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Gloria Mercedes Galán Henríquez, Fermín García-Muñoz Rodrigo Service of Neonatalogy, Complejo Hospital Universitario Insular Materno Infantil de Canarias, Las Palmas de Gran Canaria, Spain Abstract: The term chorioamnionitis (CA) is commonly used to refer to different clinical or pathological conditions characterized by an infectious and/or inflammatory process that affects primarily the chorioamniotic membranes, but also the amniotic fluid, vessels of the chorionic plate, and, eventually, the umbilical cord (funisitis) and the fetus. Its incidence is higher at lower gestational ages, and the main mechanism is believed to be the ascending bacterial infection from the maternal genital tract. It can be diagnosed by clinical criteria, amniotic fluid examination for inflammatory mediators, and/or isolation of microorganisms, or by histopathological examination of the placenta. CA is an important cause of stillbirth and is related to an increased incidence of premature rupture of membranes, preterm delivery, and adverse maternal and neonatal outcomes such as early-onset neonatal sepsis and necrotizing enterocolitis. An independent causal association to other neonatal morbidities is more controversial. The heterogeneity in the diagnostic criteria and in the operative definitions for morbidity makes comparison of studies difficult, and results are inconsistent. In addition, the intensity and duration of the process are usually not considered. For all these reasons, evidence-based recommendations for the management of mother and infant under these circumstances are difficult to establish, and clinical practice varies widely. Keywords: clinical chorioamnionitis, histological chorioamnionitis, stillbirth, prematurity, morbidity, mortality

SARS-CoV-2 infection can be a life-threatening disease. The optimal treatment of patients is not yet standardized. We use a serology-based therapeutic strategy based on the presence of antibodies against the SARS-CoV-2 virus, in which patients with positive serology receive aggressive anti-inflammatory treatment with high-dose dexamethasone and/or tocilizumab and patients with negative serology receive early convalescent plasma therapy. We also analyze the immunological impact of this therapy in the recovery of T cells, B cells and NK cells during hospitalization in a COVID-19 infectious ward. Our results suggest that aggressive therapy with early administration of convalescent plasma and high-dose dexamethasone may be of benefit in patients with SARS-CoV-2 infection and might avoid progression of lung damage or need of admission in intensive care. This strategy did not impair immune responses against SARS-CoV-2, as 93% of the patients generated antibodies against the virus. Independently of previous immunological status of the patients, serology-guided therapy might benefit even patients with a high CIRS-G score, immunosuppressed or medically debilitated individuals and elderly patients. T cell disturbances were most frequent in patients who required high-dose dexamethasone, and B cell depletion was most frequent in patients who received tocilizumab. Early passive immunotherapy with convalescent plasma does not affect lymphoid recovery., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Compared to standard-conditioned regimens, reduced-intensity conditioning and T-cell depletion deliver lower transplant-related mortality and decreased graft-vs-host disease after allogeneic hematopoietic stem-cell transplantation. These advantages may however be mitigated by increased relapse rates and delays in achievement of full donor chimerism (FDC). Pre-emptive donor lymphocyte infusions (pDLI) facilitate the conversion of mixed (MDC) to FDC. However, there is a lack of published data on the risk/benefit analysis of this intervention. We performed a retrospective analysis of 119 patients who received 276 pDLI doses for falling CD3 chimerism, CD3 < 50% or mixed XX/XY karyotype. 71/119(60%) Patients achieved FDC, with only one reverting to MDC. Cumulative incidence (CI) of relapse at 5 years was significantly lower in the FDC group (16.0 vs 41.4%, p < 0.001). Those patients who achieved FDC had improved EFS (p < 0.001) and OS (p < 0.001). Interestingly, patients with FDC who developed DLI-induced graft-vs-host disease (GvHD) showed a similar outcome to those with MDC. The majority of patients who receive pDLI convert to FDC and retain that status. Achievement of FDC after pDLI impacts on survival, and those patients who achieve FDC without GvHD, experience maximum clinical benefit. Strategies to minimise DLI-induced GvHD should be considered to maximise the therapeutic potential of this intervention.

The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV - tumours, EBV + DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV + DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy-related immunosuppression can transform either CLL cells or non-tumoural B lymphocytes into EBV + DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2 -/- IL2γc -/- mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV + B-cell clones from 95% of CLL and 64% of MBL patients samples, but not from healthy donors. Eventually, these cells generated monoclonal tumours (mostly CLL-unrelated but also CLL-related), recapitulating the principal features of EBV + DLBCL in patients. Accordingly, clonally related and unrelated EBV + DLBCL xenografts showed indistinguishable cellular, virological and molecular features, and synergistically responded to combined inhibition of EBV replication with ganciclovir and B-cell receptor signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by EBV in CLL patients receiving immunosuppressive therapies, and provides the scientific rationale for testing ganciclovir and ibrutinib in EBV + DLBCL. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

NKX2 homeobox family proteins have a role in cancer development. Here we show that NKX2-3 is overexpressed in tumour cells from a subset of patients with marginal-zone lymphomas, but not with other B-cell malignancies. While Nkx2-3-deficient mice exhibit the absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells show marginal-zone expansion that leads to the development of tumours, faithfully recapitulating the principal clinical and biological features of human marginal-zone lymphomas. NKX2-3 induces B-cell receptor signalling by phosphorylating Lyn/Syk kinases, which in turn activate multiple integrins (LFA-1, VLA-4), adhesion molecules (ICAM-1, MadCAM-1) and the chemokine receptor CXCR4. These molecules enhance migration, polarization and homing of B cells to splenic and extranodal tissues, eventually driving malignant transformation through triggering NF-κB and PI3K-AKT pathways. This study implicates oncogenic NKX2-3 in lymphomagenesis, and provides a valid experimental mouse model for studying the biology and therapy of human marginal-zone B-cell lymphomas.