Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Non-invasive scoring systems (NSS) are used to identify patients with non-alcoholic fatty liver disease (NAFLD) who are at risk of advanced fibrosis, but their reliability in predicting long-term outcomes for hepatic/extrahepatic complications or death and their concordance in cross-sectional and longitudinal risk stratification remain uncertain. METHODS: The most common NSS (NFS, FIB-4, BARD, APRI) and the Hepamet fibrosis score (HFS) were assessed in 1,173 European patients with NAFLD from tertiary centres. Performance for fibrosis risk stratification and for the prediction of long-term hepatic/extrahepatic events, hepatocarcinoma (HCC) and overall mortality were evaluated in terms of AUC and Harrell's c-index. For longitudinal data, NSS-based Cox proportional hazard models were trained on the whole cohort with repeated 5-fold cross-validation, sampling for testing from the 607 patients with all NSS available. RESULTS: Cross-sectional analysis revealed HFS as the best performer for the identification of significant (F0-1 vs. F2-4, AUC = 0.758) and advanced (F0-2 vs. F3-4, AUC = 0.805) fibrosis, while NFS and FIB-4 showed the best performance for detecting histological cirrhosis (range AUCs 0.85-0.88). Considering longitudinal data (follow-up between 62 and 110 months), NFS and FIB-4 were the best at predicting liver-related events (c-indices>0.7), NFS for HCC (c-index = 0.9 on average), and FIB-4 and HFS for overall mortality (c-indices >0.8). All NSS showed limited performance (c-indices <0.7) for extrahepatic events. CONCLUSIONS: Overall, NFS, HFS and FIB-4 outperformed APRI and BARD for both cross-sectional identification of fibrosis and prediction of long-term outcomes, confirming that they are useful tools for the clinical management of patients with NAFLD at increased risk of fibrosis and liver-related complications or death. LAY SUMMARY: Non-invasive scoring systems are increasingly being used in patients with non-alcoholic fatty liver disease to identify those at risk of advanced fibrosis and hence clinical complications. Herein, we compared various non-invasive scoring systems and identified those that were best at identifying risk, as well as those that were best for the prediction of long-term outcomes, such as liver-related events, liver cancer and death.

Presence of Serum Antinuclear Antibodies Does Not Impact Long-Term Outcomes in Nonalcoholic Fatty Liver Disease.

INTRODUCTION: We investigated the longitudinal impact of antinuclear antibody (ANA) on clinical outcomes and survival in nonalcoholic fatty liver disease (NAFLD). METHODS: ANA were found in 16.9% of 923 biopsy-proven NAFLD patients, but none of them had histologic autoimmune hepatitis (AIH) or developed AIH after a mean follow-up of 106±50 months. RESULTS: Although ANA-positive cases had a higher prevalence of nonalcoholic steatohepatitis at baseline, the occurrence of liver-related events, hepatocellula carcinoma, cardiovascular events, extrahepatic malignancy, and overall survival were similar to ANA-negative. DISCUSSION: Once AIH has been ruled out, the long-term outcomes and survival are unaffected by the presence of ANA in patients with NAFLD.

Diagnostic validity of the STRATIFY and Downton instruments for evaluating the risk of falls by hospitalised acute-care patients: a multicentre longitudinal study.

BACKGROUND: Falls are major adverse events in hospitals. The appropriateness of using risk assessment instruments for falls in hospitals has recently been questioned, although the research performed in this respect presents some methodological shortcomings. The purpose of the present study is to evaluate the accuracy of the Downton and STRATIFY instruments to determine the risk of falls and to predict their incidence in acute care hospitals in the public health system in Andalusia (Spain). METHODS: A longitudinal, multicentre prospective study was made of a cohort of patients recruited between May 2014 and March 2016. The risk of falls was assessed using each of the above instruments during the first 24 h after hospital admittance, with later re-evaluations every 72 h until discharge. Descriptive statistics were obtained, bivariate and multivariate analysis were performed. The diagnostic validity of the process was assessed by calculations of sensitivity, specificity, positive and negative predictive values and ratios of positive and negative likelihood. ROC curve analysis was performed for both instruments. RESULTS: For this study, 1247 patients were recruited, of whom 977 completed all the follow-up assessments. Twenty-three of these patients (2.35%) suffered 24 falls. ROC curve analysis showed that the optimal cut-off point for each assessment instrument was below that described by the authors: AUC STRATIFY = 0.69 (95% CI: 0.57-0.8); AUC Downton = 0.6 (95% CI: 0.48-0.72). With a cut-off point of 1, the sensitivity of STRATIFY was 47.6% and its specificity, 85%. With a cut-off point of 2, Downton presented a sensitivity of 66.7% and a specificity of 55.3%. CONCLUSIONS: The Downton and STRATIFY falls risk assessment instruments presented little utility as means of detecting the risk of falls among a sample of adult patients admitted to acute care hospitals. Fall prevention in hospitals should be based on the study of individual risk factors.

Bridging Metabolic-Associated Steatotic Liver Disease and Cardiovascular Risk: A Potential Role for Ketogenesis.

The prevalence of cardiovascular diseases (CVDs) is a growing global health concern. Recent advances have demonstrated significant reductions in acute cardiovascular events through the management of modifiable cardiovascular risk factors. However, these factors are responsible for about 50% of the global cardiovascular disease burden. Considering that CVDs are one of the top mortality causes worldwide, the concept of residual cardiovascular risk is an important emerging area of study. Different factors have been proposed as sources of residual risk markers, including non-HDL particles characterization, as well as inflammation measured by serum and imaging technics. Among these, metabolic-associated steatotic liver disease (MASLD) remains controversial. Two opposing viewpoints contend: one positing that fatty liver disease merely reflects classical risk factors and thus adds no additional risk and another asserting that fatty liver disease independently impacts cardiovascular disease incidence. To address this dilemma, one hypothetical approach is to identify specific hepatic energy-yielding mechanisms and assess their impact on the cardiovascular system. Ketogenesis, a metabolic intermediate process particularly linked to energy homeostasis during fasting, might help to link these concepts. Ketogenic metabolism has been shown to vary through MASLD progression. Additionally, newer evidence supports the significance of circulating ketone bodies in cardiovascular risk prediction. Furthermore, ketogenic metabolism modification seems to have a therapeutic impact on cardiovascular and endothelial damage. Describing the relationship, if any, between steatotic liver disease and cardiovascular disease development through ketogenesis impairment might help to clarify MASLD's role in cardiovascular risk. Furthermore, this evidence might help to solve the controversy surrounding liver steatosis impact in CVD and might lead to a more accurate risk assessment and therapeutic targets in the pursuit of precision medicine.

Datathons: fostering equitability in data reuse in ecology.

Approaches to rapidly collecting global biodiversity data are increasingly important, but biodiversity blind spots persist. We organized a three-day Datathon event to improve the openness of local biodiversity data and facilitate data reuse by local researchers. The first Datathon, organized among microbial ecologists in Uruguay and Argentina assembled the largest microbiome dataset in the region to date and formed collaborative consortia for microbiome data synthesis.

Osmotic Demyelination Syndrome in a Normonatremic Patient Under Treatment With Proton Pump Inhibitors.

A 66-year-old woman was admitted to the emergency department with diarrhea, nausea, and vomiting as well as low-grade fever. She was initially treated with ciprofloxacin and metronidazole with symptomatic improvement and was discharged. One week later, she returned to the emergency department for gait instability, dizziness, and vomiting and had a witnessed generalized tonic-clonic seizure in the hospital. During both admissions, the presence of ionic alterations such as severe hypomagnesemia, hypophosphatemia, and hypokalemia stood out, while sodium levels remained normal. Among her antecedents, she had a hiatal hernia and had been receiving treatment with omeprazole for years.

Eosinophilic Granulomatosis With Polyangiitis Presentation After Nandrolone Withdrawal.

A 41-year-old man was admitted to the Emergency Department with bilateral numbness in lower extremities and left femoral palsy. He also reported constitutional symptoms, vomiting and non-bloody diarrhoea for the last several months. He had a previous history of eosinophilic asthma with erratic follow-up. During admission, eosinophil count was 66% of white blood cells. Sural nerve biopsy revealed vasculitis with eosinophilic infiltration. Further evaluations consisted of colonoscopy and nasal endoscopy that confirmed eosinophil infiltrates on colonic ulcers and nasal polypi. The patient was started on systemic corticosteroids and cyclophosphamide. Among his personal records, he had been taking nandrolone decanoate without medical prescription, and had withdrawn a few years before the first asthma exacerbation.

How, when, and to what degree do people with alcohol dependence recover their psychological wellbeing and quality of life? The Madrid Recovery Project.

Introduction: The consensus on recovery from alcohol use disorder (AUD) has shifted toward encompassing psychological wellbeing and quality of life dimensions. However, few studies have explored the long-term recovery process and its dimensions, timing, styles, and modes. The aim of this study was to investigate the extent, timing, and process of psychological wellbeing and quality of life recovery in alcohol use disorder (AUD) patients, as well as the relationship with classic dimensions of AUD recovery. Method: A cross-sectional study has been carried out with 348 participants with AUD, in different abstinence periods (1 month-28 years), and 171 control subjects. Participants underwent a psychological evaluation, which included self-informed measures of psychological wellbeing, quality of life, negative emotionality, and coping strategies related to alcohol consumption avoidance. Statistical analysis included linear and non-linear regression models between psychological dimensions and maintenance of abstinence, as well as matching the scores of the sample with AUD to those of controls. Scatter plots were used to explore inflection points. In addition, mean comparison tests were performed between participants with AUD and controls and by gender. Results: In general, according to the regression models, there were pronounced increases in indices of wellbeing and coping strategies (and pronounced decreases in negative emotionality) during the first 5 years of abstinence, followed by less pronounced improvements. The matching of AUD subjects in wellbeing and negative emotionality indices with controls occurs at different times: (a) 1 year or less: physical health; (b) 1-4 years: psychological health; (c) 4-10 years: social relationships, wellbeing, and negative emotionality; and (d) more than 10 years: autonomy and self-acceptance. There are statistically significant differences by gender for the negative emotionality and physical health variables. Conclusion: Recovery from AUD is a long process that involves improvements in wellbeing and quality of life. Four stages can be described in this process, with the most pronounced changes occurring during the first 5 years of abstinence. However, AUD patients take more time to obtain similar scores to controls in several psychological dimensions.

Observational analysis of clinical and pathological characteristics and their prognostic impact in Mexican patients with breast cancer: A multi-center study.

Breast cancer is the most incidental and deadly neoplasm worldwide; in Mexico, very few epidemiologic reports have analyzed the pathological features and its impact on their clinical outcome. Here, we studied the relation between pathological features and the clinical presentation at diagnosis and their impact on the overall and progression-free survival of patients with breast cancer. For this purpose, we collected 199 clinical records of female patients, aged at least 18 years old (y/o), with breast cancer diagnosis confirmed by biopsy. We excluded patients with incomplete or conflicting clinical records. Afterward, we performed an analysis of overall and progression-free survival and associated risks. Our results showed an average age at diagnosis of 52 y/o (24-85), the most common features were: upper outer quadrant tumor (32%), invasive ductal carcinoma (76.8%), moderately differentiated (44.3%), early clinical stages (40.8%), asymptomatic patients (47.8%), luminal A subtype (47.8%). Median overall survival was not reached, but median progression-free survival was 32.2 months (29.75-34.64, CI 95%) associated risk were: clinical stage (p < 0.0001) symptomatic presentation (p = 0.009) and histologic grade (p = 0.02). Therefore, we concluded that symptom presence at diagnosis impacts progression-free survival, and palpable symptoms are related to an increased risk for mortality.

Influence of the Covid-19 pandemic on out-of-hospital cardiac arrest. A Spanish nationwide prospective cohort study.

AIMS: The influence of the COVID-19 pandemic on attendance to out-of-hospital cardiac arrest (OHCA) has only been described in city or regional settings. The impact of COVID-19 across an entire country with a high infection rate is yet to be explored. METHODS: The study uses data from 8629 cases recorded in two time-series (2017/2018 and 2020) of the Spanish national registry. Data from a non-COVID-19 period and the COVID-19 period (February 1st-April 30th 2020) were compared. During the COVID-19 period, data a further analysis comparing non-pandemic and pandemic weeks (defined according to the WHO declaration on March 11th, 2020) was conducted. The chi-squared analysis examined differences in OHCA attendance and other patient and resuscitation characteristics. Multivariate logistic regression examined survival likelihood to hospital admission and discharge. The multilevel analysis examined the differential effects of regional COVID-19 incidence on these same outcomes. RESULTS: During the COVID-19 period, the incidence of resuscitation attempts declined and survival to hospital admission (OR = 1.72; 95%CI = 1.46-2.04; p < 0.001) and discharge (OR = 1.38; 95%CI = 1.07-1.78; p = 0.013) fell compared to the non-COVID period. This pattern was also observed when comparing non-pandemic weeks and pandemic weeks. COVID-19 incidence impinged significantly upon outcomes regardless of regional variation, with low, medium, and high incidence regions equally affected. CONCLUSIONS: The pandemic, irrespective of its incidence, seems to have particularly impeded the pre-hospital phase of OHCA care. Present findings call for the need to adapt out-of-hospital care for periods of serious infection risk. STUDY REGISTRATION NUMBER: ISRCTN10437835.

Self-esteem and suicidal behaviour in youth: A meta-analysis of longitudinal studies.

BACKGROUND: Previous literature suggests that low self-esteem is a risk factor for suicide attempts, but no meta-analyses have been conducted to assess this association in adolescents/young adults. The present study examined the relationship between low self-esteem and suicide attempts in young people (12-26 years old). METHOD: Meta-analyses were performed using random-effects models (ES) and odds ratio (OR). Heterogeneity and sensitivity analyses were performed. RESULTS: From 26,883 initial titles, 22 studies met the inclusion criteria, of which 9 studies had data that could be included in the meta-analysis. The meta-analysis showed that youths with lower self-esteem were more likely to have future suicide attempts, with an effect size (self-esteem as continuous variable) of d = .58 (95% CI = .44 - .73) and, for low self-esteem (categorical variable) an OR = 1.99 (95% CI = 1.39-2.86; p < .001). CONCLUSION: A low level of self-esteem is a risk factor for suicide attempts in adolescents/young adults.

Characteristics, consequences and prevention of falls in institutionalised older adults in the province of Malaga (Spain): a prospective, cohort, multicentre study.

OBJECTIVES: Falls are an important adverse event among institutionalised persons. It is in this clinical setting where falls occur more frequently than in any other, despite the measures commonly taken to prevent them. This study aimed to determine the characteristics of a typical institutionalised elderly patient who suffers a fall and to describe the physical harms resulting from this event. We then examined the association between falls and the preventive measures used. METHODS: This was a prospective cohort study in 37 nursing homes in Spain. The participants were all the nursing home residents institutionalised in these centres from May 2014 to July 2016. Participants were followed up for 9 months. During this period, two observations were made to evaluate the preventive measures taken and to record the occurrence of falls. RESULTS: 896 residents were recruited, of whom 647 completed the study. During this period, 411 falls took place, affecting 213 residents. The injuries caused by the falls were mostly minor or moderate. They took place more frequently among women and provoked 22 fractures (5.35%). The most commonly used fall prevention measure was bed rails (53.53% of cases), followed by physical restraint (16.79%). The latter measure was associated with a higher incidence of injuries not requiring stitches (OR=2.06, 95% CI 1.01 to 4.22, P=0.054) and of injuries that did require stitches (OR=3.51, 95% CI 1.36 to 9.01, P=0.014) as a consequence of falls. Bed rails protected against night-time falls. CONCLUSIONS: Falls are a very common adverse event in nursing homes. The prevention of falls is most commonly addressed by methods to restrain movement. The use of physical restraints is associated with a greater occurrence of injuries caused by a fall.

Bilateral ocular involvement in encephalocraniocutaneous lipomatosis.

We report a case of encephalocraniocutaneous lipomatosis (ECCL), a rare congenital neurocutaneous syndrome, with cutaneous, ocular and neurologic malformations. The key features of ECCL are epibulbar choristomas, nevus psiloliparus, and intracranial lipomas. A full-term newborn presented at birth bilateral conjunctival tumours, right facial papulonodular lesions and an alopecic lesion consistent with lipoma on the right frontoparietal area. Brain imaging studies showed arachnoid cyst, enlarged lateral ventricle, cortical dysplasia, lipoma and leptomeningeal angiomatosis in the right hemisphere. The results were consistent with ECCL. Since ocular and skin involvement is a hallmark of the condition, children with epibulbar congenital lesions and skin lesions suggestive for ECCL should undergo a brain imaging study.

Correlation of Snail expression with histological grade and lymph node status in breast carcinomas.

Snail is a zinc finger transcription factor that triggers the epithelial-mesenchymal transition (EMT) by directly repressing E-cadherin expression. Snail is required for mesoderm and neural crest formation during embryonic development and has recently been implicated in the EMT associated with tumour progression. In a series of human breast carcinomas, we have analysed the expression of Snail and that of molecules of the E-cadherin/catenin complexes. We have also correlated these data with the pathological features of the tumours. We show that Snail expression inversely correlates with the grade of differentiation of the tumours and that it is expressed in all the infiltrating ductal carcinomas (IDC) presenting lymph node metastases that were analysed. In addition, Snail is expressed in some dedifferentiated tumours with a negative nodal status. Considering that Snail is involved in the induction of the invasive and migratory phenotype in epithelial cells, these results indicate that it is also involved in the progression of breast ductal tumours, where it could additionally serve as a marker of the metastatic potential.

Expression of EphA receptors and ligands during chick cerebellar development.

The cerebellum is a modular structure that integrates information in a topographical manner. The membrane receptors of the Eph family and their ligands play important roles in early regionalization, as well as in the formation of topographic connections of the nervous system. Here, we show that the expression of the Eph receptors -A4 and -A7, and of their ligands ephrin-A5 and -A2 correlates with the establishment of territories along the rostro-caudal axis and with the formation of topographically organized connections between the cortex and the cerebellar nuclei. While some sites where co-expression of receptors and ligands are evident, their relative expression mainly define sharp limits along the rostro-caudal axis and, at later stages, complementary gradients in the Purkinje cell layer and the deep cerebellar nuclei.

Salts and nutrients present in regenerated waters induce changes in water relations, antioxidative metabolism, ion accumulation and restricted ion uptake in Myrtus communis L. plants.

The use of reclaimed water (RW) constitutes a valuable strategy for the efficient management of water and nutrients in landscaping. However, RW may contain levels of toxic ions, affecting plant production or quality, a very important aspect for ornamental plants. The present paper evaluates the effect of different quality RWs on physiological and biochemical parameters and the recovery capacity in Myrtus communis L. plants. M. communis plants were submitted to 3 irrigation treatments with RW from different sources (22 weeks): RW1 (1.7 dS m(-1)), RW2 (4.0 dS m(-1)) and RW3 (8.0 dS m(-1)) and one control (C, 0.8 dS m(-1)). During a recovery period of 11 weeks, all plants were irrigated with the control water. The RW treatments did not negatively affect plant growth, while RW2 even led to an increase in biomass. After recovery,only plants irrigated with RW3 showed some negative effects on growth, which was related to a decrease in the net photosynthesis rate, higher Na accumulation and a reduction in K levels. An increase in salinity was accompanied by decreases in leaf water potential, relative water content and gas exchange parameters, and increases in Na and Cl uptake. Plants accumulated Na in roots and restricted its translocation to the aerial part. The highest salinity levels produced oxidative stress, as seen from the rise in electrolyte leakage and lipid peroxidation. The use of regenerated water together with carefully managed drainage practices, which avoid the accumulation of salt by the substrate, will provide economic and environmental benefits.

Microarchitectural changes during development of the cerebellar cortex.

The cerebellum is a highly conserved structure in the Central Nervous System (CNS) of vertebrates, and is involved in the coordination of voluntary motor behaviour. Supporting this function, the cerebellar cortex presents a layered structure which requires a precise spatial and temporal coordination of proliferation, migration and differentiation events. One of the characteristics of the developing cortex is the formation of the external granule cell layer (EGL) in the outermost part. The EGL is a highly proliferative transient layer which disappears when cells migrate inwards to form the inner granule cell layer. The balance between proliferation and migration leads to changes in EGL thickness, and might be related to "indentations" observed in the surface of the developing chick cerebellum. We have extended the observation of this feature to quail and mouse, supporting the idea that this phenomenon forms part of the mechanisms of cerebellar morphogenesis. Different factors involved in both mitotic activity and migration were analyzed in this study. Our results indicate that proliferation, more than formation of raphes for cell migration, is involved in the formation of indentations in the EGL. In addition, we show that vessels penetrating from the pial surface divide the EGL into regular regions at the time of the appearance of bulges and furrows. We conclude that indentations are the result of a coincidence in time of both the increase in thickness of the EGL and the establishment of the embryonic vascular pattern, which confers a characteristic transitory morphology to the surface of folia.

Snail1a and Snail1b cooperate in the anterior migration of the axial mesendoderm in the zebrafish embryo.

The Snail genes are implicated in processes that involve cell movement, both during embryonic development and tumour progression. In teleosts, the vertebrate Snail1 gene is represented by two distinct genes, snail1a and snail1b (previously snail1 and snail2). These genes are expressed in complementary mesodermal domains and their combined expression matches that of their mammalian counterpart. By analysing their loss and gain of function, we found that the most-anterior axial mesendodermal cells, the precursors of the polster, move in a cohesive manner directed by the activity of snail1a- and snail1b-expressing cells surrounding these precursors. The cell-autonomous function of Snail1 proteins regulates cell motility and influences the behaviour of Snail-negative neighbouring cells. Snail1a is required by the prechordal plate for it to reach its normal position, whereas Snail1b controls the acquisition of its normal shape. These non-redundant functions of Snail1a and Snail1b in controlling axial mesendoderm migration comply with the duplication-degeneration-complementation model, and indicate that Snail genes not only act as inducers of epithelial-to-mesenchymal transition, but also as more general regulators of cell adhesion and movement.