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Background: Multiple studies have linked COVID-19 to a higher incidence of thromboembolic disorders. However, the association of COVID-19 with other potentially life-threatening complications, such as splanchnic vein thrombosis, is less well understood. This study aims to assess the prevalence, patient characteristics, clinical presentation, and outcomes of patients with portal vein thrombosis (PVT) and COVID-19. Methods: This was a retrospective observational study. From all positive patients for a reverse-transcription polymerase chain reaction (RT-PCR) swab test from March 2020 to June 2020, we included those who were older than 18 years, had received abdominal contrast-enhanced computed tomography (CT) in the 6 months following the positive RT-PCR swab, and had no previously known splanchnic vein thrombosis. Results: A total of 60 patients with abdominal CT were selected from all those positive for SARS-CoV-2 ( n = 2987). The prevalence of PVT was 3/60 (5%). The mean age was 66.1 ± 16.5 years and 51.7% were male. In two of the three patients, there was no underlying pathology as a risk factor for PVT and one of them presented cirrhosis. The number of days from the start of COVID-19 symptoms until the PVT diagnosis were 21, 12, and 10 days. Anticoagulation treatment achieved recanalization in 100% of cases. During a mean follow-up of 803 days, none of the patients experienced long-term complications. Conclusions: Portal vein thrombosis is uncommon, and its incidence may be higher in COVID-19 patients. A greater understanding of the features of this disease in the context of COVID-19 could aid towards its diagnosis and allow for early detection and management.

Background & Aims: Both metabolic dysfunction and alcohol consumption cause steatotic liver disease (SLD). The distinction between metabolic dysfunction-associated SLD (MASLD) and MetALD categories is based on arbitrary thresholds of alcohol intake. Thus, we assessed the impact of different levels of alcohol consumption on SLD severity and their interaction with metabolic comorbidities., Methods: We performed a population-based study with transient elastography (FibroScan®) data from participants in Spain (derivation cohort) and the US (validation cohort). A controlled attenuation parameter ≥275 dB/m was used to define SLD. At least one cardiometabolic risk factor was required to define MASLD. Among patients with MASLD, low alcohol consumption was defined as an average of 5-9 drinks/week, moderate consumption as 10-13 drinks/week for females and 10-20 drinks/week for males, and increased alcohol intake (MetALD) as 14-35 drinks/week for females and 21-42 drinks/week for males. Significant fibrosis was defined as a liver stiffness measurement ≥8 kPa and at-risk metabolic dysfunction-associated steatohepatitis (MASH) as a FAST score ≥0.35., Results: The derivation cohort included 2,227 individuals with MASLD (9% reported low, 14% moderate alcohol consumption) and 76 cases with MetALD. Overall prevalences of significant fibrosis and at-risk MASH were 7.6% and 14.8%, respectively. In the multivariable analysis, alcohol consumption was independently associated with significant fibrosis and at-risk MASH. A dose-dependent increase in the prevalence of significant fibrosis and at-risk MASH was observed between the number of drinks/week and the number of cardiometabolic factors. The validation cohort included 1,732 participants with MASLD, of whom 17% had significant fibrosis and 13% at-risk MASH. This cohort validated the association between moderate intake and MASLD at risk of progression (odds ratio 1.69, 95% CI 1.06-2.71)., Conclusions: Moderate alcohol intake is commonly seen in MASLD and increases the risk of advanced disease to a level similar to that observed in MetALD., Impact and Implications: Metabolic risk factors such as overweight, diabetes or dyslipidemia, and alcohol consumption can cause liver disease. These factors frequently coexist, but their joint effects on liver fibrosis remain uncertain. In this study, we have analyzed individuals from the general population with MASLD (metabolic dysfunction-associated steatotic liver disease) enrolled in Spain and the US. We show that moderate alcohol consumption has a supra-additive effect with metabolic risk factors, exponentially increasing the risk of liver fibrosis. These results suggest that there are no safe limits of daily alcohol intake in patients with unhealthy metabolic status and MASLD., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Squamous cell carcinoma (SCC) is a common tumor of the uterine cervix, usually related to human papillomavirus (HPV). While osteoclast-like giant cells (OGCs) have been reported to be associated with tumors at various locations, to the best of our knowledge, only six cases have been reported in the cervix to date. The present study describes the case of a 38-year-old woman with a medical history of ectopic pregnancy and vaginal childbirth, who presented with coitorrhagia. On physical examination, a mass of ~4 cm was found in the uterine cervix. A biopsy of this lesion revealed infiltrating SCC, leading to a radical hysterectomy 2 months later. The surgical specimen displayed an exophytic lesion with a maximum diameter of 3.5 cm confined to the uterine cervix, histologically consistent with an infiltrating non-keratinizing SCC. There was a prominent intra- and peritumoral chronic inflammatory reaction, and a high number of OGCs. Immunohistochemically, tumoral cells were positive for cytokeratin βE12, epithelial membrane antigen, p40, p63 and p16, and negative for CD68, vimentin and CD163. OGCs exhibited an inverted expression pattern, with positivity only for histiocytic markers. PCR for HPV detection revealed a HPV 34 genotype (probable high oncogenic risk). This profile suggests the non-neoplastic nature of OGCs, i.e. they should be considered as part of the immune response to the tumor. To the best of our knowledge, this case is the seventh instance of SCC with OGCs in the uterine cervix. Similar findings in other organs, such as the breast, pancreas or stomach, have been associated with a favorable prognosis. While two of the three reported cases with poor outcomes in the uterine cervix had an associated sarcomatoid component, the limited number of cases described to date in this location does not yet allow for an accurate prediction of behavior., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Castillo et al.)

Aim: To explore what factors determine communication with awake intubated critically ill patients from the point of view of critical care nursing professionals., Background: Impaired communication frequently affects mechanically ventilated patients with artificial airways in the intensive care unit. Consequences of communication breaches comprise emotional and ethical aspects as well as clinical safety, affecting both patients and their conversation partners. Identification of determining factors in communication with awake intubated patients is needed to design effective action strategies., Design: A qualitative phenomenological approach was used., Methods: Semi-structured interviews were used as the data collection method. A total of 11 participants from three intensive care units of three Majorcan public hospitals, selected by purposive sampling, were interviewed., Findings: Three major themes regarding the communication determinants of the awake intubated critically ill patients were identified from the interviewees' statements: factors related to the patient (physical and cognitive functionality to communicate, their relational and communicative style and their personal circumstances), to the context (family presence, ICU characteristics, workload, availability/adequacy of communication aids, features of the messages and communication situations) and, finally, those related to the professionals themselves (professional experience and person-centredness)., Conclusions: The present study reveals determinants that influence communication with the awake intubated patient, as there are attitudes and professional beliefs., Relevance to Clinical Practice: The discovery of relations between different kinds of determinants (of patient, context or professionals) provides a multi-factor perspective on the communicative problem which should be considered in the design of new approaches to improve communicative effectiveness. This study is reported according to the COREQ checklist.

It is essential to monitor organic pollutants to control contamination levels in environmental water bodies. In this respect, the development of new materials based on functionalised polymeric films for the measurement of toxic compounds is of interest. In this study, we prepare new films based on polymer cellulose triacetate modified with multi-walled carbon nanotubes for the monitoring of selected compounds: a fungicide (chlorpyrifos) and two emerging contaminants, the musk tonalide and the bactericide triclosan, which are used in the formulation of personal care products. The films, upon contact with water samples and following the principles of thin film microextraction, allow the determination of organic pollutants at low concentration levels. The contact time of the film with a predetermined volume of water is fixed at 60 min, and the compounds are eluted with a small volume (1 mL) of organic solvent for GC-MS analysis. Parameters such as repeatability for different films and detection limits are found to be satisfactory. Applying the method to river water demonstrates its suitability and, in the cases of chlorpyrifos and tonalide, the absence of a significant matrix effect.

Introduction and Objectives: Sarcopenia is one of the most common complications of cirrhosis, associated with an increased risk of morbidity and mortality. It is therefore necessary to perform a proper nutritional evaluation in these patients. Although CT scans are the gold standard for diagnosing sarcopenia, they are not widely used in clinical practice. There is thus a need to find indirect methods for identifying sarcopenia in patients with cirrhosis., Material and Methods: This is a cross-sectional study consecutively including all cirrhotic outpatients who underwent CT scans., Results: A total of 174 patients met all the inclusion criteria and none of exclusion criteria. Fifty-five patients (31.6%) showed sarcopenia on CT scans. Multivariate analysis revealed that the factors that were independently associated with the presence of sarcopenia on CT scans were: male sex (OR 11.27, 95% CI 3.53-35.95; p<0.001), lower body mass index (BMI) (OR 1.22, 95% CI 1.11-1.34; p<0.001) and lower phase angle by bioelectrical impedance analysis (OR 2.83, 95% CI 1.74-4.6; p<0.001). With the variables identified from the multivariate study we developed a nomogram that allows ruling out the presence of sarcopenia. Our model rules out sarcopenia with an area under the receiver operating characteristic curve value of 0.8. The cutoff point of the probability to rule out sarcopenia was 0.6 (sensitivity 85%, specificity 73%, Youden index 0.58, PPV 82.5% and NPV 91.3%)., Conclusion: Since CT scans involve exposure to radiation and their availability is limited, we propose using this nomogram as an indirect method to rule out sarcopenia in cirrhotic patients., Competing Interests: Conflicts of interest None, (Copyright © 2022. Published by Elsevier España, S.L.U.)

Background: Serum-based scores (SBS) appear to be a high applicability strategy for assessment of liver fibrosis in primary care. Aim of the study was to evaluate their performance to detect ≥F2 in a general population and to design a highly-applicable strategy for screening., Methods: prospective population-based cohort study in randomly identified subjects, aged 40-70y. Medical history, blood tests and elastography were obtained, ≥F2 was determined by using LSM cutoff ≥9.2/7.8 kPa for M/XL probe and SBS diagnostic accuracies were evaluated., Results: 986 patients were analyzed. LSM prevalence estimate suggestive of ≥F2 was 1.9% and Metabolic Sindrome (MS) (OR 3.4, 1.3-9.0;p = 0.01), was the only factor independently associated with ≥F2, with increasing prevalence according to the number of criteria (0 criterion:0%,1:0.3%,2:2.8%,3:2.4%,4:6.9%,5:14.3%;p<0.001). FLI and NFS were the two best-performing tests in the cross-sectional study, with AUROCs for ≥F2 of 0.89 (95%CI,0.84- 0.95) and 0.82 (95%CI,0.74-0.90), respectively. Predefined cutoff for FLI≥60 (Sn89.5%, Sp72.1%, NPV99.9%) and NFS≥-1.455 (Sn83.3%, Sp68%, NPV99.6%) showed adequate diagnostic accuracy. Based on these findings, a 3- step algorithm strategy to detect liver fibrosis in the community setting is proposed (Sn84.2%, Sp75.2%, NVP99.6%)., Conclusions: A staged risk-stratification model improves the detection of ≥F2 in the community setting, while reducing unnecessary referrals., Competing Interests: Conflict of interest José Luis Calleja is Advisor for Intercept, Gilead Sciences, Echosens. None of the other authors have conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background & Aims: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population., Methods: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered., Results: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection., Conclusions: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Aim: To analyze the attitude of university nursing students at Spanish universities toward organ donation and transplantation and the factors affecting to their attitude., Background: The opinion of future nurses toward organ transplant donation could have an important influence on the population. Knowing that opinion and what factors influence it is important to improve the attitude towards organ donation and transplantation., Design: A multicenter, sociological, interdisciplinary and observational study including university nursing diploma students in a complete academic year., Methods: Selected and randomized sample was taken of students from 52 of the 111 faculties and nursing schools and faculties in Spain with teaching activity PARTICIPANTS: A sample of 10,566 students was selected stratified by geographical area and year., Measurement Instrument: The instrument used was a validated questionnaire of attitude toward organ donation and transplantation, self-administered and completed anonymously., Results: Completion rate: 85 % (n = 9001). Of the students surveyed, 78 % (n = 7040) would donate their organs after dying. Variables related to a favourable attitude: (1) Interest in listening to a talk about organ donation and transplantation [Odds ratio 1.66, 95 % confidence interval 2.05-1.35]; (2) Family discussion [Odds ratio 2.30, 95 % confidence interval 2.79-1.90] or discussion with friends about organ donation and transplantation [Odds ratio 1.56, 95 % confidence interval 1.86-1.31]; (3) Knowing that one's father [Odds ratio 1.54, 95 % confidence interval 1.94-1.22], mother's [Odds ratio 1.44, 95 % confidence interval 1.82-1.13] or partner [Odds ratio 1.28, 95 % confidence interval 1.60-1.03] has a favourable opinion; (4) Having a good self-assessment of information about organ donation and transplantation [Odds ratio 2.94, 95 % confidence interval 4.90-1.78]; (5) Not being worried about possible mutilation of the body after donation [Odds ratio 2.73, 95 % confidence interval 3.36-1.72]., Conclusions: Nursing students in Spain tend to have a favourable attitude toward organ donation and transplantation although more than 20 % of those surveyed are not in favour., Tweetable Abstract: To maintain a high rate of organ donation for organ transplantation, it is necessary to improve the social awareness of future generations of nurses towards organ donation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Aims: Monitoring of acute or chronic response to beta-blockers in patients with liver cirrhosis is based on the measurement of the HVPG. Our aim was to evaluate the response to beta-blockers with non-invasive techniques., Patients and Methods: This is a prospective observational study. Consecutive patients with an indication of primary or secondary prophylaxis of variceal bleeding who did not meet exclusion criteria were included. Acute response and chronic response were evaluated. Baseline and after acute and chronic response hepatosplenic measurements of TE and ARFI were obtained. Contrast-enhanced Doppler ultrasound was performed before and after acute and chronic responses., Results: From June 2015 to May 2018, 55 patients (14 with exclusion criteria) were included. We analyzed 41 patients, mean age 57 ( SD : 8), 82.9% men, alcohol 43.9%, children A/B/C 78%/17.1%/4.9%, and 87.8% on primary prophylaxis. In all, the acute response was performed and was positive in 68.3% (CI 95: 55-85%). The chronic response was performed in 30 (73.2%) and was positive in 36.7% (CI 95: 18-55%). Basal measurements significantly related to acute response were spleen TE [responders 58.4 ( SD : 23.0) KPa vs. non-responders 75 ( SD : 0) KPa; p = 0.02] and damping index [non-responders 0.96 (0.8) vs. responders 0.44 (0.4), p = 0.01], and with chronic response, the spleen TE [responders 58.1 ( SD : 21.4) KPa vs. non-responders 73.2 ( SD : 5.5) KPa; p = 0.02], and damping index [non-chronic responders 0.8 (0.7) vs. chronic responders 0.4 (0.4), p = 0.04]. A spleen TE ≥ 74 KPa had a high sensitivity of 100% and specificity of 60% and a high NPV100% for predicting poor acute response to beta-blockers. The damping index > 0.6 showed moderate sensitivity of 67% and specificity of 69% with a high NPV of 82% for predicting poor acute response to beta-blockers. The combination of both measurements for predicting poor acute response to beta-blockers had an AUC of 0.8 (CI 95: 0.5-0.9). A spleen TE ≥ 74 KPa had a high sensitivity of 87% and specificity of 71% with a high NPV of 71% for predicting poor chronic response to beta-blockers. A damping index > 0.6 had moderate sensitivity of 60%, specificity of 82%, and NPV of 56% for predicting poor chronic response to beta-blockers. The combination of both measurements for predicting poor chronic response to beta-blockers had an AUC of 0.8 (CI 95: 0.7-0.9)., Conclusion: Spleen TE and damping index can identify a subgroup of patients with poor acute or chronic response to beta-blockers., Competing Interests: JC reports consultancy and lecture fees from Abbvie, Gilead Sciences, MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Llop, Perelló, Fontanilla, de la Revilla, Conde, López, Minaya, Ferre, Abad, Carrillo, Martínez, Puga, Trapero, Hajra, Santos and Calleja.)

Background: Although the emotional and psychological impact of nurses' work had been identified before the COVID-19 pandemic, the pandemic aggravated risk indicators for their mental health., Aim: The objective of this study was to analyse the levels of anxiety, depression, post-traumatic stress and burnout of nurses in the Balearic Islands (Spain) during the pandemic to identify possible sociodemographic and related occupational factors., Design: A cross-sectional study of 892 nurses was conducted during four weeks from February to March 2021., Methods: Sociodemographic data related to the pandemic were collected and anxiety, depression, burnout and post-traumatic stress were measured with validated scales. A multivariate and predictive analysis was carried out with risk estimates., Findings: About 75.6% of the nurses had experience in COVID-19 units, and 49.1% had worked for more than 10 months in a COVID-19 unit. Nurses in COVID-19 units (hospital ward or ICU) were more likely to report emotional fatigue (OR 1.9, p < 0.001) and anxiety (OR 1.5, p = 0.021). In general, moderate post-traumatic stress was evident in general nurses (p = 0.027), and severe post-traumatic stress was evident in ICU nurses (p = 0.027). A 1.24-month reduction in COVID-19 patient care predicted reduced levels of emotional fatigue (5.45 points), depersonalisation (1.87 points) and post-traumatic stress (4.65 points) in nurses., Conclusion: Given the occurrence of new waves of COVID-19, the need to establish preventive strategies that focus on the personal and occupational characteristics related to these indicators and to implement urgent psychological support strategies is demonstrated., Impact: Given these findings, it is imperative solutions are urgently applied in order to prevent compounding risk to the health system., Competing Interests: None., (© 2021 Australian College of Nursing Ltd. Published by Elsevier Ltd.)

Introduction: liver enzyme elevation has been reported in SARS-CoV-2 disease (COVID-19) in heterogeneous cohorts, mainly from China. Comprehensive reports from other countries are needed. In this study, we dissect the pattern, evolution, and predictive value of such abnormalities in a cohort from Madrid, Spain., Methods: a retrospective study with a prospective 14-day follow-up of 373 patients with confirmed COVID-19 in five Madrid hospitals, including 50 outpatients. A COVID-19 severe course was defined as the need for mechanical ventilation., Results: a total of 33.1 % of hospitalized patients showed baseline AST elevation and 28.5 % showed ALT elevation, compared with 12 % and 8 % of outpatients (p ≤ 0.001). Baseline AST, ALT and GGT levels correlated with LDH and C-reactive protein (CRP) levels (r ≤ 0.598, p < 0.005). AST elevation was associated with other severity markers such as male sex, lymphopenia, and pneumonia on X-Ray (p < 0.05 for all). ALP and bilirubin levels were rarely increased. Patients with elevated baseline AST showed a progressive normalization of this enzyme and an increase in ALT and GGT levels. Patients with normal baseline AST showed a flattened evolution pattern with levels within the range. Patients with a severe course of COVID-19 more frequently showed elevated baseline AST than those with a milder evolution (54.2 % vs. 25.4 %, p < 0.001). Age, AST and CRP were independent risk factors for a severe course of COVID-19., Conclusion: mild liver enzyme elevation is associated with COVID-19 severity. Baseline AST is an independent predictor of severe COVID-19 course, and tends to normalize over time. ALT and GGT show a late elevation.

Introduction: The effect of branched-chain amino acid (BCAA) supplementation on muscle mass in patients with cirrhosis and sarcopenia is unknown., Methods: This is a pilot, prospective, randomized, and double-blind study of a cohort of 32 patients with cirrhosis and sarcopenia diagnosed by computed tomography scan who underwent a nutritional and physical activity intervention for 12 weeks. They were divided into 2 groups (placebo: 17 patients; BCAA: 15 patients). The study protocol was registered at ClinicalTrials.gov (NCT04073693)., Results: Baseline characteristics were similar in both groups. After treatment, only the BCAA group presented a significant improvement in muscle mass (43.7 vs 46 cm2/m2; P = 0.023). Seventeen patients (63%) presented improvement in muscle mass overall, which was more frequent in the BCAA group (83.3 vs 46.7%; P = 0.056). Regarding frailty, there was a significant improvement in the Liver Frailty Index in the global cohort (n = 32) after the 12 weeks (4.2 vs 3.9; P < 0.001). This difference was significant in both groups: in the placebo group (4.2 vs 3.8; P < 0.001) and in the BCAA group (4.2 vs 3.9; P < 0.001). After treatment, the BCAA group had a higher increase in zinc levels than the placebo group (Δzinc: 12.3 vs 5.5; P = 0.026). In addition, there was a trend for greater improvement of albumin levels in the BCAA group (Δalbumin: 0.19 vs 0.04; P = 0.091)., Discussion: BCAA supplementation improves muscle mass in cirrhotic patients with sarcopenia., (Copyright © 2021 by The American College of Gastroenterology.)

Background and Aims: Transient elastography (TE) to estimate liver stiffness has proved to be very useful in the diagnosis of chronic liver disease. Here, we intend to evaluate its use in a large Spanish cohort., Method: Nested study within the PREVHEP-ETHON (Epidemiological sTudy of Hepatic infectiONs; NCT02749864) population-based, cross-sectional study performed between July 2015 and April 2017. An epidemiological questionnaire, laboratory tests and TE and anthropometric measurements were obtained., Results: Data from 11,440 subjects were analyzed. Mean age was 50.3 (SD 12.4), of which 58.1% were women. 15.4% showed metabolic syndrome (NCEP ATP-III), 1.3% were positive for hepatitis C antibodies, 0.8% positive for HBsAg, 9.1% reported harmful use of alcohol. The prevalence of significant fibrosis (LSM > 8 kPa), suggestive compensated advanced chronic liver disease (cACLD) (LSM ≥ 10 kPa) and highly suggestive cACLD (LSM > 15 kPa) was 5.6%, 2.9%, and 1.2% respectively. Risk factors associated with significant fibrosis were age (OR 1.03 [1.02-1.04; p < 0.001]), sex (OR 0.8 [0.6-0.95; p = 0.02]), AST (OR 1.01 [1.01-1.02; p < 0.001]), GGT (OR 1.005 [1.003-1.006; p < 0.001]) and metabolic syndrome (OR 2.1 [1.7-2.6; p < 0.001]); risk factors associated with suggestive cACLD were age (OR 1.04 [1.02-1.05; p < 0.001]), AST (OR 1.01 [1.01-1.02; p < 0.001]), GGT (OR 1.006 [1.004-1.008; p < 0.001]), low platelets (OR 0.997 [0.994-0.999; p = 0.02]) and metabolic syndrome (OR 2.2 [1.6-2.9; p < 0.001]); and risk factors associated with highly suggestive cACLD were age (OR 1.04 [1.02-1.06; p = 0.001]), AST (OR 1.02 [1.01-1.03; p < 0.001]), GGT (OR 1.005 [1.003-1.007; p < 0.001]), low platelets (OR 0.993 [0.989-0.997; p < 0.001]), metabolic syndrome (OR 2.1 [1.4-3.3; p = 0.001]) and alcohol consumption (OR 1.8 [1.05-3.1; p = 0.03]). A non-negligible proportion of patients with normal transaminase levels, even with healthy transaminase levels, showed significant fibrosis and suggestive and highly suggestive cACLD 4.6% (95% CI 2.4-3.0), 2.1% (95% CI 1.9-2.5) and 1% (95% CI 0.7-1.1), respectively., Conclusion: We found high proportion of significant fibrosis and cACLD measured by TE. The most relevant factor associated with significant fibrosis was metabolic syndrome, however TE is still an imperfect method since it overestimated the fibrosis stage in 50% of the histologically analyzed subjects., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Aim: Non-malignant portal vein thrombosis (PVT) is a complication of liver cirrhosis. The aim of this study was to evaluate the annual incidence of PVT and related risk factors., Methods: We retrospectively reviewed clinical, laboratory, and radiological data collected prospectively from September 2016 to September 2017. A follow-up of 36 months was performed in a subset of patients to determine the cumulative incidence of PVT and related complications., Results: The study included 567 patients. The incidence of PVT at 12, 24, and 36 months was 3.7%, 0.8%, and 1.4%, respectively. Patients with PVT were compared with patients without PVT, and showed differences in albumin (p = 0.04), aspartate aminotransferase (p = 0.04), hemoglobin (p = 0.01), and prothrombin activity (p = 0.01). The presence of hydropic decompensation (57.1% vs. 30.1%; p 0.004), gastroesophageal varices (76.2% vs. 39.5%; p = 0.05), variceal bleeding (52.4% vs. 22.7%; p < 0.001), hepatic encephalopathy (38.1% vs. 9.9%; p = 0.01), spontaneous bacterial peritonitis (9.5% vs. 1.7%; p < 0.001), and use of beta-blockers (71.4% vs. 27.7%; p < 0.001) were significantly associated. In the multivariate analysis, use of beta-blockers and hepatic encephalopathy appeared as risk factors, and high albumin levels a protective factor., Conclusions: The incidence of PVT was 3.7%. Beta-blockers and hepatic encephalopathy were risks factors. High albumin levels were a protective factor., (© 2021 The Japan Society of Hepatology.)

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans , and cell cultures. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. An organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging, and to design personalized approaches for the prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging, paving the way to personalized interventions targeting the biology of aging.

Background: Midwives look after women during pregnancy, childbirth and puerperium. In Spain, the first wave of COVID was particularly virulent. There are few studies about the experiences of midwives providing care during the COVID pandemic and very few have been undertaken in the countries of southern Europe such as Spain. This article sets out to take a more in-depth look at the experiences of midwives who were on the frontline of care during the early months of the COVID-19 pandemic as well as to identify new needs and resilience strategies that can help midwives., Methods: A qualitative methodology of phenomenological tradition was used, interviewing 10 midwives from primary care, hospital and independent care., Results: After content analysis, three central categories emerged: (a) cascade of emotions; (b) professional occupation and concern for the women; (c) resisting the day-to-day; resilience and resistance strategies., Conclusions: Despite the difficulties, midwives are concerned about the loss of rights and autonomy and about the increased vulnerability of women. Midwives have become aware of the power they have in their actions both in health management and administration, as well as in the care of women, creating strategies to provide dignified care to their users.

Background & Aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic., Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave., Results: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37)., Conclusions: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making., Lay Summary: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes., Competing Interests: SM.-M.: Speaker fees from Bayer and travel funding from 10.13039/100004326Bayer and 10.13039/501100014382Eisai. V.S.: Travel grants from 10.13039/100004326Bayer. A.F.: Lecture fees from Bayer, Gilead and MSD; consultancy fees from Bayer, AstraZeneca, Roche and Guerbert. J-C.N.: Received research grant from 10.13039/100004326Bayer for Inserm UMR1138. L.R.: Reports receiving consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Celgene, Eisai, Exelixis, Hengrui, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi; lectures fees from AbbVie, Amgen, Eisai, Gilead, Incyte, Ipsen, Lilly, Roche, Sanofi; travel fees from Ipsen; and institutional research funding from Agios, ARMO BioSciences, 10.13039/100004325AstraZeneca, BeiGene, 10.13039/501100003769Eisai, 10.13039/100010544Exelixis, 10.13039/100006591Fibrogen, Incyte, 10.13039/501100014382Ipsen, 10.13039/100004312Lilly, 10.13039/100007054MSD, 10.13039/100004337Roche. B.S.: Reports consultancy fees from Adaptimmune, AstraZeneca, Bayer, BMS, BTG, Eli Lilly, Ipsen, Novartis, Merck, Roche, Sirtex Medical, Terumo; and research grants from 10.13039/100002491BMS and Sirtex Medical. J. Bruix: Consultancy: AbbVie, ArQule, Astra, Basilea, Bayer, BMS, Daiichi Sankyo, GlaxoSmithKline, Gilead, Kowa, Lilly, Medimune, Novartis, Onxeo, Polaris, Quirem, Roche, Sanofi-Aventis, Sirtex, Terumo/Grants: 10.13039/100004326Bayer and 10.13039/501100014382Ipsen. M.S.Z.: Received speaker fees and travel grants from 10.13039/100004326Bayer and 10.13039/100014869BTG, 10.13039/100007054MSD. M.B.: Consultant and Advisory Board for: Bayer Pharma, Ipsen, BMS, Eisai, Roche, AstraZeneca, Sirtex Medical. D.J.P.: Received lecture fees from ViiV Healthcare and Bayer Healthcare and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, and AstraZeneca; received research funding (to institution) from MSD and BMS. T.M.: Consultancy: Eisai, Roche, BTG, Ipsen, Bayer, Adaptimmune. Research funding: Bayer, BTG. H.W.: Served as speaker for Bayer, Eisai, and Ipsen, and as a consultant for Bayer, Eisai, Lilly, BMS, Roche, and Ipsen. B.M.: Consultancy: Bayer-Shering Pharma /Speaker fees: Eisai, MSDG. C. Consultancy fees from Bayer, Ipsen. P.R.G.: Bayer, BMS, MSD, AstraZeneca, Adaptimmune, Sirtex, Lilly Ipsen, Roche, Eisai. M.R.A.S.: Has received Research grants, advisory board or speaker fees for 10.13039/100006483AbbVie, 10.13039/100004326Bayer, Biolab, Intercept, 10.13039/501100014382Ipsen, 10.13039/100008799Gilead, 10.13039/100009947MSD, 10.13039/100004336Novartis, and 10.13039/100004337Roche. J.T.: Has received research grants from 10.13039/100004337Roche and 10.13039/501100014382Ipsen. He has received speaker and consulting honoraria from AstraZeneca, Amgen, Bayer Healthcare, Bristol Myers-Squibb, Eisai, Ipsen, Merck Serono, Merck Sharp & Dome, Lilly Imclone, and Roche. J. Bridgewater: Consultancy Bayer, BMS, Incyte, Taiho, Roche, MSD and Merck Serono. Research funding from Incyte. G.C.: Consultancy fees from Bayer, Ipsen. A.L.: Consultancy CAScination, Advisory Board Neuwave and Histosonics. H.T.: Speaker fees from AbbVie, Gilead, MSD, and Bayer. R.V.: Research grant from 10.13039/100006483Abbvie. A.M.M.P.: Speaker honorarium from Bayer, BMS, Boston Scientific and EISAI. Consulting honorarium from Bayer, AstraZeneca and EISAI. Advisory honorarium from Bayer, AstraZeneca and EISAI. Grants from 10.13039/100004326Bayer and 10.13039/100008497Boston Scientific. M.D.: Has received consulting and training fees from Bayer and Eisai. B.B.: Reports Consultancy for GenMab (paid to Institution); Advisory Boards for Roche (paid to Institution), Eisai Europe Limited (paid to Institution), research grant from 10.13039/100006436Celgene Ltd (paid to Institution), Speakers Bureau for Eisai Europe Limited (paid to Institution), Travel and registration for Congress from Bayer. L.d.F.: Lectures fees from BMS, Roche and Bayer. B.M.M.: Advisory/Speaker: Amgen, AstraZeneca, Bayer, BMS, Eisai, Ipsen, Merck, Roche, Sanoffi Genzyme, Taiho. Expert Testimony: Eisai, Roche. Travel: Eisai, Merck. Research: Sillajen (Individual); AstraZeneca, H3/Eisai, Galera, GSK, Exelixis (Institution). M.S.: Travel/ accommodation/meeting expenses: Bayer. Eisai. Speaker fees: Bayer. C.R.L.: Travel grants from 10.13039/100004326Bayer. M.R-G.: Reports grants from Intercept, grants from 10.13039/100005564Gilead-Sciences, personal fees from Shionogi, personal fees from Alfa-Wasserman, personal fees from Prosciento, personal fees from Kaleido, personal fees from Novonrdisk, personal fees from MSD, personal fees from BMS, personal fees from Allergan, personal fees from Boehriger-Ingelheim, personal fees from Zydus, personal fees from Intercept Pharma, personal fees from Gilead-Sciences, outside the submitted work. F.P.: Disclosures: Received speaker honoraria from Bayer, Roche, LKM-Biotoscana, RAFFO. Research Grants from INC Argentinean 10.13039/100013137National Institute of Corrections, 10.13039/100004337Roche. V.M.: Lectures sponsored by Bayer. G.B.: Advisory board Eli-Lilly and Incyte. M. Vergara: Travel grants from 10.13039/100004326Bayer, 10.13039/100008799Gilead, 10.13039/100009947MSD and 10.13039/100006483Abbvie. Lectures sponsored by Gilead, Abbvie, Intercept, and MSD. M.L.: Lectures and educational presentations: Abbvie. Travel/accommodation, meeting expenses covered by Bayer, Gilead, Abbvie. M.I.: Received speaker honoraria from Bayer, Gilead Sciences, BMS, Janssen, Ipsen, MSD, BTG-Boston Scientific, AbbVie, EISAI, and was consultant for BTG-Boston Scientific, Bayer, and Guerbet. M.R.: Consultancy: Bayer-Schering Pharma, BMS, Roche, Ipsen, AstraZeneca, Lilly, BTG/Paid conferences: Bayer-Schering Pharma, BMS, Gilead, Lilly/Research Grants: 10.13039/100004326Bayer-Schering Pharma, 10.13039/501100014382Ipsen. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Authors.)

Background and Aims: Immune-checkpoint inhibitors are effective in many advanced tumors. However, there is scarce information regarding the radiological response to these agents in hepatocellular carcinoma outside clinical trials. We aimed to describe the radiological response in a retrospective cohort of hepatocellular carcinoma patients treated with nivolumab and to analyze the radiological evolution according to tumor response at first post-treatment radiological assessment., Methods: We reviewed pre-treatment and post-treatment images (CT or MRI) obtained at different time-points in patients with hepatocellular carcinoma treated with nivolumab outside clinical trials at seven Spanish centers, assessing the response according to RECIST 1.1 and iRECIST and registering atypical responses. We also analyzed the imaging findings on subsequent assessments according to tumor status on the first posttreatment imaging assessment., Results: From the 118 patients with hepatocellular carcinoma treated with nivolumab, we finally analyzed data from 31 patients (71 % Child-Pugh A; 74 % BCLC-C). Median follow-up was 8.39 months [IQR 5.00-10.92]; median overall survival was 12.82 months (95 %CI 10.92-34.79). According to RECIST 1.1, the objective response rate was 16 % and according to iRECIST, the objective response rate was 22.6 %. Findings at the first post-treatment assessment varied, showing stable disease in 44.8 % of patients; findings during follow-up also varied widely, including 4 hyperprogressions and 3 pseudoprogressions., Conclusion: Imaging findings during nivolumab treatment are heterogeneous between and within patients. Progression of disease does not always signify treatment failure, and surrogate end-points may not reflect survival outcomes, making the management of hepatocellular carcinoma patients under immunotherapy challenging., (Copyright © 2020. Published by Elsevier B.V.)

Background: Obesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), although obese patients with NAFLD do not always develop significant fibrosis. The distribution of body fat could predict the risk of NAFLD progression., Aim: To investigate the role of bioelectrical impedance-estimated visceral fat (VF) in assessing NAFLD severity., Methods: In this cross-sectional study, patients with biopsy-proven NAFLD were prospectively included. All patients underwent anthropometric evaluation, blood tests and bioelectrical impedance analysis., Results: Between 2017 and 2020, 119 patients were included [66.4% male, 56 years (SD 10.7), 62.2% obese, 61.3% with metabolic syndrome]. Sixty of them (50.4%) showed significant fibrosis (≥ F2) in liver biopsy. Age, VF and metabolic syndrome were associated with significant fibrosis (61 years vs 52 years, 16.4 vs 13.1, 73.3% vs 49.2%, respectively; P < 0.001 for all). In the multivariate analysis, VF and age were independently associated with significant fibrosis (VF, OR: 1.11, 95%CI: 1.02-1.22, P = 0.02; age, OR: 1.08, 95%CI: 1.03-1.12, P < 0.01). A model including these variables showed and area under the receiver operating characteristic curve (AUROC) of 0.75, which was not inferior to transient elastography or NAFLD fibrosis score AUROCs. We developed a nomogram including age and VF for assessing significant fibrosis in routine practice., Conclusion: VF is a surrogate marker of liver fibrosis in patients with NAFLD. Bioelectrical impedance analysis is an inexpensive and simple method that can be combined with age to guide patient referral when other resources may be unavailable., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest relevant to this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The latest epidemiological data in Spain were obtained a decade ago and revealed a prevalence of hepatitis B surface antigen (HBsAg) of 0.7%; hence, updated epidemiological data are necessary. Our aim was to determine the prevalence of hepatitis B virus (HBV) infection, and to analyse associated factors and characterize chronic infection. A population-based, cross-sectional study was performed in Spain between July 2015 and April 2017. Participants from three regions were selected using two-stage conglomerate sampling and stratified by age. Anthropometric and demographic data were collected, and blood samples were taken to detect serological markers of HBV infection and to quantify HBV-DNA. The characterization of chronic HBV infection was based on ALT (alanine aminotransferase) values, HBV-DNA levels, and results of transient elastography. The overall prevalence rates of HBsAg and antibody to hepatitis B core antigen (anti-HBc) among 12 246 participants aged 20-74 years (58.4% females) were 0.6% (95% CI [0.4-0.7]) and 8.2% (7.7-8.7), respectively. The risk factors for HBV infection identified in the multivariate analysis were age, nosocomial risk, and non-Spanish nationality. Moreover, most patients HBsAg positive (76.6%) presented as hepatitis B e antigen (HBeAg)-negative chronic infection (formerly 'inactive carriers') and only 6 (9.4%) HBsAg carriers fulfilled current criteria for treatment. The current HBV burden in Spain remains low but virtually unchanged over the past 15 years. Increased efforts are still needed to reach the goal set forth by the World Health Organization (WHO) for HBV elimination by 2030., (© 2020 John Wiley & Sons Ltd.)

Background: COVID-19 is a potentially severe disease caused by the recently described SARS-CoV-2. Whether liver fibrosis might be a relevant player in the natural history of COVID-19 is currently unknown. We aimed to evaluate the association between FIB-4 and the risk of progression to critical illness in middle-aged patients with COVID-19., Methods: In this multicenter, retrospective study with prospective follow-up of 160 patients aged 35-65 years with COVID-19, FIB-4, clinical, and biochemical variables were collected at baseline. FIB-4 ≥2.67 defined patients with risk for advanced liver fibrosis., Results: Risk for advanced fibrosis was estimated in 28.1% of patients. Patients with FIB-4 ≥2.67 more frequently required mechanical ventilation (37.8% vs 18.3%; P = .009). In multivariate analysis, FIB-4 ≥2.67 (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.30-8.92), cardiovascular risk factors (OR, 5.05; 95% CI, 1.90-13.39), previous respiratory diseases (OR, 4.54; 95% CI, 1.36-15.10), and C-reactive protein (OR, 1.01; 95% CI, 1.01-1.02) increased significantly the risk of ICU admission. Bootstrap confirmed FIB-4 as an independent risk factor., Conclusions: In middle-aged patients with COVID-19, FIB-4 may have a prognostic role. The link between liver fibrosis and the natural history of COVID-19 should be evaluated in future studies., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The knowledge acquired during university education about organ donation and transplantation (ODT) decisively influences the information future health professionals transmit. This is important in ODT where the participation of the general public is essential to obtain organs., Objective: To determine notions of Spanish medicine and nursing students on ODT and its relationship with attitude toward ODT., Methods and Design: and design. We conducted a sociologic, multicenter, and observational study. The population for our study consisted of medical and nursing students in Spanish universities. Our database was the Collaborative International Donor Project, stratified by geographic area and academic course. A validated questionnaire (PCID-DTO-RIOS) was self-administered and completed anonymously. Our sample consisted of 9598 medical and 10,566 nursing students (99% confidence interval; precision of ±1%), stratified by geographic area and year of study., Results: The completion rate for our study was 90%. Only 20% (n=3640) of students thought their notions on ODT were good; 41% (n=7531) thought their notions were normal; 36% (n=6550) thought their notions were scarce. Comparing groups, there were differences between those who believed that their notions on ODT were good (44% nursing vs 56% medical students; P < .000), and those who believed it scarce (54% nursing vs 46% medical students; P < .000). Notions on ODT were related with attitude toward the donation of one's own organs: those who considered their notions were good were more in favor then those who considered it scarce (88% vs 72%; P < .000)., Conclusion: Only 20% of Spanish medical and nursing students thought their notions on ODT were good. Having good knowledge is related to a favorable attitude towards ODT. Receiving specific information on the subject could improve their knowledge about ODT during their training., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background & Aims: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population., Methods: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded., Results: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges [IQR], 0.8-3.8), 10.8 months (IQR, 4.5-16.9), and 17.5 months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE., Conclusions: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Accurate HCV prevalence estimates are necessary for guiding elimination policies. Our aim was to determine the HCV prevalence and assess the cost-effectiveness of a screen-and-treat strategy in the Spanish population. A population-based, cross-sectional study (PREVHEP-ETHON Cohort, Epidemiological sTudy of Hepatic infectiONs; NCT02749864) was performed from July 2015-April 2017. Participants from three Spanish regions were selected using two-stage conglomerate sampling, and stratified by age, with randomized subject selection. Anthropometric and demographic data were collected, and blood samples were taken to detect anti-HCV antibodies/quantify HCV RNA. The cost-effectiveness of the screening strategies and treatment were analysed using a Markov model. Among 12 246 participants aged 20-74 (58.4% females), the overall anti-HCV prevalence was 1.2% (95% CI 1.0-1.4), whereas the detectable HCV-RNA prevalence was 0.3% (0.2-0.4). Infection rates were highest in subjects aged 50-74 years [anti-HCV 1.6% (1.3-1.9), HCV RNA 0.4% (0.3-0.6]. Among the 147 anti-HCV + subjects, 38 (25.9%) had active infections while 109 (74.1%) had been cleared of infection; 44 (40.4%) had cleared after antiviral treatment, whereas 65 (59.6%) had cleared spontaneously. Overall, 59.8% of the anti-HCV + participants were aware of their serological status. Considering a cost of treatment of €7000/patient, implementing screening programmes is cost-effective across all age cohorts, particularly in patients aged 50-54 (negative incremental cost-effectiveness ratio which indicates a cost-saving strategy). The current HCV burden is lower than previously estimated, with approximately 25% of anti-HCV + individuals having an active infection. A strategy of screening and treatment at current treatment prices in Spain is cost-effective across all age cohorts., (© 2019 John Wiley & Sons Ltd.)

MicroRNAs (miRNAs) plays an important role in the human brain from the embryonic period to adulthood. In this sense, they influence the development of neural stem cells (NSCs), regulating cellular differentiation and survival. Therefore, due to the importance of better comprehending the regulation of miRNAs in NSCs differentiation and the lack of studies that show the panorama of miRNAs and their signaling pathways studied until now we aimed to systematically review the literature to identify which miRNAs are currently being associated with neuronal differentiation and using bioinformatics analysis to identify their related pathways. A search was carried out in the following databases: Scientific Electronic Library Online (Scielo), National Library of Medicine National Institutes of Health (PubMed), Scopus, Web of Science and Science Direct, using the descriptors "(microRNA [MeSH])" and "(neurogenesis [MeSH])". From the articles found, two independent and previously calibrated reviewers, using the EndNote X7 (Thomson Reuters, New York, NY, US), selected those that concern miRNA in the development of NSCs, based on in vitro studies. After, bioinformatic analysis was performed using the software DIANA Tools, mirPath v.3. Subsequently, data was tabulated, analyzed and interpreted. Among the 106 miRNAs cited by included studies, 55 were up-regulated and 47 were down-regulated. The bioinformatics analysis revealed that among the up-regulated miRNAs there were 24 total and 6 union pathways, and 3 presented a statistically significant difference (p ≤ 0.05). Among the down-regulated miRNAs, 46 total and 13 union pathways were found, with 7 presenting a significant difference (p ≤ 0.05). The miR-125a-5p, miR-423-5p, miR-320 were the most frequently found miRNAs in the pathways determined by bioinformatics. In this study a panel of altered miRNAs in neuronal differentiation was created with their related pathways, which could be a step towards understanding the complex network of miRNAs in neuronal differentiation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Information provided by health care professionals is crucial to create a climate of social opinion. This is important in organ donation and transplantation (ODT), where the participation of the general public is essential to obtain organs., Objective: To determine the attitude toward the Law of Presumed Consent (LPC) among Spanish university students and to analyze their relation with attitude toward ODT., Methods: and design. The type of study was a sociologic, multicenter, observational study. The population included medical and nursing students in Spanish universities. Database of Collaborative International Donor Project was used stratified by geographic area and academic course. A validated questionnaire (Collaborative International Donor Project, organ donation and transplantation questionnaire in Spanish [PCID-DTO-RIOS]) was self-administered and completed anonymously. A sample of 9598 medical and 10,566 nursing students was analyzed (99% confidence and precision of ±1%) and stratified by geographic area and year of study., Results: Completion rate was 90%. Regarding attitude toward LPC, 66% of the students were against the law, whereas 34% accepted it. Of the students surveyed, 9% considered the law as a gesture of solidarity, 25% as an effective way of not wasting organs, 48% as an abuse of power, and 18% as offenses against the family. Those students who were in favor of LPC also had a more favorable attitude toward ODT (86% vs 76%; P < .001). Comparing groups, nursing students were less in favor of LPC than medical students (32% vs 36%; P < .000)., Conclusion: Sixty-six percent of Spanish university medical and nursing students were against the LPC. The favorable attitude toward ODT is associated with considering the law as a gesture of solidarity or as an effective way of not wasting organs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A primary care physician (PCP) not only accompanies the patient in the process of an illness, but throughout his or her life. The confidence we have in these health professionals is fundamental, and their favorable attitude toward organ donation and transplantation (ODT) has a significant influence on the population., Objective: To analyze trust in PCPs among Spanish medical and nursing students, the relationship with their attitude toward ODT, and the factors that condition it., Methods and Design: A sociologic, multicenter, and observational study., Population: medical and nursing students in Spanish universities., Database: Collaborative International Donor Project, stratified by geographic area and academic course. A validated questionnaire (PCID-DTO-RIOS) was self-administered and completed anonymously. A sample of 9598 medical and 10,566 nursing students (99% confidence and precision of ±1%), stratified by geographic area and year of study., Results: Completion rate: 90%. With respect to students' trust in their physician, 18% (n = 3267) of them totally trust (completely), 45% (n = 8101) trust enough, 30% (n = 5478) of them have not enough trust, and 7% not at all. Comparing groups, medical students totally trust more in PCPs than nursing students (55% vs 45%; P < .000), however, nursing students have less than enough trust in their PCP than medical students (53% vs 47%; P < .000). Students that totally trust in their PCP were more in favor toward ODT than students with not enough trust (83% vs 77%; P < .000)., Conclusion: Only 18% of Spanish medical and nursing students totally trust in their PCP. Attitude toward ODT is related to a higher level of trust in PCPs among these students., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Health care professionals and the information that they provide to the public on organ donation and transplantation (ODT) influence attitudes toward this option., Objective: The objective was to analyze the knowledge of university nursing students at Spanish universities toward ODT and the factors affecting it., Methods and Design: The methods and design included a multicenter, sociologic, and observational study including university nursing diploma students in a complete academic year., Participants: A sample of 10,566 students was selected stratified by geographic area and year., Instrument: A validated questionnaire of knowledge toward ODT (PCID-DTO RIOS), self-administered and completed anonymously., Results: Questionnaire completion rate: 85% (n = 9001). Only 18% (n = 1580) believed that their knowledge about ODT was good, 40% (n = 3578) believed that the information they had was normal, and 39% believed that their knowledge was sparse. Of the students, 96% believed that organ needs are not covered and 79% that they might need a transplant in the future. Only 39% (n = 3493) had attended a talk about ODT. Furthermore, 83% (n = 7435) believed that attending a talk would be interesting. The following variables were associated with having a more adequate knowledge: gender (62% men vs 57% women; P < .001); academic year (P < .001); knowing a donor (P < .001); knowing a transplant patient (P < .001); believing the possibility of needing a transplant oneself in the future (P < .001); attitude toward deceased donation (P < .001); and interest in receiving an informative talk about ODT (P < .001)., Conclusion: Only 18% of nursing students in Spain believed that their knowledge about ODT was adequate. These results must be considered for possible training plans for these future professionals., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background : Central obesity, due to the accumulation of visceral fat(VF), is one of the main risk factors for venous thrombosis. The aim of this study was to determine if VF may be a risk factor for development of portal vein thrombosis(PVT) in cirrhotic patients. Methods : A total of 214 cirrhotic patients at the outpatient clinic were consecutively included, undergoing an anthropometric evaluation, blood tests and bioimpedance. Results : Median MELDscore was10. Prior liver decompensation occurred in 44.9% of patients and 35.6% of patients had large esophageal varices. Mean body mass index was 28.7 Kg/m2 (39.3%were obese) and mean waist circumference(WC) was 103.8 cm. A 7.5% of patients had PVT at the time of inclusion. PVT was more frequent in males(93.8 vs. 68.2%, p = 0.03). Patients with PVT had a higher WC(111.9 vs. 103.2 cm, p = 0.02) and VF (17.1 vs. 14.5, p = 0.04). PVT was also more frequent in patients with prior decompensation (81.3 vs. 41.9%, p < 0.01) and with large esophageal varices(62.5 vs. 33.3%, p = 0.02). In the simplified multivariate analysis, PVT was independently associated with the presence of portal hypertension(OR 13, 95%CI 1.6-108.3, p = 0.02) and VF(OR 1.2, 95%CI 1.03-1.3, p = 0.01). Conclusion : VF was independently associated with PVT in cirrhotic patients. VF may be more reliable than conventional anthropometric measurements for cirrhotic patients.

Background & Aims: Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC., Methods: This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years., Results: A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96-4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55-5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased., Conclusion: These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation., Lay Summary: In this cohort of cirrhotic patients, interferon-free therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clear-cut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased., (Copyright © 2019. Published by Elsevier B.V.)

Introduction and Aims: To determine the prevalence of minimal hepatic encephalopathy(MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE., Materials and Methods: We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment., Results: 64 patients were included. 51.6% were male, the median age was 62 years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8kPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24 weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p<0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p=0.02), higher Child-Pugh scores at 24-weeks post-treatment (p=0.04), higher baseline INR levels (1.4 vs. 1.1; p<0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p=0.02). During follow-up, those patients without MHE at 24 weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p=0.04)., Conclusion: We found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis., (Copyright © 2019 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

In randomized controlled trials of patients with chronic HCV infection, elbasvir/grazoprevir (EBR/GZR) demonstrated high cure rates and a good safety profile. This study assessed the effectiveness and safety of EBR/GZR, with and without ribavirin, in a real-world HCV patient cohort. HEPA-C is a collaborative, monitored national registry of HCV patients directed by the Spanish Association for the Study of the Liver and the Networked Biomedical Research Centre for Hepatic and Digestive Diseases. Patients entered into HEPA-C between December 2016 and May 2017, and treated with EBR/GZR with at least end-of-treatment response data, were included. Demographic, clinical and virologic data were analysed, and adverse events (AEs) recorded. A total of 804 patients were included in the study. The majority were male (57.9%), with a mean age of 60 (range, 19-92) years. Genotype (GT) distribution was GT 1, 86.8% (1a, 14.3%; 1b, 72.5%); GT 4, 13.2% and 176 patients (21.9%) were cirrhotic. Overall, among 588 patients with available data, 570 (96.9%) achieved sustained virologic response at 12 weeks post-treatment (SVR12). SVR12 rates by genotype were GT 1a, 97.7%; GT 1b, 98.6%; and GT 4, 98.1%. No significant differences in SVR12 according to fibrosis stage were observed. Eighty patients experienced an AE, resulting in treatment discontinuation in three. In this large cohort of patients with chronic HCV managed in a real-world setting in Spain, EBR/GZR achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with a similarly good safety profile., (© 2018 John Wiley & Sons Ltd.)

Most current management systems of healthcare institutions correspond to a model of market ethics with its demands of competitiveness. This approach has been called managerialism and is couched in terms of much-needed efficiencies and effective management of budgetary constraints. The aim of this study was to analyse the decision-making of nurses through the impact of health institution management models on clinical practice. Based on Foucault's ethical theory, a qualitative study was conducted through a discourse analysis of the nursing records in a hospital unit. The results revealed that the health institution standardises health care practice, which has an impact on professional and patient autonomy as it pertains to decision-making. The results of this research indicate that resistance strategies in the internal structures of health organisations can replace the normalisation and instrumentalisation of professional practice aimed at promoting patient self-determination., (© 2017 John Wiley & Sons Ltd.)

Interprofessional relationships may impact the decision making of patients in a clinical setting. The objective of this study was to analyse the decision-making capabilities of patients from nurses' perspectives of interprofessional relationships using Foucauldian ethics. This qualitative study was based on poststructuralist Foucault references with in-depth interviews of nurses working in internal medicine and specialties in a general hospital. The patients constantly appeared in the definition of teamwork, but also as a passive element used by every professional to communicate with others. Nurses continue modelling a type of patient passivity, or what Foucault called passive subjectivity in relation to oneself, because the patient is guided and directed to take charge of a truth provided by professionals. Nurses must break the rigid design of sections or professional skills, and adopt a model of teamwork that meets the needs of the patient and increases their decision-making power. The quality of care will increase to the extent that professionals establish a relationship of equality with the patient, allowing the patient to make real decisions about their care. An egalitarian model of teamwork is beneficial to the patient, abandoning the idea of a team where the patient and family are constantly excluded from decisions about their care., Competing Interests: The authors declare no conflict of interest.

Background & Aims: Clinical trials evaluating second-generation direct-acting antiviral agents (DAAs) have shown excellent rates of sustained virologic response (SVR) and good safety profiles in patients with chronic hepatitis C virus (HCV) genotype 1 infection. We aimed to investigate the effectiveness and safety of two oral DAA combination regimens, ombitasvir/paritaprevir/ritonavir plus dasabuvir (OMV/PTV/r+DSV) and ledipasvir/sofosbuvir (LDV/SOF), in a real-world clinical practice., Methods: Data from HCV genotype 1 patients treated with either OMV/PTV/r+DSV±ribavirin (RBV) (n=1567) or LDV/SOF±RBV (n=1758) in 35 centers across Spain between April 1, 2015 and February 28, 2016 were recorded in a large national database. Demographic, clinical and virological data were analyzed. Details of serious adverse events (SAEs) were recorded., Results: The two cohorts were not matched with respect to baseline characteristics and could not be compared directly. The SVR12 rate was 96.8% with OMV/PTVr/DSV±RBV and 95.8% with LDV/SOF±RBV. No significant differences were observed in SVR according to HCV subgenotype (p=0.321 [OMV/PTV/r+DSV±RBV] and p=0.174 [LDV/SOF]) or degree of fibrosis (c0.548 [OMV/PTV/r/DSV±RBV] and p=0.085 [LDV/SOF]). Only baseline albumin level was significantly associated with failure to achieve SVR (p<0.05) on multivariate analysis. Rates of SAEs and SAE-associated treatment discontinuation were 5.4% and 1.7%, in the OMV/PTV/r+DSV subcohort and 5.5% and 1.5% in the LDV/SOF subcohort, respectively. Hepatocellular carcinoma (HCC) recurred in 30% of patients with a complete response to therapy for previous HCC. Incident HCC was reported in 0.93%., Conclusions: In this large cohort of patients managed in the real-world setting in Spain, OMV/PTV/r+DSV and LDV/SOF achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with similarly good safety profiles., Lay Summary: In clinical trials, second-generation direct-acting antiviral agents (DAAs) have been shown to cure over 90% of patients chronically infected with the genotype 1 hepatitis C virus and have been better tolerated than previous treatment regimens. However, patients enrolled in clinical trials do not reflect the real patient population encountered in routine practice. The current study, which includes almost 4,000 patients, demonstrates comparable rates of cure with two increasingly used DAA combinations as those observed in the clinical trial environment, confirming that clinical trial findings with DAAs translate into the real-world setting, where patient populations are more diverse and complex., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To describe the actions taken by the Pharmacy Unit in a tertiary hospital in order to adapt to the recommendations established by NIOSH 2014 for handling Hazardous Drugs. Method: A retrospective observational study. A list was prepared including all hazardous drugs according to NIOSH 2014 that were available at the hospital as marketed or foreign drugs, or used in clinical trials, and there was a review of the processes of acquisition, repackaging, preparation, circuits, organizational, dispensing and identification. Results: After the analysis, a report including all needs was prepared and sent to the Hospital Management. Any relevant information about the handling and administration of hazardous drugs was included in the prescription computer program. There were changes in the acquisition process of two drugs, in order to avoid splitting and multi-dose formulations. An alternative or improvement was found for 35 253 of the 75 779 units of hazardous drugs repackaged in one year. The Pharmacy Unit took over the preparation of four non-sterile medications, as well as the preparation of all sterile parenteral medications included in Lists 1 and 2 that were not previously prepared there, as well as one from List 3. Information was also included about the preparation processes of Magistral Formulations that involved hazardous drugs from Lists 2 or 3., Conclusion: The adaptation to the recommendations by NIOSH 2014 has represented a change, but also a significant reduction in the handling process of hazardous drugs by the healthcare staff, therefore reducing the risk of occupational exposure., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)