Usefulness of transesophageal echocardiography in the assessment of aortic dissection

The acute dissection of the ascending aorta requires prompt and reliable diagnosis to reduce the high risk of mortality; in addition, prognosis is influenced by longterm complications. The aim of this article is to discuss transesophageal echocardiography (TEE) and (1) its diagnostic accuracy in the presurgical evaluation of patients, (2) its role in reducing time of diagnosis and surgery, and (3) its ability to reduce hospital mortality. TEE has also been tested as a screening method in the postsurgical follow-up of these patients. The retrospective investigation concerns a sample of 80 cases of acute dissection of the aorta, submitted for surgical intervention from April 1986 to February 1999. TEE has allowed a precise estimation of aortic diameters and optimal visualization of intimal flap and tear entry with a fine distinction between true and false lumen. A direct comparison of the results of TEE and of transthoracic echocardiography has demonstrated that some elements (visualization of flap and diameters in descending aorta, sites of entry and reentry, direction of let trough intimal tears, phasic intimal flap movement, diastolic collapse of flap on the valvular plane, false lumen thrombosis, coronary involvement, intramural hematoma, and aortic fissuration) were identified only by TEE, whereas other additional diagnostic elements (cardiac tamponade, aortic valve insufficiency, left ventricular function) show a similar pattern of significance. Routine employment of this method has confirmed a reduction of hospitalization time (about 1.5 hours of waiting time), and hospital mortality has changed from 42.8% to 17.3%. In the follow-up of patients operated on for aortic dissection, fundamental information may be obtained from TEE (assessment of the progression of thrombosis in the false lumen with its complete obliteration and modifications in aortic diameter with a consequent, possible worsening of aortic valve insufficiency). In conclusion, our study demonstrated that TEE may provide fast and efficient detection of acute aortic dissection. In the postsurgical follow-up, TEE has confirmed detection of major complications that can influence long-term prognosis and may be proposed as a method with easy access-one that is repeatable and inexpensive for the screening of aortic dissection surgical patients. (C) 2000 by Excerpta Medica, Inc

Diagnostic and prognostic value of B4GALT1 hypermethylation and its clinical significance as a novel circulating cell-free DNA biomarker in colorectal cancer

Epigenetic modifications of glyco-genes have been documented in different types of cancer and are tightly linked to proliferation, invasiveness, metastasis, and drug resistance. This study aims to investigate the diagnostic, prognostic, and therapy-response predictive value of the glyco-gene B4GALT1 in colorectal cancer (CRC) patients. A Kaplan-Meier analysis was conducted in 1418 CRC patients (GEO and TCGA datasets) to assess the prognostic and therapy-response predictive values of the aberrant expression and methylation status of B4GALT1. Quantitative methylation-specific PCR (QMSP) and droplet digital quantitative methylation-specific PCR (dd-QMSP) were respectively used to detect hypermethylated B4GALT1 in metastasis and plasma in four cohorts of metastatic CRC cases (mCRC). Both the downregulated expression and promoter hypermethylation of B4GALT1 have a negative prognostic impact on CRC. Interestingly a low expression level of B4GALT1 was significantly associated with poor cetuximab response (progression-free survival (PFS) p = 0.01) particularly in wild-type (WT)-KRAS patients (p = 0.03). B4GALT1 promoter was aberrantly methylated in liver and lung metastases. The detection of hypermethylated B4GALT1 in plasma of mCRC patients showed a highly discriminative receiver operating characteristic (ROC) curve profile (area under curve (AUC) value 0.750; 95% CI: 0.592-0.908, p = 0.008), clearly distinguishing mCRC patients from healthy controls. Based on an optimal cut-off value defined by the ROC analysis, B4GALT1 yield a 100% specificity and a 50% sensitivity. These data support the potential value of B4GALT1 as an additional novel biomarker for the prediction of cetuximab response, and as a specific and sensitive diagnostic circulating biomarker that can be detected in CRC

Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

Brain invasion by glioblastoma determines prognosis, recurrence, and lethality in patients, but no master factor coordinating the invasive properties of glioblastoma has been identified. Here we report evidence favoring such a role for the noncanonical WNT family member Wnt5a. We found the most invasive gliomas to be characterized by Wnt5a overexpression, which correlated with poor prognosis and also discriminated infiltrating mesenchymal glioblastoma from poorly motile proneural and classical glioblastoma. Indeed, Wnt5a overexpression associated with tumor-promoting stem-like characteristics (TPC) in defining the character of highly infiltrating mesenchymal glioblastoma cells (Wnt5aHigh). Inhibiting Wnt5a in mesenchymal glioblastoma TPC suppressed their infiltrating capability. Conversely, enforcing high levels of Wnt5a activated an infiltrative, mesenchymal-like program in classical glioblastoma TPC and Wnt5aLow mesenchymal TPC. In intracranial mouse xenograft models of glioblastoma, inhibiting Wnt5a activity blocked brain invasion and increased host survival. Overall, our results highlight Wnt5a as a master regulator of brain invasion, specifically TPC, and they provide a therapeutic rationale to target it in patients with glioblastoma

“La relazione terapeutica e prospettiva evolutiva in psicoanalisi. Sviluppi recenti del paradigma freudiano"

Uno degli assunti principali della psicopatologia evolutiva è che le esperienze relazionali vissute a partire dalla prima infanzia esercitano un'influenza rilevante sullo sviluppo della personalità; da qui derivano l'interesse per l'influenza esercitata dai modelli di funzionamento dell'infanzia sui modelli di funzionamento dell'adulto, e l'attenzione rivolta all'influenza dei modelli di funzionamento presenti e delle circostanze attuali, tenendo in considerazione il fatto che le relazioni successive possono modificare i modelli di funzionamento appresi nell'età evolutiva. L'orientamento evolutivo assume un ruolo chiave all'interno della concezione della relazione terapeutica, in cui possono funzionare come dimensioni silenti i motori fondamentali dello sviluppo (attività, autoregolazione, adattamento sociale, monitoraggio affettivo, assimilazione cognitiva), il cui processo può riattivare in senso trasformativo una forma peculiare di esperienza evolutiva il cui prototipo è la responsività contingenete caratterizzante la relazione madre-bambino

Oncocytic nonsecretory multiple myeloma. A clinicopathologic study of a case and review of the literature.

We report on a morphologic variant of multiple myeloma, identified in a 39-year-old man, with osteolytic lesions in two ribs and three lumbar vertebrae. Serum electrophoresis was normal and immunofixation of serum and urine was negative. Histologic examination of a resected rib revealed a homogeneous population of neoplastic plasma cells with granular and eosinophilic cytoplasm. Immunohistochemical stains showed monoclonality for lambda light chain and negativity for all heavy chains. At the ultrastructural level, the cytoplasm of the neoplastic plasma cells was almost totally occupied by round and elongated mitochondria, pushing the rough endoplasmic reticulum to the periphery. To the best of our knowledge, only two similar cases have been reported in the literature so far. The usefulness of obtaining a clinicopathologic correlation for the behaviour of this extremely rare variant of multiple myeloma is discussed

Genetics of rotator cuff tears: No association of col5a1 gene in a case-control study

BackgroundThe incidence of RC tears increases with aging, affecting approximately 30 to 50% of individuals older than 50years, and more than 50% of individuals older than 80years. Intrinsic factors (age or gender), extrinsic factors (sports activity or occupation), and biological factors were identified in the onset and progression of RC tears. The attention in the study of aetiology of RC tendinopathy has shifted to the identification of gene variants. Genes encoding for proteins regulating the concentration of pyrophosphate in the extracellular matrix and genes encoding for fibroblastic growth factors, defensin beta 1 and estrogen-related receptor-beta were analyzed. However, only in one study the role of variants of collagen type V alpha 1 (col5a1) gene in RC tears was assessed. The objective of this study was to determine whether a col5a1 DNA sequence variant, rs12722 (C/T) was associated with rotator cuff (RC) tears in a case-control study.MethodsThe study included 93 Caucasian patients undergoing surgery for RC tears and 206 patients with no history and sign of RC disease as evaluated by MRI. Patients were divided into two groups. Group 1 included patients with RC tear diagnosed on clinical and imaging grounds and confirmed at the time of surgery. Group 2 (control group) included patients without history or clinical symptoms of RC disorders and with a MRI negative for RC disease. DNA was obtained from approximately 1.2ml of venous blood using the MagCore extractor system H16 with a MagCore Genomic DNA Large Volume Whole Blood Kit (RBC Bioscience Corp., Taiwan). All study participants were genotyped for SNPs rs12722.ResultsWe first estimated that our study had 92% power at p<0.05 to detect a genetic effect size of 2.05 in the RT tears (93 individuals) and healthy population (206 individuals) cohorts, assuming a minor allele frequency for col5a1 variant rs12722 of 0.5707 in the Italian population (gnomAD frequency). No significant difference in allele and genotype frequencies was observed between RT tears patients and healthy controls. Similarly, no significant association was seen between the RT tears and healthy controls participants in the combined genotype distributions.ConclusionIn conclusion, no correlations between the SNP rs12722 of col5a1 gene and RC tears susceptibility was found

TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways

Background: We recently reported TRIM8, encoding an E3 ubiquitin ligase, as a gene aberrantly expressed in glioblastoma whose expression suppresses cell growth and induces a significant reduction of clonogenic potential in glioblastoma cell lines. Methods: we provided novel insights on TRIM8 functions by profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells by RNA-sequencing and bioinformatic analysis. Functional analysis including luciferase assay, western blot, PCR arrays, Real time quantitative PCR were performed to validate the transcriptomic data. Results: Our study identified enriched pathways related to the neurotransmission and to the central nervous system (CNS) functions, including axonal guidance, GABA receptor, Ephrin B, synaptic long-term potentiation/depression, and glutamate receptor signalling pathways. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3. Conclusions: Our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different CNS-related pathways, including JAK-STAT. General significance: This study provides novel insights on the physiological TRIM8 function by profiling for the first time the primary Neural Stem Cell over-expressing TRIM8 by using RNA-Sequencing methodology

Focal ultrasound lesions in cirrhotic liver diagnosed as regenerative nodules by biopsy. A morphometric analysis

Ten cirrhotic patients with ultrasonically discernible focal liver masses underwent fine cutting needle biopsy. Specimens were obtained from the focal lesions under ultrasound guidance and histologically diagnosed as regenerative nodules. An image analyzer was then used to determine the cytoplasmic area, nuclear area, and nuclear/cytoplasmic ratio for 100 randomly selected cells from each specimen. Data were then compared with data for specimens of normal liver tissue and data from patients with alcoholic or posthepatic cirrhosis or well-differentiated hepatocellular carcinoma (HCC). The morphometric parameters for the group of regenerative nodule specimens fell within an intermediate range between those for HCC and the nondysplastic samples, strongly suggesting a preneoplastic nature. Nine of the 10 regenerative lesions showed liver cell dysplasia, and 3 of these patients developed HCC during follow-up. Ultrasonically discernible focal masses in a cirrhotic liver should be considered preneoplastic, if not neoplastic lesions and treated aggressively to prevent their progression to outright malignancy