Electrochemical bioplatform to manage alpha-gal syndrome by tracking the carbohydrate allergen in meat.

This work presents the first bioplatform described to date for the determination of galactose-α-1,3-galactose (α-Gal), a non-primate mammalian oligosaccharide responsible for almost all cases of red meat allergy. The bioplatform is based on the implementation of an indirect competitive immunoassay and enzymatic labeling with the enzyme horseradish peroxidase (HRP) built on the surface of magnetic microparticles (MBs) and amperometric transduction on screen-printed carbon electrodes (SPCEs) using the H2O2/hydroquinone (HQ) system. The target α-Gal competed with biotinylated α-Gal immobilized on the surface of neutravidin-modified MBs for the limited immunorecognition sites of a detection antibody enzymatically labeled with an HRP-conjugated secondary antibody. The resulting magnetic immunoconjugates were trapped on the surface of the SPCE working electrode and amperometric transduction was performed, providing a cathodic current variation inversely proportional to the concentration of α-Gal in the analyzed sample. The developed biotool was optimized, characterized and applied with satisfactory results to the determination of the target allergen in different samples of raw and processed meats.

Towards a scalable approach to assess speech organization across the psychosis-spectrum -online assessment in conjunction with automated transcription and extraction of speech measures.

Automatically extracted measures of speech constitute a promising marker of psychosis as disorganized speech is associated with psychotic symptoms and predictive of psychosis-onset. The potential of speech markers is, however, hampered by (i) lengthy assessments in laboratory settings and (ii) manual transcriptions. We investigated whether a short, scalable data collection (online) and processing (automated transcription) procedure would provide data of sufficient quality to extract previously validated speech measures. To evaluate the fit of our approach for purpose, we assessed speech in relation to psychotic-like experiences in the general population. Participants completed an 8-minute-long speech task online. Sample 1 included measures of psychometric schizotypy and delusional ideation (N = 446). Sample 2 included a low and high psychometric schizotypy group (N = 144). Recordings were transcribed both automatically and manually, and connectivity, semantic, and syntactic speech measures were extracted for both types of transcripts. 73%/86% participants in sample 1/2 completed the experiment. Nineteen out of 25 speech measures were strongly (r > 0.7) and significantly correlated between automated and manual transcripts in both samples. Amongst the 14 connectivity measures, 11 showed a significant relationship with delusional ideation. For the semantic and syntactic measures, On Topic score and the Frequency of personal pronouns were negatively correlated with both schizotypy and delusional ideation. Combined with demographic information, the speech markers could explain 11-14% of the variation of delusional ideation and schizotypy in Sample 1 and could discriminate between high-low schizotypy with high accuracy (0.72-0.70, AUC = 0.78-0.79) in Sample 2. The moderate to high retention rate, strong correlation of speech measures across manual and automated transcripts and sensitivity to psychotic-like experiences provides initial evidence that online collected speech in combination with automatic transcription is a feasible approach to increase accessibility and scalability of speech-based assessment of psychosis.

Intestinal factors promoting the development of RORγt+ cells and oral tolerance.

The gastrointestinal tract has to harmonize the two seemingly opposite functions of fulfilling nutritional needs and avoiding the entry of pathogens, toxins and agents that can cause physical damage. This balance requires a constant adjustment of absorptive and defending functions by sensing environmental changes or noxious substances and initiating adaptive or protective mechanisms against them through a complex network of receptors integrated with the central nervous system that communicate with cells of the innate and adaptive immune system. Effective homeostatic processes at barrier sites take the responsibility for oral tolerance, which protects from adverse reactions to food that cause allergic diseases. During a very specific time interval in early life, the establishment of a stable microbiota in the large intestine is sufficient to prevent pathological events in adulthood towards a much larger bacterial community and provide tolerance towards diverse food antigens encountered later in life. The beneficial effects of the microbiome are mainly exerted by innate and adaptive cells that express the transcription factor RORγt, in whose generation, mediated by different bacterial metabolites, retinoic acid signalling plays a predominant role. In addition, recent investigations indicate that food antigens also contribute, analogously to microbial-derived signals, to educating innate immune cells and instructing the development and function of RORγt+ cells in the small intestine, complementing and expanding the tolerogenic effect of the microbiome in the colon. This review addresses the mechanisms through which microbiota-produced metabolites and dietary antigens maintain intestinal homeostasis, highlighting the complementarity and redundancy between their functions.

Egg yolk lipids induce sensitization to egg white proteins in a mouse model without adjuvant and exacerbate Th2 responses to egg white in cells from allergic patients.

This study evaluates the influence of egg lipid fractions in the induction of allergic sensitization to egg white (EW) proteins, using a mouse model of orally adjuvant-free induced allergy. Egg triglycerides (TG) and phospholipids (PL), and to a higher extent the whole egg lipid fraction (EL), induced allergy to EW proteins characterized by increased EW-specific IgG1. EL also increased EW-specific IgE. The administration to mice of a mixture of EW and EL increased the intestinal expression of Il33, Il25, and Tslp, the secretion of IL-33 and IL-6, the expansion of group 2 innate lymphoid cells, the regulation of Gata3, Il4 and Il13, dendritic cell (DC) activation and expression of DC molecules that drive Th2 differentiation. TG promoted the absorption of proteins through the intestinal epithelium, enhancing local Th2 responses, while PL favoured the delivery of antigens to the Peyer's Patches. This differential modulation of the site of absorption of egg proteins determined the different behaviour of TG and PL. Egg yolk lipids also induced activation of Th2-inducing innate responses on intestinal human cells in vitro and enhanced adaptive Th2 functions through the activation of DCs in egg-allergic subjects.

Evaluation of the innate immune response of caprine neutrophils against Mycobacterium avium subspecies paratuberculosis in vitro.

Neutrophils constitute an essential component of the innate immune response, readily killing most bacteria through phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETs) among other mechanisms. These cells play an unclear role in mycobacterial infections such as Mycobacterium avium subspecies paratuberculosis (Map), the etiological agent of paratuberculosis, and its response is particularly understudied in ruminants. Herein, a wide set of techniques were adapted, or newly developed, to study the in vitro response of caprine neutrophils after Map infection. Immunofluorescence was used to demonstrate, simultaneously, chemotaxis, phagocytosis, degranulation, and NETs. The quantification of neutrophil phagocytic activity against Map at a 1:10 multiplicity of infection (MOI), through flow cytometry, showed values that varied from 4.54 to 5.63% of phagocyting neutrophils. By immunofluorescence, a 73.3 ± 14.5% of the fields showed NETs, and the mean release of DNA, attributable to NETosis, calculated through a fluorometric method, was 16.2 ± 3.5%. In addition, the RNA expression of TGF-ß, TNF and IL-1ß cytokines, measured through reverse transcription qPCR, was significantly higher in the two latter. Overall, neutrophil response was proportional to the number of bacteria. This work confirms that the simultaneous study of several neutrophil mechanisms, and the combination of different methodologies, are essential to reach a comprehensive understanding of neutrophil response against pathogens, demonstrates that, in vitro, caprine neutrophils display a strong innate response against Map, using their entire repertoire of effector functions, and sets the basis for further in vitro and in vivo studies on the role of neutrophils in paratuberculosis.

Telemedicine and HIV Care Quality Measures During the COVID-19 Pandemic.

BACKGROUND: During the COVID-19 pandemic, telemedicine was adopted to ensure continuity of HIV care. We examined how introducing televisits affected technical quality of care for people with HIV (PWH) during this time. METHODS: PWH receiving HIV care at Howard Brown Health Centers and Northwestern University in Chicago, Illinois were included. HIV care quality indicators were calculated using data extracted from electronic medical records during 4 timepoints every 6 months from March, March 1, 2020 to September 1, 2021. Generalized linear mixed models estimated differences in indicators across timepoints within each site while controlling for multiple observations of individuals. Generalized linear mixed models were also used to compare differences in outcomes among PWH who attended all versus a combination of in-person and televisits versus no televisits across the study time periods. RESULTS: 6447 PWH were included in the analysis. Compared with prepandemic levels, there were significant declines in care utilization and processes of care measures. Measures of HIV virologic suppression, blood pressure control, and HbA1C <7% (in both people with and without diabetes) were stable with no significant differences noted across the study timepoints. Similar trends were observed across all age, race, and sex subgroups. In multivariable models, televisits were not associated with decreased HIV viral suppression. CONCLUSIONS: During the COVID-19 pandemic and rapid implementation of televisits, indicators of care utilization and processes of care decreased compared with prepandemic levels. Among PWH who remained in care, televisits were not associated with worse virologic, blood pressure, and glycemic control in PWH.

Bos d 13, A Novel Heat-Stable Beef Allergen.

SCOPE: Red meat, a staple food of Western diets, can also induce IgE-mediated allergic reactions. Yet, apart from the heat-labile protein serum albumin and the carbohydrate α-Gal, the molecules causing allergic reactions to red meat remain unknown. METHODS AND RESULTS: IgE reactivity profiles of beef-sensitized individuals are analyzed by IgE-immunoblotting with protein extracts from raw and cooked beef. Two IgE-reactive proteins are identified by peptide mass fingerprinting as myosinlight chain 1 (MYL1) and myosin light chain 3 (MYL3) in cooked beef extract and are designated Bos d 13 isoallergens. MYL1 and MYL3 are produced recombinantly in Escherichia coli. ELISAs proved their IgE reactivity and circular dichroism analysis showed that they represent folded molecules with remarkable thermal stability. In vitro gastrointestinal digestion experiments showed the higher stability of rMYL1 as compared to rMYL3. Exposure of a monolayer of Caco-2 cells to rMYL1 indicated that the molecule is able to cross intestinal epithelial cells without disturbing the integrity of the tight junctions, suggesting the sensitizing capacity of MYL1. CONCLUSION: MYLs are identified as novel heat-stable bovine meat allergens.

Meta-analyses of teacher-delivered trauma-based and trauma-informed care interventions.

OBJECTIVE: Children impacted by adversity and trauma often experience psychological, emotional, behavioral, and academic difficulties. To address these concerns, there is a growing call for trauma-informed school systems to better support students with trauma histories. Teacher involvement in trauma-informed approaches is vital but understudied. METHOD: We conducted a meta-analytic review of the literature published between 1990 and 2019 to evaluate outcomes for teachers and students involved in teacher-delivered trauma interventions. Inclusion criteria specified peer-reviewed studies, dissertations, and nonacademic reports that used randomized controlled and nonrandomized pre-post intervention designs. RESULTS: We found 20 articles, of which, 12 were pre-post and eight were randomized designs. Seven articles specifically incorporated trauma-informed care (TIC), whereas the other 13 were traditional trauma-based mental health interventions. We conducted meta-analyses to assess student trauma symptom severity and teacher knowledge of trauma-informed practices. Results revealed that after participating in teacher-delivered trauma interventions, students reported significantly reduced trauma symptom severity postintervention and less severity of symptoms than students in the control conditions. There were no differences between trauma-based and TIC intervention student outcomes. Teachers exhibited greater knowledge acquisition after participating in TIC interventions. CONCLUSION: These findings suggest that trauma interventions, both with and without explicitly referencing TIC principles, are evidence-based in the context of teacher-facilitated school interventions. Additional research is needed to evaluate the organizational benefits of TIC, particularly to determine if the benefits of trauma-informed schools extend beyond students. We conclude with research, policy, and practice recommendations for transformative change to create trauma-informed schools. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Untargeted serum metabolomic analysis reveals a role for purinergic signaling in FPIES.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with a typical onset in infancy. Its symptoms are distinct from those of IgE-mediated food allergies and include severe repetitive vomiting, lethargy, and pallor. FPIES reactions are associated with TH17 cytokines and a systemic innate immune activation; however, the link between immune activation and symptoms is poorly understood. OBJECTIVE: Our aim was to use an untargeted metabolomics approach to identify novel pathways associated with FPIES reactions. METHODS: Serum samples were obtained before, during, and after oral food challenge (OFC) (10 subjects with FPIES and 10 asymptomatic subjects), and they were analyzed by untargeted metabolomics. Two-way ANOVA with false discovery rate adjustment was used for analysis of metabolites. Stomach and duodenal biopsy specimens from non-FPIES donors were stimulated with adenosine in vitro and serotonin measured by immunoassay. RESULTS: The levels of a total of 34 metabolites, including inosine and urate of the purine signaling pathway, were increased during OFCs performed on the patients with symptomatic FPIES compared with the levels found for asymptomatic subjects. Expression of the purine receptors P2RX7 and P2RY10 and the ectonucleotidase CD73 in peripheral blood was significantly reduced after OFC of the patients with FPIES. The level of the serotonin metabolite 5-hydroxyindoleacetate was significantly elevated after reaction. Adenosine stimulation of gastric and duodenal biopsy specimens from FPIES-free donors induced a significant release of serotonin, suggesting a link between purinergic pathway activation and serotonin release. CONCLUSIONS: Activation of the purinergic pathway during FPIES reactions provides a possible mechanism connecting inflammation and vomiting by triggering serotonin release from gastric and duodenal mucosa.

A Learning Health System Approach to Cancer Survivorship Care Among LGBTQ+ Communities.

PURPOSE: Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) individuals who receive primary care services at community health centers are often referred to external specialty care centers after cancer diagnosis, upon which primary care services are disrupted and may be discontinued because of gaps in communication between primary and oncologic care providers. This qualitative study evaluated barriers and facilitators to effective care coordination for LGBTQ+ patients with cancer and the utility of a novel cancer care coordination tool to mitigate identified barriers. MATERIALS AND METHODS: Semistructured interviews with LGBTQ+ cancer survivors, caregivers to LGBTQ+ persons, clinical team members who provide care to LGBTQ+ patients, and members of community-based organizations that work with LGBTQ+ patients were conducted. Interview analysis was a multistage process, wherein a constant comparison approach was used. Transcripts were reviewed and coded using Atlas.ti Cloud. RESULTS: A total of 26 individuals were interviewed: 10 patients, four caregivers, 10 clinical care team members, and two community organization representatives. Interview analysis yielded insight regarding (1) LGBTQ+ patient experiences engaging with primary and oncologic care at the clinic level and (2) perceptions of patient-provider and provider-provider communication and coordination. CONCLUSION: Interview findings indicate a need for further development of interventions aimed at improving care coordination, patient experience, and outcomes in the cancer care continuum for LGBTQ+ patients. Learning health systems, like the one studied, show great potential for contributing to the development of such interventions.

IgE-Binding and Immunostimulating Properties of Enzymatic Crosslinked Milk Proteins as Influenced by Food Matrix and Digestibility.

Dairy foods are essential in the diet, although in some susceptible individuals they may cause allergy to cow's milk proteins. Therefore, alternative methods are sought to reduce their allergenicity. Transglutaminase (TG) is widely used in dairy products mainly to improve texture. Although it has been claimed that TG can be used to modify the digestibility and allergenicity of foods, its impact within a real matrix has been rarely studied. The aim of this work was to assess the allergenic potential of crosslinked skim milk (SM), milk casein fraction (CN), and whey protein (WP). To this purpose, inhibition ELISA with sera from milk allergic patients, in vitro activation tests of mouse mast cells and splenocytes, and simulated gastrointestinal digestion assays were performed. The results showed that cross-linking increased the binding of IgE to WP, but decreased IgE-binding to SM and CN. However, no differences were observed in the ability of cross-linked proteins to induce mast cell degranulation compared to native proteins. The cross-linking of SM and CN reduced Th2 cytokine release from the splenocytes of sensitized mice. All TG-treated samples exhibited more resistance to in vitro digestion than the untreated proteins and the human IgE binding capacity after digestion was higher. In conclusion, TG treatment of milk proteins does not reduce the risk of eliciting allergic symptoms in cow's milk allergic patients.

Caco-2 Cell Response Induced by Peptides Released after Digestion of Heat-Treated Egg White Proteins.

The heat treatment of food proteins induces structural modifications that influence their interaction with human fluids and cells. We aimed to evaluate the Caco-2 cell response induced by peptides produced after digestion of heat-treated egg white proteins. In vitro digestion of ovalbumin (OVA), ovomucoid (OM), and lysozyme (LYS), untreated or previously heated, was performed. The digestibility of proteins and the response of Caco-2 cells exposed to peptides (<10 kDa) generated during digestion were evaluated. Intact OVA and LYS persisted after the digestion of native proteins, whereas OM was completely hydrolysed. A heat treatment at 65 °C for 30 min did not alter the digestibility of OVA, whereas at 90 °C for 3 min, protein degradation was favoured. The digestibility of OM and LYS was not affected by heat treatment. Peptides derived from OVA and OM digestion induced IL-6 and IL-8 production. OVA and LYS digestion promoted the expression of Tslp, and Il6 and Il33, respectively. A heat treatment prior to OVA digestion reduced IL-6 production and Tslp expression. It was concluded that heat treatments can reduce the release of OVA-derived peptides, but not OM and LYS, with proinflammatory activity during digestion.

Escala para la identificación del paciente pediátrico crónico complejo (Escala PedCom). Estudio piloto / A scale for the identification of the complex chronic pediatric patient (PedCom Scale): A pilot study

Introducción y objetivos: La condición crónica compleja (CCC) es una realidad cada vez más prevalente en pediatría. Sin embargo, padecer una CCC no supone necesariamente ser un paciente crónico complejo (PCC). Desde esta perspectiva, nos propusimos el desarrollo de un instrumento (Escala PedCom) que facilitase la identificación del PCC. Material y métodos: Inicialmente se definieron aspectos generales para la clasificación de un paciente como PCC. Posteriormente se desarrollaron los ítems de la escala puntuándolos de 0,5 a 4 puntos. Se realizó análisis factorial confirmatorio (AFC) y se estudió la consistencia interna mediante alfa de Cronbach. La concordancia se evaluó mediante estudio intra- e interobservador. El gold standard fue la clasificación realizada por 2 evaluadores tras valoración de la historia clínica del paciente. El punto de corte para considerar al paciente como PCC se estableció mediante curva ROC. Resultados: La versión inicial incluyó 43 ítems con índice de validez de contenido global (IVC) de 0,94. Para el estudio se incluyeron 180 pacientes. Tras el AFC se eliminó un ítem, por lo que la versión final consta de 42 ítems con IVC de 0,95. El valor alfa de Cronbach fue 0,723. El índice de correlación intraclase del análisis test-retest fue de 0,998 y 0,996 para el estudio interobservador. El punto de corte para considerar a un paciente como PCC se estableció en 6,5 puntos, con el que se obtuvo una sensibilidad del 98% y especificidad del 94%. Conclusiones: La Escala PedCom es una herramienta de fácil uso enfocada a la identificación del PCC. En nuestra muestra, presentó adecuada consistencia interna y niveles adecuados de concordancia intra- e interobservador; con buenos resultados de sensibilidad y especificidad para la identificación del PCC. (AU)

Introduction and objectives: The complex chronic condition (CCC) is an increasingly prevalent reality in pediatrics. However, having a CCC does not necessarily mean being a complex chronic patient (CCP). From this perspective, we developed an instrument (PedCom Scale) that would facilitate the identification of the PCC. Material and methods: Initially, general aspects for the classification of patients as CCP were defined. Subsequently, the items of the scale were developed, scoring them from 0.5 to 4 points. We performed a confirmatory factor analysis (CFA) and the internal consistency was studied using alpha-Cronbach. Concordance was evaluated by intra- and inter-observer study. The gold standard was the classification performed by two evaluators after assessing the patient's medical history. The cut-off point for considering the patient as a CCP was established using the ROC curve. Results: The initial version included 43 items with a global content validity index (CVI) of 0.94. A total of 180 patients were included. After the CFA, one item was eliminated, so the final version consists of 42 items with an CVI of 0.95. The alpha-Cronbach value was 0.723. The intraclass correlation coefficient of the test–retest analysis was 0.998 and 0.996 for the inter-observer study. The cut-off point for considering a patient as a CCP was established at 6.5 points, with these results we obtained a sensitivity of 98% and specificity of 94%. Conclusions: The PedCom Scale is an easy-to-use tool focused on the identification of the CCP. In our sample, it presented satisfactory levels of internal consistency and adequate levels of intra- and inter-observer agreement, with good sensitivity and specificity for the identification of the PCC. (AU)

Is There Evidence of Health Risks From Exposure to Micro- and Nanoplastics in Foods?

The human health impact of exposure to micro (MP) and nanoplastics (NP) from food remains unknown. There are several gaps in knowledge that prevent a complete risk assessment of them. First, the fact that some plastics may be chemically harmful, either directly toxic themselves or because they absorb and carry other components, which makes these particles may possess 3 types of hazards, physical, chemical and biological. In addition, the levels at which toxic effects may occur are unknown and there is a lack of studies to estimate the levels to which we are exposed. Plastic particles can induce physical stress and damage, apoptosis, necrosis, inflammation, oxidative stress and immune responses, which could contribute to the development of diseases such as cancer, metabolic disorders, and neurodevelopmental conditions, among others. In addition, they may have effects on other pathologies that have not yet been studied, such as food allergy, where they could act modifying the digestibility of food allergens, increasing intestinal permeability, promoting an intestinal inflammatory environment or causing intestinal dysbiosis, which could promote food allergen sensitization. However, given the limited information on the presence of MP and especially NP in food, further research is needed to estimate whether they could amplify the risk of allergic sensitization to food proteins and to elucidate the risk to human health.

A scale for the identification of the complex chronic pediatric patient (PedCom Scale): A pilot study.

INTRODUCTION AND OBJECTIVES: The complex chronic condition (CCC) is an increasingly prevalent reality in pediatrics. However, having a CCC does not necessarily mean being a complex chronic patient (CCP). From this perspective, we developed an instrument (PedCom Scale) that would facilitate the identification of the CCP. MATERIAL AND METHODS: Initially, general aspects for the classification of patients as CCP were defined. Subsequently, the items of the scale were developed, scoring them from 0.5 to 4 points. We performed a confirmatory factor analysis (CFA) and the internal consistency was studied using alpha-Cronbach. Concordance was evaluated by intra- and inter-observer study. The gold standard was the classification performed by two evaluators after assessing the patient's medical history. The cut-off point for considering the patient as a CCP was established using the ROC curve. RESULTS: The initial version included 43 items with a global content validity index (CVI) of 0.94. A total of 180 patients were included. After the CFA, one item was eliminated, so the final version consists of 42 items with an CVI of 0.95. The alpha-Cronbach value was 0.723. The intraclass correlation coefficient of the test-retest analysis was 0.998 and 0.996 for the inter-observer study. The cut-off point for considering a patient as a CCP was established at 6.5 points, with this results we obtained a sensitivity of 98% and specificity of 94%. CONCLUSIONS: The PedCom Scale is an easy-to-use tool focused on the identification of the CCP. In our sample, it presented satisfactory levels of internal consistency and adequate levels of intra- and inter-observer agreement, with good sensitivity and specificity for the identification of the CCP.

Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress.

We have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month follow-up. Infarcted animals presented cardiac hypertrophy and a reduction in the left ventricular ejection fraction (LVEF) and E- and A-waves (E/A) ratio when compared to controls. Myocardial infarction (MI) rats also showed cardiac fibrosis and endoplasmic reticulum (ER) stress activation. Binding immunoglobulin protein (BiP) levels, a marker of ER stress, were correlated with collagen I levels. MitoQ reduced oxidative stress and prevented all these changes without affecting the infarct size. The LVEF and E/A ratio in patients with MI were 57.6 ± 7.9% and 0.96 ± 0.34, respectively. No major changes in cardiac function, extracellular volume fraction (ECV), or LV mass were observed at follow-up. Interestingly, the myeloperoxidase (MPO) levels were associated with the ECV in basal conditions. BiP staining and collagen content were also higher in cardiac samples from autopsies of patients who had suffered an MI than in those who had died from other causes. These results show the interactions between mitochondrial oxidative stress and ER stress, which can result in the development of diffuse fibrosis in the context of MI.

Prospective Real-World Gynaecological Cancer Clinical Registry with Associated Biospecimens: A Collaborative Model to Promote Translational Research between GEICO and the Spanish Biobank Network.

Patient registries linked to biorepositories constitute a valuable asset for clinical and translational research in oncology. The Spanish Group of Ovarian Cancer Research (GEICO), in collaboration with the Spanish Biobank Network (RNBB), has developed a multicentre, multistakeholder, prospective virtual clinical registry (VCR) associated with biobanks for the collection of real-world data and biological samples of gynaecological cancer patients. This collaborative project aims to promote research by providing broad access to high-quality clinical data and biospecimens for future research according to the needs of investigators and to increase diagnostic and therapeutic opportunities for gynaecological cancer patients in Spain. The VCR will include the participation of more than 60 Spanish hospitals entering relevant clinical information in harmonised electronic case report forms (eCRFs) in four different cohorts: ovarian, endometrial, cervical, and rare gynaecological cancers (gestational trophoblastic disease). Initial data for the cases included till December 2021 are presented. The model described herein establishes a real-world win-win collaboration between multicentre structures, promoted and supported by GEICO, that will contribute to the success of translational research in gynaecological cancer.

Efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis: a protocol for a multicentre, randomised, parallel three arms, active-controlled, phase III open label with blinded outcome assessment study.

INTRODUCTION: Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet. METHODS AND ANALYSIS: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects' subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers. ETHICS AND DISSEMINATION: The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation. TRIAL REGISTRATION NUMBER: 2020-000130-18; NCT04798755.