Diagnostic accuracy of serum calprotectin measured by CLIA and EIA in juvenile idiopathic arthritis: a proof-of-concept study.

Objective: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are used to assess disease activity in juvenile idiopathic arthritis (JIA). However, because these biomarkers do not always differentiate between active and inactive disease, there is a need for alternative markers such as serum calprotectin (sCal). The main aim of this proof-of-concept study was to assess the diagnostic accuracy of sCal in patients with JIA. Secondary aims were to identify the optimal sCal cut-off levels to define active disease and evaluate the association between these biomarkers and disease activity status. Methods: Serum samples were obtained from 25 pediatric patients with JIA. Serum calprotectin levels were determined by two different assays, the QUANTA FLASH chemiluminescence immunoassay (CLIA) from Inova Diagnostics and the solid-phase enzyme immunoassay (EIA) from Bühlmann Laboratories. Diagnostic accuracy was assessed for sCal CLIA, sCal EIA, CRP, and ESR. The results obtained by the CLIA and EIA methodologies were compared. We also evaluated the association between the individual each biomarkers (sCal CLIA, sCal EIA, CRP, and ESR) and disease activity (according to JADAS-27 criteria and the ACR criteria modified by Anink and colleagues). Results: For both sCal assays (CLIA and EIA), the optimal cut-off level (ROC analysis) was the same (2.3 µg/ml). Serum calprotectin levels measured by CLIA and EIA were strongly correlated with each other (Kendall's tau-b, 0.71; p < 0.001). Compared to ESR and CRP, sCal CLIA and EIA were both more accurate (i.e., greater sensitivity) in identifying patients with active disease. By contrast, ESR and CRP were more effective in identifying patients in remission (i.e., better specificity). Conclusion: This proof-of-concept study shows that determination of serum calprotectin levels with CLIA or EIA can accurately identify the presence of active disease in patients with JIA.

Target engagement of an anti-MT1-MMP antibody for triple-negative breast cancer PET imaging and beta therapy.

PURPOSE: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks effective diagnostic and therapeutic options. Membrane type 1 matrix metalloproteinase (MT1-MMP) is an attractive biomarker for improving patient selection. This study aimed to develop a theranostic tool using a highly tumour-selective anti-MT1-MMP antibody (LEM2/15) radiolabelled with 89Zr for PET and 177Lu for therapy in a TNBC murine model. METHODS: The LEM2/15 antibody and IgG isotype control were radiolabelled with 89Zr. PET imaging was performed in a TNBC orthotopic mouse model at 1, 2, 4, and 7 days after administration. Tissue biodistribution and pharmacokinetic parameters were analysed and Patlak linearisation was used to calculate the influx rate of irreversible uptake. The TNBC mice were treated with [177Lu]Lu-DOTA-LEM2/15 (single- or 3-dose regimen) or saline. Efficacy of [177Lu]Lu-DOTA-LEM2/15 was evaluated as tumour growth and DNA damage (γH2AX) in MDA 231-BrM2-831 tumours. RESULTS: At 7 days post-injection, PET uptake in tumour xenografts revealed a 1.6-fold and 2.4-fold higher tumour-to-blood ratio for [89Zr]Zr-Df-LEM2/15 in the non-blocked group compared to the blocked and IgG isotype control groups, respectively. Specific uptake of LEM2/15 in TBNC tumours mediated by MT1-MMP-binding was demonstrated by the Patlak linearisation method, providing insights into the potential efficacy of LEM2/15-based treatments. A similar uptake was found for [89Zr]Zr-Df-LEM2/15 and [177Lu]Lu-DOTA-LEM2/15 in tumours 7 days post-injection (6.80 ± 1.31 vs. 5.61 ± 0.66 %ID/g). Tumour doubling time was longer in the [177Lu]Lu-DOTA-LEM2/15 3-dose regimen treated group compared to the control (50 vs. 17 days, respectively). The percentage of cells with γH2AX-foci was higher in tumours treated with [177Lu]Lu-DOTA-LEM2/15 3-dose regimen compared to tumours non-treated or treated with [177Lu]Lu-DOTA-LEM2/15 single-dose (12 % vs. 4-5 %). CONCLUSIONS: The results showed that the 89Zr/177Lu-labelled anti-MT1-MMP mAb (LEM2/15) pair facilitated immune-PET imaging and reduced tumour growth in a preclinical TNBC xenograft model.

Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues.

Cellular senescence is a hallmark of advanced age and a major instigator of numerous inflammatory pathologies. While endothelial cell (EC) senescence is aligned with defective vascular functionality, its impact on fundamental inflammatory responses in vivo at single-cell level remain unclear. To directly investigate the role of EC senescence on dynamics of neutrophil-venular wall interactions, we applied high resolution confocal intravital microscopy to inflamed tissues of an EC-specific progeroid mouse model, characterized by profound indicators of EC senescence. Progerin-expressing ECs supported prolonged neutrophil adhesion and crawling in a cell autonomous manner that additionally mediated neutrophil-dependent microvascular leakage. Transcriptomic and immunofluorescence analysis of inflamed tissues identified elevated levels of EC CXCL1 on progerin-expressing ECs and functional blockade of CXCL1 suppressed the dysregulated neutrophil responses elicited by senescent ECs. Similarly, cultured progerin-expressing human ECs exhibited a senescent phenotype, were pro-inflammatory and prompted increased neutrophil attachment and activation. Collectively, our findings support the concept that senescent ECs drive excessive inflammation and provide new insights into the mode, dynamics, and mechanisms of this response at single-cell level.

Accuracy of the 6-Minute Walk Test for Assessing Functional Capacity in Patients With Heart Failure With Preserved Ejection Fraction and Other Chronic Cardiac Pathologies: Results of the ExIC-FEp Trial and a Meta-Analysis.

BACKGROUND: Heart diseases, particularly heart failure, significantly impact patient quality of life and mortality rates. Functional capacity assessment is vital for predicting prognosis and risk in these patients. While the cardiopulmonary exercise test is considered the gold standard, the 6-minute walk test has emerged as a more accessible alternative. However, the screening accuracy and optimal cut-off points of the 6-minute walk test for detecting severely reduced functional capacity in cardiac pathologies, including heart failure with preserved ejection fraction, are unclear. The study aimed to analyse the diagnostic accuracy of the 6-minute walk test for detecting reduced functional capacity, defined as VO2max < 14 ml/kg/min, compared with the cardiopulmonary exercise test in participants with heart failure with preserved ejection fraction using data from the "Ejercicio en Insuficiencia Cardiaca con Fracción de Eyección Preservada" (ExIC-FEp) trial; and to compare these results with previous studies investigating the screening accuracy for assessing functional capacity of the 6-minute walk test in participants with other chronic cardiac pathologies through a meta-analysis. RESULTS: The ExIC-FEp trial involved 22 participants with heart failure with preserved ejection fraction, who were not treated with beta-blockers, using the cardiopulmonary exercise test, specifically VO2max, as the reference test. The 6-minute walk test had a sensitivity of 70%, a specificity of 80%, and an area under the curve of 76% in the ExIC-FEp trial. Five studies were included in the meta-analysis showing a sensitivity of 79%, a specificity of 78%, and an area under the curve of 85%. CONCLUSION: In conclusion, the 6-minute walk test holds promise as a screening tool for assessing functional capacity in heart failure with preserved ejection fraction and chronic heart diseases, with a VO2max < 14 ml/kg/min as a reference point. It demonstrates moderate to good screening accuracy. However, the screening accuracy and optimal cut-off points of the 6-minute walk test for detecting severely reduced functional capacity, regardless of aetiology, are unclear. TRIAL REGISTRATION: NCT05726474. Registered 16 February 2023, https://clinicaltrials.gov/study/NCT05726474 .

Percutaneous Endoscopic Gastrostomy with T-Fasteners versus "Pull Technique": Analysis of Complications.

INTRODUCTION: The T-fasteners gastrostomy (T-PEG) has become increasingly popular over recent years as an alternative to the "pull-technique" gastrostomy (P-PEG). This study aimed to compare P-PEG and T-PEG complications. MATERIALS AND METHODS: A retrospective observational study of pediatric patients who underwent percutaneous endoscopic gastrostomy (PEG) placement. P-PEG was performed using the standard Ponsky technique and was replaced after 6 months by a balloon gastrostomy under sedation. T-PEG was performed using three percutaneous T-fasteners (that allow a primary insertion of a balloon gastrostomy). The balloon was replaced by a new one after 6 months without sedation. Complications were recorded. RESULTS: In total, 146 patients underwent PEG placement, 70 P-PEG and 76 T-PEG. The mean follow-up was 3.9 years (standard deviation = 9.6). Age, weight, and associated comorbidities were comparable (p > 0.05). The overall complications were 17 (24.2%) in the P-PEG group and 16 (21.0%) in the T-PEG group (p > 0.05). P-PEG was associated with more sedation for button replacement (97 vs. 2.6% [p < 0.05]). P-PEG was associated with more early tube dislodgement during the first replacement (7.2 vs. 1.4% [p = 0.092]). Two of the five dislodged gastrostomies in the P-PEG group underwent laparotomy due to peritonitis, whereas the only dislodged gastrostomy in the T-PEG group was solved endoscopically. Altogether, P-PEG was associated with more complications that required urgent endoscopy, laparotomy, or laparoscopy (18.6 vs. 6.6% [p < 0.05]). CONCLUSIONS: P-PEG was associated with more sedation, complications during first button replacement, and complications requiring urgent endoscopy, laparotomy, or laparoscopy compared with T-PEG.

Dissecting the polygenic contribution of attention-deficit/hyperactivity disorder and autism spectrum disorder on school performance by their relationship with educational attainment.

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) are strongly associated with educational attainment (EA), but little is known about their genetic relationship with school performance and whether these links are explained, in part, by the genetic liability of EA. Here, we aim to dissect the polygenic contribution of ADHD and ASD to school performance, early manifestation of psychopathology and other psychiatric disorders and related traits by their relationship with EA. To do so, we tested the association of polygenic scores for EA, ADHD and ASD with school performance, assessed whether the contribution of the genetic liability of ADHD and ASD to school performance is influenced by the genetic liability of EA, and evaluated the role of EA in the genetic overlap between ADHD and ASD with early manifestation of psychopathology and other psychiatric disorders and related traits in a sample of 4,278 school-age children. The genetic liability for ADHD and ASD dissected by their relationship with EA show differences in their association with school performance and early manifestation of psychopathology, partly mediated by ADHD and ASD symptoms. Genetic variation with concordant effects in ASD and EA contributes to better school performance, while the genetic variation with discordant effects in ADHD or ASD and EA is associated with poor school performance and higher rates of emotional and behavioral problems. Our results strongly support the usage of the genetic load for EA to dissect the genetic and phenotypic heterogeneity of ADHD and ASD, which could help to fill the gap of knowledge of mechanisms underlying educational outcomes.

Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

[Exploring Needs, Motivations, and Limitations Towards Healthy Eating and Digital Resources: A Qualitative Study in a Mexican Primary Education Setting]. / Exploración de necesidades, motivaciones y limitaciones en relación con la alimentación saludable y recursos digitales: un estudio cualitativo en un entorno de educación primaria en México.

OBJECTIVE: To explore the needs, motivations, and limitations related to healthy eating and digital materials, as well as to identify patterns for their design as a strategy aimed at Mexican families. DESIGN: A qualitative observational study of the phenomenon through focus group sessions. LOCATION: A public primary education center in the city of Querétaro, Mexico. PARTICIPANTS: Children aged 9 to 11 years and parents, mothers, or caregivers with children in primary education. METHOD: Twelve sessions were conducted with three groups of students and two sessions with parents, mothers, or caregivers using an interview guide. Various digital materials, developed based on social cognitive theory, were presented during the sessions. The sessions were recorded with the participants' or their guardians' prior consent and transcribed for analysis. Coding was performed for key points of analysis, and information saturation was confirmed. RESULTS: Students expressed motivation towards digital material that promotes play and experimentation, especially within the family context. The main perceived barrier was the caregivers' resistance to change. Parents expressed motivation and a need for explanatory material on diseases, with economic and time-related barriers. CONCLUSIONS: Digital material based on social cognitive theory, designed to improve nutrition, can be an effective strategy in nutritional education if it considers the circumstances of the target population. It is advisable to include affective and behavioral elements to achieve meaningful learning within households.

Impact of memory bias in the dietary estimation of older adults measured through a food frequency questionnaire and weighed food records: A cross-sectional study in older adults and primary caregivers.

Introduction: Introduction: changes in cognitive performance and memory of older adults (OA) can interfere in their reporting their diet. Objective: to evaluate the impact of memory bias in dietary estimation between OA and their primary caregivers (PC) through the food frequency questionnaire (FFQ) for Mexican OA and weighed food records (WFR). Methods: the present analysis uses the estimated dietary information based on the response provided by 51 older adults (OA) and their primary caregivers (PC) from the validation study of the FFQ for Mexicans OA was conducted during lockdowns for COVID-19. The personnel who applied FFQ and WFR were trained with standardized instruments and procedures. The Wilcoxon test was used to compare the intake per day of the foods and food groups, the Spearman correlation coefficient was used to evaluate the grams of intake per day of the food groups, and kappa coefficient was used to compare the level of food items and food groups between OA and PC. Results: in 11 of 14 food groups, no significant differences were observed between the amounts of intake reported by OA and PC. In the groups of dairy products, fruits, vegetables, and legumes, moderate agreement was observed (κ = 0.63 to 0.79), and in the rest of the groups was strong to perfect (κ ≥ 0.80). Correlation of the amount of intake between OA and PC was high in all food groups (r ≥ 0.87). Conclusion: the high correlation and high agreement between the amounts and frequencies of the food groups consumed as reported by the older adults and primary caregivers indicate that the information from both respondents is reliable.

Introducción: Introducción: los cambios cognitivos y la memoria que presentan los adultos mayores (AM) pueden interferir al momento de reportar los alimentos de su dieta. Objetivo: evaluar el impacto del sesgo de memoria en la estimación de la dieta entre AM y sus cuidadores principales (CP) a través del cuestionario de frecuencia de alimentos (CFA) para AM mexicanos y el registro de peso de alimentos (RPA). Métodos: el presente análisis utiliza la información dietética estimada con base en la respuesta proporcionada por 51 adultos mayores (AM) y sus cuidadores principales (CP) del estudio de validación del CFA para AM mexicanos que se realizó durante el confinamiento por COVID-19. El personal que aplicó CFA y RPA fue capacitado con instrumentos y procedimientos estandarizados. Se utilizó prueba de Wilcoxon para comparar la ingesta por día de los alimentos y grupos de alimentos, el coeficiente de correlación de Spearman para evaluar los gramos de ingesta por día de los grupos de alimentos y el coeficiente kappa para comparar el nivel de alimentos y grupos de alimentos entre AM y CP. Resultados: en 11 de 14 grupos de alimentos no se observaron diferencias significativas entre las cantidades de ingesta reportadas por AM y CP. En los grupos de lácteos, frutas, verduras y legumbres se observó concordancia moderada (κ = 0,63 a 0,79), y en el resto de los grupos fue de fuerte a perfecta (κ ≥ 0,80). La correlación de la cantidad de ingesta entre AM y CP fue alta en todos los grupos de alimentos (r ≥ 0,87). Conclusión: La alta correlación y la alta concordancia entre las cantidades y frecuencias de los grupos de alimentos consumidos según lo informado por los adultos mayores y los cuidadores principales indican que la información de ambos encuestados es confiable.

Diagnostic Value of Krebs von den Lungen (KL-6) for Interstitial Lung Disease: A European Prospective Cohort.

INTRODUCTION: Krebs von den Lungen 6 (KL-6) is a mucin-1 glycoprotein produced by type II pneumocytes. High levels of KL-6 in blood may be found in patients with lung fibrosis. In Asia this biomarker is used for diagnosis and prognosis in interstitial lung diseases (ILD). There is a lack of information regarding KL-6 cut-off point for diagnosis and prognosis in European population. The aim of this study was to establish the cut-off point for serum KL-6 associated with the presence of ILD in the Spanish population. METHODS: Prospective study including subjects who underwent chest HRCT, PFTs and autoimmune blood analysis. Two groups were created: non-ILD subjects and ILD patients. Serum KL-6 concentrations were measured using a Lumipulse KL-6 reagent assay and the optimal cut-off value was evaluated by a ROC analysis. Data on demographics and smoking history was also collected. RESULTS: One hundred seventy-nine patients were included, 102 with ILD. Median serum KL-6 values overall were 762U/mL, 1080 (±787)U/mL for the ILD group vs 340 (±152)U/mL for the non-ILD group (p<0.0001). The main radiological pattern was NSIP (43%). ROC analysis showed greater specificity (86%) and sensitivity (82%) for KL-6 465U/mL for detecting ILD patients. The multivariate logistic regression model pointed to the male sex, higher KL-6 values, lower FVC and low DLCO values as independent factors associated with ILD. CONCLUSION: Serum KL-6 values greater than 465U/mL have excellent sensitivity and specificity for detecting ILD in our Spanish cohort. Multicentre studies are needed to validate our results.

Inter-laboratory comparison of routine autoantibody detection methods for autoimmune neuropathies and myasthenia gravis.

Serological tests are important to detect autoantibodies (autoAbs) in patients with autoimmune neuropathies (AN) and myasthenia gravis (MG) as they are biomarkers for diagnosis, stratification, treatment selection, and monitoring. However, tests to detect autoAbs frequently lack proper standardization and results differ across diagnostic laboratories. We compared results for tests routinely performed in Spanish diagnostic laboratories to detect AN and MG autoAbs. In the Spanish Society of Immunology Autoimmunity Group national workshop, serum samples from 13 patients with AN or MG were tested for anti-ganglioside, anti-myelin-associated glycoprotein (MAG), anti-nicotinic acetylcholine receptor (AChR), and anti-muscle-specific kinase (MuSK) autoAbs using reference methods and were distributed for analysis to 27 participating laboratories using their routine methods. Overserved were inter-laboratory variability and worryingly low sensitivity, especially for anti-ganglioside immunoglobulin G and anti-MAG autoAb detection. This pilot study reflects autoAbs detection state of the art in AN and MG testing in leading diagnostic laboratories in Spain, highlighting the need for standardization prior to clinical use.

Validación de una escala enfermera para evaluar las actitudes del profesorado en la atención diabética / Validation of a nursing scale for assessing teachers' attitudes to diabetes care

Objetivo: Validar el Inventario de Actitudes Negativas del Profesorado hacia la Atención del Alumnado con Diabetes Mellitus tipo 1 (INAPAD) y estudiar su fiabilidad mediante los coeficientes Alfa de Cronbach y Omega de McDonald. Material y método: Este estudio describe el proceso de diseño y validación de la escala enfermera INAPAD en una muestra de 382 docentes en las etapas de Educación Infantil, Educación Primaria, Educación Secundaria Obligatoria, Bachillerato y Formación Profesional en una provincia española. El INAPAD pretende valorar diversas dimensiones actitudinales sobre la atención educativa al alumnado con Diabetes Mellitus tipo 1, incidiendo tanto en el perfil docente y profesional del profesorado, como en las características y necesidades específicas de este alumnado. Por su parte, la validez de constructo se ha evaluado mediante análisis factoriales exploratorios por componentes principales y rotación varimax. Resultados y Conclusión: Los resultados obtenidos informan de la viabilidad del INAPAD para ser utilizado como un instrumento útil para el diagnóstico del prejuicio o predisposición del profesorado hacia la atención del alumnado con DM tipo 1 y, por ende, para predecir el éxito de las medidas psicopedagógicas y los cuidados del niño y adolescente con diabetes. (AU)

Objective: To validate the Inventory of Teachers' Negative Attitudes towards the Care of Students with Diabetes Mellitus type 1 (INAPAD) and to study its reliability using Cronbach's Alpha and McDonald's Omega coefficients. Enfermería GlobalNº 74 Abril 2024Página 195Methods: This study describes the design and validation process of the INAPAD nursing scale in a sample of 382 teachers in the stages of Early Childhood Education, Primary Education, Compulsory Secondary Education, Baccalaureate and Vocational Training in a Spanish province. In order to validate the INAPAD, its reliability has been studied using Cronbach's Alpha and McDonald's Omega Coefficients. Hence, the construct validity has been evaluated through exploratory factor analysis by principal components and varimax rotation. Results and conclusion: The findings obtained inform the viability of the INAPAD to be used as an effective instrument for the diagnosis of prejudice or predisposition of educators towards the care of learners with type 1 DM and for the prediction of the success of psycho-pedagogical measures and of the care for children and adolescents with diabetes. (AU)

Sex differences on constitutive long non-coding RNA expression: Modulatory effect of estradiol and testosterone in muscle cells.

INTRODUCTION: Despite the growing awareness of sexual dimorphism between males and females under pathological and physiological conditions, sex bias in biomedical research in animal models and patients is still present nowadays. The main objective of this work was to investigate sex differences in constitutive long non-coding RNA expression in spinal cord and skeletal muscle from wild-type mice. MATERIALS AND METHODS: To assess the influence of gender on long non-coding RNAs, we extracted RNA from tissues of male and female mice and analyzed the expression on nine long non-coding RNAs, selected for being among the most commonly studied or exerting an important role in muscle, at 50, 60, and 120 days of age. RESULTS AND DISCUSSION: We observed age- and tissue-dependent significant sex differences, being more prominent in skeletal muscle. We also studied the effect of sex steroid hormones on long non-coding RNA expression in vitro, noticing a modulation of long non-coding RNA levels upon estradiol and dihydrotestosterone treatment in muscle. CONCLUSIONS: Taken together, results obtained evidenced sex differences on constitutive long non-coding RNA expression and suggested an influence of steroid hormones complementary to other possible factors. These findings emphasize the importance of including both sexes in experimental design to minimize any potential sex bias.

Fossil Collection at the Zoology Museum of the University of Concepción: enhancing understanding of Chile's past biodiversity.

Background: The digital inventory of paleontological material stored in Chilean museums is highly relevant as it increases accessibility to information, both locally and over long distances, while reducing wear and tear on specimens caused by physical manipulation. The Fossil Collection database of the Museum of Zoology of the University of Concepción (UCC_MZUC_FOS) includes 144 records, with the main representatives being marine invertebrates of the Bivalvia, Echinoidea and Gastropoda classes. Notable species include Encopecalderensis, Hemiasterwayensis, Zygochlamyspatagonica and Retrotapesexalbidus, most of which come from important Chilean fossil sites. Material was collected between 1970 and 2017, with a large portion of it being donated and identified by Professor Emeritus Hugo I. Moyano and Dr. Alberto Larraín. Although the specimens contained in the resource offer basic collecting information, they substantially contribute to sharing knowledge on the fossils kept in the museums throughout the country, while providing data on their distribution. New information: This resource corresponds to the first publication of data on faunal fossils from a museum collection in Chile on the Global Biodiversity Information Facility (GBIF) platform, thereby enhancing the understanding and documentation of Chile's paleontological heritage and its national biodiversity.

Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren's syndrome: a 3-year follow-up cohort study.

Introduction: This was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren's syndrome (SS). Methods: The inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted. Results: A total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers. Discussion: Patients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci.

Membrane Proteome-Wide Screening of Autoantibodies in CIDP Using Human Cell Microarray Technology.

BACKGROUND AND OBJECTIVES: Autoantibody discovery in complex autoimmune diseases is challenging. Diverse successful antigen identification strategies are available, but, so far, have often been unsuccessful, especially in the discovery of protein antigens in which conformational and post-translational modification are critical. Our study assesses the utility of a human membrane and secreted protein microarray technology to detect autoantibodies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: A cell microarray consisting of human embryonic kidney-293 cells expressing >5,000 human proteins was used. First, a validation step was performed with 4 serum samples from patients with autoimmune nodopathy (AN) to assess the ability of this technology to detect circulating known autoantibodies. The ability of the cell microarray technology to discover novel IgG autoantibodies was assessed incubating the array with 8 CIDP serum samples. Identified autoantibodies were subsequently validated using cell-based assays (CBAs), ELISA, and/or tissue immunohistochemistry and analyzed in a cohort of CIDP and AN (n = 96) and control (n = 100) samples. RESULTS: Serum anti-contactin-1 and anti-neurofascin-155 were detected by the human cell microarray technology. Nine potentially relevant antigens were found in patients with CIDP without other detectable antibodies; confirmation was possible in six of them: ephrin type-A receptor 7 (EPHA7); potassium-transporting ATPase alpha chain 1 and subunit beta (ATP4A/4B); leukemia-inhibitory factor (LIF); and interferon lambda 1, 2, and 3 (IFNL1, IFNL2, IFNL3). Anti-ATP4A/4B and anti-EPHA7 antibodies were detected in patients and controls and considered unrelated to CIDP. Both anti-LIF and anti-IFNL antibodies were found in the same 2 patients and were not detected in any control. Both patients showed the same staining pattern against myelinating fibers of peripheral nerve tissue and of myelinating neuron-Schwann cell cocultures. Clinically relevant correlations could not be established for anti-LIF and anti-IFNL3 antibodies. DISCUSSION: Our work demonstrates the utility of human cell microarray technology to detect known and discover unknown autoantibodies in human serum samples. Despite potential CIDP-associated autoantibodies (anti-LIF and anti-IFNL3) being identified, their clinical and pathogenic relevance needs to be elucidated in bigger cohorts.

Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017.

BACKGROUND: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population. METHODS: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe+ (includes Iran) , Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb-body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age. RESULTS: Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals [CI]: 3.01, 3.11), with marked regional variation. European+ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European+ , four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic. CONCLUSIONS: Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.