Search

On July 23, 2022, monkeypox disease (mpox) was declared a Public Emergency of International Concern (PHEIC) by the World Health Organization (WHO) due to a multicountry outbreak. In Europe, several cases of mpox virus (MPXV) infection related to this outbreak were detected in the Canary Islands (Spain). Here we describe the combination of viral DNA sequencing and bioinformatic approaches, including methods for de novo genome assembly and short- and long-read technologies, used to reconstruct the first MPXV genome isolated in the Canary Islands on the 31st of May 2022 from a male adult patient with mild symptoms. The same sequencing and bioinformatic approaches were then validated with three other positive cases of MPXV infection from the same mpox outbreak. We obtained the best results using a reference-based approach with short reads, evidencing 46–79 nucleotide variants against viral sequences from the 2018–2019 mpox outbreak and placing the viral sequences in the new B.1 sublineage of clade IIb of the MPXV classification. This study of MPXV demonstrates the potential of metagenomics sequencing for rapid and precise pathogen identification.

Following the example of national pledges and strategies to tackle climate change, cities are mobilising themselves towards decarbonisation, playing a key role in the achievement of those commitments due to their relevance within national energy systems. However, despite cities ambitions, there is a need for coordinating the efforts from national and local scales in order to ensure the effective fulfilment of energy and climate goals at both levels. In this paper a method for the transposition of national energy planning to the local level is proposed based on the downscaling, adaptation, and allocation of specific targets and energy measures from the national plan to the city scale. The further modelling of downscaled national energy measures allows to quantify the reach of their impacts, thus supporting the establishment of realistic goals aligned with national ones and achieving the effective contribution of urban areas towards higher climate targets. The methodology is demonstrated through the downscaling and comparison of the measures from the Spanish national energy strategy with the ones included in the energy plan of the Spanish city of Valencia. A mismatch between the two is evidenced with some local measures outperforming the national plan, while others proving themselves insufficient. These results show that urban energy planners should consider the real capacities and competences of the city when setting energy measures and goals in accordance with national ones. A correct downscaling and modelling of the former are key in this work.

Summary: Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNβ-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 μg subcutaneous pegylated IFNβ-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNβ-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNβ-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = −0.2%, 95% CI = −8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = −3.6% to 11.3%). Treatment with IFNβ-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNβ-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as ‘Plegridy (peginterferon beta-1a).’ The study was substantially funded by BHP Holdings Pty Ltd.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide affecting a third of adults and 12% of children in Western countries. In around 50–60%% of cases, NAFLD and type 2 diabetes mellitus (T2DM) coexist and act synergistically to increase the risk of adverse hepatic and extra-hepatic outcomes. T2DM is a strong risk factor for rapid progression of NAFLD to nonalcoholic steatohepatitis (NASH), cirrhosis or hepatocellular carcinoma (HCC), which have become frequent indications of liver transplantation.The pathophysiology of NAFLD is complex and its relationship with T2DM is bidirectional, where lipotoxicity and insulin resistance (IR), act as the strongest pillars.To date, no pharmacological treatment has been approved for NAFLD. However, there is an intense research with numerous drugs focused on reversing inflammation and liver fibrosis through modulation of molecular targets without good results.It has been known for some time that weight reduction >10% is associated to histological improvement of NAFLD. Recently, glycemic control has been shown to induce similar results. Diet and physical exercise for weight reduction have limitations, so alternative methods (pharmacologic, endoscopic or surgical) may be required. Currently, new antidiabetic drugs inducing weight loss, have been recently approved for the treatment of obesity. Nevertheless, their therapeutic effects on NAFLD have not been extensively studied.We will review here, recently published data on the effects of weight loss and glycemic control on the histological and metabolic parameters of NAFLD and recent published data on therapeutic studies of NAFLD with new antidiabetic drugs.

Non-alcoholic fatty liver disease (NAFLD) affects one-third of the world's adult population and is linked to metabolic syndrome. It can progress to steatohepatitis, cirrhosis and hepatocellular carcinoma. During the last four decades, it has been the subject of exhaustive research in multiple aspects to define its epidemiology, pathophysiological mechanisms and therapy.In 2020, a group of international experts proposed the change of name to metabolic-associated fatty liver disease (MAFLD) with the main objective of making it an inclusive diagnosis prioritizing metabolic abnormalities. However, the change in terminology included the modification of the diagnostic criteria allowing the non-exclusion of other concomitant liver diseases such as alcohol liver disease, and chronic hepatitis B or C.The proposal precipitated a wave of debates among experts based on theoretical opinions on the desirability of the rapid adoption of the new terminology. But it also precipitated a wave of epidemiological and clinical studies which, two years later, have provided clinical evidence on the differences and similarities of the two entities, specially, those that could be considered for future refinements of the diagnostic criteria of MAFLD. Likewise, this evidence may contribute to deciding the time of adoption of this terminology.In this text, we discuss, in general terms, important aspects of the clinical evidence that has been generated to date in cross-sectional and longitudinal studies focusing on clinical characteristics and outcomes, mainly on all-cause and specific mortality of MAFLD.

The aim of our work was to study whether taurine administration has neuroprotective effects in dystrophic Royal College of Surgeons (RCS) rats, suffering retinal degeneration secondary to impaired retinal pigment epithelium phagocytosis caused by a MERTK mutation. Dystrophic RCS-p + female rats (n = 36) were divided into a non-treated group (n = 16) and a treated group (n = 20) that received taurine (0.2 M) in drinking water from postnatal day (P)21 to P45, when they were processed. Retinal function was assessed with electroretinogram. Retinal morphology was assessed in cross-sections using immunohistochemical techniques to label photoreceptors, retinal microglial and macroglial cells, active zones of conventional and ribbon synaptic connections, and oxidative stress. Retinal pigment epithelium function was examined using intraocular fluorogold injections. Our results document that taurine treatment increases taurine plasma levels and photoreceptor survival in dystrophic rats. The number of photoreceptor nuclei rows at P45 was 3–5 and 6–11 in untreated and treated animals, respectively. Electroretinograms showed increases of 70% in the rod response, 400% in the a-wave amplitude, 30% in the b-wave amplitude and 75% in the photopic b-wave response in treated animals. Treated animals also showed decreased numbers of microglial cells in the outer retinal layers, decreased glial fibrillary acidic protein (GFAP) expression in Müller cells, decreased oxidative stress in the outer and inner nuclear layers and improved maintenance of synaptic connections. Treated animals showed increased FG phagocytosis in the retinal pigment epithelium cells. In conclusion, systemic taurine treatment decreases photoreceptor degeneration and increases electroretinographic responses in dystrophic RCS rats and these effects may be mediated through various neuroprotective mechanisms.

Objectives: Limited testing capacity has characterized the ongoing coronavirus disease 2019 (COVID-19) pandemic in Spain, hampering timely control of outbreaks and opportunities to reduce the escalation of community transmission. This study investigated the potential to use sample pooling, followed by one-step retrotranscription and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) to increase testing capacity for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods: Various pool sizes (five, 10 and 15 samples) were evaluated prior to RNA extraction followed by standard RT-qPCR for the diagnosis of COVID-19. The pool size achieving reproducible results with individual sample testing was subsequently used to assess nasopharyngeal samples in a tertiary hospital in August 2020. Results: A pool size of five samples had higher sensitivity compared with pool sizes of 10 and 15 samples, showing a mean cycle threshold (Ct) shift of 3.5 [standard deviation (SD) 2.2] between the pooled test and positive samples in the pool. Next, a pool size of five was used to test a total of 895 pools (4475 prospective samples) using two different RT-qPCR kits. The Real Accurate Quadruplex corona-plus PCR Kit (PathoFinder) reported the lowest mean Ct shift [2.2 (SD 2.4)] between the pool and individual samples. This strategy enables detection of individual positive samples in positive pools with Ct of 16.7–39.4. Conclusions: Grouping samples into pools of five for RT-qPCR resulted in an increase in SARS-CoV-2 testing capacity with minimal loss of sensitivity compared with testing each sample individually.

Introduction: Cirrhosis and liver cancer are currently common causes of death worldwide. The global epidemic of obesity has increased the incidence of nonalcoholic fatty liver disease (NAFLD) and cirrhosis in recent years. Advanced fibrosis increases the morbimortality rate in NAFLD. The Mexican population has one of the highest prevalence of obesity and diabetes mellitus (DM) worldwide. Aim: To determine the prevalence of advanced liver fibrosis in Mexican general population. Methods: Adult individuals, without a history of liver disease nor heavy alcohol consumption were randomly sampled from 20,919 participants of a health and nutrition survey applied to the general population. Clinical and laboratory evaluations were performed to calculate the NAFLD fibrosis score (NFS) (an extensively validated non-invasive method). Two cut-off points were used. Advanced fibrosis was defined as a result >0.676. Results: In total 695 individuals were included. The mean age was 47.8 ± 16.4. The majority were between 20 and 50 years (59%), 70.2% were female, 35.5% showed obesity and 15.8% DM. The 93% had normal serum ALT. Based on the NFS results, 56 individuals (8.1%) had a high probability of fibrosis. Most patients from this subgroup showed normal serum ALT (92.9%), 89.3% were >45 yr. old, 52% were obese and 27% suffered from DM. Conclusions: Based on these results, 8.1% of Mexican general population without a history of liver disease is at high risk of having advanced liver fibrosis and complications and death derived from cardiovascular disease and cirrhosis. Most of them showed normal ALT serum levels.

Objectives: The ongoing COVID-19 pandemic continues to impose demands on diagnostic screening. In anticipation that the recurrence of outbreaks and the measures for lifting the lockdown worldwide may cause supply chain issues over the coming months, this study assessed the sensitivity of a number of one-step retrotranscription and quantitative polymerase chain reaction (RT-qPCR) solutions to detect SARS-CoV-2. Methods: Six different RT-qPCR alternatives were evaluated for SARS-CoV-2/COVID-19 diagnosis based on standard RNA extractions. The one with best sensitivity was also assessed with direct nasopharyngeal swab viral transmission medium (VTM) heating; thus overcoming the RNA extraction step. Results: A wide variability in the sensitivity of RT-qPCR solutions was found that was associated with a range of false negatives from 2% (0.3–7.9%) to 39.8% (30.2–50.2%). Direct preheating of VTM combined with the best solution provided a sensitivity of 72.5% (62.5–81.0%), in the range of some of the solutions based on standard RNA extractions. Conclusions: Sensitivity limitations of currently used RT-qPCR solutions were found. These results will help to calibrate the impact of false negative diagnoses of COVID-19, and to detect and control new SARS-CoV-2 outbreaks and community transmissions.

Objectives: The gold-standard COVID-19 diagnosis relies on detecting SARS-CoV-2 using RNA purification and one-step retrotranscription and quantitative PCR (RT-qPCR). Based on the urgent need for high-throughput screening, we tested the performance of three alternative, simple and affordable protocols to rapidly detect SARS-CoV-2, bypassing the long and tedious RNA extraction step and reducing the time to viral detection. Methods: We evaluated three methods based on direct nasopharyngeal swab viral transmission medium (VTM) heating before the RT-qPCR: a) direct without additives; b) in a formamide-EDTA (FAE) buffer, c) in a RNAsnapTM buffer. Results: Although with a delay in cycle threshold compared to the gold-standard, we found consistent results in nasopharyngeal swab samples that were subject to a direct 70°C incubation for 10 min. Conclusions: Our findings provide valuable options to overcome any supply chain issue and help to increase the throughput of diagnostic tests, thereby complementing standard diagnosis.

Resumen: Introducción: En el año 2015 la Escuela de Medicina de la Pontificia Universidad Católica de Chile inició un proceso de reforma curricular que favorece la inmersión temprana de los estudiantes al oficio de la medicina y espera fortalecer el aprendizaje de competencias transversales. Objetivos: Describir la experiencia de diseñar, implementar y evaluar un curso de Medicina Comunitaria en el primer año de la carrera de Medicina de la Pontificia Universidad Católica de Chile destinado a promover el contacto precoz de los estudiantes y el desarrollo de competencias transversales. Métodos: Descripción del diseño e implementación del curso siguiendo el modelo de diseño curricular de Kern et al. Resultados: El análisis por etapas de Kern mostró una falta de contacto precoz de los estudiantes con la clínica, falta de conocimiento en áreas de promoción y prevención en salud y una falta de formación curricular explícita en algunas áreas de profesionalismo. El curso propuso el desarrollo de competencias transversales a través de la realización de actividades preventivas con pacientes de la Atención Primaria de Salud. Se diseñó un curso de 5 semanas de duración que utiliza la metodología de aprendizaje y servicio. El curso lleva 3 años de implementación (376 estudiantes), un logro de cumplimiento de objetivos de 95,6% y las competencias transversales de responsabilidad social y trabajo en equipo son mencionadas como desarrolladas en el curso por la mayoría de los estudiantes. Conclusiones: La exposición precoz de los estudiantes de medicina a la clínica en Atención Primaria de Salud asociada a una metodología de aprendizaje y servicio proporciona un espacio para el logro de los objetivos del curso y el desarrollo de competencias transversales. Abstract: Introduction: In 2015, the UC School of Medicine initiated a process of curriculum reform. This showed, among other aspects, the need to expose students to the medical profession early, and to strengthen the learning of transversal competences. Objectives: To describe the experience of designing, implementing, and assessing a Community Medicine course in the first year of the Medical degree of the Pontificia Universidad Católica de Chile, in order to promote early contact and transversal competences. Methods: A descriptive study was conducted with a quantitative and qualitative analysis following the 6-steps approach of Kern et al, describing the steps taken for each stage in the curriculum design of the Community Medicine module. Results: They are described based on the Kern stages. A lack of early contact of students was identified, including a lack of knowledge in areas of promotion and prevention in health, as well as lack of explicit curriculum training in some areas of professionalism. The course proposes the development of transversal competences through preventive activities, all this inserted into a Primary Health Care system. A 5-week course with Service and Learning methodology was designed, through which students developed skills through community service. The course lasted 3 years (376 students), a goal achievement of 95.6% and the transversal competences of social responsibility and teamwork are mentioned, as developed in the course, by the majority of students. Conclusions: Early exposure of medical students to Primary Health Care, with a service learning methodology, provides a space for the acquisition of transversal competences. Palabras clave: Educación médica, Prevención, Medicina comunitaria, Responsabilidad social, Keywords: Medical education, Prevention, Community medicine, Accountability

Background & Aims. It is unclear whether portal vein thrombosis (PVT) unrelated to malignancy is associated with reduced survival or it is an epiphenomenon of advanced cirrhosis. The objective of this study was to assess clinical outcome in cirrhotic patients with PVT not associated with malignancy and determine its prevalence.Material and methods. Retrospective search in one center from June 2011 to December 2014.Results. 169 patients, 55 women and 114 men, median age 54 (19-90) years. Thirteen had PVT (7.6%). None of the patients received anticoagulant treatment. The PVT group was younger (49 [25-62] vs. 55 [19-90] years p = 0.025). Child A patients were more frequent in PVT and Child C in Non-PVT. Median Model for End Stage Liver Disease (MELD) score was lower in PVT (12 [8-21] vs. 19 [7-51] p ≤ 0.001) p ≤ 0.001). There was no difference between upper gastrointestinal bleeding and spontaneous bacterial peritonitis in the groups. Encephalopathy grade 3-4 (4 [30.8%] vs. 73 [46.8%] p = 0,007) and large volume ascites (5 [38.5%] vs. 89 [57.1%] p= 0,012) was more common in non-PVT. Survival was better for PVT (16.5 ± 27.9 vs. 4.13 ± 12.2 months p = 0.005). Conclusions: We found that PVT itself does not lead to a worse prognosis. The most reliable predictor for clinical outcome remains the MELD score. The presence of PVT could be just an epiphenomenon and not a marker of advanced cirrhosis.

About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.

Aims. To define if there is an imbalance in plasma levels of proinflammatory, fibrogenic and antifibrogenic cytokines in patients with liver cirrhosis (LC) and impaired glucose tolerance (IGT) or diabetes mellitus (DM).Material and methods. We randomly selected 54 out of 100 patients with LC who had normal fasting plasma glucose (FPG) levels. Three groups were formed based on an oral glucose tolerance test (OGTT) results: 18 patients were normal, 18 had IGT, and 18 had DM. Plasma levels of cytokines were measured: TNF-α, soluble tumor necrosis factor receptor 1 (sTNF-R1), leptin, TGF-β1, and hepatocyte growth factor (HGF). Also, fasting plasma insulin (FPI) levels were determined and HOMa2-IR was calculated. Results were compared with those of a control group of 18 patients without liver disease nor DM. Intergroup comparison was performed using non parametric tests.Results. Significantly higher sTNF-R1 and lower TGF-β1 were found in patients with IGT and DM compared to controls. Leptin, HGF, and TNF-α levels showed no significant differences. According to Child-Pugh classification all cytokines levels were impaired in groups B or C as compared to group A. Positive correlations between sTNF-R1 and HOMA2-IR and between leptin and HOMA2-IR were found.Conclusions. IGT and DM were associated with abnormalities of sTNF-R1 and TGF-β1 compared to non cirrhotic controls. Among cirrhotic patients impairment of all cytokines were more marked in advanced liver disease. Finally, sTNF-R1and leptin correlated with IR. These findings suggest that IGT and DM may be causally implicated with liver inflammation process.

Aims. To define the prevalence and clinical characteristics of glucose metabolism disorders (GMD) in patients with compensated liver cirrhosis (LC).Material and methods. Fasting plasma glucose (FPG) levels were measured to 130 patients with clinically stable LC. Oral glucose tolerance tests (OGTT) and fasting plasma insulin determinations were performed to patients with normal FPG. Insulin resistance (IR) was calculated with HOMA2-IR index. GMD were classified according to FPG and OGTT tests results and to the chronologic relation between diagnosis of diabetes mellitus (DM) and LC as follows: type-2 DM (T2DM), hepatogenous diabetes (HD) and impaired glucose tolerance. Patients from all groups were compared.Results. The prevalence of GMD were as follows: T2DM in 25 patients (19.2%, 95% CI 12.5-25.9), HD in 28 (21.5%, 95% CI 14.5-28.5) and IGT in 36 (38.5%, 95% CI 30.1-46.7). The total of patients with GMD was 79.2% (95% CI 72.3-86.1). In 41% of cases GMD were subclinical and 48.7% of patients had IR. Patients with T2DM had a higher number of variables with significant differences compared with the other groups (more marked compared to the patients without GMD). The only differences between the patients with T2DM and HD were hypercreatininemia: 1.14 ± 0.53 vs. 0.84 ± 0.22 mg/dL (p = 0.005) and family history of DM: 8 (32%) vs. 2 (7%) (p = 0.02).Conclusion. Almost 80% of patients with compensated LC had GMD. Half of them were subclinical. The patients with T2DM had marked clinical differences compared to patients from the other groups, particularly renal impairment.

Background. Clinical and endoscopic features of cirrhotic patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) have been rarely reported and clinical outcomes and predictors of mortality have not been evaluated.Aims. 1) To describe the clinical features; 2) To define the clinical outcomes; and 3) To identify the predictors of in-hospital mortality of cirrhotic patients with NVUGIB.Methods. One hundred sixty cirrhotic patients with NVUGIB were prospectively studied. Clinical features, endoscopic findings, clinical outcomes and in-hospital mortality rate were studied. Predictors of death were identified by means of univariate and multiple logistic regression analysis.Results. The mean age was 56.5 ± 14.4, male gender prevailed. Alcohol was the most frequent etiology. Hemodynamic instability was reported in 29.4%. Mean serum hemoglobin was 9.5 ± 3.3 g/dL and blood transfusions were required in 59.4%. Gastroduodenal ulcers were the most frequent source of bleeding (50.6%). In endoscopy “high-risk” bleeding stigmata (HRBS) at the ulcer base were found in 53.1%. All patients with HRBS received endoscopic treatment. Rebleeding occurred in 3 patients (1.9%) and mortality was of 13.8%. By univariate analysis: Cryptogenic etiology, BUN, hypoalbuminemia, active bleeding at ulcer base, and endoscopic treatment were predictors of mortality. However, only cryptogenic etiology, hypoalbuminemia and active bleeding at ulcer base were independent predictors of death in multivariate analysis.Conclusions. Gastroduodenal ulcers as a source of NVUGIB are frequent in cirrhotic patients. They were severe; half of them had HRBS, and required frequently endos-copic treatment. In-hospital mortality of these patients seemed to be greater than that of non-cirrhotic patients, and it was significantly related to cryptogenic etiology of cirrhosis, renal dysfunction, severe hepatic failure, and active bleeding ulcers on admission to the hospital.

Background. It has been suggested that DM may reduce survival of patients with liver cirrhosis (LC). Nevertheless only few prospective studies assessing the impact of DM on mortality of cirrhotic patients have been published, none in compensated LC.Aims. (i) to study the impact of DM on mortality and (ii) to identify predictors of death.Methods. Patients with compensated LC with and without DM were studied. Survival was analyzed by the Kaplan-Meier Method. Univariate and multivariate analysis was performed to determine independent predictors of mortality.Results. 110 patients were included: 60 without DM and 50 with DM. Diabetic patients had significantly higher frequency of cryptogenic cirrhosis, anemia, hypoalbuminemia, and hypercreatininemia. They also had significantly higher BMI and Child-Pugh score. The 2.5-years cumulative survival was significantly lower in patients with DM (48 vs. 69%, p < 0.05). By univariate analysis: DM, female gender, serum creatinine > 1.5 mg/dL, Child-Pugh score class C and cryptogenic cirrhosis were significant. However, only serum creatinine > 1.5 mg/dL and Child-Pugh score class C were independent predictors of death.Conclusion: DM was associated with a significant increase in mortality in patients with compensated liver cirrhosis. Serum creatinine > 1.5 mg/dL and Child-Pugh score class C were independent predictors of death.

Corneal refractive therapy is a non-surgical procedure whose main purpose is to improve uncorrected visual acuity during the day, without spectacles or contact lenses. We report an adult woman who shows contact lens intolerance and does not want to wear eyeglasses. We used dual axis contact lens to improve lens centration. We demonstrate a maintained unaided visual acuity during one year of treatment. In conclusion, we can consider refitting with dual axis lens for corneal refractive therapy as a non-surgical option for patients who show contact lens intolerance.

Diabetes developed as a complication of cirrhosis is known as «hepatogenous diabetes» (HD). Around 30% to 60% of cirrhotic patients suffer from this metabolic disorder. Insulin resistance in muscular, hepatic and adipose tissues as well as hyperinsulinemia, seem to be pathophysiologic bases for HD. An impaired response of the islet β-cells of the pancreas and the hepatic insulin resistance are also contributing factors. Diabetes develops when defective oxidative and nonoxidative muscle glucose metabolism develops. Non-alcoholic fatty liver disease (NAFLD), alcoholic cirrhosis, chronic hepatitis C (CHC), and hemochromatosis are more frequently associated with HD. HD in early cirrhosis stages may be sub clinical. Only insulin resistance and glucose intolerance may be observed. As liver disease advances, diabetes becomes clinically manifest, therefore HD may be considered as a marker for liver function deterioration. HD is clinically different from that of type 2 DM since it is less frequently associated with microangiopathy and patients suffer complications of cirrhosis more frequently as well as increased mortality. Insulin resistance and HD associate to a decrease in the sustained response to antiviral therapy and an increased progression of fibrosis in patients with CHC. Diabetes treatment is complex due to liver damage and hepatotoxicity of oral hypoglycemic drugs that are frequently prescribed to these patients. This paper will review current concepts in relation to the pathopysiolo-gy, the impact on the clinical outcome of cirrhosis, and the therapy of HD. Finally, the role of HD as a risk factor for the occurrence and exacerbation of hepatocel-lular carcinoma (HCC) will also be reviewed.

Aim: The Child Pugh and MELD are good methods for predicting mortality in patients with chronic liver disease. We investigated their performance as risk factors for failure to control bleeding, in-hospital overall mortality and death related to esophageal variceal bleeding episodes. Methods: From a previous collected database, 212 cirrhotic patients with variceal bleeding admitted to our hospital were studied. The predictive capability of Child Pugh and MELD scores were compared using c statistics. Results: The Child-Pugh and MELD scores showed marginal capability for predicting failure to control bleeding (the area under receiver operating characteristics curve (AUROC) values were < 0.70 for both). The AUROC values for predicting inhospital overall mortality of Child-Pugh and MELD score were similar: 0.809 (CI 95%, 0.710 - 0.907) and 0.88 (CI 95% 0.77-0.99,) respectively. There was no significant difference between them (p > 0.05). The AU-ROC value of MELD for predicting mortality related to variceal bleeding was higher than the Child-Pugh score: 0.905 (CI 95% 0.801-1.00) vs 0.794 (CI 95% 0.676 - 0.913) respectively (p < 0.05). Conclusions: MELD and Child-Pugh were not efficacious scores for predicting failure to control bleeding. The Child-Pugh and MELD scores had similar capability for predicting in-hospital overall mortality. Nevertheless, MELD was significantly better than Child-Pugh score for predicting in-hospital mortality related to variceal bleeding.

Transjugular liver biopsy was first reported in 1967. Since then, this technique has been broadly performed in many medical centers around the world. The number of its indications has increased, and by modifying the needles, the quality of the liver tissue sample has improved. The advantage of transjugular biopsy is that it can be performed in patients in whom the use of percutaneous biopsy is contraindicated Indications for transjugular liver biopsy are, precisely, most of the contraindications for percutaneous liver biopsy. This fact increases the number of patients that can benefit from this procedure.In most cases, the procedure is successfully performed. Minor complications may occur in 1% to 15% and major complications (perforation of the hepatic capsule, cholangitis, and intra-peritoneal bleeding) are observed in 1-3% of the cases. Mortality related to the procedure varies form 0.2 to 0.3%.It has been reported that diagnosis yielded by transjugular liver biopsy induced changes of treatment in 50% of patients with an acute hepatic illness, in 62% of the patients with a chronic hepatic illness, and in 87% of the patients with liver transplants. In conclusion, transjugular liver biopsy is a useful procedure in the diagnosis of hepatic diseases. Its success rate is high; it is a very safe procedure because complications and mortality are rare; and it is well tolerated by patients.

Intravenous albumin infusion prevents complications after large-volume paracentesis (LVP), particularly paracentesis-induced circulatory dysfunction (PCD), and improves patient survival. However, albumin is expensive. We compared a low-molecular weight dextran (Dextran-40) with albumin in treating LVP in cirrhotic patients with tense ascites. Sixty-nine cirrhotic patients were included and 96 LVPs were performed. Any repeat punctures on the same patient were at least three months apart. Patients were randomized to receive either i.v. Dextran-40 infusion (Group I, n = 48) or i.v. albumin infusion after LVP (Group II, n = 48). Clinical, biochemical, and hormonal evaluations were done before and after LVP. Patients were followed up for the detection of any recurrence of ascites or complications.The two groups were similar in age, sex, and etiology of cirrhosis, and in the volumes of ascites recovered. Significant decreases in mean arterial pressure were observed in both groups 24 and 48 h after LVP. Urine volumes increased significantly at 24 h in both groups (p < 0.05), but remained high only in Group I. Plasma renin activity and aldosterone concentrations increased in both groups 48 h after LVP, but they were more marked in Group I. Complications developed in 17 % of patients treated with Dextran-40 and in 23 % treated with albumin (p > 0.05). Ascites recurrence rates and survival were similar in the two groups. In conclusion, Dextran-40 was thus not as efficacious as albumin for preventing PCD.

The endangered Pyrenean Capercaillie (Tetrao urogallus aquitanicus) inhabits perennial forests of the Pyrenees (Spain, France and Andorre). Feces of domestic animals (e.g., horses and cattle) are often found in this species’ habitat as evidence of land use overlapping, especially during spring and summer. As a result, pharmaceutical residues found in feces of these domestic ungulates may be absorbed by plants and insects that are part of the diet of Pyrenean Capercaillies (e.g., blueberries [Vaccinium uliginosum, Vaccinium myrtillus], red wood ants [Formica rufa]). Based on the absence of data regarding the exposure of Pyrenean Capercaillie to residues of veterinary medicinal products (VMP), we selected 71 compounds as indicators of anthropogenically-related environmental contamination, analyzed in 90 samples collected in several subalpine forests, northwestern Spain. Residues of several VMP were detected in feces (capercaillie [ciprofloxacin, enrofloxacin, tetracycline and florfenicol], horse [ciprofloxacin, enrofloxacin, tetracycline and ivermectin], and cattle [ciprofloxacin and enrofloxacin]), and in entomofauna (ciprofloxacin and ivermectin). No VMP residues were detected in blueberry plants. Herein, we present novel data about the presence of VMP residues in the Pyrenean Capercaillie’s environment, and identify potential VMP sources (i.e., livestock feces and entomofauna) and an exposure route (i.e., food chain) for Capercaillie chicks. Further studies are necessary to investigate the potential indirect or chronic effects of VMP residues in the species’ breeding success and adult fitness, which must be taken into account by managers and policy makers to improve management and conservation actions.

Cryptosporidium, Giardia, and Blastocystis are significant causes of diarrhea worldwide. However, studies on their prevalence in wild animals are limited, compared to humans and domestic animals. In this study, we collected 23 stool samples from captive wild rescued animals in Boyacá, Colombia. Using conventional PCR, we detected Cryptosporidium spp., Giardia spp., and Blastocystis in over half of the samples (69.6%). Cryptosporidium spp. (43.5%) were the most commonly found, followed by Giardia spp. (39.1%) and Blastocystis (13.0%). Co-infections involving these parasites were also observed. Subsequent genotyping revealed Cryptosporidium canis and Cryptosporidium ryanae as the predominant species. These findings contribute valuable information about the ecoepidemiology of intestinal parasites in Colombian wild animals.