Functional characterization of Cullin-1-RING ubiquitin ligase (CRL1) complex in Leishmania infantum.

Cullin-1-RING ubiquitin ligases (CRL1) or SCF1 (SKP1-CUL1-RBX1) E3 ubiquitin ligases are the largest and most extensively investigated class of E3 ligases in mammals that regulate fundamental processes, such as the cell cycle and proliferation. These enzymes are multiprotein complexes comprising SKP1, CUL1, RBX1, and an F-box protein that acts as a specificity factor by interacting with SKP1 through its F-box domain and recruiting substrates via other domains. E3 ligases are important players in the ubiquitination process, recognizing and transferring ubiquitin to substrates destined for degradation by proteasomes or processing by deubiquitinating enzymes. The ubiquitin-proteasome system (UPS) is the main regulator of intracellular proteolysis in eukaryotes and is required for parasites to alternate hosts in their life cycles, resulting in successful parasitism. Leishmania UPS is poorly investigated, and CRL1 in L. infantum, the causative agent of visceral leishmaniasis in Latin America, is yet to be described. Here, we show that the L. infantum genes LINF_110018100 (SKP1-like protein), LINF_240029100 (cullin-like protein-like protein), and LINF_210005300 (ring-box protein 1 -putative) form a LinfCRL1 complex structurally similar to the H. sapiens CRL1. Mass spectrometry analysis of the LinfSkp1 and LinfCul1 interactomes revealed proteins involved in several intracellular processes, including six F-box proteins known as F-box-like proteins (Flp) (data are available via ProteomeXchange with identifier PXD051961). The interaction of LinfFlp 1-6 with LinfSkp1 was confirmed, and using in vitro ubiquitination assays, we demonstrated the function of the LinfCRL1(Flp1) complex to transfer ubiquitin. We also found that LinfSKP1 and LinfRBX1 knockouts resulted in nonviable L. infantum lineages, whereas LinfCUL1 was involved in parasite growth and rosette formation. Finally, our results suggest that LinfCul1 regulates the S phase progression and possibly the transition between the late S to G2 phase in L. infantum. Thus, a new class of E3 ubiquitin ligases has been described in L. infantum with functions related to various parasitic processes that may serve as prospective targets for leishmaniasis treatment.

Myocardial proteome changes in aortic stenosis rats subjected to long-term aerobic exercise.

The effects of exercise training (ET) on the heart of aortic stenosis (AS) rats are controversial and the mechanisms involved in alterations induced by ET have been poorly clarified. In this study, we analyzed the myocardial proteome to identify proteins modulated by moderate-intensity aerobic ET in rats with chronic supravalvular AS. Wistar rats were divided into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary aortic stenosis (AS-Sed), and exercised AS (AS-Ex). ET consisted of five treadmill running sessions per week for 16 weeks. Statistical analysis was performed by ANOVA or Kruskal-Wallis and Goodman tests. Results were discussed at a significance level of 5%. At the end of the experiment, AS-Ex rats had higher functional capacity, lower blood lactate concentration, and better cardiac structural and left ventricular (LV) functional parameters than the AS-Sed. Myocardial proteome analysis showed that AS-Sed had higher relative protein abundance related to the glycolytic pathway, oxidative stress, and inflammation, and lower relative protein abundance related to beta-oxidation than C-Sed. AS-Ex had higher abundance of one protein related to mitochondrial biogenesis and lower relative protein abundance associated with oxidative stress and inflammation than AS-Sed. Proteomic data were validated for proteins related to lipid and glycolytic metabolism. Chronic pressure overload changes the abundance of myocardial proteins that are mainly involved in lipid and glycolytic energy metabolism in rats. Moderate-intensity aerobic training attenuates changes in proteins related to oxidative stress and inflammation and increases the COX4I1 protein, related to mitochondrial biogenesis. Protein changes are combined with improved functional capacity, cardiac remodeling, and LV function in AS rats.

The autophagy proteome in the brain.

As one of the most important cellular housekeepers, autophagy directly affects cellular health, homeostasis, and function. Even though the mechanisms behind autophagy are well described, how molecular alterations and dysfunctions can lead to pathology in disease contexts still demands deeper investigation. Proteomics is a widely employed tool used to investigate molecular alterations associated with pathological states and has proven useful in identifying alterations in protein expression levels and post-translational modifications in autophagy. In this narrative review, we expand on the molecular mechanisms behind autophagy and its regulation, and further compile recent literature associating autophagy disturbances in context of brain disorders, utilizing discoveries from varying models and species from rodents and cellular models to human post-mortem brain samples. To outline, the canonical pathways of autophagy, the effects of post-translational modifications on regulating each step of autophagy, and the future directions of proteomics in autophagy will be discussed. We further aim to suggest how advancing proteomics can help further unveil molecular mechanisms with regard to neurological disorders.

Synaptotagmins at the endoplasmic reticulum-plasma membrane contact sites maintain diacylglycerol homeostasis during abiotic stress.

Endoplasmic reticulum-plasma membrane contact sites (ER-PM CS) play fundamental roles in all eukaryotic cells. Arabidopsis thaliana mutants lacking the ER-PM protein tether synaptotagmin1 (SYT1) exhibit decreased PM integrity under multiple abiotic stresses, such as freezing, high salt, osmotic stress, and mechanical damage. Here, we show that, together with SYT1, the stress-induced SYT3 is an ER-PM tether that also functions in maintaining PM integrity. The ER-PM CS localization of SYT1 and SYT3 is dependent on PM phosphatidylinositol-4-phosphate and is regulated by abiotic stress. Lipidomic analysis revealed that cold stress increased the accumulation of diacylglycerol at the PM in a syt1/3 double mutant relative to wild-type while the levels of most glycerolipid species remain unchanged. In addition, the SYT1-green fluorescent protein fusion preferentially binds diacylglycerol in vivo with little affinity for polar glycerolipids. Our work uncovers a SYT-dependent mechanism of stress adaptation counteracting the detrimental accumulation of diacylglycerol at the PM produced during episodes of abiotic stress.

Gastric dysplasia in random biopsies: the influence of Helicobacter pylori infection and alcohol consumption in the presence of a lesion.

BACKGROUND: Gastric dysplasia in the absence of an endoscopically defined lesion is rare, usually either a false positive diagnosis or a previously unidentified precancerous lesion during esophagogastroduodenoscopy (EGD). AIMS: Evaluate factors associated with the presence of an endoscopically visible lesion during follow-up in patients with histologic diagnosis of gastric dysplasia in random biopsies. METHODS: Retrospective cohort study including patients referred to our institution for gastric dysplasia in random biopsies during Index EGD. Endoscopic evaluation was performed with a high-definition endoscope using narrow band imaging (HD EGD-0). If no lesion was detected, endoscopic surveillance (HD EGD-FU) was conducted within 6 months for high grade dysplasia (HGD) or 12 months for low grade (LGD) or indefinite for dysplasia (IFD). RESULTS: From a total sample of 96 patients, 5 (5.2%) presented with an endoscopically visible lesion during HD EGD-0, while 10 lesions (10.4%) were identified during HD EGD-FU. Patients with Helicobacter pylori infection at Index EDG and with regular alcohol consumption (≥25 g/day) were 8 and 4 times more likely to have an endoscopically visible lesion on HD EGD-FU (p = 0.012 and p = 0.047). In binary logistic regression, both factors were independent predictors of the presence of gastric lesion on HD EGD-FU (OR 9.284, p = 0.009 and OR 5.025, p = 0.033). CONCLUSIONS: The presence of an endoscopically visible lesion after the histologic diagnosis of gastric dysplasia in random biopsies was more frequent during HD EGD-FU. H. pylori infection at Index EGD and regular alcohol consumption were significant predictors of the presence of gastric lesion on HD EGD-FU.

Recurrence rate after piecemeal endoscopic mucosal resection of <20 mm non-pedunculated colorectal lesions: should we worry about the risk?

INTRODUCTION: There is scarce data focused on recurrence neoplasia rate (RR) after piecemeal endoscopic mucosal resection (pEMR) of 10-19 mm non-pedunculated colorectal lesions (NPL). We aimed to analyze the RR after pEMR of 10-19 mm NPL, identify risk factors for its development and compare it with RR after pEMR of ≥ 20 mm NPL. METHODS: Retrospective cohort-study including all ≥10 mm NPL resected by pEMR in our center between 2018-2022 with an early repeat colonoscopy (ERC). RR was defined as recurrence neoplasia identified in the ERC EMR scar with virtual chromoendoscopy or histological confirmation. RESULTS: A total of 444 NPL were assessed, 124 (27.9%) with 10-19 mm. In the ERC, performed a median of 6 months after pEMR, RR was significantly lower for 10-19 mm NPL compared to ≥ 20 mm NPL (13/124 vs 68/320, p = 0.005). In subgroup analysis, RR after pEMR of 15-19 mm NPL was significantly higher compared to 10-14 mm NPL (13/98 vs 0, p = 0.041) but not significantly different compared to ≥ 20 mm NPL (13/98 vs 68/320, p = 0.073). In multivariable analysis, size of NPL (HR 1.501, 95% CI 1.012-2.227, p = 0.044) was the only independent risk factor identified for RR for 10-19 mm NPL. CONCLUSION: Although the early RR after pEMR of 10-19 mm NPL is significantly lower compared to ≥ 20 mm NPL, it is non-negligible (10.5%) and appears to be the highest among 15-19 mm NPL. The size of the lesion was the only independent risk factor for RR. Our findings should be accounted in the selection of the most appropriate post-polypectomy endoscopic surveillance.

Effects of supplementation with different zinc-based products on the growth and health of Nile tilapia.

Zinc is one of the essential microelements for the metabolism of animals. Zinc nanoparticles may have higher bioavailability due to their low specific surface area, facilitating absorption by fish. The present study aimed to evaluate the effects of supplementation with different zinc-based products on the growth and health of Nile tilapia Oreochromis niloticus. Zinc, in different sizes (nanoparticles or bulk) and forms (inorganic or organic), were used as a supplement in the tilapia diet at a dose of 15 mg kg feed-1 for 60 days. At the end of the feeding trial, production performance, hemato-immunological parameters, activity of antioxidant system enzymes, exposure to Streptococcus agalactiae and zinc concentration in the muscle were examined. After the bacterial challenge, the mean corpuscular hemoglobin concentration (MCHC) significantly increased in the fish treated with organic zinc, inorganic nano zinc, and organic nano zinc, while in the control group (inorganic zinc), MCHC remained unchanged. Regarding defense cells, dietary inorganic nano zinc increased the number of basophils (1.50 ± 1.10) compared to organic zinc (0.80 ± 0.90). Lymphocyte count increased after the challenge only in the organic zinc treatments (bulk and nanoparticles). Neutrophils decreased in the control (inorganic zinc) (2.20 ± 1.70) and inorganic nano zinc (2.60 ± 2.70) treatments after the challenge. When compared before and after the bacterial challenge, the plasma antimicrobial titer significantly increased after the bacterial challenge in all treatments. No significant differences were observed for total proteins, enzymes (SOD and CAT), cumulative survival and zinc deposition on fillet. In conclusion, organic zinc in nanoparticles or bulk size increased Nile tilapia innate defense during bacterial infection. However, the other parameters evaluated were not affected by zinc particle size or form (organic or inorganic), indicating that further evaluations should be conducted with organic zinc in nanoparticles or bulk size in the tilapia diet.

A stronger antibody response in increased disease severity of SARS-CoV-2.

BACKGROUND: An assessment of the factors that interfere with serum levels and the persistence of anti-SARs-CoV-2 IgG antibodies is essential in order to estimate the risk of reinfection and to plan vaccination. We analyzed the impact of the severity of coronavirus disease 2019 (COVID-19) and the clinical and biological factors regarding the persistence of SARs-CoV-2 anti-spike protein (IgG-S) antibodies at 12 months. METHODS: This was an observational, longitudinal study with individuals who had recovered from COVID-19 between August 2020 and June 2021. Peripheral blood samples were collected from volunteers who were hospitalized (SERIOUS COVID-19) and those who required no hospitalization (COVID-19 LIGHT). Samples were grouped according to days after symptom onset: up to 90, between 91 and 180, ≥ 180 days after symptom onset. A semiquantitative test for IgG anti-spike protein S1(IgG-S1) was used. RESULTS: We analyzed 238 individuals who had recovered from COVID-19, of whom 87 had been hospitalized and 151 had not. They provided 148 and 220 samples, respectively. Among those hospitalized, males (65.5%), volunteers aged over 60 years (41.1%), comorbidities such as arterial hypertension (67.8%) and diabetes mellitus (37.9%) were most frequent. We observed higher median serum IgG-S1 titers among those who had recovered from COVID-19 and had been hospitalized, at all collection time intervals (p < 0.001). We observed a weak correlation of increasing age with humoral IgG-S1 response (Spearman correlation = 0.298). There was a greater probability of IgG-S1 antibody persistence over time among samples from hospitalized individuals compared to samples from non-hospitalized participants (p = 0.001). CONCLUSION: This study has revealed higher titers and a higher probability of the persistence of IgG-S1 in severe cases after SARs-CoV-2 primary infection in unvaccinated recovered patients. Thus, in this study, the severe clinical presentation of COVID-19 was the main factor influencing serum levels and the persistence of IgG-S1 antibodies in COVID-19.

Acute Nonvariceal Upper Gastrointestinal Bleeding in Patients Using Anticoagulants: Does the Timing of Endoscopy Affect Outcomes?

BACKGROUND: In patients with acute nonvariceal upper gastrointestinal bleeding (NVUGIB), early (≤ 24 h) endoscopy is recommended following hemodynamic resuscitation. Nevertheless, scarce data exist on the optimal timing of endoscopy in patients with NVUGIB receiving anticoagulants. OBJECTIVE: To analyze how the timing of endoscopy may influence outcomes in anticoagulants users admitted with NVUGIB. METHODS: Retrospective cohort study which consecutively included all adult patients using anticoagulants presenting with NVUGIB between January 2011 and June 2020. Time from presentation to endoscopy was assessed and defined as early (≤ 24 h) and delayed (> 24 h). The outcomes considered were endoscopic or surgical treatment, length of hospital stay, intermediate/intensive care unit admission, recurrent bleeding, and 30-day mortality. RESULTS: From 636 patients presenting with NVUGIB, 138 (21.7%) were taking anticoagulants. Vitamin K antagonists were the most frequent anticoagulants used (63.8%, n = 88). After adjusting for confounders, patients who underwent early endoscopy (59.4%, n = 82) received endoscopic therapy more frequently (OR 2.4; 95% CI 1.1-5.4; P = 0.034), had shorter length of hospital stay [7 (IQR 6) vs 9 (IQR 7) days, P = 0.042] and higher rate of intermediate/intensive care unit admission (OR 2.7; 95% CI 1.3 - 5.9; P = 0.010) than patients having delayed endoscopy. Surgical treatment, recurrent bleeding, and 30-day mortality did not differ significantly between groups. CONCLUSION: Early endoscopy (≤ 24 h) in anticoagulant users admitted with acute nonvariceal upper gastrointestinal bleeding is associated with higher rate of endoscopic treatment, shorter hospital stay, and higher intermediate/intensive care unit admission. The timing of endoscopy did not influence the need for surgical intervention, recurrent bleeding, and 30-day mortality.

BEST-J Score: Validation of a Predicting Model for Delayed Bleeding After Gastric Endoscopic Submucosal Dissection on a European Sample.

BACKGROUND: Delayed bleeding (DB) is a possible adverse event following gastric endoscopic submucosal dissection (ESD). The BEST-J score was created as a risk prediction model for DB following gastric ESD, but is yet to be validated in Western populations. AIMS: We aimed to validate the BEST-J score on a European sample and to perform a subgroup analysis according to histological classification. METHODS: Retrospective study of all consecutive patients undergoing gastric ESD on a European Endoscopic Unit. DB was defined as hemorrhage with clinical symptoms and confirmed by emergency endoscopy from the time of completion to 28 days after ESD. BEST-J score was calculated in each patient and confronted with the outcome (DB). RESULTS: Final sample included 161 patients. From these, 10 (6.2%) presented DB following ESD, with a median time to bleeding of 7 days (IQR 6.8). BEST-J score presented an excellent accuracy predicting DB in our sample, with an AUC = 0.907 (95%CI 0.801-1.000; p < 0.001). Subgroup analysis by histological classification proved that the discriminative power was still excellent for each grade: low-grade dysplasia-AUC = 0.970 (p < 0.001); high-grade dysplasia-AUC = 0.874 (p < 0.001); early gastric cancer-AUC = 0.881 (p < 0.001). The optimal cut-off value to predict DB was a BEST-J score ≥ 3, which matches the cut-off value for high-risk of bleeding in the original investigation. CONCLUSIONS: The BEST-J score still presents excellent accuracy in risk stratification for post-ESD bleeding in European individuals. Thus, this score may help to guide which patients benefit the most from prophylactic therapies following gastric ESD in this setting.

Development of cellulose-based biosorbents from the residue of the peach palm agribusiness and simulation of industrial scale-up for copper removal from Brazilian spirit.

BACKGROUND: Cachaça (Brazilian spirit) is an alcoholic beverage of cultural and economic importance in Brazil. Its artisanal production is usually conducted in copper alembics, which results in contamination. The development of effective biosorbents from cheap matrices is an alternative to minimize both solid waste generation and copper levels in cachaça. The present work evaluates the obtention of nanocellulose-based materials from the major residue generated during the processing of palm heart from the Brazilian peach palm, through different processing techniques. Materials were characterized by physicochemical composition and their sorbent capacities for copper removal from aqueous solutions, and a simulation was conducted to evaluate potential application in the adequacy of cachaça to meet Brazilian legislation requirements. RESULTS: The different processing methods resulted in different cellulose concentrations, with the highest concentration in the bleached material (B3, 694 g kg-1 of cellulose), and different specific surface areas (1.02-12.4 m2 g-1). Copper adsorption onto nanocellulose obtained from peach palm external sheath is fast, with a predominance of a chemisorption mechanism. Isotherms were best represented by Langmuir's model, suggesting a monolayer adsorption. Simulations indicate that B3 is a suitable material for the removal of copper from cachaça, and small amounts of biosorbent (733.5 g) are required for the reduction of copper concentrations (10 to 3 mg L-1) in 1000 L of cachaça. CONCLUSION: This study demonstrated that the obtention of biosorbents from peach palm solid residues is promising and this nanocellulose-based material can be used for copper removal from contaminated cachaça. © 2024 Society of Chemical Industry.

Dietary supplementation of mineral nanoparticles for channel catfish (Ictalurus punctatus).

This study evaluated the supplementation of iron and copper nanoparticles in channel catfish diets and their influences on growth and health. A comparative feeding trial was carried out for 9 weeks to evaluate combinations of iron and copper nanoparticles: only iron nanoparticles (IronNP), only copper nanoparticles (CopperNP), CopperNP + IronNP, and a control diet supplemented with inorganic iron and copper (FeSO4 and CuSO4). After a 9-week feeding trial, growth performance, hematological parameters, whole-body proximate composition, and intestinal microbiota were evaluated, and fish were subjected to a bacterial challenge against Edwardsiella ictaluri to evaluate the contribution of the experimental treatments to fish health status. No statistical differences were detected for catfish fed the various diets in terms of production performance or survival after bacterial challenge. The hematocrit and RBC counts from fish fed the diet containing copper nanoparticles were significantly lower than the control group. A higher relative abundance of gram-positive bacteria was found in the digesta of catfish fed diets containing copper nanoparticles. Furthermore, in the context of hematology, iron nanoparticles did not impact the blood parameters of channel catfish; however, reduced hematocrits were observed in fish fed the copper nanoparticle diet, which lacked supplemental dietary iron, thus reinforcing the importance of dietary iron to catfish hematopoiesis. Nonetheless, additional studies are needed to investigate the effects of dietary copper nanoparticle supplementation in catfish diets to better illuminate its effects on the intestinal microbiota.

Genetic Algorithm for Feature Selection Applied to Financial Time Series Monotonicity Prediction: Experimental Cases in Cryptocurrencies and Brazilian Assets.

Since financial assets on stock exchanges were created, investors have sought to predict their future values. Currently, cryptocurrencies are also seen as assets. Machine learning is increasingly adopted to assist and automate investments. The main objective of this paper is to make daily predictions about the movement direction of financial time series through classification models, financial time series preprocessing methods, and feature selection with genetic algorithms. The target time series are Bitcoin, Ibovespa, and Vale. The methodology of this paper includes the following steps: collecting time series of financial assets; data preprocessing; feature selection with genetic algorithms; and the training and testing of machine learning models. The results were obtained by evaluating the models with the area under the ROC curve metric. For the best prediction models for Bitcoin, Ibovespa, and Vale, values of 0.61, 0.62, and 0.58 were obtained, respectively. In conclusion, the feature selection allowed the improvement of performance in most models, and the input series in the form of percentage variation obtained a good performance, although it was composed of fewer attributes in relation to the other sets tested.

Effects of early exercise on cardiac function and lipid metabolism pathway in heart failure.

We employed an early training exercise program, immediately after recovery from surgery, and before severe cardiac hypertrophy, to study the underlying mechanism involved with the amelioration of cardiac dysfunction in aortic stenosis (AS) rats. As ET induces angiogenesis and oxygen support, we aimed to verify the effect of exercise on myocardial lipid metabolism disturbance. Wistar rats were divided into Sham, trained Sham (ShamT), AS and trained AS (AST). The exercise consisted of 5-week sessions of treadmill running for 16 weeks. Statistical analysis was conducted by anova or Kruskal-Wallis test and Goodman test. A global correlation between variables was also performed using a two-tailed Pearson's correlation test. AST rats displayed a higher functional capacity and a lower cardiac remodelling and dysfunction when compared to AS, as well as the myocardial capillary rarefaction was prevented. Regarding metabolic properties, immunoblotting and enzymatic assay raised beneficial effects of exercise on fatty acid transport and oxidation pathways. The correlation assessment indicated a positive correlation between variables of angiogenesis and FA utilisation, as well as between metabolism and echocardiographic parameters. In conclusion, early exercise improves exercise tolerance and attenuates cardiac structural and functional remodelling. In parallel, exercise attenuated myocardial capillary and lipid metabolism derangement in rats with aortic stenosis-induced heart failure.

A "new" option in Helicobacter pylori eradication: High-dose amoxicillin dual therapy outperforms bismuth quadruple therapy in a high dual resistance setting.

BACKGROUND: Currently, bismuth quadruple therapy (BQT) is indicated as a first-line treatment for Helicobacter pylori eradication in areas with high dual metronidazole and clarithromycin resistance, with its use being limited by its low tolerability and significant cost. A novel regimen with high-dose amoxicillin dual therapy (HDADT) has emerged as an alternative. The aim of this study was to compare the results of these two treatments on HP eradication. MATERIALS AND METHODS: Prospective randomized study including 100 consecutive patients undergoing H. pylori eradication. Each patient was randomized (in a 1:1 ratio) to one group of treatment: BQT (bismuth 140 mg + metronidazole 125 mg + tetracycline 125 mg, four times a day, for 10 days) or HDADT (amoxicillin 1000 mg alternating with amoxicillin 500 mg, four times a day, for 14 days), both associated with esomeprazole 40 mg twice a day. The primary aim was to compare treatments' efficacies. Secondary aims were to assess symptoms persistence and tolerability. RESULTS: A total of 100 patients were included, 54% women, with a mean age of 55 ± 14 years. From these, five were lost to follow-up. Effective eradication proven by negative stool antigen test was significantly higher in patients randomized to HDADT when compared to BQT for both intention-to-treat (ITT) (96.2% vs. 81.4%; p = .022) and per-protocol (PP) (95.9% vs. 81%; p = .025) analysis. These differences were even more pronounced when only considering second line treatment (100% vs. 62.5%; p = .028). Side effects did not differ significantly between BQT and HDADT groups for both ITT (7.0% vs. 2.0%; p = .254) and PP (4.8% vs. 0%; p = .210) analysis. CONCLUSIONS: When compared to BQT, treatment with HDADT presented higher and near 100% efficacy in eradicating H. pylori, without differences in reported side effects or compliance. This treatment represents an important alternative for populations with increasing incidences of resistance to the currently recommended antibiotic regimens.

Real-life patency of plastic biliary stents in the pandemic era: is stent removal after 6 months safe and effective?

BACKGROUND: The SARS-CoV-2 pandemic conditioned the optimal timing of some endoscopic procedures. ESGE guidelines recommend replacement or removal of the plastic biliary stents within 3-6 months to reduce the risk of complications. Our aim was to analyse the outcomes of patients who had delayed plastic biliary stent removal following endoscopic retrograde cholangiopancreatography (ERCP) in the pandemic era. METHODS: Retrospective study including consecutive ERCPs with plastic biliary stent placement between January 2019 and December 2021. Delayed removal was defined as presence of biliary stent >6 months after ERCP. The evaluated outcomes were stent migration, stent dysfunction, obstructive jaundice, cholangitis, acute pancreatitis, hospitalization, and biliary pathology-related mortality. RESULTS: One-hundred and twenty ERCPs were included, 56.7% male patients, with a mean age of 69.4 ± 15.7 years. Indications for plastic biliary stent insertion were choledocholithiasis (72.5%), benign biliary stricture (20.0%), and post-cholecystectomy fistula (7.5%). Delayed stent removal occurred in 32.5% of the cases. The median time to stent removal was 3.5 ± 1.3 months for early removal and 8.6 ± 3.1 months for delayed removal. Patients who had delayed stent removal did not have a significantly higher frequency of stent migration (20.5 vs 11.1%, p = 0.17), stent dysfunction (17.9 vs 13.6%, p = 0.53), hospitalization (17.9 vs 14.8%, p = 0.66), obstructive jaundice (2.6 vs 0.0%, p = 0.33), cholangitis (10.3 vs 13.6%, p = 0.77), acute pancreatitis (0.0 vs 1.2%, p = 1.0), or biliary pathology-related mortality (2.6 vs 1.2%, p = 0.55). CONCLUSIONS: Delayed plastic biliary stent removal does not seem to have a negative impact on patients' outcomes. In the current pandemic situation, while scheduled endoscopic procedures may have to be postponed, elective removal of plastic biliary stents can be safely deferred.

Identifying inflammatory bowel disease patients at risk of metabolic dysfunction-associated fatty liver disease: usefulness of non-invasive steatosis predictive scores.

BACKGROUND: Inflammatory bowel disease (IBD) patients have a higher risk of metabolic dysfunction-associated fatty liver disease (MAFLD) compared with the general population. However, it is not known whether available non-invasive hepatic steatosis scores are useful in predicting MAFLD in IBD patients. We aimed to analyze the performances of MAFLD screening score (MAFLD-S), Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI) and Clinical Prediction Tool for NAFLD in Crohn's Disease (CPN-CD), in identifying MAFLD in IBD patients. METHODS: A cross-sectional study was carried out including consecutive adult IBD outpatients submitted to transient elastography (TE). MAFLD criteria were assessed, and hepatic steatosis (HS) was defined by a controlled attenuation parameter (CAP) >248 dB/m using TE. MAFLD-S, FLI, HSI, and CPN-CD were calculated and their accuracy for the prediction of MAFLD was evaluated through their areas under the receiver-operating characteristic (AUROC) curves. RESULTS: Of 168 patients, body mass index ≥25, type 2 diabetes mellitus, dyslipidemia and arterial hypertension were present in 76 (45.2%), 10 (6.0%), 53 (31.5%), 20 (11.9%), respectively. HS was identified in 77 (45.8%) patients, of which 65 (84.4%) fulfilled MAFLD criteria. MAFLD-S (AUROC, 0.929 [95% CI, 0.888-0.971]) had outstanding and FLI (AUROC, 0.882 [95% CI, 0.830-0.934]), HSI (AUROC, 0.803 [95% CI, 0.736-0.871]), and CPN-CD (AUROC, 0.822 [95% CI, 0.753-0.890) had excellent discrimination in predicting MAFLD. CONCLUSIONS: MAFLD-S, FLI, HSI and CPN-CD scores can accurately identify MAFLD in IBD patients, allowing the selection of those in whom hepatic steatosis and metabolic risk factors assessment may be particularly beneficial.

Reply to comment on "Ultrasonographic scores for ileal Crohn's disease assessment: better, worse or the same as contrast­enhanced ultrasound?

We read the comments by Nylund K et al. regarding our paper "Ultrasonographic scores for ileal Crohn's disease assessment: Better, worse or the same as contrast­enhanced ultrasound?". Intestinal ultrasound has become one of the most valuable developments in the past decade, a non-invasive, well-tolerated exam, with an easy repeatability, and absence of sedation, ionizing radiation, or preparation. Particularly for inflammatory bowel disease, where there is a lack of agreement of patient's symptoms with disease activity, in an era where the paradigm of mucosal healing is changing to transmural healing, and with the emergence of several therapies leading to repeated imaging surveillance, it is essential to highlight the role of intestinal ultrasound. Although intestinal ultrasound is an increasingly used tool to monitor inflammatory bowel disease activity, there is no widely accepted reproducible activity index, since the methodology for the development of the scores was shown to be insufficient in most studies and none have been adequately validated (Bots et al., J Crohns Colitis 12:920-9, 2018). In our study, we showed that the contrast-enhanced ultrasound (CEUS) peak enhancement derived from the time-intensity curve (TIC) is a promising non-invasive emerging method with a good accuracy to correlate clinical and endoscopic activity in the terminal ileum, superior to intestinal ultrasound scores relying on bowel wall thickness and colour Doppler.

Gastrostomy Button Diameter and Length Variations after Percutaneous Endoscopic Gastrostomy: One Size Does Not Fit All.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a useful option for long-term enteral nutrition. Low-profile gastrostomy tubes ("buttons") may afterward be placed in the stomach through the abdominal wall following maturation of the preexisting ostomy. Regular verification is essential since inadequate sizing is associated with accidental exteriorization or food leakage. We aimed to evaluate gastrostomy buttons diameter or length variations on the first year after their placement and possible factors associated with these variations. METHODS: We analyzed consecutive PEGs between 2016 and 2018. A minimum follow-up of 12 after gastrostomy button placement was required. Diameter or length variations were assessed in a specialized PEG appointment during the follow-up period. RESULTS: Final sample included 94 patients, from which 65 (69.1%) were women, and 29 (30.9%) were men, with a mean age of 76.9 ± 13.3 years. Measurements variations occurred in 44 (46.8%) patients. Diameter variation was significantly more frequent in patients living in a nursing home (OR = 5.43; 95% CI = 1.32-22.27; p = 0.019), patients with previous PEG tube dislodgement (OR = 3.84; 95% CI = 1.21-12.20; p = 0.023), and male patients (OR = 3.50; 95% CI = 1.06-11.49, p = 0.039). Length variation occurred more frequently in patients with a weight change during the follow-up period greater than 5 kg (OR = 3.71; 95% CI = 1.14-12.05; p = 0.029). CONCLUSIONS: A significant proportion of patients with gastrostomy buttons required a change in their measurements, especially if male, living in nursing homes, having significant weight changes, or accidental tube exteriorization. This emphasizes the importance of having a specialized PEG appointment to regularly assure the best fitted button for each patient and ultimately guarantee an adequate nutritional intake.

Stepping it up: Physical activity is associated with a lower incidence of prolonged gastric transit time in capsule endoscopy.

BACKGROUND AND AIM: Physical activity has been proposed as a potential factor influencing capsule endoscopy (CE) gastric transit time (GTT). However, there is no reported factual evidence confirming this association. We aimed to prospectively assess the effect of physical activity in the first hour of CE in the occurrence of prolonged GTT. METHODS: This is a prospective study including consecutive patients undergoing CE. For each patient, a step counter was attached to the CE register. The number of steps during the first hour of the procedure was registered. The main outcome was prolonged GTT (CE remaining in the stomach for > 1 h). Outcomes were adjusted for possible confounders by multivariate analysis. RESULTS: We included 100 patients, 60% undergoing small bowel CE and 40% colon CE. The mean number of steps in the first hour was significantly lower in patients with prolonged GTT (2009 ± 1578 steps) comparatively with those without prolonged GTT (3597 ± 1889 steps) (P < 0.001). On multivariate analysis including significant confounders, steps in the first hour were an independent predictor of prolonged GTT (P = 0.018). Single-handedly, the number of steps taken in the first hour had a good acuity for predicting prolonged GTT (area under the curve = 0.74; P < 0.001), with an optimal cut-off of 2000 steps (sensitivity 81.3% and specificity 70%). CONCLUSIONS: Physical activity during the first hour of CE significantly decreased the occurrence of prolonged GTT. These findings pave the way for further definition of clear instructions to give to patients undergoing CE.