Impact of 1-Year Supplementation with High-Rich Docosahexaenoic Acid (DHA) on Clinical Variables and Inflammatory Biomarkers in Pediatric Cystic Fibrosis: A Randomized Double-Blind Controlled Trial.

A randomized, double-blind, and placebo-controlled study was conducted to assess the effect of dietary supplementation with high-rich docosahexaenoic acid (DHA) (Tridocosahexanoin-AOX® 70%) at 50 mg/kg/day in pediatric patients with cystic fibrosis (CF) as compared with placebo. The duration of supplementation was 12 months. A total of 22 patients were included, with 11 in the DHA group and 11 in the placebo group. The mean age was 11.7 years. The outcome variables were pulmonary function, exacerbations, sputum cellularity, inflammatory biomarkers in sputum and peripheral blood, and anthropometric variables. In the DHA group, there was a significant increase in FVC (p = 0.004) and FVE1 expressed in liters (p = 0.044) as compared with placebo, and a lower median number of exacerbations (1 vs. 2). Differences in sputum cellularity (predominantly neutrophilic), neutrophilic elastase, and sputum and serum concentrations of resolvin D1 (RvD1), interleukin (IL)-8 (IL-8), and tumor necrosis factor alpha (TNF-α) between the study groups were not found. Significant increases in weight and height were also observed among DHA-supplemented patients. The administration of the study product was safe and well tolerated. In summary, the use of a highly concentrated DHA supplement for 1 year as compared with placebo improved pulmonary function and reduced exacerbations in pediatric CF.

On the use of fractional calculus to improve the pulse arrival time (PAT) detection when using photoplethysmography (PPG) and electrocardiography (ECG) signals.

The pulse arrival time (PAT) has been considered a surrogate measure for pulse wave velocity (PWV), although some studies have noted that this parameter is not accurate enough. Moreover, the inter-beat interval (IBI) time series obtained from successive pulse wave arrivals can be employed as a surrogate measure of the RR time series avoiding the use of electrocardiogram (ECG) signals. Pulse arrival detection is a procedure needed for both PAT and IBI measurements and depends on the proper fiducial points chosen. In this paper, a new set of fiducial points that can be tailored using several optimization criteria is proposed to improve the detection of successive pulse arrivals. This set is based on the location of local maxima and minima in the systolic rise of the pulse wave after fractional differintegration of the signal. Several optimization criteria have been proposed and applied to high-quality recordings of a database with subjects who were breathing at different rates while sitting or standing. When a proper fractional differintegration order is selected by using the RR time series as a reference, the agreement between the obtained IBI and RR is better than that for other state-of-the-art fiducial points. This work tested seven different traditional fiducial points. For the agreement analysis, the median standard deviation of the difference between the IBI and RR time series is 5.72 ms for the proposed fiducial point versus 6.20 ms for the best-performing traditional fiducial point, although it can reach as high as 9.93 ms for another traditional fiducial point. Other optimization criteria aim to reduce the standard deviation of the PAT (7.21 ms using the proposed fiducial point versus 8.22 ms to 15.4 ms for the best- and worst-performing traditional fiducial points) or to minimize the standard deviation of the PAT attributable to breathing (3.44 ms using the proposed fiducial point versus 4.40 ms to 5.12 ms for best- and worst-performing traditional fiducial points). The use of these fiducial points may help to better quantify the beat-to-beat PAT variability and IBI time series.

Gene editing: a near future for the treatment of genetic kidney diseases.

The study by Chen et al. is the first to apply the revolutionary genetic engineering tool, base editing, in a rat model for the treatment of primary hyperoxaluria type 1, a disease that originates in the liver but in which the kidney is the main organ affected. This commentary contextualizes and describes the gene-editing technology applied by the authors, provides an interpretation and opinion of their results, and indicates possible future applications.

SARS-CoV-2 infection in children with cystic fibrosis: A cross-sectional multicenter study in Spain. New waves, new knowledge.

INTRODUCTION: The association between viral infections and pulmonary exacerbations in children with cystic fibrosis (cwCF) is well established. However, the question of whether cwCF are at a higher risk of COVID-19 or its adverse consequences remains controversial. METHODS: We conducted an observational, multicenter, cross-sectional study of cwCF infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) between March 2020 and June 2022, (first to sixth COVID-19 pandemic waves) in Spain. The study aimed to describe patients' basal characteristics, SARS-CoV-2 clinical manifestations and outcomes, and whether there were differences across the pandemic waves. RESULTS: During study time, 351 SARS-CoV2 infections were reported among 341 cwCF. Median age was 8.5 years (range 0-17) and 51% were female. Cases were unevenly distributed across the pandemic, with most cases (82%) clustered between November 2021 and June 2022 (sixth wave, also known as Omicron Wave due to the higher prevalence of this strain in that period in Spain). Most cwCF were asymptomatic (24.8%) or presented with mild Covid-19 symptoms (72.9%). Among symptomatic, most prevalent symptoms were fever (62%) and increased cough (53%). Infection occurring along the sixth wave was the only independent risk factor for being symptomatic. Just eight cwCF needed hospital admission. No multisystem inflammatory syndrome, persisting symptoms, long-term sequelae, or deaths were reported. CONCLUSIONS: Spanish current data indicate that cwCF do not experience higher risks of SARS-CoV-2 infection nor worse health outcomes or sequelae. Changes in patients' basal characteristics, clinical courses, and outcomes were detected across waves. While the pandemic continues, a worldwide monitoring of COVID-19 in pediatric CF patients is needed.

Estimation of liver fibrosis using elastography in cholestatic diseases: systematic review and meta-analysis.

INTRODUCTION: staging fibrosis extent in liver disease is highly relevant for appropriate management. Liver biopsy remains the reference standard for assessment, but noninvasive methods such as elastography are becoming increasingly accurate and relevant. However, evidence regarding elastography in cholestatic diseases is lower than in other etiologies. METHODS: we searched MEDLINE, EMBASE and Web of Science for publications on the diagnostic accuracy of transient elastography and sonoelastography in cholestatic diseases (PBC and PSC) using biopsy as the reference standard. A systematic review and meta-analysis of the results was then carried out. RESULTS: a total of 13 studies were included. Using transient elastography in PBC sensitivity and specificity were estimated to be 0.76 and 0.93; 0.88 and 0.9; and 0.91 and 0.95 for ≥ F2, ≥ F3 and = F4, respectively. For sonoelastography in PBC sensitivity and specificity estimates were 0.79 and 0.82; 0.95 and 0.86; and 0.94 and 0.85 for ≥ F2, ≥ F3 y = F4, respectively. In PSC, transient elastography had a sensivity and specificity of 0.76 and 0.88; 0.91 and 0.86; and 0.71 and 0.93 for ≥ F2, ≥ F3 and = F4, respectively. CONCLUSION: elastography has adequate diagnostic accuracy in the assessment of fibrosis stages in cholestatic liver diseases.

Changes of Erythrocyte Fatty Acids after Supplementation with Highly Concentrated Docosahexaenoic Acid (DHA) in Pediatric Cystic Fibrosis: A Randomized Double-Blind Controlled Trial.

We characterized the fatty acid profiles in the erythrocyte membrane of pediatric patients with cystic fibrosis (CF) receiving highly concentrated docosahexaenoic acid (DHA) supplementation (Tridocosahexanoin-AOX® 70%) at 50 mg/kg/day (n = 11) or matching placebo (n = 11) for 12 months. The mean age was 11.7 years. The DHA group showed a statistically significant improvement in n-3 polyunsaturated fatty acids (PUFAs), which was observed as early as 6 months and further increased at 12 months. Among the n-3 PUFAs, there was a significant increase in DHA and eicosapentaenoic acid (EPA). Additionally, a statistically significant decrease in n-6 PUFAs was found, primarily due to a decrease in arachidonic acid (AA) levels and elongase 5 activity. However, we did not observe any changes in linoleic acid levels. The long-term administration of DHA over one year was safe and well tolerated. In summary, the administration of a high-rich DHA supplement at a dose of 50 mg/kg/day for one year can correct erythrocyte AA/DHA imbalance and reduce fatty acid inflammatory markers. However, it is important to note that essential fatty acid alterations cannot be fully normalized with this treatment. These data provide timely information of essential fatty acid profile for future comparative research.

Hepatic Insulin Resistance Model in the Male Wistar Rat Using Exogenous Insulin Glargine Administration.

Metabolic diseases are a worldwide health problem. Insulin resistance (IR) is their distinctive hallmark. For their study, animal models that provide reliable information are necessary, permitting the analysis of the cluster of abnormalities that conform to it, its progression, and time-dependent molecular modifications. We aimed to develop an IR model by exogenous insulin administration. The effective dose of insulin glargine to generate hyperinsulinemia but without hypoglycemia was established. Then, two groups (control and insulin) of male Wistar rats of 100 g weight were formed. The selected dose (4 U/kg) was administered for 15, 30, 45, and 60 days. Zoometry, a glucose tolerance test, insulin response, IR, and the serum lipid profile were assessed. We evaluated insulin signaling, glycogenesis and lipogenesis, redox balance, and inflammation in the liver. Results showed an impairment of glucose tolerance, dyslipidemia, hyperinsulinemia, and peripheral and time-dependent selective IR. At the hepatic level, insulin signaling was impaired, resulting in reduced hepatic glycogen levels and triglyceride accumulation, an increase in the ROS level with MAPK-ERK1/2 response, and mild pro-oxidative microenvironmental sustained by MT, GSH, and GR activity. Hepatic IR coincides with additions in MAPK-p38, NF-κB, and zoometric changes. In conclusion, daily insulin glargine administration generated a progressive IR model. At the hepatic level, the IR was combined with oxidative conditions but without inflammation.

Hepatic splenosis, description of an unusual behavior at contrast-enhanced ultrasonography (CEUS).

The case was a 47-year-old male, asymptomatic, with a personal history of splenectomy in childhood. He was referred to our outpatient clinic to complete the study of space-occupying liver lesion. The initial diagnostic suspicion was liver adenoma, given its behavior on magnetic resonance imaging and the absence of previous liver disease. We performed an intravascular contrast-enhanced ultrasound (CEUS) (SonoVue©). The lesion showed rapid centripetal enhancement, remaining enhanced in the portal phase with dim washout in the late venous phase. Given the therapeutic implications of the diagnosis of a hepatic adenoma, an ultrasound-guided percutaneous biopsy with an 18-gauge core needle was performed. The anatomopathological study confirmed the presence of hepatic splenosis. Hepatic splenosis can present as isolated or multiple foci (1). There is little published information on the behavior of hepatic splenosis in CEUS (2, 3, 4), which prevents any behavior from being generalized. The most frequently described behavior is hyperenhancement in the arterial phase without subsequent washout, not a specific behavior that can lead to the misdiagnosis of other entities such as hemangioma. In our case, it was caused by an isolated focus of splenosis that did not show the most frequent described behavior at CEUS, since it presented a faint washout in the venous phase, making it necessary to rule out malignancy.

Agreement between two photoplethysmography-based wearable devices for monitoring heart rate during different physical activity situations: a new analysis methodology.

Wearables are being increasingly used to monitor heart rate (HR). However, their usefulness for analyzing continuous HR in research or at clinical level is questionable. The aim of this study is to analyze the level of agreement between different wearables in the measurement of HR based on photoplethysmography, according to different body positions and physical activity levels, and compared to a gold-standard ECG. The proposed method measures agreement among several time scales since different wearables obtain HR at different sampling rates. Eighteen university students (10 men, 8 women; 22 ± 2.45 years old) participated in a laboratory study. Participants simultaneously wore an Apple Watch and a Polar Vantage watch. ECG was measured using a BIOPAC system. HR was recorded continuously and simultaneously by the three devices, for consecutive 5-min periods in 4 different situations: lying supine, sitting, standing and walking at 4 km/h on a treadmill. HR estimations were obtained with the maximum precision offered by the software of each device and compared by averaging in several time scales, since the wearables obtained HR at different sampling rates, although results are more detailed for 5 s and 30 s epochs. Bland-Altman (B-A) plots show that there is no noticeable difference between data from the ECG and any of the smartwatches while participants were lying down. In this position, the bias is low when averaging in both 5 s and 30 s. Differently, B-A plots show that there are differences when the situation involves some level of physical activity, especially for shorter epochs. That is, the discrepancy between devices and the ECG was greater when walking on the treadmill and during short time scales. The device showing the biggest discrepancy was the Polar Watch, and the one with the best results was the Apple Watch. We conclude that photoplethysmography-based wearable devices are suitable for monitoring HR averages at regular intervals, especially at rest, but their feasibility is debatable for a continuous analysis of HR for research or clinical purposes, especially when involving some level of physical activity. An important contribution of this work is a new methodology to synchronize and measure the agreement against a gold standard of two or more devices measuring HR at different and not necessarily even paces.

Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study

Background and aim: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain.Methods: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated.Results: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups.Conclusion: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation. (AU)

Long-term outcome of omalizumab-assisted desensitisation to cow's milk and eggs in patients refractory to conventional oral immunotherapy: real-life study.

BACKGROUND: Oral immunotherapy (OIT) is a promising approach to cow's milk and egg allergies, but reactions are frequent and some patients cannot be desensitized. OBJECTIVE: To evaluate long-term OIT outcomes with omalizumab (OMZ) in paediatric patients with severe egg and/or milk allergies. METHODS: This retrospective real-life study analysed findings in children with Immunoglobulin E-mediated allergy to cow's milk and/or hen eggs refractory to conventional OIT, who underwent OIT with OMZ in our department between 1 January 2010 and 31 December 2015. RESULTS: In all, 41 patients were included (median age: 7 years; interquartile range [IQR]: 5.5-9.5); 26/41 (63.4%) underwent OIT for milk, 8/41 (19.5%) for egg and 7/41 (17.1%) for both. The median time between initiation of OMZ and OIT was 27 weeks (IQR: 22-33). Forty (97.56%) patients reached the maintenance phase (200 mL of cow's milk and 30 mL of raw egg or 1 cooked egg) in a median time of 27 weeks (IQR: 18-37). The median total time with OMZ was 117 weeks (IQR: 88-144). During the OMZ period, 2.44% (1/41) of patients presented anaphylaxis. After discontinuation of OMZ, 29.3% (12/41) presented anaphylaxis, 50% of them had a poor adherence to daily ingestion. One patient (2.44%) was diagnosed with eosinophilic esophagitis after 2 years of discontinuation of OMZ. Currently, after a median time of 9 years (IQR: 7-10) since the initiation of OMZ, 75.6% (31/41) are desensitized (27/31 without OMZ). CONCLUSIONS: Omalizumab allows desensitisation of children with severe allergies to cow's milk and/or egg without developing severe reactions while receiving this treatment. However, discontinuation of OMZ leads to severe allergic reactions, and hence must be monitored carefully.

Genetic Kidney Diseases (GKDs) Modeling Using Genome Editing Technologies.

Genetic kidney diseases (GKDs) are a group of rare diseases, affecting approximately about 60 to 80 per 100,000 individuals, for which there is currently no treatment that can cure them (in many cases). GKDs usually leads to early-onset chronic kidney disease, which results in patients having to undergo dialysis or kidney transplant. Here, we briefly describe genetic causes and phenotypic effects of six GKDs representative of different ranges of prevalence and renal involvement (ciliopathy, glomerulopathy, and tubulopathy). One of the shared characteristics of GKDs is that most of them are monogenic. This characteristic makes it possible to use site-specific nuclease systems to edit the genes that cause GKDs and generate in vitro and in vivo models that reflect the genetic abnormalities of GKDs. We describe and compare these site-specific nuclease systems (zinc finger nucleases (ZFNs), transcription activator-like effect nucleases (TALENs) and regularly clustered short palindromic repeat-associated protein (CRISPR-Cas9)) and review how these systems have allowed the generation of cellular and animal GKDs models and how they have contributed to shed light on many still unknown fields in GKDs. We also indicate the main obstacles limiting the application of these systems in a more efficient way. The information provided here will be useful to gain an accurate understanding of the technological advances in the field of genome editing for GKDs, as well as to serve as a guide for the selection of both the genome editing tool and the gene delivery method most suitable for the successful development of GKDs models.

Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study.

BACKGROUND AND AIM: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain. METHODS: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. RESULTS: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups. CONCLUSION: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.

Sildenafil prevents right ventricular hypertrophy and improves heart rate variability in rats with pulmonary hypertension secondary to experimental diabetes.

Chronic treatment with sildenafil (SILD) is an effective protector on the development of cardiovascular complications of pulmonary hypertension (PH) and diabetes. However, to date, no studies have evaluated the effect of SILD on cardiopulmonary pathophysiology during PH secondary to type 1 diabetes. AIM: The present study aimed to evaluate the beneficial effects of chronic SILD treatment on pulmonary arterial pressure, right ventricular hypertrophy (RVH) and cardiac autonomic dysfunction in rats with PH secondary to diabetes. METODOLOGY: Male Sprague Dawley rats were randomly distributed into the control group (saline), diabetic group (60 mg/kg with streptozotocin), SILD-treated control group (20 mg/kg) and SILD-treated diabetic group. RESULTS: After 8 weeks the type 1 diabetic animals presented PH, endothelial dysfunction of the pulmonary arteries, electrocardiographic alterations, RVH and overexpression of phosphodiesterase type 5 in the heart. In type 1 diabetic animals, SILD treatment prevented the development of PH, endothelial dysfunction and RVH. SILD treatment also prevented alterations in the corrected QT period and heart rate variability and prevented overexpression of phosphodiesterase type 5. CONCLUSION: Our results indicate for the first time that SILD treatment prevents pulmonary arterial endothelial dysfunction, pulmonary hypertension, right ventricular hypertrophy and improves heart rate variability in type 1 diabetic rats.

Combination therapy of specific aeroallergens immunotherapy and omalizumab, in children with severe asthma

Background In most cases, severe asthma in children has an allergic etiology, but allergen-specific immunotherapy (AIT) is contraindicated.Objective This study aimed at analyzing the safety and efficacy of AIT in patients with severe asthma treated with omalizumab (OM).Methods A descriptive real-life study was carried out by reviewing medical records. Effectiveness was measured by the degree of control (CAN questionnaire), number of hospitalizations per year, number of exacerbations per year, and maintenance treatment and lung function (FEV1). Some adverse reactions occurred (AAI-EAACI-WAO guidelines).Results The retrospective study included 29 patients up to 18 years of age with severe asthma with OM plus AIT treatment. AIT treatment was started in a cluster schedule when patients treated with OM achieved disease control. Before starting AIT, patients were treated with OM for 1 year for achieving asthmatic control. AIT to mites (51%), Alternaria (37.9%), or pollens (10.3%) was administered. After one year with OM plus AIT,statistically significant differences in CAN scores and FEV1 measures were observed (P < 0.001). No patients under treatment with OM plus AIT required hospital admission. During the clustering schedule, only 3/64 doses showed systemic adverse reactions. During the AIT maintenance treatment, 348 doses were administered, with no significant adverse reactions (AU)

Quantitative Proteomic Study Unmasks Fibrinogen Pathway in Polycystic Liver Disease.

(1) Background: Polycystic liver disease (PLD) is a heterogeneous group of congenital disorders characterized by bile duct dilatation and cyst development derived from cholangiocytes. Nevertheless, the cystogenesis mechanism is currently unknown and the PLD treatment is limited to liver transplantation. Novel and efficient therapeutic approaches are th6us needed. In this context, the present work has a principal aim to find novel molecular pathways, as well as new therapeutic targets, involved in the hepatic cystogenesis process. (2) Methods: Quantitative proteomics based on SWATH-MS technology were performed comparing hepatic proteomes of Wild Type and mutant/polycystic livers in a polycystic kidney disease (PKD) murine model (Pkd1cond/cond;Tam-Cre-/+). (3) Results: We identified several proteins altered in abundance, with two-fold cut-off up-regulation or down-regulation and an adjusted p-value significantly related to hepatic cystogenesis. Then, we performed enrichment and a protein-protein analysis identifying a cluster focused on hepatic fibrinogens. Finally, we validated a selection of targets by RT-qPCR, Western blotting and immunohistochemistry, finding a high correlation with quantitative proteomics data and validating the fibrinogen complex. (4) Conclusions: This work identified a novel molecular pathway in cystic liver disease, highlighting the fibrinogen complex as a possible new therapeutic target for PLD.

Aortic dysfunction by chronic cadmium exposure is linked to multiple metabolic risk factors that converge in anion superoxide production.

CONTEXT: The chronic exposure to Cadmium (Cd) constitute an risk to develop hypertension and cardiovascular diseases associated with the increase of oxidative stress. OBJECTIVE: In this study, we investigate the role of metabolic changes produced by exposure to Cd on the endothelial dysfunction via oxidative stress. METHODS: Male Wistar rats were exposed to Cd (32.5-ppm) for 2-months. The zoometry and blood pressure were evaluated, also glucose and lipids profiles in serum and vascular reactivity evaluated in isolated aorta rings. RESULTS: Rats exposed to Cd showed an increase of blood pressure and biochemical parameters similar to metabolic syndrome. Additionally, rats exposed to Cd showed a reduced relaxation in aortic rings, which was reversed after the addition of SOD and apocynin an inhibitor of NADPH. CONCLUSION: The Cd-exposition induced hypertension and endothelial injury by that modifying the vascular relaxation and develop oxidative stress via NADPH oxidase, superoxide and loss nitric oxide bioavailability.

Characteristics and outcome of incidental hepatocellular carcinoma after liver transplantation: a cohort study.

INTRODUCTION: despite advances in imaging diagnostic modalities, hepatocellular carcinoma is sometimes incidentally diagnosed on histological examination of the liver explant. The objectives of the study were: a) to compare the characteristics between incidental and known hepatocellular carcinoma; and b) to estimate survival and tumor recurrence after liver transplantation. MATERIAL AND METHODS: a retrospective, single-center study was performed. The inclusion criteria were: a) cirrhotic patients, age ≥ 18 years; b) liver transplantation between 1998 and 2018; and c) hepatocellular carcinoma diagnosed via histopathologic examination of the explanted liver. Cholangiocarcinoma and patients with early retransplantation were excluded. Multivariate analysis was performed using binomial logistic regression to assess the factors associated with incidental hepatocellular carcinoma. Kaplan-Meier curves were plotted to explore the impact on overall survival and recurrence free survival. RESULTS: two hundred and sixty-nine patients were enrolled. The prevalence of incidental hepatocellular carcinoma was 4.18 % (95 % CI: 2.89-6.01 %) of all liver transplants performed in cirrhotic patients. The median diameter of the main nodule was smaller in incidental hepatocellular carcinoma (20 vs 27 mm, p = 0.004), although they were more likely to be beyond the Up-to-Seven criteria on explant examination (22.2 % vs 7.5 %, p = 0.001), with no differences in any other histological features. No differences were found in overall survival rates (incidental 70.2 % vs 70.4 %, p = 0.87) or recurrence-free survival (incidental 100 % vs 83.8 %, p = 0.07) at five years. CONCLUSION: incidental hepatocellular carcinoma are smaller in size and are more frequently found to be beyond the Up-to-Seven criteria. However, no differences were found in overall survival rates or recurrence-free survival, although there was no tumor recurrence in the incidental hepatocellular carcinoma group.

Long-term outcome of omalizumab-assisted desensitisation to cow’s milk and eggs in patients refractory to conventional oral immunotherapy: real-life study

Background: Oral immunotherapy (OIT) is a promising approach to cow’s milk and egg aller-gies, but reactions are frequent and some patients cannot be desensitized. Objective: To evaluate long-term OIT outcomes with omalizumab (OMZ) in paediatric patients with severe egg and/or milk allergies.Methods: This retrospective real-life study analysed findings in children with Immunoglobulin E-mediated allergy to cow’s milk and/or hen eggs refractory to conventional OIT, who under-went OIT with OMZ in our department between 1 January 2010 and 31 December 2015. Results: In all, 41 patients were included (median age: 7 years; interquartile range [IQR]: 5.5–9.5); 26/41 (63.4%) underwent OIT for milk, 8/41 (19.5%) for egg and 7/41 (17.1%) for both. The median time between initiation of OMZ and OIT was 27 weeks (IQR: 22–33). Forty (97.56%) patients reached the maintenance phase (200 mL of cow’s milk and 30 mL of raw egg or 1 cooked egg) in a median time of 27 weeks (IQR: 18–37). The median total time with OMZ was 117 weeks (IQR: 88–144). During the OMZ period, 2.44% (1/41) of patients presented anaphy-laxis. After discontinuation of OMZ, 29.3% (12/41) presented anaphylaxis, 50% of them had a poor adherence to daily ingestion. One patient (2.44%) was diagnosed with eosinophilic esoph-agitis after 2 years of discontinuation of OMZ. Currently, after a median time of 9 years (IQR: 7–10) since the initiation of OMZ, 75.6% (31/41) are desensitized (27/31 without OMZ).Conclusions: Omalizumab allows desensitisation of children with severe allergies to cow’s milk and/or egg without developing severe reactions while receiving this treatment. However, dis-continuation of OMZ leads to severe allergic reactions, and hence must be monitored carefully.© 2022 Codon Publications. Published by Codon Publications (AU)