When conducted at late timepoints after transplantation, immunosuppression withdrawal is successful in a high proportion of carefully selected liver recipients. A combination of clinical parameters could be useful to predict the success of this strategy. Additional prospective studies are now needed to confirm these results and to validate clinically applicable diagnostic biomarkers.

Following organ transplantation, lifelong immunosuppressive therapy is required to prevent the host immune system from destroying the allograft. This can cause severe side effects and increased recipient morbidity and mortality. Complete cessation of immunosuppressive drugs has been successfully accomplished in selected transplant recipients, providing proof of principle that operational allograft tolerance is attainable in clinical transplantation. The intra-graft molecular pathways associated with successful drug withdrawal, however, are not well defined. In this study, we analyzed sequential blood and liver tissue samples collected from liver transplant recipients enrolled in a prospective multicenter immunosuppressive drug withdrawal clinical trial. Before initiation of drug withdrawal, operationally tolerant and non-tolerant recipients differed in the intragraft expression of genes involved in the regulation of iron homeostasis. Furthermore, as compared with nontolerant recipients, operationally tolerant patients exhibited higher serum levels of hepcidin and ferritin and increased hepatocyte iron deposition. Finally, liver tissue gene expression measurements accurately predicted the outcome of immunosuppressive withdrawal in an independent set of patients. These results point to a critical role for iron metabolism in the regulation of intra-graft alloimmune responses in humans and provide a set of biomarkers to conduct drug-weaning trials in liver transplantation.

In a retrospective analysis of almost 2000 patients, we found 60% to have SPSS; prevalence increases with deterioration of liver function. SPSS increase risk for HE and with a chronic course. In patients with preserved liver function, SPSS increase risk for complications and death. ClinicalTrials.gov ID NCT02692430.

A proportion of transplant recipients can spontaneously accept their grafts in the absence of immunosuppression (operational tolerance). Previous studies identified blood transcriptional and cell-phenotypic markers characteristic of either liver or kidney tolerant recipients. However, the small number of patients analyzed and the use of different transcriptional platforms hampered data interpretation. In this study we directly compared samples from kidney and liver tolerant recipients in order to identify potential similarities in immune-related parameters. Liver and kidney tolerant recipients differed in blood expression and B-cell immunophenotypic patterns and no significant overlaps were detectable between them. Whereas some recipients coincided in specific NK-related transcripts, this observation was not reproducible in all cohorts analyzed. Our results reveal that certain immune features, but not others, are consistently present across all cohorts of operationally tolerant recipients. This provides a set of reproducible biomarkers that should be explored in future large-scale immunomonitoring trials.

The coronavirus disease 2019 (COVID-19) pandemic has represented a major impact to health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. The mother and fetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-fetal medicine practice have suffered profound changes to adapt to the pandemic. In addition, there are aspects specific to and gestation that should be known by specialists in order to correctly diagnose the disease, classify the severity, distinguish specific signs of COVID-19 from those of obstetric complications, and take the most appropriate management decisions. In this review we present in a highly concise manner an evidence-based protocol for the management of CO-VID-19 in pregnancy. We briefly contemplate all relevant as-pects that we believe a specialist in obstetrics and maternal medicine should know, ranging from basic concepts about the disease and protection measures in the obstetric setting to more specific aspects related to maternal-fetal management and childbirth.[1]. With 220,000 infections and more than 22,000 deaths, Spain is the third country in number of cases [1]. In this paper, we aimed to share our management protocol and address considerations for maternal-fetal medicine practice based on a qualitative review of existing data. Disease TransmissionAvailable information [2] suggests that the infection was originally zoonotic. Still, the current transmission is person to person by respiratory droplets after contact with an infected person (< 2 m) or direct contact with contaminated surfaces by infected secretions [3]. Transmission could also occur through infected faeces, but the propagation throughout this route is much less relevant [4]. The possibility of vertical transmission is highly unlikely and has not been demonstrated in the Chinese CO-VID-19 outbreak [5] or in previous epidemics by other similar coronaviruses (severe acute respiratory syndrome [SARS]-CoV and Middle East respiratory syndrome [MERS]-CoV) [6,7]. Based on limited data, there is no evidence of the presence of the virus in genital fluids, urine, amniotic fluid, or breast milk [8]. The low maternal viremia found in this infection [9] also suggests a negligible placental seeding. However, most data on vertical transmission are based on women who had infection during the third trimester, and information regarding vertical transmission earlier in pregnancy is lacking.Reported cases of newborn infection probably came from horizontal transmission. The usual incubation period is about 4-6 days, which can vary between 2 and 14 days [10]. The median duration of viral shedding is 20.0 days (being the 75th centile at 24 days) [11].

5mm 5 mm Highlights Total cross-sectional SPSS area (TSA) predicts survival in patients with advanced chronic liver disease. The cutoff for TSA that is associated with worse survival corresponds to a single shunt of >10 mm diameter. This study may impact on the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.

Objective

Pregnancy triggers immunological changes aimed to tolerate the fetus, but its impact on B lymphocytes is poorly understood. In addition, exposure to the Plasmodium parasite is associated with altered distribution of peripheral memory B cell (MBC) subsets. To study the combined impact of high malaria exposure and pregnancy in B cell subpopulations, we analyzed PBMCs from pregnant and nonpregnant individuals from a malaria-nonendemic country (Spain) and from a high malaria-endemic country (Papua New Guinea). In the malaria-naive cohorts, pregnancy was associated with a significant expansion of all switched (IgD−) MBC and a decrease of naive B cells. Malaria-exposed women had more atypical MBC and fewer marginal zone–like MBC, and their levels correlated with both Plasmodium vivax– and Plasmodium falciparum–specific plasma IgG levels. Classical but not atypical MBC were increased in P. falciparum infections. Moreover, active atypical MBC positively correlated with proinflammatory cytokine plasma concentrations and had lower surface IgG levels than the average. Decreased plasma eotaxin (CCL11) levels were associated with pregnancy and malaria exposure and also correlated with B cell subset frequencies. Additionally, active atypical and active classical MBC expressed higher levels of eotaxin receptor CCR3 than the other B cell subsets, suggesting a chemotactic effect of eotaxin on these B cell subsets. These findings are important to understand immunity to infections like malaria that result in negative outcomes for both the mother and the newborn and may have important implications on vaccine development.