations in Psoriatic Arthritis patients at the end of the decade. • Male gender, older age, higher baseline DAPSA scores, and initial polyarticular involvement are predictive factors influencing the progression of bone destruction  in Psoriatic Arthritis patients., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)