Repeated TACE in HCC after Fontan surgery and situs viscerum inversus: A case report

We describe the case of a 32-year-old man who developed a liver neoplasm due to previous Fontan surgery (FS) for a single ventricle anomaly and situs viscerum inversus. He was admitted to our hospital for suspected hepatocellular carcinoma during an Ultrasound (US) follow up. Computed tomography (CT) showed features of chronic liver disease and 7 cm hepatic nodule with arterial enhancement. Laboratory analyses documented preserved liver function and increased levels of alpha-fetoprotein. Trans-arterial-chemoembolization (TACE) was performed obtaining complete necrosis at 4 weeks of follow up and significant reduction of alpha-fetoprotein. The patient is currently in follow-up, being evaluated for further treatments and/or combined liver-heart transplantation. TACE is a therapeutic option for the treatment of patients with unresectable hepatocellular carcinoma (HCC) and with severe heart disease, like those submitted to FS and with also other vascular abnormalities like those correlated to situs viscerum inversus

Presentation of peptides by cultured monocytes or activated T cells allows specific priming of human cytotoxic T lymphocytes in vitro

The conditions favouring effective specific cytotoxic T lymphocyte (CTL) priming have been exploited to set up a simple and reproducible method to induce a primary CTL response in vitro. We report that cultured monocytes, as well as activated T cells, pulsed with exogenous HLA-A2 binding immunogenic peptides, can induce primary peptide-specific CTL responses in vitro in a Th-independent manner. Primary viral peptide-induced CTL were HLA-A2 restricted, and recognized both peptide-pulsed target cells and targets infected with recombinant vaccinia virus expressing viral endogenous antigens. In addition, both cultured monocytes and activated T cells primed peptide-specific CD8+ T cells depleted from the CD45RO+ memory cell fraction. The efficiency of CTL priming by monocytes was dependent upon the strong up-regulation of class I, adhesion and co-stimulatory molecules occurring spontaneously upon in vitro culture. The inability of unseparated peripheral blood mononuclear cells to mount a peptide-specific CTL response could be reverted by direct co-stimulation of responding CD8+ T cells by soluble B7.1 or a stimulatory anti-CD28 antibody, that allowed a specific response to take place. Although co-stimulation via the B7-CD28 interaction appeared sufficient to trigger CTL responses, It was not essential for CTL priming, since neither anti-B7.1 mAb nor soluble CTLA-4 inhibited induction of primary CTL response. This new method for induction of specific CD8+ T cell response in vitro may be exploited in adoptive immunotherapy in cancer or in HIV-infected patient

Age-related DNA methylation changes are sex-specific: a comprehensive assessment

The existence of a sex gap in human health and longevity has been widely documented. Autosomal DNA methylation differences between males and females have been reported, but so far few studies have investigated if DNA methylation is differently affected by aging in males and females. We performed a meta-analysis of 4 large whole blood datasets, comparing 4 aspects of epigenetic age-dependent remodeling between the two sexes: differential methylation, variability, epimutations and entropy. We reported that a large fraction (43%) of sex-associated probes undergoes age-associated DNA methylation changes, and that a limited number of probes show age-by-sex interaction. We experimentally validated 2 regions mapping in FIGN and PRR4 genes and showed sex-specific deviations of their methylation patterns in models of decelerated (centenarians) and accelerated (Down syndrome) aging. While we did not find sex differences in the age-associated increase in epimutations and entropy, we showed that the number of probes having an age-related increase in methylation variability is 15 times higher in males compared to females. Our results can offer new epigenetic tools to study the interaction between aging and sex and can pave the way to the identification of molecular triggers of sex differences in longevity and age-related diseases prevalence

Risk Factors of Right Ventricular Dysfunction and Adverse Cardiac Events in Patients with Repaired Tetralogy of Fallot

Aim: This study evaluates the risk factors associated with right ventricular (RV) dilation and dysfunction leading to pulmonary valve replacement (PVR) or adverse cardiac events in repaired Tetralogy of Fallot (rToF) patients. Methods: Data from all rToF patients who underwent magnetic resonance imaging (MRI) evaluation at our hospital between February 2007 and September 2020 were collected. Results: Three hundred and forty-two patients (60% males, 42% older than 18 years), with a median age of 16 years (IQR 13–24) at the time of MRI, were included. All patients underwent complete repair at a median age of 8 months (IQR 5–16), while palliation was performed in 56 patients (16%). One hundred and forty-four patients (42%) subsequently received pulmonary valve replacement (PVR). At the multivariate analysis, male gender was an independent predictor for significant RV dilation, RV and left ventricular (LV) dysfunction. Transventricular ventricular septal defect (VSD) closure and previous palliation significantly affected LV function and RV size, respectively. Male gender and the transventricular VSD closure were independent predictors for PVR. Conclusions: Male gender and surgical history (palliation, VSD closure approach) significantly affected the long-term outcomes in rToF patients and should be taken into consideration in the follow-up management and in PVR timing in this patient population

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P &lt; 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.</p

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P &lt; 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.</p