Early changes of left atrial function in chronic asymptomatic alcoholics by two-dimensional speckle-tracking echocardiography.

Background Chronic excessive alcohol intake has been reported as a possible cause of dilated cardiomyopathy. Two-dimensional speckle-tracking echocardiography (2D-STE) is a novel method for the angle-independent and objective quantification of myocardial deformation. This study sought to assess left atrial function changes among alcoholics related to the duration of heavy drinking by 2D-STE. Methods We classified 92 asymptomatic alcoholics into mild, moderate and severe groups. Thirty age-matched controls were also recruited. We measured left atrial (LA) phasic volumes (max, min and pre-atrial contraction volume) using Simpson's method in apical four-chamber view. Passive emptying (LAPEF) and active emptying (LAAEF) indices were calculated. Global longitudinal strain rate (SRs) during left ventricular (LV) ejection, early diastolic strain rate (SRe) during LV early diastole and peak negative strain rate (SRa) after the P-wave were also obtained by averaging all atrial segments. Results The alcoholics had larger LA volumes (max, min and pre-atrial contraction volume) since moderate stage (P < 0.01). LAPEF, SRs SRe, and E/A ratio showed progressive decrease according to the grades of alcoholism. The differences between the groups were significant, beginning from the moderate group (P < 0.01). During LAAEF, SRa values increased with the disease severity up to moderate alcoholics and then deteriorated significantly in severe alcoholics (P < 0.01). Conclusions These data suggest that 2D-STE may be considered a promising tool for the early detection of impairment of LA function in alcoholics.

Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European Prospective Study.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.

Initiation of aberrant DNA methylation patterns and heterogeneity in precancerous lesions of human hepatocellular cancer.

While intratumor heterogeneity contributes to disease progression, metastasis, and resistance to chemotherapy, it also provides a route to understanding the evolution and drivers of disease. Defects in epigenetic landscapes are intimately linked to pathogenesis of a variety of human diseases, with epigenetic deregulation promoting tumorigenesis. Understanding epigenetic heterogeneity is crucial in hepatocellular carcinoma (HCC), where epigenetic alterations are frequent, early, and pathogenic events. We determined genome-wide DNA methylation and copy number variation leveraging the Infinium 450K in a series of regenerative nodules from within single patient livers. Bioinformatics strategies were used to ascertain within-patient heterogeneity, link epigenetic changes to clinical features, and determine their relevance to disease pathogenesis. Our data demonstrate that DNA methylation and copy number alterations evolve during the pre-neoplastic phase of HCC and independently segregate regenerative nodules into distinct clusters. Regenerative nodules with a high frequency of epigenetic changes have significantly lower copy number variation, suggesting that individual nodules have differential enrichment of epigenetic and genetic components, with both contributing to disease progression. Regenerative nodules were scored based on 'epigenetic progression' with higher scores associated with increased proliferation measured by Ki67 staining. Early events observed in epigenetically 'aggressive' nodules are enriched for genes involved in liver cancer. Our study demonstrates that marked epigenetic and genetic heterogeneity exists in early pre-neoplastic liver tissue within individual patients, emphasizing the potential contributions of each mechanism to driving liver disease progression, and it unveils strategies for identifying epigenetic drivers of hepatocellular carcinoma.

Early Changes in Platelet Size and Number in Patients with Acute Coronary Syndrome.

A strong relationship exists between acute coronary syndrome (ACS) and platelets (PLTs) volume. Mean platelet volume (MPV) is a parameter of PLT functions and a marker for increased PLT activation. The aim of this study was to determine early changes in number of total PLT and MPV in different manifestation of ACS and to find out predictive value of MPV in the spectrum of ACS. This was a prospective study. One hundred thirty-four ACS patients were enrolled, 76 of them finished the study. PLT and MPV in patients with unstable angina, non-ST elevation, and ST elevation myocardial infarctions were determined on arrival and 1, 3, 72 hours, and 7 days after the admission to hospital. There was decrease in PLT and MPV in all three groups after 3 hours of arrival in hospital in comparison with admission values. In the later time period (72 hours and 7 days), there was an increase in PLT and MPV only in patients with acute myocardial infarction (AMI). We have revealed completely new dynamics in early changes in MPV and PLT count in patients with AMI. Biphasic changes were found in early phase after admission to the hospital. Fast response in these parameters raises new questions about their origin.

Diagnostic value of high field intensity MRI in early changes of wrist RA / 中国医学装备

Objective: To explore the diagnostic value of high field intensity magnetic resonance imaging(MRI) in the early changes of wrist rheumatoid arthritis(RA). Methods: 150 patients with joint pain were enrolled in the retrospective analysis. And in these patients, the patients with RA who were diagnosed by using high field intensity MRI were divided into observation group(102 cases), and others were divided into control group (48 cases). The diagnostic value of high field intensity MRI for the early change of wrist RA were further explored and discussed. Results: The diagnostic sensitivities of early change, synovial thickening, bone marrow edema, bone erosion, arthroedema and myotenositis of high field intensity MRI for RA were higher than 60%, and the diagnostic specificity of them were higher than 50%, and the diagnostic sensitivity of synovial thickening of these indicators even achieved to 100%. The positive rates of these indicators of observation group was significantly higher than that of control group, respectively (x2=108.147, x2=27.943, x2=50.473, x2=51.549, x2=17.558, P<0.05). And all of synovial thickening, bone marrow edema, bone erosion, arthroedema and myotenositis were the independent influence factors of early diagnosis of wrist RA(OR=9.631, OR=10.114, OR=25.867, OR=26.258, OR=14.027, P<0.05). Conclusion: MRI is one of the reliable methods for diagnosing early wrist RA. Synovial thickening, bone marrow edema, bone erosion, joint effusion and tendonitis can be used as the main symptom in diagnosis. And they can be combined with clinical symptom, sign and laboratory examination results to carry out comprehensive judgment for RA of wrist.

Steroid / 대한정형외과학회잡지

Osteonecrosis has been found in association with non-traumatic pathological conditions such as alcoholism, sickle cell hemoglobinopathies, Gaucher's disease and decompression sickness. It is also a major compcation in surviving renal transplantation patients where it is generally believed to be a result of immunosupressive systemic corticosteroid administration. The precise etiology of osteonecrosis is still unknown, but many hypotheses have presented; interruption of the blood supply, direct cytotoxic effect, incresed intraosseous pressure and decreased venous return. Whatever the caused or the starting point, and whatever the pathologic process, blockage of the osseous microcirculation with intramedullary stasis appears to be the common denominator. In the present study, our purpose is to examine the microvascular structural changes and corresponding pathological changes of rabbit's femoral head by disturbance of lipid metabolism resulting from the administration of a large dose of the steroid. The results were as follows:1. In the study group (steroid-treated);there was a relatively increased empty lacuna within the rabbit's femoral head suchondral bone at 3 weeks in contrast with the control group. (control:10.72%, study:20.8%,P<0.01.). 2. Early definite marrow necrosis was found since 3 wekks, a marrow focal osteonecrosis since 5 weeks, and roentgenographically osteoporosis since 5 weeks in the study group. 3. In the histological study, the more degenerative vascular changes were found in the subchondral plate as weekly time was relapsed (H & E), and the subchondral vessels were filled with fat in most of the steroid-treated group (Oil-red 0). 4. In the microangiographic study, the chnges of vascular pattern of the subchondral area was found in the more steroid treated group. ie, it was shown to be dissimilar in size, irregulary spaced and not orderly arranged side by side in a line with disappearing focal vascular shadow.