Neurological Screening in Elderly Liver Transplantation Candidates: A Single Center Experience

Background: Cerebral small vessels disease (cSVD) is an age-related disorder and risk factor for stroke and cognitive/motor impairments. Neurological complications (NCs) are among the causes of adverse outcomes in older liver transplant recipients. This study sought to determine whether cSVD predicts acute NCs in over 65-year-old liver transplant patients. Methods: Data were collected, from a retrospective medical chart review, of 22 deceased donor liver transplant recipients aged 65 years or older with a pre-operative brain magnetic resonance imaging (MRI). We used the Fazekas score (0–3) as a quantitative measurement of the vascular lesion load seen in the MRI. We analyzed all post-operative acute NCs occurring during the hospital stay and any other non-NC. Results: cSVD was recognized in all patients. Neurological complications (NCs) occurred in 18.1% of patients with toxic-metabolic encephalopathy the most frequent diagnosis (13.64%). More severe cSVD was associated with seizures (p = 0.0362), longer hospital stay (p 0.0299), and disability (p 0.0134). In our elderly cohort, hepatic encephalopathy (HE) (p 0.0287) and ascites (p 0.0270) were predictors of NCs after liver transplantation. Ascites and/or variceal bleeding and severity of liver disease were associated with adverse post-operative outcomes. The small sample size limited the statistical analysis power. Conclusions: We present the preliminary data of a single-center retrospective study aimed at understanding the cSVD role on NCs and non-NCs after a liver transplantation in elderly patients. This would encourage a more appropriate multicenter prospective study that will definitely confirm if a neurological screening in old age liver transplant candidates is appropriate

Phenotypical and molecular assessment of the virulence potential of KPC-3-producing Klebsiella pneumoniae ST392 clinical isolates

Klebsiella pneumoniae is a Gram-negative bacterium of clinical importance, due to its resistance to several antibiotic classes. We have identified 4 clinical isolates of K. pneumoniae sequence type (ST) 392 KPC-3-producing strains from patients at the Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), a Southern Italian transplantation health facility, during a routine surveillance for carbapenemase-producing Enterobacterales from in-house clinical samples. Since those were among, to the best of our knowledge, the first KPC-producing K. pneumoniae ST392 isolated in Europe, we assessed their virulence potential, to understand if this particular ST can become an endemic clinical threat. ST392 isolates were investigated to assess their virulence potential, namely resistance to human sera, formation of abiotic biofilms, adhesion to biotic surfaces, exopolysaccharide production and in vivo pathogenesis in the wax moth Galleria mellonella animal model. ST392-belonging strains were highly resistant to human sera. These strains also have a high capacity to form abiotic biofilms and high levels of adhesion to the human epithelial colorectal adenocarcinoma HT-29 cell line. An increase of transcriptional levels of genes involved in serum resistance (aroE and traT) and adhesion (pgaA) was observed when compared with the Klebsiella quasipneumoniae subsp. similipneumoniae strain ATCC 700603 reference strain. Infection of G. mellonella larvae with ST392 clinical isolates showed that the latter were not highly pathogenic in this model. Together, our results indicate that ST392 isolates have the potential to become a strain of clinical relevance, especially in health settings where patients are immunosuppressed, e.g., transplant recipients

Finite element model with imposed slip surfaces for earth mass safety evaluation

The study of earth masses requires numerical methods that provide the quantification of the safety factor without requiring detrimental assumptions. For that, equilibrium analysis can perform fast computations but require assumptions that limit its potentiality. Limit analysis does not require detrimental assumptions but are numerically demanding. This work provides a new approach that combines the advantage of both the equilibrium method and the limit analysis. The defined hybrid model allows probabilistic analysis and optimization approaches without the assumption of interslice forces. It is compared with a published case and used to perform probabilistic studies in both a homogeneous and a layered foundation. Analyses show that the shape of the density probability functions is highly relevant when computing the probability of failure, and soil elasticity hardly affects the safety of factor of the earth mass.Programa Operacional Factores de Competitividade—COMPETE, and by Portuguese Funds through FCT–Fundação para a Ciência e a Tecnologia, within the projects PEst –C/MAT/UI0013/2011 and PEst–OE/ECM/UI4047/2011

Role of non-coding RNAs in age-related vascular cognitive impairment: An overview on diagnostic/prognostic value in Vascular Dementia and Vascular Parkinsonism

Age is the pivotal risk factor for different common medical conditions such as cardiovascular diseases, cancer and dementia. Among age-related disorders, cardiovascular and cerebrovascular diseases, represent the leading causes of premature mortality strictly related to vascular ageing, a pathological condition characterized by endothelial dysfunction, atherosclerosis, hypertension, heart disease and stroke. These features negatively impact on the brain, owing to altered cerebral blood flow, neurovascular coupling and impaired endothelial permeability leading to cerebrovascular diseases (CVDs) as Vascular Dementia (VD) and Parkinsonism (VP). It is an increasing opinion that neurodegenerative disorders and cerebrovascular diseases are associated from a pathogenetic point of view, and in this review, we discuss how cerebrovascular dysfunctions, due to epigenetic alterations, are linked with neuronal degeneration/dysfunction that lead to cognitive impairment. The relation between neurodegenerative and cerebrovascular diseases are reviewed with a focus on role of ncRNAs in age-related vascular diseases impairing the endothelium in the blood–brain barrier with consequent dysfunction of cerebral blood flow. In this review we dissert about different regulatory mechanisms of gene expression implemented by ncRNAs in the pathogenesis of age-related neurovascular impairment, aiming to highlight the potential use of ncRNAs as biomarkers for diagnostic/prognostic purposes as well as novel therapeutic targets

Impact of Extended-Criteria Donor Liver Grafts on Benchmark Metrics of Clinical Outcome After Liver Transplantation: A Single Center Experience

Background: The adoption of extended criteria for donors remains the best strategy to widen the pool of available liver graft against the chronic shortage of donors. Benchmarking in liver transplantation (LT) offers the unprecedented opportunity to compare clinical outcome measures to a set of validated reference values. We aimed to evaluate the impact of marginal grafts usage in a cohort of low-risk benchmark cases from an area with a very low rate of deceased donation. Methods: A cohort of low-risk benchmark cases was identified from all adult patients who underwent LT at our center. Among these patients, those transplanted with a graft from an extended-criteria donor (ECD) were identified. Benchmark metrics (length of hospital and intensive care unit stay, incidences of mortality, graft loss, and postoperative complication) were compared with benchmark cutoffs and between the 2 groups. Results: Two hundred forty-five patients satisfied the inclusion criteria, 146 (60%) of whom received an organ from an ECD. Overall, all benchmark metrics where within the cutoffs limits, except for graft loss (14% vs 11%) and mortality (10% vs 9% 1 year after LT). The ECD group was associated with more grade III complications (60% vs 45%, P = .031), graft loss (18% vs 8%, P = .038), and mortality (14% vs 4%, P = .009). Hepatocellular carcinoma diagnosis was found to be associated with less mortality (odds ratio = 0.42, P = .048). Conclusion: While ECD graft usage is associated with slightly worse prognosis, our experience suggests that their use can be considered safe, especially when matched on hepatocellular carcinoma recipients