Consensus statement from the AEDV Psoriasis Working Group (SWG) and Pediatric Working group (PWG) on the management of pediatric psoriasis. / Documento de consenso del Grupo Español de Psoriasis (GPS) y del grupo Español de Dermatología Pediátrica (GEDP) de la AEDV sobre el manejo de la psoriasis pediátrica.

Justification and objectives: The Spanish Academy of Dermatology and Venereology (AEDV) Psoriasis and Pediatric Working Groups (PSW and PWG) have developed a set of recommendations for the management of pediatric psoriasis based on the best available evidence and experts' opinion. Methodology: The methodology of nominal groups was followed, with help from a scoping review. A coordinator was designated, and a group of experts was selected based on their experience and knowledge on the management of psoriasis. The coordinator defined both the objectives and the key points of the document. Then, with help from a documentalist, a systematic literature review was conducted across Medline, Embase and Cochrane Library until May 2023. Systematic literature reviews, meta-analyses, and observational studies were included. National and international clinical practice guidelines and consensus documents were reviewed. With this information, the coordinator proposed preliminary recommendations that were discussed and modified in a nominal group meeting with all experts. After several review processes, which included an external review, the final document was generated. Results: Practical recommendations on the evaluation and management of patients with pediatric psoriasis are presented in association with other AEDV documents. The evaluation of the pediatric patient, the definition of the therapeutic objectives, the criteria for indication and selection of treatment are addressed. Practical issues such as therapeutic failure, response maintenance, comorbidity and risk management are also included.

Embryo Quality Conditions the Secretory Profile of Tolerogenic Dendritic Cell DC-10 During the Peri-Implantation Period.

PROBLEM: The decidualization process conditions monocytes to the immunosuppressive and tolerogenic dendritic cell (DC)-10 profile, a DC subset with high IL-10 production. Since the implantation process implies an embryo-endometrium-immune crosstalk, here we focused on the ability of embryonic soluble factors to modify decidual DC conditioning accordingly with its quality. METHOD OF STUDY: Human endometrial stromal cell line (HESC) decidualized with medroxyprogesterone and dibutyryl-cAMP (Dec) was stimulated with human embryo-conditioned media (ECM), classified as normal (ND) or impaired developed (ID) for 48 h (n = 18/group). Monocytes isolated from six healthy women were differentiated to DCs with rhGM-CSF+rhIL-4 in the presence/absence of conditioned media (CM) from decidualized cells stimulated with ECM or nontreated. RESULTS: We found that decidualized cells stimulated with ECM sustain a myeloid regulatory cell profile on monocyte-derived culture with increased frequency of CD1a-CD14+ and CD83+CD86low cells. ND-Dec sustained the higher expression of the DC-10 markers, HLA-G and IL-10 whereas ID-Dec diminished IL-10 production (ID-Dec: 135 ± 37.4 vs. Dec: 223.3 ± 49.9 pg/mL, p < 0.05). The treatment with ECM-Dec sustained a higher IL-10 production and prevented the increase of CD83/CD86 after LPS challenge regardless of embryo quality. Notably, TNF-α production increased in ID-Dec cultures (ID-Dec: 475.1 ± 134.7 vs. Dec: 347.5 ± 98 pg/mL, p < 0.05). CONCLUSIONS: Although remaining in a tolerogenic profile compatible with DC-10, DCs can differentially respond to decidual secreted factors based on embryo quality, changing their secretome. These results suggest that in the presence of arrested embryo, DCs could differentially shape the immunological microenvironment, contributing to arrested embryo clearance during the menstrual phase.

MHC class II proteins mediate sialic acid independent entry of human and avian H2N2 influenza A viruses.

Influenza A viruses (IAV) pose substantial burden on human and animal health. Avian, swine and human IAV bind sialic acid on host glycans as receptor, whereas some bat IAV require MHC class II complexes for cell entry. It is unknown how this difference evolved and whether dual receptor specificity is possible. Here we show that human H2N2 IAV and related avian H2N2 possess dual receptor specificity in cell lines and primary human airway cultures. Using sialylation-deficient cells, we reveal that entry via MHC class II is independent of sialic acid. We find that MHC class II from humans, pigs, ducks, swans and chickens but not bats can mediate H2 IAV entry and that this is conserved in Eurasian avian H2. Our results demonstrate that IAV can possess dual receptor specificity for sialic acid and MHC class II, and suggest a role for MHC class II-dependent entry in zoonotic IAV infections.

Extrauterine growth restriction in very-low-birthweight infants: prevalence and concordance according to Fenton, Olsen, and INTERGROWTH-21st growth charts in a multicenter Spanish cohort.

Multiple criteria and growth references have been proposed for extrauterine growth restriction (EUGR). We hypothesized that these may impact the diagnosis of EUGR. The objective was to evaluate the prevalence of EUGR with its different definitions and the concordance according to Fenton, Olsen, and INTERGROWTH-21st in very-low-birthweight (VLBW) infants. This is an observational, retrospective, and multicenter study including VLBW infants from the Spanish SEN1500 Network from 2011 to 2020. Patients with major congenital anomalies, embryopathies, and gestational age less than 24 weeks were excluded. EUGR prevalence was calculated at discharge with cross-sectional, longitudinal, "true" cross-sectional, and "true" longitudinal definitions. Concordance was assessed with Fleiss' kappa coefficient. 23582 VLBW infants from 77 NICUs were included. In total, 50.4% were men with a median of gestational age of 29 (4) weeks. The prevalence of EUGR (cross-sectional, longitudinal, and "true") was variable for weight, length, and head circumference. Overall, the prevalence was higher with Fenton and lower with Olsen (cross-sectional and "true" cross-sectional) and INTERGROWTH-21st (longitudinal and "true" longitudinal). Agreement among the charts by weight was good only for cross-sectional EUGR and moderate for longitudinal, "true" cross-sectional, and "true" longitudinal. Concordance was good or very good for EUGR by length and head circumference.Conclusions: The prevalence of EUGR with the most commonly used definitions was variable in the cohort. Agreement among growth charts was moderate for all the definitions of EUGR by weight except cross-sectional and good or very good for length and head circumference. The choice of reference chart can impact the establishment of the diagnosis of EUGR. What is known: • EUGR has been defined in the literature and daily practice considering weight, length and head circumference with multiple criteria (cross-sectional, longitudinal, and "true" definition) • Different growth charts have been used for EUGR diagnosis What is new: • Prevalence of EUGR is variable depending on the definition and growth chart used in our cohort of VLBW infants • For the most frequently EUGR criteria used, traditionally considering weight, concordance among Fenton, Olsen and INTERGROWTH-21st growth charts is only moderate for all the definitions of EUGR by weight except cross-sectional definition. Concordance among the charts is good or very good for the different criteria of EUGR by head circumference and length.

Dual excitation spectral autofluorescence lifetime and reflectance imaging for fast macroscopic characterization of tissues.

Advancements in optical imaging techniques have revolutionized the field of biomedical research, allowing for the comprehensive characterization of tissues and their underlying biological processes. Yet, there is still a lack of tools to provide quantitative and objective characterization of tissues that can aid clinical assessment in vivo to enhance diagnostic and therapeutic interventions. Here, we present a clinically viable fiber-based imaging system combining time-resolved spectrofluorimetry and reflectance spectroscopy to achieve fast multiparametric macroscopic characterization of tissues. An essential feature of the setup is its ability to perform dual wavelength excitation in combination with recording time-resolved fluorescence data in several spectral intervals. Initial validation of this bimodal system was carried out in freshly resected human colorectal cancer specimens, where we demonstrated the ability of the system to differentiate normal from malignant tissues based on their autofluorescence and reflectance properties. To further highlight the complementarity of autofluorescence and reflectance measurements and demonstrate viability in a clinically relevant scenario, we also collected in vivo data from the skin of a volunteer. Altogether, integration of these modalities in a single platform can offer multidimensional characterization of tissues, thus facilitating a deeper understanding of biological processes and potentially advancing diagnostic and therapeutic approaches in various medical applications.

Real world effectiveness and safety of nivolumab in patients with relapsed or refractory classical hodgkin lymphoma. / Efectividad y seguridad en vida real de nivolumab en pacientes con linfoma de hodgkin clásico en recaída o refractario.

OBJECTIVE: The primary objective is to describe the real-life effectiveness and safety of nivolumab treatment in patients with relapsed or refractory classical Hodgkin's lymphoma. The secondary objective is to describe the therapeutic management after nivolumab monotherapy. METHOD: Observational, retrospective, multidisciplinary study including all patients with relapsed or refractory classical Hodgkin's lymphoma treated with nivolumab monotherapy from November 2015 to March 2023. Patient and treatment-related variables were collected. Effectiveness was measured as overall response rate, progression-free survival and overall survival. Safety was measured as percentage of patients with adverse effects and severity. RESULTS: Thirteen patients were included, median age 37.5 years (RIQ: 25.3-54.7), 84.6% male. The median number of previous lines of therapy was 3 (RIQ: 2.0-4.5), including autologous hematopoietic stem cell transplantation (84.6%) and brentuximab vedotin (100%). All received nivolumab 3 mg/kg/14 days, with a median of 11 cycles (RIQ: 6.5-20.5) per patient. Median time on treatment was 4.9 months (RIQ: 3.0-9.6) and median follow-up time was 9.2 months (RIQ: 5.6-32.3). Complete response was achieved by 3 patients (23.1%), partial response by 3 (23.1%), stable disease by 3 (23.1%) and progression by 4 (30.8%). The objective response rate was 46.2%. Median progression-free survival was 23.9 months (95%CI: 0-49.1), median overall survival was not reached. At the study cutoff date, five patients had died (38.5%), four were in complete remission without active treatment (30.8%) and four were continuing treatment (30.8%). Adverse events occurred in 76.9% of patients, 44% of severity ≥3, the most frequent being hypothyroidism and hepatotoxicity. One patient discontinued treatment due to pneumonitis, two suffered treatment delays (thrombocytopenia and hypertransaminemia) and one changed the regimen to monthly (pulmonary toxicity). CONCLUSIONS: Nivolumab in the treatment of relapsed or refractory classical Hodgkin's lymphoma has confirmed in the study sample favorable effectiveness data, expressed as objective response rate of 46.2% and clinical benefit of 69.2%. Safety was acceptable, manageable, and consistent with that described in the literature.

Zebrafish Avatar-test forecasts clinical response to chemotherapy in patients with colorectal cancer.

Cancer patients often undergo rounds of trial-and-error to find the most effective treatment because there is no test in the clinical practice for predicting therapy response. Here, we conduct a clinical study to validate the zebrafish patient-derived xenograft model (zAvatar) as a fast predictive platform for personalized treatment in colorectal cancer. zAvatars are generated with patient tumor cells, treated exactly with the same therapy as their corresponding patient and analyzed at single-cell resolution. By individually comparing the clinical responses of 55 patients with their zAvatar-test, we develop a decision tree model integrating tumor stage, zAvatar-apoptosis, and zAvatar-metastatic potential. This model accurately forecasts patient progression with 91% accuracy. Importantly, patients with a sensitive zAvatar-test exhibit longer progression-free survival compared to those with a resistant test. We propose the zAvatar-test as a rapid approach to guide clinical decisions, optimizing treatment options and improving the survival of cancer patients.

Metabolic and Low-Grade Inflammation Risk in Young Adults with a History of Extrauterine Growth Restriction.

Children with a history of extrauterine growth restriction (EUGR), later at prepubertal age, exhibit an increased metabolic risk including risen insulin resistance and low-grade inflammation. However, the progression of such metabolic changes after puberty and the lasting health implications have not yet been investigated. The objective of this study was to ascertain whether young adults with a history of EUGR faced increased vulnerability to metabolic disorders. A study was conducted comparing a group of adults with a history of EUGR with a healthy reference group. A total of 110 young adults (36 from the EUGR group and 74 from the control group) were included. Anthropometric variables, blood pressure (BP), general biochemical parameters, plasma inflammatory biomarkers, and adipokines were assessed. Compared to the reference group, the EUGR group had a shorter height and body weight with higher lean mass and waist circumference, as well as a greater percentage of individuals with high BP. In addition, EUGR patients had higher values of insulin, HOMA-IR, nerve growth factor, and leptin, and lower levels of adiponectin and resistin. The present study suggests that young adults with a history of EUGR present increased metabolic risk factors therefore, clinical follow-up should be considered.

The Increased Burden of Rare Variants in Four Matrix Metalloproteinase-Related Genes in Childhood Glaucoma Suggests a Complex Genetic Inheritance of the Disease.

Childhood glaucoma encompasses congenital and juvenile primary glaucoma, which are heterogeneous, uncommon, and irreversible optic neuropathies leading to visual impairment with a poorly understood genetic basis. Our goal was to identify gene variants associated with these glaucoma types by assessing the mutational burden in 76 matrix metalloproteinase-related genes. We studied 101 childhood glaucoma patients with no identified monogenic alterations using next-generation sequencing. Gene expression was assessed through immunohistochemistry. Functional analysis of selected gene variants was conducted in cultured cells and in zebrafish. Patients presented a higher proportion of rare variants in four metalloproteinase-related genes, including CPAMD8 and ADAMTSL4, compared to controls. ADAMTSL4 protein expression was observed in the anterior segment of both the adult human and zebrafish larvae's eye, including tissues associated with glaucoma. In HEK-293T cells, expression of four ADAMTSL4 variants identified in this study showed that two variants (p.Arg774Trp and p.Arg98Trp) accumulated intracellularly, inducing endoplasmic reticulum stress. Additionally, overexpressing these ADAMTSL4 variants in zebrafish embryos confirmed partial loss-of-function effects for p.Ser719Leu and p.Arg1083His. Double heterozygous functional suppression of adamtsl4 and cpamd8 zebrafish orthologs resulted in reduced volume of both the anterior eye chamber and lens within the chamber, supporting a genetic interaction between these genes. Our findings suggest that accumulation of partial functional defects in matrix metalloproteinase-related genes may contribute to increased susceptibility to early-onset glaucoma and provide further evidence supporting the notion of a complex genetic inheritance pattern underlying the disease.

Sex and Gender-related Disparities in Clinical Characteristics and Outcomes in Heart Transplantation.

PURPOSE OF REVIEW: Limited research has been conducted on sex disparities in heart transplant (HT). The aim of this review is to analyse the available evidence on the influence of sex and gender-related determinants in the entire HT process, as well as to identify areas for further investigation. RECENT FINDINGS: Although women make up half of the population affected by heart failure and related mortality, they account for less than a third of HT recipients. Reasons for this inequality include differences in disease course, psychosocial factors, concerns about allosensitisation, and selection or referral bias in female patients. Women are more often listed for HT due to non-ischaemic cardiomyopathy and have a lower burden of cardiovascular risk factors. Although long-term prognosis appears to be similar for both sexes, there are significant disparities in post-HT morbidity and causes of mortality (noting a higher incidence of rejection in women and of malignancy and cardiac allograft vasculopathy in men). Additional research is required to gain a better understanding of the reasons behind gender disparities in eligibility and outcomes following HT. This would enable the fair allocation of resources and enhance patient care.

Cancer is not a risk factor for severe COVID-19 in children, except in patients with recent allogeneic hematopoietic stem cell transplantation or comorbidities.

The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.

Glucose metabolism outcomes after pituitary surgery in patients with acromegaly.

AIM: To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of remission of diabetes after pituitary surgery in patients with acromegaly. METHODS: A national multicenter retrospective study of patients with acromegaly undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study) was performed. Surgical remission of acromegaly was evaluated according to the 2000 and 2010 criteria. RESULTS: A total of 604 acromegaly patients were included in the study with a total median follow up of 91 months (interquartile range [IQR] 45-163). At the acromegaly diagnosis, 23.8% of the patients had diabetes mellitus (DM) with a median glycated hemoglobin (HbA1c) of 6.9% (IQR 6.4-7.9) [51.9 mmol/mol (IQR 46.4-62.8)]. In the multivariate analysis, older age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), dyslipidemia (OR 5.25, 95% CI 2.81 to 9.79), arthropathy (OR 1.39, 95% CI 2.82 to 9.79), and higher IGF-I levels (OR 1.30, 95% CI 1.05 to 1.60) were associated with a greater prevalence of DM. At the last follow-up visit after surgery, 21.1% of the DM patients (56.7% of them with surgical remission of acromegaly) experienced diabetes remission. The cure rate of DM was more common in older patients (hazard ratio [HR] 1.77, 95% CI 1.31 to 2.43), when surgical cure was achieved (HR 2.10, 95% CI 1.01 to 4.37) and when anterior pituitary function was not affected after surgery (HR 3.38, 95% CI 1.17 to 9.75). CONCLUSION: Glucose metabolism improved in patients with acromegaly after surgery and 21% of the diabetic patients experienced diabetes remission; being more frequent in patients of older age, and those who experienced surgical cure and those with preserved anterior pituitary function after surgery.

Pegvisomant and pasireotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Comprehensive Stress Stability Studies Reveal the Prominent Stability of the Liquid-Formulated Biotherapeutic Asymmetric Monovalent Bispecific IgG1 Monoclonal Antibody Format.

The developed asymmetric monovalent bispecific IgG1 or Duet monoclonal antibody (Duet mAb) has two distinct fragment antigen-binding region (Fab) subunits that target two different epitope specificities sequentially or simultaneously. The design features include unique engineered disulfide bridges, knob-into-hole mutations, and kappa and lambda chains to produce Duet mAbs. These make it structurally and functionally complex, so one expects challenging developability linked to instability, degradation of products and pathways, and limited reports available. Here, we have treated the product with different sources of extreme stress over a lengthy period, including varying heat, pH, photo stress, chemical oxidative stress, accelerated stress in physiological conditions, and forced glycation conditions. The effects of different stress conditions on the product were assessed using various analytical characterization tools to measure product-related substances, post-translational modifications (PTMs), structural integrity, higher-order disulfide linkages, and biological activity. The results revealed degradation products and pathways of Duet mAb. A moderate increase in size, charge, and hydrophobic variants, PTMs, including deamidation, oxidation, isomerization, and glycation were observed, with most conditions exhibiting biological activity. In addition, the characterization of fractionated charge variants, including deamidated species, showed satisfactory biological activity. This study demonstrated the prominent stability of the Duet mAb format comparable to most marketed mAbs.

Keeping prior anticoagulation treatment in the acute phase of ischaemic stroke: the REKOALA study.

INTRODUCTION: A consensus on the management of anticoagulated patients in the acute phase of ischaemic stroke has not yet been established. We aimed to evaluate clinical outcomes in such patients based on the continuation or discontinuation of anticoagulation. METHODS: Retrospective study of patients with acute ischaemic stroke and cardioembolic source receiving anticoagulant therapy is done. Patients were classified based on the continuation or discontinuation of anticoagulation at admission. Clinical outcomes, haemorrhagic and ischaemic events were assessed. Multivariate logistic regression analysis, propensity score matching (PSM) analysis and a sub-analysis of patients with severe ischaemic stroke at admission (NIHSS score ≥ 15) were performed. RESULTS: Anticoagulation was continued in 147 (78.8%) of 186 patients. Patients continuing anticoagulant had lower NIHSS (median 5 vs 18, p < 0.001). There were no differences in haemorrhagic or ischaemic events. In the multivariate analysis, good functional outcome at discharge was higher in the continuation group, OR (CI95%) 3.77 (1.2-11.2). PSM analysis adjusted for potential confounders such as NIHSS had higher rates of good functional outcomes at discharge (80% vs 36%, p = 0.004) and at 90 days (76% vs 44%, p = 0.042) in the continuation group. Patients with severe stroke in this group had lower 90-day mortality (34.6% vs 62.5%, p = 0.045) and higher rates of good clinical outcome at discharge (33.3% vs 8.3%, p = 0.032). No differences were observed in 90-day haemorrhagic or ischaemic events. CONCLUSION: Continuation of anticoagulation in patients with acute ischaemic stroke and cardioembolic source did not increase the risk of intracranial haemorrhage and may be associated with better functional outcomes.

ABCG2 Transports the Flukicide Nitroxynil and Affects Its Biodistribution and Secretion into Milk.

The ABCG2 transporter plays a key role in pharmacological and toxicological processes, affecting bioavailability, tissue accumulation and milk secretion of its substrates. This protein is expressed in several biological barriers acting as a protective mechanism against xenobiotic exposure by pumping out a broad range of compounds. However, its induced expression during lactation in alveolar cells of mammary gland represents a relevant route for active transport of unwanted chemicals into milk. This work aimed to characterize the involvement of ABCG2 in systemic exposure and milk secretion of the flukicide nitroxynil. Using MDCK-II cells overexpressing the transporter, we showed that nitroxynil is an in vitro substrate of different species variants of ABCG2. Moreover, using wild-type and Abcg2-/- mice, we showed that murine Abcg2 clearly affects plasma levels of nitroxynil. We also reported differences in nitroxynil accumulation in several tissues, with almost 2-fold higher concentration in kidney, small intestine and testis of Abcg2-/- mice. Finally, we proved that nitroxynil secretion into milk was also affected by Abcg2, with a 1.9-fold higher milk concentration in wild-type compared with Abcg2-/- mice. We conclude that ABCG2 significantly impacts nitroxynil biodistribution by regulating its passage across biological barriers.

Variability in Definitions and Criteria of Extrauterine Growth Restriction and Its Association with Neurodevelopmental Outcomes in Preterm Infants: A Narrative Review.

Extrauterine growth restriction (EUGR) has been used in the literature and clinical practice to describe inadequate growth in preterm infants. Significant variability is seen in the criteria for EUGR, with no standard definition reached to date. Moreover, no consensus on the optimal timing for assessment or the ideal growth monitoring tool has been achieved, and an ongoing debate persists on the appropriate terminology to express poor postnatal growth. To ensure an adequate understanding of growth and early intervention in preterm infants at higher risk, it is critical to relate the diagnostic criteria of EUGR to the ability to predict adverse outcomes, such as neurodevelopmental outcomes. This narrative review was conducted to present evidence that evaluates neurodevelopmental outcomes in preterm infants with EUGR, comparing separately the different definitions of this concept by weight (cross-sectional, longitudinal and "true" EUGR). In this article, we highlight the challenges of comparing various published studies on the subject, even when subclassifying by the definition of EUGR, due to the significant variability on the criteria used for each definition and for the evaluation of neurodevelopmental outcomes in different papers. This heterogeneity compromises the obtention of a single firm conclusion on the relation between different definitions of EUGR and adverse neurodevelopmental outcomes.

A Systematic review of the presence and participation of students with intellectual disabilities in Spanish universities.

Inclusive education remains a challenge to be embraced by the national educational system, and this challenge becomes even more pronounced when considering the access and participation of young individuals with intellectual disabilities (ID) in higher education. The present systematic review aims to delve into the scientific literature addressing the theme of the presence of students with ID in Spanish university classrooms. To achieve this, a thorough examination of 34 scientific articles published between 2012 and 2022 was conducted across the databases of Dialnet, RedALyC, SCOPUS, Web of Science, and Google Scholar. Through the analysis of the selected studies, a research trend regarding the inclusion of students with ID in Spanish universities is identified, and the results are summarized. These results indicate a disparity between the increasing response of Spanish universities to students with ID and the limited production of scientific literature on the subject. The review concludes by emphasizing the need to promote high-quality inclusive research processes within the university environment, with a focus on accessibility and equal opportunities for young individuals with ID in higher education.