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BACKGROUND: Fetal inflammatory response syndrome (FIRS), the fetal equivalent of chorioamnionitis, is associated with poorer neonatal outcomes. FIRS is diagnosed through placental histology, namely by the identification of funisitis (inflammation of the umbilical cord) and chorionic vasculitis (inflammation of fetal vessels within the chorionic plate). The aim of this study was to identify and evaluate associations between FIRS and neonatal outcomes in preterm neonates. METHODS: We performed a retrospective cohort study at a level III neonatal intensive care unit (NICU), from January 1st 2008 to December 31st 2022, involving all inborn neonates with a gestational age below 30 weeks. We compared preterm neonates based on whether their placental histology described funisitis with chorionic vasculitis (FCV) or not. RESULTS: The study included 113 preterms, 27 (23.9%) of those had FCV and 86 (76.1%) did not. After adjusting to gestational age, prolonged rupture of membranes and preeclampsia, FCV was independently associated with the development of early-onset sepsis (OR = 7.3, p = 0.021) and cystic periventricular leukomalacia (OR = 4.6, p = 0.004). CONCLUSION: The authors identified an association between FIRS and the development of early-onset sepsis and cystic periventricular leukomalacia, highlighting the importance of early detection and management of this condition in order to improve long-term neonatal outcomes. [ABSTRACT FROM AUTHOR]

The low prevalence of European paediatric transplanted patients and scarcity of resources and expertise led to the need for a multidisciplinary network able to improve the quality of life of paediatric patients and families requiring a solid organ or haematopoietic stem cell transplantation. The European Reference Network (ERN) TransplantChild is one of the 24 ERNs established in a European legal framework to improve the care of patients with rare diseases. ERN TransplantChild is the only ERN focused on both solid organ and haematopoietic stem cell paediatric transplantation, based on the understanding of paediatric transplantation as a complex and highly specialised process where specific complications appear regardless the organ involved, thus linking the skills and knowledge of different organ disciplines. Gathering European centres of expertise in paediatric transplantation will give access to a correct and timely diagnosis, share expertise and knowledge and collect a critical mass of patients and data that increases the speed and value of clinical research outcomes. Therefore, the ERN TransplantChild aims for a paediatric Pan-European, Pan-transplant approach. [ABSTRACT FROM AUTHOR]

Omphalocele is a malformation of the abdominal wall varying in size and located at the base of the umbilical cord. Meckel's diverticulum is the most common congenital malformation of the gastrointestinal tract with an increased prevalence in newborns with congenital malformations of the umbilicus and gastrointestinal tract. The association between Meckel's diverticulum and omphalocele has been described in rare cases. We present the case of a newborn diagnosed with both entities., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Valente et al.)

Background Aims: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA - memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment., Methods: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 10 6 /kg CD45RA - memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA - memory T cells and the most frequent human leukocyte antigen typing in the Spanish population., Results: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events., Conclusions: Adoptive cell therapy with off-the-shelf CD45RA - memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia., Trial Registration: NCT04578210., Competing Interests: Declaration of Competing Interest CF, AP-M and BS filed patent PCT/EP2021/076516 on Memory T cells as adoptive cell therapy for viral diseases. All other authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: Refractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation., Methods: In this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA - ) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells' cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality., Results: In vitro , we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo , NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo , they exhibited functional properties of leukemia initiating cells., Discussion: The data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL., Competing Interests: MB-P was previously employed by the company Medpace Germany, GmbH, though not at the time of the study, and is currently employed by the company Medpace Spain. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor FM declared a shared committee the National Network of Advanced therapies TerAv with the author AP-M at the time of review., (Copyright © 2023 Ibáñez-Navarro, Fernández, Escudero, Esteso, Campos-Silva, Navarro-Aguadero, Leivas, Caracuel, Rodríguez-Antolín, Ortiz, Navarro-Zapata, Mestre-Durán, Izquierdo, Balaguer-Pérez, Ferreras, Martínez-López, Valés-Gómez, Pérez-Martínez and Fernández.)

Background: Inborn errors of immunity (IEI) are a group of monogenic diseases that confer susceptibility to infection, autoimmunity, and cancer. Despite the life-threatening consequences of some IEI, their genetic cause remains unknown in many patients., Objective: We investigated a patient with an IEI of unknown genetic etiology., Methods: Whole-exome sequencing identified a homozygous missense mutation of the gene encoding ezrin (EZR), substituting a threonine for an alanine at position 129., Results: Ezrin is one of the subunits of the ezrin, radixin, and moesin (ERM) complex. The ERM complex links the plasma membrane to the cytoskeleton and is crucial for the assembly of an efficient immune response. The A129T mutation abolishes basal phosphorylation and decreases calcium signaling, leading to complete loss of function. Consistent with the pleiotropic function of ezrin in myriad immune cells, multidimensional immunophenotyping by mass and flow cytometry revealed that in addition to hypogammaglobulinemia, the patient had low frequencies of switched memory B cells, CD4 + and CD8 + T cells, MAIT, γδ T cells, and central naive CD4 + cells., Conclusions: Autosomal-recessive human ezrin deficiency is a newly recognized genetic cause of B-cell deficiency affecting cellular and humoral immunity., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies suggest that some hematological parameters and ratios provided by blood count collected on the first day of life may be predictors for the development of retinopathy of prematurity (ROP). The aims of this study were to assess whether hematological parameters and ratios in blood count collected on the first day of life are associated with ROP., Methods: Retrospective data collection from electronic clinical files of inborn preterm infants with a gestational age of less than 30 weeks delivered from January 2008 to December 2022, in a level III Neonatal Intensive Care Unit (NICU). We collected detailed clinical and demographic data on the mother, pregnancy, mode of delivery, resuscitation, in-hospital neonatal morbidity, pathological examination of the placenta, and hematological parameters and ratios provided by blood count collected on the first day of life. We compared neonates with or without ROP and performed a subgroup analysis on patients with ROP≥2., Results: We included 140 preterm infants with ophthalmic examination; 81(57.9%) developed ROP. The need for platelet transfusions (OR=5.28; 95% CI: 1.31-21.21; P=0.019) and bronchopulmonary dysplasia (BPD) (OR=5.12; 95% CI: 1.14-22.98; P=0.033) were independent risk factors for ROP. In the multivariate analysis, no associations were found between any of the hematological parameters or ratios studied and ROP., Conclusions: In our study, hematological parameters and ratios on the first day of life were not associated with the development of ROP. However, thrombocytopenia that required platelet transfusions was associated with ROP development and severity.

An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19's pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients., Competing Interests: AP-M, CF and BS filed patents on this topic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gonzaga, Andreu, Hernández-Blasco, Meseguer, Al-Akioui-Sanz, Soria-Juan, Sanjuan-Gimenez, Ferreras, Tejedo, Lopez-Lluch, Goterris, Maciá, Sempere-Ortells, Hmadcha, Borobia, Vicario, Bonora, Aguilar-Gallardo, Poveda, Arbona, Alenda, Tarín, Marco, Merino, Jaime, Ferreres, Figueira, Cañada-Illana, Querol, Guerreiro, Eguizabal, Martín-Quirós, Robles-Marhuenda, Pérez-Martínez, Solano and Soria.)