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Background Previous studies highlighted the utility of individual urinary biomarkers in the prediction of interstitial fibrosis in IgA Nephropathy patients. However, it´s uncertain which biomarker or combination of biomarkers provides a more accurate estimation of renal interstitial fibrosis Surface. Herein, we measured the urinary excretion of a set of seven tubular injury biomarkers in a group of patients with primary IgA Nephropathy and analyzed their utility as non-invasive estimators of interstitial fibrosis area found on kidney biopsy. Methods Two hundred forty-seven adults with primary IgA Nephropathy diagnosed by kidney biopsy and a control group of 50 healthy control were included. The urinary excretion of EGF, MCP-1, NGAL, KIM-1, L-FABP, β2-microglobulin and DKK-3 was measured in urine samples collected at the day of the renal biopsy. Estimated glomerular filtration rate was measured by the CKD-EPI formula. Interstitial fibrosis area was quantified using a quantitative morphometric procedure and graded according to Oxford Classification. Predictive multivariate models were developed to predict the interstitial fibrosis surface. Results Patients with primary IgA Nephropathy showed significantly higher urinary levels of DKK-3, L-FABP and β2-microglobulin, and lower EGF levels than healthy controls. Interstitial fibrosis was negatively correlated with urinary EGF levels and positively with age, proteinuria, eGFR and urinary DKK-3, L-FABP and β2-microglobulin. The best model to predict interstitial fibrosis area accounted for > 60% of its variability and included age, eGFR, proteinuria, DKK-3, EGF, L-FABP and β2-microglobulin. Conclusions Our study provides a model to estimate the IFS in IgA Nephropathy which could be useful to monitor the progression of chronic kidney injury.

ABSTRACT Background In anti-phospholipase A2 receptor (PLA2R) membranous nephropathy (MN) there is controversy whether spontaneous remission (SR) can be predicted using a single titre or by assessing the dynamic changes in anti-PLA2R antibody (ab) titres. The study objective was to identify the optimal dynamics of anti-PLA2Rab titres to predict SR in MN. Methods A total of 127 nephrotic patients with anti-PLA2R-MN were prospectively followed up for 6 months under conservative treatment. Anti-PLA2Rabs and proteinuria were assessed at diagnosis and monthly thereafter. The primary endpoint (PEP) was a reduction of proteinuria ≥50% at 6 months. Logistic models with baseline and evolutive anti-PLA2Rab titres were developed to predict the PEP. Results A total of 28 patients (22%) reached the PEP. These patients were more frequently female and had significantly lower baseline proteinuria and anti-PLA2Rab titres. An anti-PLA2R titre ≤97.5 RU/mL at diagnosis had a sensitivity of 71% and a specificity of 81% to predict the PEP. The model including baseline anti-PLA2Rabs and a reduction ≥15% at 3 months predicted the PEP with a sensitivity of 93% and a specificity of 80%, with an area under the curve that was significantly greater than that obtained with relative changes of proteinuria in the same period of time {odds ratio [OR] 0.95 [95% confidence interval (CI) 0.91–0.98 versus OR 0.79 [95% CI 0.70–0.88], respectively; P = 0.0013}. Conclusions Combining the baseline anti-PLA2Rab titres with their relative changes at 3 months after diagnosis gives the earliest prediction for achieving a reduction of urinary protein excretion ≥50% at 6 months in MN, thereby shortening the observation period currently recommended to make individualized decisions to start immunosuppressive therapy. Graphical Abstract Graphical Abstract

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system aging. In this prospective cohort study, we describe a straightforward methodology for quantifying biomarkers of aging, such as DNA methylation and telomere length, in PLWH and in the context of another relevant condition, such as MAFLD. Fifty-seven samples in total, thirty-eight from PLWH and nineteen from non-PLWH participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). Global DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. Our results show an increased association of these biomarkers in PLWH regardless of their MAFLD status. Thus, we propose including the quantification of these age-related factors in studies of comorbidities. This will allow a better understanding of the effect of comorbidities of HIV infection and MAFLD and prevent their effects in these populations in the future.

Acute liver failure (ALF) is a rare and severe condition with high mortality. Liver transplantation (LT) has improved patient outcomes. This study analysed trends in aetiology, characteristics, and outcomes of ALF patients undergoing LT in Spain. We retrospectively reviewed 217 adult ALF-LT cases from 11 Spanish centers (2001 -2020), divided into two 10-year periods. Clinical, biochemical, and outcome data were collected, and predictors of mortality were identified. 217 adult ALF-LT patients were included (61.8% women, mean age: 41 years). Common aetiologies were cryptogenic (26.7%), autoimmune (26.3%), and viral (18%), with sex differences. Over time, autoimmune and drug-induced liver injury increased (22.3% vs 29.8% and 13.6% vs 21.1%), with a low prevalence of acetaminophen toxicity, and hepatitis B virus declined (23.3% vs 11.4%). Despite higher infection rates (52.5% vs 66.2%) linked to stronger immunosuppression, respiratory failure (29.1% vs 16.1%), chronic kidney disease (27.1% vs 13.6%), cardiovascular events (10.6% vs 1%), and mortality (37.6% vs 17.9%) decreased. Pre-LT hypertension, pre-LT acute kidney injury, and hypernatremia at LT were independently associated with worse survival. This large multicenter study revealed temporal changes in aetiologies, immunosuppressive treatment, and post-LT complications, with an improvement in outcome.

Metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as an increasingly recognized problem among people living with HIV (PLWH). The gut-liver axis is considered to be strongly implicated in the pathogenesis of MASLD. We aimed to characterize the gut microbiota composition in PLWH and MASLD and compare it with that of two control groups: PLWH without MASLD and individuals with MASLD without HIV infection. We collected clinical data and stool samples from participants. Bacterial 16S rRNA genes were amplified, sequenced, and clustered into operational taxonomic unit. Alpha diversity was studied by Shannon and Simpson indexes. To study how different the gut microbiota composition is between the different groups, beta diversity estimation was evaluated by principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity. To further analyze differences in microbiome composition we performed a linear discriminant analysis (LDA) effect size (LEfSe). We included 30 HIV MASLD , 30 HIV MASLD and 20 HIV MASLD participants. Major butyrate producers, including , , and dominated the microbiota in all three groups. Shannon's and Simpson's diversity metrics were higher among MASLD individuals (Kruskal-Wallis p = 0.047). Beta diversity analysis showed distinct clustering in MASLD , with MASLD participants overlapping regardless of HIV status (ADONIS significance <0.001). MASLD was associated with increased homogeneity across individuals, in contrast to that observed in the HIV+NAFDL- group, in which the dispersion was higher (Permanova test, p value <0.001; ANOSIM, p value <0.001). MASLD but not HIV determined a different microbiota structure (HIV vs. HIV MASLD , q-value = 0.002; HIV MASLD vs. HIV MASLD , q-value = 0.930; and HIV MASLD vs. HIV MASLD , q-value < 0.001). The most abundant genera in MASLD- were , and . In contrast, the most enriched genera in MASLD+ were , and We found a microbiome signature linked to MASLD, which had a greater influence on the overall structure of the gut microbiota than HIV status alone.

Purpose: Home mechanical ventilation (HMV) use in chronic obstructive pulmonary disease (COPD) is becoming increasingly widespread. The aim of this study was to provide an accurate description of the current practices and clinical characteristics of COPD patients on HMV in Portugal. Methods: The study was designed as a cross-sectional, multicenter real-life study of COPD patients established on HMV for at least 30 days. Data related to clinical characteristics, adaptation and ventilatory settings were collected. Results: The study included 569 COPD patients on HMV from 15 centers. The majority were male, with a median age of 72 years and a high prevalence of obesity (43.2%) and sleep apnea (45.8%). A high treatment compliance was observed (median 8h/day), 48.7% with inspiratory positive airway pressure [greater than or equal to] 20 cm[H.sub.2]O and oronasal masks were the preferred interface (91.7%). There was an equal distribution of patients starting HMV during chronic stable condition and following an exacerbation. Patients in stable condition were initiated in the outpatient setting in 92.3%. Despite the differences in criteria and setting of adaptation and a slightly lower BMI in patients starting HMV following an exacerbation, we found no significant differences regarding age, gender, ventilation pressures, time on HMV, usage, severity of airflow obstruction or current arterial blood gas analysis (ABGs) in relation to patients adapted in stable condition. Conclusion: Patients were highly compliant with the therapy. In agreement with most recent studies and recommendations, there seems to be a move towards higher ventilation pressures, increased use of oronasal masks and an intent to obtain normocapnia. This study shows that chronic hypercapnic and post exacerbation patients do not differ significantly regarding patient characteristics, physiological parameters or ventilatory settings with one exception: chronic hypercapnic patients are more often obese and, subsequently, more frequently present OSA. Keywords: home mechanical ventilation, chronic obstructive pulmonary disease, noninvasive ventilation, outpatient adaptation

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH. Methods This is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers. Results Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75–1); CAP, 0.94 (0.88–1); FLI, 0.81 (0.58–1); HSI, 0.74 (0.62–0.87); and TyG, 0.75 (0.49–1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82–1), 0.96 (0.90–1), 0.97 (0.93–1), and 0.85 (0.68–1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97–1, P < .001) and 0.92 (0.77–1, P < .001). Conclusions Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD. An easy-to-implement algorithm diminishes diagnostic uncertainty and the likelihood of diagnostic errors, thus eventually reducing the need for liver biopsy. Ultrasound and controlled attenuation parameter perform very well in diagnosing liver steatosis in persons with HIV.

Sensors, combined with intelligent systems, can enhance the quality of the Telecare services deployed at home, improving the capability for detection of risk situations and the users care. However, there are no specific studies that evaluate this kind of Telecare systems by professionals that work in a Telecare center. This paper shows the results of an assessment of the current satisfaction and future expectations of the Telecare professionals when using advanced Telecare solutions deployed at home. The study has been conducted through structured interviews with 24 Telecare experts working in the Telecare center of the Spanish Red Cross for attending alarm calls for elderly people. The interviews had the support of the TALISMAN Telecare system that is a next-generation Telecare service deployed in the accessible digital home of Universidad Politécnica de Madrid. All participants showed overall satisfaction with TALISMAN and their intention to use it. Results showed that perceived usefulness is an important influencing factor to the intention to use it and the Quality of the Information is a key factor in the perceived usefulness. TALISMAN, as an example of a next-generation Telecare system, is seen as a tool with high potential for improving the care of elderly people at home.

Despite its high prevalence, the mechanisms underlying non-alcoholic fatty liver disease (NAFLD) in people living with HIV (PLWH) are still unclear. In this prospective cohort study, we aim to evaluate differences in plasma fatty acid profiles between HIV-infected and HIV-uninfected participants with NAFLD. We included participants diagnosed with NAFLD, both HIV-infected and HIV-uninfected. Fatty acid methyl esters were measured from plasma samples. Ratios ([product]/[substrate]) were used to estimate desaturases and elongases activity. We used linear regression for adjusted analyses. We included 31 PLWH and 22 HIV-uninfected controls. We did not find differences in the sum of different types of FA or in FA with a greater presence of plasma. However, there were significant differences in the distribution of some FA, with higher concentrations of ALA, trans-palmitoleic, and behenic acids, and a lower concentration of lignoceric acid in PLWH. PLWH had lower C24:0/C22:0 and C16:0/C14:0 ratios, which estimates the activity of elongases ELOVL1 and ELOVL6. Both groups had similar fatty acid distribution, despite differences in traditional risk factors. PLWH had a lower proportion of specific ratios that estimate ELOVL1 and ELOVL6 activity, which had been previously described for other inflammatory conditions, such as psoriasis.

Background Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. Methods We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. Results We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920–0.952, p < 0.001). MetSCORE is also able to discriminate the intermediate phenotypes, identifying the early risk of MetS in a quantitative way and ranking individuals according to their risk of undergoing MetS (for general population) or according to the severity of the syndrome (for MetS patients). Conclusions We believe that MetSCORE may be an insightful tool for early intervention and lifestyle modifications, potentially preventing the aggravation of metabolic syndrome.