Attitudes and barriers to pulmonary arterial hypertension screening in systemic sclerosis patients: A survey of UK-based rheumatologists.

Objectives: The objectives were to explore rheumatologists' current clinical screening practices of pulmonary arterial hypertension in patients with systemic sclerosis in the United Kingdom and to identify barriers to screening and consider potential solutions. Methods: A survey of 31 questions was developed and included six sections: clinician demographics, the importance of screening, screening practices, barriers to screening, treatment and patient education. The survey was disseminated among rheumatologists working in the United Kingdom. Results: Forty-four rheumatologists working in the United Kingdom participated in the study, and the majority completed all the questions. Around one-third (37.0%) worked in specialised systemic sclerosis units (university or general hospitals (54.5% and 45.4%, respectively)). The majority recognised that systemic sclerosis-pulmonary arterial hypertension is a major cause of morbidity and mortality. Over half (60.0%) reported using the DETECT algorithm to screen for systemic sclerosis-pulmonary arterial hypertension, although other algorithms were also sometimes used. All of the respondents utilised transthoracic echocardiogram, and almost all (95.0%) performed pulmonary function tests for screening purposes. Various challenges and barriers were identified relating to systemic sclerosis-pulmonary arterial hypertension screening, with the difficulty in interpreting results from other hospitals and extended wait times for diagnostic tests being the most reported (76.0% and 74.0%, respectively). Most respondents agreed that access to key investigations (87.0%), ongoing clinician education (82.0%), multidisciplinary meetings (79.5%) and a better understanding of proposed screening algorithms (79.5%) could be potential solutions. Conclusion: Screening patients with systemic sclerosis for pulmonary arterial hypertension is crucial to improve survival, but variable practices exist among UK rheumatologists. Solutions include educating healthcare professionals on guidelines, sharing information between centres and integrating care services.

Specific Cellular and Humoral Response after the Third Dose of Anti-SARS-CoV-2 RNA Vaccine in Patients with Immune-Mediated Rheumatic Diseases on Immunosuppressive Therapy.

OBJECTIVE: Data on cellular and humoral immunogenicity after the third dose of anti-SARS-CoV-2 vaccines in patients with immune-mediated rheumatic diseases (IMRDs) are scarce. Herein, we evaluated the adaptive immune response in IMRD patients treated with different immunosuppressive therapies (conventional synthetic disease-modifying antirheumatic drugs [csDMARDs], biological disease-modifying antirheumatic drugs [bDMARDs], and targeted synthetic disease-modifying antirheumatic drugs [tsDMARDs]) after the booster of the anti-SARS-CoV-2 vaccine to determine whether any drug reduced the vaccine's response. METHODS: A single-center prospective study was conducted, including patients presenting with IMRD and healthy controls (HC). Specific anti-SARS-CoV-2 interferon-gamma (IFN-γ) production was evaluated between 8-12 weeks after the third dose of the SARS-CoV-2 vaccine. In addition, anti-Spike IgG antibody titers were also measured. RESULTS: Samples were obtained from 79 IMRD patients (51 women, 28 men; mean age 57 ± 11.3 years old): 43 rheumatoid arthritis, 10 psoriatic arthritis, 14 ankylosing spondylitis, 10 undifferentiated spondyloarthritis, and 2 inflammatory bowel disease-associated spondyloarthritis (IBD-SpA). In total, 31 HC (mean age 50.9 ± 13.1 years old, 67.7% women) were included in the study. Post-vaccine results displayed positive T-cell immune responses in 68 out of 79 (86.1%) IMRD patients (82.3% of those without prior COVID-19). All HC and IMRDs patients had an antibody response against the SARS-CoV-2 receptor-binding domain; however, the HC response was significantly higher (median of 18,048 AU/mL) than in IMRDs patients (median of 6590.3 AU/mL, p < 0.001). MTX and leflunomide were associated with lower titers of IgG and IFN-γ responses. Among bDMARDs, adalimumab, etanercept, and guselkumab are associated with reduced cellular responses. CONCLUSION: Our preliminary data show that the majority of our IMRD patients develop cellular and humoral responses after the SARS-CoV-2 booster vaccination, emphasizing the relevance of vaccination in this group. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. Specific vaccination protocols and personalized decisions about boosters are essential for these patients.

Long-Term Benefit of Perlingual Polybacterial Vaccines in Patients with Systemic Autoimmune Diseases and Active Immunosuppression.

INTRODUCTION: We have previously shown that trained-immunity-based vaccines, namely TIbV, significantly reduce the rate of recurrent infections, both of the respiratory tract (RRTI) and urinary tract infections (RUTI) in SAD patients on disease-modifying drugs (DMARDs). OBJECTIVE: We evaluated the frequency of RRTI and RUTI from 2018 to 2021 in those SAD patients that received TIbV until 2018. Secondarily, we evaluated the incidence and clinical course of COVID-19 in this cohort. METHODS: A retrospective observational study was conducted in a cohort of SAD patients under active immunosuppression immunized with TIbV (MV130 for RRTI and MV140 for RUTI, respectively). RESULTS: Forty-one SAD patients on active immunosuppression that were given TIbV up to 2018 were studied for RRTI and RUTI during the 2018-2021 period. Approximately half of the patients had no infections during 2018-2021 (51.2% no RUTI and 43.5% no RRTI at all). When we compared the 3-year period with the 1-year pre-TIbV, RRTI (1.61 ± 2.26 vs. 2.76 ± 2.57; p = 0.002) and RUTI (1.56 ± 2.12 vs. 2.69 ± 3.07; p = 0.010) episodes were still significantly lower. Six SAD patients (four RA; one SLE; one MCTD) with RNA-based vaccines were infected with SARS-CoV-2, with mild disease. CONCLUSIONS: Even though the beneficial protective effects against infections of TIbV progressively decreased, they remained low for up to 3 years, with significantly reduced infections compared to the year prior to vaccination, further supporting a long-term benefit of TIbV in this setting. Moreover, an absence of infections was observed in almost half of patients.

Dietas vegetarianas en niños: conocimientos de pediatras de la Sociedad Uruguaya de Pediatría: encuesta 2020 / Vegetarian diet in children: pediatric knowledge from the Uruguayan Society of Pediatrics: 2020 survey / Dietas vegetarianas em crianças: conhecimento dos pediatras da Sociedade Uruguaia de Pediatria: inquérito 2020

Introducción: en los últimos años el incremento de vegetarianos es considerable. Se debe tener cautela al incorporar este tipo de dietas en la población pediátrica. No son contempladas en las actuales guías de nutrición nacionales, generando incertidumbre al realizar recomendaciones. Objetivo: describir los conocimientos sobre dietas vegetarianas en niños por parte de médicos pediatras, posgrados y residentes socios de la Sociedad Uruguaya de Pediatría en el período de junio-setiembre 2020. Determinar la necesidad de incorporar dietas vegetarianas a las guías uruguayas de nutrición pediátrica por parte de los encuestados. Material y método: estudio observacional descriptivo, tipo encuesta transversal, en el período entre junio y setiembre de 2020. Los criterios de inclusión fueron médicos residentes/posgrados en pediatría y pediatras de la Sociedad Uruguaya de Pediatría, de Montevideo y el interior del país. La fuente de datos fue una encuesta online anónima. El análisis de datos fueron frecuencias relativas y absolutas para variables cualitativas. Resultados: se enviaron 1.080 encuestas online, de las que se incluyeron 119. Sobre la autopercepción en el conocimiento de los encuestados, el 58,0% se calificó dentro del rango medio. Acerca del concepto de dieta ovolactovegetariana, 63,9% seleccionó la opción correcta. Más de 50,0% respondió correctamente acerca de conocimientos sobre nutrientes en la mayoría de los ítems. Iniciar estas dietas en la alimentación complementaria fue desaconsejado por el 58% de los socios. Un 79,8% pretende adquirir más conocimientos del tema. Conclusiones: más de la mitad de los profesionales tiene los conocimientos correctos acerca de la correcta planificación y suplementación de dietas vegetarianas en niños. Se destaca la necesidad de incluir dietas vegetarianas en las guías de alimentación pediátrica en territorio uruguayo.

Introduction: the number of vegetarian people has increased considerably in recent years. Caution is suggested when incorporating this type of diet to the pediatric population. This diet has not been contemplated in the current national nutritional guidelines, generating uncertainty among pediatricians when making recommendations. Objective: describe the knowledge Pediatric Physicians and graduate / resident members of the Uruguayan Society of Pediatrics have regarding vegetarian diets in children during the period June-September 2020. Determine the need of the participants of the survey to incorporate vegetarian diet information into the Uruguayan Pediatric Nutritional Guidelines. Materials and methods: descriptive observational study, cross-sectional survey carried out from June to September 2020. The inclusion criteria included resident doctors / postgraduate pediatricians and pediatricians from the Uruguayan Society of Pediatrics of Montevideo and the interior of the country. The data source was an anonymous online survey. The data analyses were relative and absolute frequencies of qualitative variables. Results: 1.080 online surveys were sent and 119 were included. Regarding the respondents' self-perception of knowledge, 58.0% were rated within the medium range. Regarding the concept of lacto-ovo-vegetarian diet, 63.9% selected the correct option. Regarding knowledge about nutrients, we obtained more than 50.0% of correct answers in most of the items. Starting these diets as supplementary food was discouraged by 58% of the participants. 79.8% expressed the intention to acquire more knowledge regarding the subject. Conclusions: more than half of the professionals have the correct knowledge about the correct planning and supplementation of vegetarian diets in children. They stressed the need to include vegetarian diets in pediatric food guidelines in Uruguay.

Introdução: nos últimos anos, o aumento das pessoas vegetarianas tem sido considerável. Deve-se ter cuidado ao incorporar esse tipo de dieta na população pediátrica. Ela não está incluída nas atuais diretrizes nacionais de nutrição, gerando incerteza nos pediatras no momento de fazer recomendações. Objetivo: descrever o conhecimento sobre dietas vegetarianas em crianças dos Pediatras e pós-graduados/residentes da Sociedade Uruguaia de Pediatria no período de junho a setembro de 2020 para poder determinar a necessidade de incorporar dietas vegetarianas às diretrizes nutricionais pediátricas uruguaias. Material e métodos: estudo observacional descritivo, tipo de pesquisa transversal realizada no período de junho a setembro de 2020. Os critérios de inclusão foram médicos residentes/pós-graduados em pediatria e pediatras da Sociedade Uruguaia de Pediatria, Montevidéu e interior do país. A fonte de dados foi uma pesquisa on-line anônima sobre a necessidade de incorporar dietas vegetarianas às diretrizes uruguaias para nutrição pediátrica. As análises dos dados foram frequências relativas e absolutas de variáveis qualitativas. Resultados: 1.080 pesquisas online foram enviadas e 119 foram incluídas. Quanto à autopercepção de conhecimento dos entrevistados, 58,0% foram avaliados dentro da faixa média. Quanto ao conceito de dieta lacto-ovo-vegetariana, 63,9% selecionaram a opção correta. Quanto ao conhecimento sobre nutrientes, obtivemos mais de 50,0% das respostas corretas na maioria dos itens. O início dessas dietas como alimentos suplementares foi desencorajado por 58% dos participantes. 79,8% expressaram a intenção de adquirir mais conhecimento sobre o assunto. Conclusões: mais da metade dos profissionais têm o conhecimento correto sobre o planejamento correto e suplementação de dietas vegetarianas em crianças. Eles enfatizaram a necessidade de incluir dietas vegetarianas nas diretrizes de alimentos pediátricos no Uruguai.

HBD3 Induces PD-L1 Expression on Head and Neck Squamous Cell Carcinoma Cell Lines.

Human ß-defensin 3 (HBD3) is an antimicrobial peptide up-regulated in the oral tissues of individuals with head and neck squamous cell carcinomas (HNSCC) and oral squamous cell carcinomas (SCC) and present in high concentrations in their saliva. In this study, we determined if HBD3 contributes to HNSCC pathogenesis by inducing programmed death-ligand 1 (PD-L1) expression on HNSCC cell lines. For this, SCC cell lines SCC4, SCC15, SCC19, SCC25, and SCC99 (5.0 × 104 viable cells) were used. Cells were incubated with IFNγ (0.6 µM) and HBD3 (0.2, 2.0, or 20.0 µM) for 24 h. Cells alone served as controls. Cells were then treated with anti-human APC-CD274 (PD-L1) and Live/Dead Fixable Green Dead Cell Stain. Cells treated with an isotype antibody and cells alone served as controls. All cell suspensions were analyzed in a LSR II Violet Flow Cytometer. Cytometric data was analyzed using FlowJo software. Treatment with IFNγ (0.6 µM) increased the number of cells expressing PD-L1 (p < 0.05) with respect to controls. Treatment with HBD3 (20.0 µM) also increased the number of cells expressing PD-L1 (p < 0.05) with respect to controls. However, treatment with IFNγ (0.6 µM) was not significantly different from treatment with HBD3 (20.0 µM) and the numbers of cells expressing PD-L1 were similar (p = 1). Thus, HBD3 increases the number of cells expressing PD-L1. This is a novel concept, but the role HBD3 contributes to HNSCC pathogenesis by inducing PD-L1 expression in tumors will have to be determined.

Matrix metalloproteinase (MMP) and immunosuppressive biomarker profiles of seven head and neck squamous cell carcinoma (HNSCC) cell lines.

BACKGROUND: Biomarkers like programmed death ligand-1 (PDL1) have become a focal point for immunotherapeutic checkpoint inhibition in head and neck squamous cell carcinoma (HNSCC). However, it's only part of the total immunosuppressive biomarker profile of HNSCC cells. Matrix metalloproteinases (MMPs) are enzymes that break down the basement membrane allowing cancer cells to metastasize and play an important role in the tumor microenvironment. MMPs can also activate certain cytokines, growth factors, and chemokines post-translationally. The objective of this study was to determine MMP and biomarker profiles of seven different HNSCC cell lines. METHODS: Authenticated cell lines were grown in minimal media at 1×106 viable cells/mL and incubated at 37 °C. After 24 hrs supernatants were collected, and adhering cells were lysed. Multiplex immunoassays were used to determine MMP1, MMP7, MMP9, IL-6, VEGFA, IL-1α, TNF-α, GM-CSF, IL-1RA, and IL-8 concentrations in supernatants. ELISAs were used to determine PDL1, CD47, FASL, and IDO concentrations in cell lysates. A one-way ANOVA was fit to examine log-transformed concentrations of biomarkers between seven HNSCC cell lines, and pairwise group comparisons were conducted using post- hoc Tukey's honest significance test (α=0.05). RESULTS: Significant differences (P<0.05) in MMP and biomarker concentrations were found between the seven HNSCC cell lines. For example, MMP9 was highest in SCC25 and UM-SCC99, MMP7 was highest in SCC25 and UM-SCC19, and MMP1 was highest in SCC25. CONCLUSIONS: These results suggest different patients' HNSCC cells can express distinct profiles of select biomarkers and MMPs, which could be due to metastatic stage of the cancer, primary tumor site, type of tissue the tumor originated from, or genomic differences between patients. MMP and biomarker expression profiles should be considered when choosing cell lines for future studies. The results support the reason for personalized medicine and the need to further investigate how it can be used to treat HNSCC.

Collective and self-diffusion coefficients in an ionic critical mixture: 3-methylpyridine+water+NaBr.

The dynamics of concentration fluctuations of three critical samples of the 3-methylpyridine (3MP)+water+NaBr system have been measured by photon correlation spectroscopy. The collective-diffusion coefficient D shows the usual Ising behavior near the critical temperature T(c). However, as |T-T(c)| increases, the dynamic correlation length calculated from D, xi, takes values higher than the correlation length of the critical fluctuations calculated from static light scattering, xi(s). At the largest |T-T(c)| measured, xi approaches the value, xi(0,d) approximately equal to 1.13 nm, while the amplitude of xi(s) is xi(0,s)=0.38 nm. Pulsed-gradient NMR spectroscopy points out the existence of two dynamic contributions. One of them is consistent with the existence of molecular entities of hydrodynamic radius 0.31 nm, while the other one indicates the existence of aggregates rich in 3MP of radius 1.16 nm. The existence of the aggregates may explain the apparent anomalous behavior of the dynamic light scattering experiments for this system far from the critical point.