The simplicity and low cost of rapid point-of-care tests greatly facilitate large-scale population testing, which can contribute to controlling the spread of the COVID-19 virus. We evaluated the ...applicability of a self-testing strategy for SARS-CoV2 in a population-based, cross-sectional study in Cantabria, Spain, between April and May 2020. For the self-testing strategy, participants received the necessary material for the self-collection of blood and performance of a rapid antibody test using lateral flow immunoassay at home without the supervision of healthcare personnel. A total of 1,022 participants were enrolled. Most participants correctly performed the COVID-19 self-test the first time (91.3% 95% CI 89.4-92.9). Only a minority of the participants (0.7%) needed the help of healthcare personnel, while 6.9% required a second kit delivery, for a total valid test result in 96.9% of the participants. Incorrect use of the self-test was not associated with the educational level, age over 65, or housing area. Prevalence of IgG antibodies against SARS-CoV2 for subjects with a valid rapid test result was 3.1% (95% CI 2.2-4.4), similar to the seroprevalence result obtained using a conventional approach carried out by healthcare professionals. In conclusion, COVID-19 self-testing should be considered as a screening tool.
LOXL2-A New Target in Antifibrogenic Therapy? Puente, Angela; Fortea, Jose Ignacio; Cabezas, Joaquin ...
International journal of molecular sciences,
04/2019, Letnik:
20, Številka:
7
Journal Article
Recenzirano
Odprti dostop
The concept of liver fibrosis and cirrhosis being static and therefore irreversible is outdated. Indeed, both human and animal studies have shown that fibrogenesis is a dynamic and potentially ...reversible process that can be modulated either by stopping its progression and/or by promoting its resolution. Therefore, the study of the molecular mechanisms involved in the pathogenesis of liver fibrosis is critical for the development of future antifibrotic therapies. The fibrogenesis process, common to all forms of liver injury, is characterized by the increased deposition of extracellular matrix components (EMCs), including collagen, proteoglycans, and glycoproteins (laminin and fibronectin 2). These changes in the composition of the extracellular matrix components alter their interaction with cell adhesion molecules, influencing the modulation of cell functions (growth, migration, and gene expression). Hepatic stellate cells and Kupffer cells (liver macrophages) are the key fibrogenic effectors. The antifibrogenic mechanism starts with the activation of Ly6C
macrophages, which can differentiate into macrophages with antifibrogenic action. The research of biochemical changes affecting fibrosis irreversibility has identified lysyl oxidase-like 2 (LOXL2), an enzyme that promotes the network of collagen fibers of the extracellular matrix. LOXL2 inhibition can decrease cell numbers, proliferation, colony formations, and cell growth, and it can induce cell cycle arrest and increase apoptosis. The development of a new humanized IgG4 monoclonal antibody against LOXL2 could open the window of a new antifibrogenic treatment. The current therapeutic target in patients with liver cirrhosis should focus (after the eradication of the causal agent) on the development of new antifibrogenic drugs. The development of these drugs must meet three premises: Patient safety, in non-cirrhotic phases, down-staging or at least stabilization and slowing the progression to cirrhosis must be achieved; whereas in the cirrhotic stage, the objective should be to reduce fibrosis and portal pressure.
Background & Aims: Hepatorenal syndrome is common in patients with advanced cirrhosis and constitutes a major problem in liver transplantation. There is no effective medical treatment for hepatorenal ...syndrome. Methods: Forty-six patients with cirrhosis and hepatorenal syndrome, hospitalized in a tertiary care center, were randomly assigned to receive either terlipressin (1–2 mg/4 hour, intravenously), a vasopressin analogue, and albumin (1 g/kg followed by 20–40 g/day) (n = 23) or albumin alone (n = 23) for a maximum of 15 days. Primary outcomes were improvement of renal function and survival at 3 months. Results: Improvement of renal function occurred in 10 patients (43.5%) treated with terlipressin and albumin compared with 2 patients (8.7%) treated with albumin alone ( P = .017). Independent predictive factors of improvement of renal function were baseline urine volume, serum creatinine and leukocyte count, and treatment with terlipressin and albumin. Survival at 3 months was not significantly different between the 2 groups (terlipressin and albumin: 27% vs albumin 19%, P = .7). Independent predictive factors of 3-month survival were baseline model for end-stage liver disease score and improvement of renal function. Cardiovascular complications occurred in 4 patients treated with albumin alone and in 10 patients treated with terlipressin and albumin, yet permanent terlipressin withdrawal was required in only 3 cases. Conclusions: As compared with albumin, treatment with terlipressin and albumin is effective in improving renal function in patients with cirrhosis and hepatorenal syndrome. Further studies with large sample sizes should be performed to test whether the improvement of renal function translates into a survival benefit.
The consumption of alcoholic beverages is harmful to human health. In recent years, consumption patterns of alcoholic beverages have changed in our society, and binge drinking has generalized. It is ...considered to be a socio-sanitary problem with few known consequences in terms of individual and third-party social impacts(in the form of violence or traffic accidents) and its organic impact(affects the liver and other organs and systems, such as the nervous and cardiovascular systems) and represents an important financial burden due to its increasing economic impact. This review provides a global approach to binge drinking and emphasizes its epidemiological character, the effect of this type of consumption and the possible management of a problem with an increasing tendency in our society.
Background and Aims
Spleen stiffness measurement (SSM) by vibration‐controlled transient elastography (VCTE) has been tested in a limited number of studies versus hepatic venous pressure gradient ...(HVPG), especially with the 100 Hz spleen‐specific module. The current study aims to evaluate the diagnostic performance of this novel module for detecting clinically significant portal hypertension (CSPH) in a cohort of compensated patients with metabolic‐associated fatty liver disease (MAFLD) as the main aetiology and to improve the performance of the Baveno VII criteria for CSPH diagnosis by including SSM.
Methods
This is a retrospective single‐centre study including patients with available measurements of HVPG, Liver stiffness measurement (LSM) and SSM by VCTE with the 100 Hz module. Area under the receiver operating characteristic (AUROC) curve analysis was conducted to identify dual cut‐offs (rule‐out and rule‐in) associated with the absence/presence of CSPH. The diagnostic algorithms were adequate if negative predictive value (NPV) and positive predictive values (PPV) were >90%.
Results
A total of 85 patients were included, 60 MAFLD and 25 non‐MAFLD. SSM showed a good correlation with HVPG (MAFLD: r = .74; p < .0001; non‐MAFLD: r = .62; p < .0011). In MAFLD patients, SSM had a high accuracy in discarding/diagnosing CSPH (cut‐off values of <40.9 and >49.9 kPa, AUC 0.95). The addition of these cut‐offs in a sequential or combined approach to the Baveno VII criteria significantly reduced the grey zone (60% vs. 15%–20%), while maintaining adequate NPV and PPV.
Conclusions
Our findings support the utility of SSM for diagnosing CSPH in MAFLD patients and demonstrate that the addition of SSM to the Baveno VII criteria increases accuracy.
AIM: To investigate the plasma levels of betatrophin in patients with cirrhosis.METHODS: Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic,or ...histological criteria were included.The severity of cirrhosis was classified according to Pugh’s modification of Child’s classification and MELD score. Insulin resistance(IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched subjects.Fasting blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay(DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were < 4% and < 10%,respectively. The normal values were between 2 and17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA(Aviscera Bioscience). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility were< 6% and < 10%, respectively.RESULTS: Plasma betatrophin levels were significantly increased in patients with cirrhosis compared with those in healthy subjects(P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B(P< 0.0005) and in patients who displayed a MELD score higher than 14 points compared to patients with lower punctuation(P = 0.01). In addition, we found a positive correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification(r = 0.53; P < 0.01) or MELD score(r = 0.45; P <0.01). In the overall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin(r= 0.39; P < 0.01) has been observed, as well as an inverse correlation between betatrophin and albumin(r =-0.41; P < 0.01) or prothrombin time(r =-0.44;P <0.01). Moreover, insulin resistance was observed in82.5% of the cirrhotic patients. In this group of patients,betatrophin levels were significantly higher than those in the group of patients without IR(P < 0.05).CONCLUSION: Plasma betatrophin is increased in patients with cirrhosis. This increase is related to the severity of cirrhosis, as well as with the emergence of insulin resistance.
Rationale
Patients with schizophrenia spectrum disorders have increased morbidity and mortality, largely due to cardiovascular disease, which is associated with antipsychotic treatment.
Objectives
...Because of the link between cardiometabolic risk, non-alcoholic fatty liver disease (NAFLD), and antipsychotics, we aimed to investigate the development of NAFLD during the first 3 years of antipsychotic treatment in first episode non-affective psychosis patients.
Results
A sample of 191 subjects was included in final analyses, randomly assigned to aripiprazole (
N
= 83), risperidone (
N
= 12), quetiapine (
N
= 46), and ziprasidone (
N
= 50). At intake, 180 patients were antipsychotic naïve. The NAFLD fibrosis score, FIB-4 score, and the fatty liver index (FLI) were calculated at baseline, at 3 months, and then yearly for 3 years. None of the patients showed significant liver fibrosis according to the mentioned scores at baseline, prior to randomization. At 3 years follow-up, 25.1 % individuals showed a FLI score ≥60, which is a predictor of steatosis. Of the individuals considered indeterminate at baseline, 64.7 % developed a FLI score ≥60 and only 16.6 % who had a FLI score <30 at baseline, showed a FLI score predictor of steatosis at endpoint. The FLI score ≥60 at endpoint was associated with an increase of more than 7 % of the body mass index (FLI score ≥ 60, 91.7 %; FLI < 60, 55.9 %;
p
< 0.001), increased triglyceride levels (FLI score ≥ 60, 54.2 %; FLI < 60, 5.6 %;
p
< 0.001), decreased HDL levels (FLI score ≥ 60, 41.7 %; FLI < 60, 17.5 %;
p
= 0.001), hypertension (FLI score ≥ 60, 19.5 %; FLI < 60, 4.5 %;
p
= 0.002), and waist circumference increase (steatosis 68.8 %; FLI < 60, 14.0 %;
p
< 0.001).
Conclusions
Our results support the importance of assessing the potential development of NAFLD in schizophrenia spectrum patients receiving antipsychotic medication.
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