Bile acids profile and redox status in healthy infants.

BACKGROUND: At birth, human neonates are more likely to develop cholestasis and oxidative stress due to immaturity or other causes. We aimed to search for a potential association between bile acids profile, redox status, and type of diet in healthy infants. METHODS: A cross-sectional, exploratory study enrolled 2-month-old full-term infants (n = 32). We measured plasma bile acids (total and conjugated), and red blood cell (RBC) oxidative stress biomarkers. The type of diet (breastfeeding, mixed, formula) was used as an independent variable. RESULTS: Plasma total bile acids medium value was 14.80 µmol/L (IQR: 9.25-18.00). The plasma-conjugated chenodeoxycholic acid percentage (CDCA%) correlated significantly and negatively with RBCs membrane-bound hemoglobin percentage (MBH%) (r = -0.635, p < 0.01) and with RBC-oxidized glutathione (r = -0.403, p < 0.05) levels. RBC oxidative stress biomarkers (especially MBH%) were predictors of conjugated CDCA%, and this predictive ability was enhanced when adjusted for the type of diet (MBH, r = 0.452, p < 0.001). CONCLUSIONS: Our data suggest that the bile acid profile might play a role in the regulation of redox status (or vice versa) in early postnatal life. Eventually, the type of diet may have some impact on this process. IMPACT: The conjugated CDCA% in plasma is negatively correlated with biomarkers of RBC oxidative stress in healthy infants. Specific biomarkers of RBC oxidative stress (e.g. MBH, GSH, GSSG) may be promising predictors of conjugated CDCA% in plasma. The type of diet may influence the predictive ability of hit RBC oxidative stress biomarkers (e.g. MBH, GSH, GSSG). Our findings suggest a link between plasma bile acids profile and the RBC redox status in healthy infants, eventually modulated by the type of diet. The recognition of this link may contribute to the development of preventive and therapeutic strategies for neonatal cholestasis.

Time trend prevalence of helicobacter pylori infection and endoscopic findings in symptomatic children in Portugal: A retrospective study based on three time points in 2009, 2014, and 2019.

BACKGROUND: Helicobacter pylori infection acquisition occurs mainly in childhood and may be a critical factor in developing long-term complications. In contrast to other developed countries, previous studies have reported a relatively high H. pylori infection prevalence in Portugal, both in children and adults. However, there are no recent data concerning pediatric population. MATERIALS AND METHODS: We performed a retrospective observational study concerning an 11 years period (2009, 2014, 2019), that included patients under 18 years old who underwent upper endoscopy at a pediatric tertiary center. Demographic, clinical-pathological, and microbiological data were collected. RESULTS: Four hundred and sixty one children were included. The average age was 11.7 ± 4.4 years. In total, H. pylori infection was confirmed in 37.3% of cases (histology and/or culture) and a decreasing infection trend was observed (p = .027). The most common indication for endoscopy was abdominal pain, which was a good predictor of infection. Antral nodularity was present in 72.2% of the infected children (p < .001). In the oldest age groups, moderate/severe chronic inflammation, H. pylori density and lymphoid aggregates/follicles were positive predictors for the presence of antral nodularity. For all ages, the presence of antral nodularity, neutrophilic activity in the antrum and corpus and lymphoid follicles/aggregates in the antrum were positive predictors for the presence of H. pylori infection. Among the 139 strains tested for antibiotic susceptibility, 48.9% were susceptible to all tested antibiotics. Resistance to clarithromycin, metronidazole, and both was detected in 23.0%, 12.9%, and 6.5% of the strains, respectively; furthermore, resistance to ciprofloxacin and to amoxicillin was observed in 5.0% and 1.4% of the strains, respectively. CONCLUSIONS: The present study reports (for the first time in Portugal) a significant decreasing trend in the prevalence of pediatric H. pylori infection, although it remains relatively high compared to the recently reported prevalence in other South European countries. We confirmed a previously recognized positive association of some endoscopic and histological features with H. pylori infection, as well as a high prevalence rate of resistance to clarithromycin and to metronidazole. The clinical relevance of these findings requires confirmation with further studies at a national level, taking into account the high incidence rate of gastric cancer in Portugal and the potential need for country-specific intervention strategies.

Emergency endoscopy in pediatrics during the SARS-CoV-2 pandemic in a tertiary center - A changing pattern?

A retrospective analysis of admissions to the pediatric emergency department that required emergency endoscopy was performed, to evaluate if changes in the lifestyle and hospital practices imposed by the pandemic had an impact on the frequency and profile of the emergency endoscopy. The first 6 months of the pandemic (Group A) were compared with the homologous period of the previous year (Group B). Eight-nine cases were analyzed. Most emergency endoscopies occurred in children under the age of two (28%) and most of these were in Group A (p = 0.009). More foreign bodies were removed in Group A (p = 0.026). There were no statistically significant differences in the time to reach the emergency department (p = 0.934) or in the time delay since emergency room admission until the endoscopic procedure (p = 0.266). Overall, the pandemic did not seem to affect the quality of healthcare practice regarding emergency endoscopic procedures.

Neonatal cholestasis: development of a diagnostic decision algorithm from multivariate predictive models.

Despite the recent advances involving molecular studies, the neonatal cholestasis (NC) diagnosis still relays on the expertise of medical teams. Our aim was to develop models of etiological diagnosis and unfavourable prognosis which may support a rationale diagnostic approach. We retrospectively analysed 154 patients born between January 1985 and October 2019. The cohort was divided into two main groups: (A) transient cholestasis and (B) other diagnosis (with subgroups) and also in two groups of outcomes: (I) unfavourable and (II) favourable. Multivariate logistic regression analysis identified the lower gestational age as the only variable independently associated with an increased risk of transient cholestasis and signs and/or symptoms of sepsis with infectious or metabolic diseases. Gamma-glutamyl transferase serum levels > 300 IU/L had a positive predictive value for both diagnosis of biliary atresia and for alpha-1-antitrypsin deficiency (A1ATD) and for unfavourable prognosis. A model of diagnosis for A1ATD (n = 34) showed an area under the ROC curve = 0.843 [confidence interval (CI): 0.773-0.912].Conclusion: This study identified some predictors of diagnosis and prognosis which helped to build a diagnostic decision algorithm. The unusually large subgroup of patients with A1ATD in this cohort emphasizes its predictive diagnostic model. What Is Known • The etiological diagnosis of neonatal cholestasis (NC) requires a step-by-step guided approach, and diagnostic models have been developed only for biliary atresia. • Current algorithms neither address the epidemiology changes nor the application of the new molecular diagnostic tools. What Is New • This study provides diagnostic predictive models for patients with A1ATD, metabolic/infectious diseases, and transient cholestasis, and two models of unfavourable prognosis for NC. • A diagnostic decision algorithm is proposed based on this study, authors expertise and the literature.

Helicobacter pylori Infection in Pediatric Patients Living in Europe: Results of the EuroPedHP Registry 2013 to 2016.

OBJECTIVES: The aim of the study was to assess clinical presentation, endoscopic findings, antibiotic susceptibility and treatment success of Helicobacter pylori (H. pylori) infected pediatric patients. METHODS: Between 2013 and 2016, 23 pediatric hospitals from 17 countries prospectively submitted data on consecutive H. pylori-infected (culture positive) patients to the EuroPedHP-Registry. RESULTS: Of 1333 patients recruited (55.1% girls, median age 12.6 years), 1168 (87.6%) were therapy naïve (group A) and 165 (12.4%) had failed treatment (group B). Patients resided in North/Western (29.6%), Southern (34.1%) and Eastern Europe (23.0%), or Israel/Turkey (13.4%). Main indications for endoscopy were abdominal pain or dyspepsia (81.2%, 1078/1328). Antral nodularity was reported in 77.8% (1031/1326) of patients, gastric or duodenal ulcers and erosions in 5.1% and 12.8%, respectively. Primary resistance to clarithromycin (CLA) and metronidazole (MET) occurred in 25% and 21%, respectively, and increased after failed therapy. Bacterial strains were fully susceptible in 60.5% of group A, but in only 27.4% of group B. Primary CLA resistance was higher in Southern and Eastern Europe (adjusted odds ratio [ORadj] = 3.44, 95% confidence interval [CI] 2.22-5.32, P < 0.001 and 2.62, 95% CI: 1.63-4.22, P < 0.001, respectively) compared with Northern/Western Europe. Children born outside Europe showed higher primary MET resistance (ORadj = 3.81, 95% CI: 2.25-6.45, P < 0.001). Treatment success in group A reached only 79.8% (568/712) with 7 to 14 days triple therapy tailored to antibiotic susceptibility. CONCLUSIONS: Peptic ulcers are rare in dyspeptic H. pylori-infected children. Primary resistance to CLA and MET is markedly dependent on geographical regions of birth and residence. The ongoing survey will show whether implementation of the updated ESPGHAN/NASPGHAN guidelines will improve the eradication success.

Predicting mortality in patients admitted to the intensive care unit after open vascular surgery.

PURPOSES: Vascular surgery (VS) has a higher perioperative mortality than other types of surgery. We compared different scores for predicting mortality in patients admitted to the intensive care unit (ICU) after open VS. METHODS: Patients admitted to the ICU after open VS from 2006 to 2013 were included. We calculated the Acute Physiology and Chronic Health Evaluation (APACHE), Simplified Acute Physiology Score (SAPS), Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) and Preoperative Score to Predict Postoperative Mortality (POSPOM). We performed multivariate logistic regression to assess independent factors with the calculation of odds ratios (ORs) and 95% confidence intervals (CIs). We tested the predictive ability of the scores using the area under the receiver operating characteristics curve (AUROC). RESULTS: A total of 833 consecutive patients were included. Hospital mortality was 5.1% (1.3% after intermediate-risk and 8.4% after high-risk surgery). In the multivariate analysis, the age (OR 1.04, 95% CI 1.01-1.08, p = 0.013), smoking status (OR 2.46, 95% CI 1.16-5.21, p = 0.019), surgery risk (OR 2.92, 95% CI 1.05-8.08, p = 0.040), serum sodium level (OR 1.17, 95% CI 1.10-1.26, p < 0.001), urea (OR 1.01, 95% CI 1.01-1.02, p = 0.001) and leukocyte count (OR 1.05, 95% CI 1.01-1.10, p = 0.009) at admission were considered independent predictors. Hematocrit (0.86, 95% CI 0.80-0.93, p < 0.001) was considered an independent protective factor. The AUROC of our model was 0.860, compared to SAPS (0.752), APACHE (0.774), POSPOM (0.798) and POSSUM (0.829). CONCLUSION: The observed mortality was within the predicted range (1-5% after intermediate-risk and > 5% after high-risk surgery). POSSUM and POSPOM had slightly better predictive capacity than SAPS or APACHE.

Intramural esophageal dissection. A rare occurrence in pediatric eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal disease, with a rising incidence in childhood. The diagnosis is confirmed by esophageal mucosa eosinophil-predominant inflammation. Rare complications, such as intramural esophageal dissection (IED) due to progressive transmural inflammatory and fibrotic process, may occur in young adults. While severe cases can require immediate surgical intervention, conservative management may be also effective, as recently reported by Ibáñez-Sanz et al., decreasing the risk of surgery-related complications.

Pediatric Crohn's disease, iron deficiency anemia and intravenous iron treatment: a follow-up study.

BACKGROUND AND AIMS: Increasing evidence in adults demonstrates efficacy and safety of IV iron in inflammatory Bowel disease (IBD) associated iron deficiency anemia; however, evidence in pediatric patients is yet scarce and no previous study has included a long follow-up. This study aimed to evaluate safety and efficacy of IV iron (primary end point), and the need of re-treatment (secondary end point), in this setting. METHODS: Prospective recruitment (40 months); PCDAI determined before and after treatment; anemia defined according to WHO criteria; IV iron treatment included iron sucrose and ferric carboxymaltose. Primary and secondary endpoints included hemoglobin, serum ferritin, transferrin saturation at baseline and 4-6 weeks after treatment; and the need of re-treatment during the median follow-up period (18 months), respectively. RESULTS: Nineteen patients (median age: 15.5 years) with remissive/mild disease were included. At recruitment, the median hemoglobin was 10.5 g/dl, (median s-ferritin: 20.1 ug/l, median transferrin saturation; 6%) and 4-6 weeks after treatment was 12.7 g/dl. Median hemoglobin according to age groups before vs. after treatment: <12 years:11 vs. 12.0 g/dl; females ≥12 years:9.9 vs. 12.6 g/dl; and males ≥12 years:11.1 vs. 13.3 g/dl. Patients with remissive vs. mild disease had median Hb of 10.5 g/dl vs. 10.6 g/dl, and median s-ferritin: 6.8 ug/dl vs. 43.3 ug/dl, respectively). Nine patients were treated with iron sucrose (median dose 672.6 mg/dl) and 10 patients with ferric carboxymaltose (median dose 811.5 mg/dl). No major adverse reactions occurred. Six patients needed re-treatment after a median 15.5 months period. CONCLUSIONS: Our prospective study, concerning pediatric IBD anemia patients with remission/mild disease and a significant follow-up, emphasizes efficacy and safety of IV-iron and the importance of long-term follow-up of iron status. SUMMARY: In pediatric IBD iron anemia, the evidence supporting the efficacy and safety of IV-iron is scare. This prospective study aims to evaluate the safety and efficacy (short and long term) of IV-iron in these patients. Nineteen pediatric CD patients were evaluated before and after IV iron treatment (40-month period).The median Hb before and after IV iron was 10.5 and 12.7 g/dl, respectively. No major adverse reactions were documented. Six patients needed re-treatment (median period of 15.5 months). This study further demonstrates the efficacy and safety of IV iron. It reinforces the importance of long-term follow-up of the iron status in pediatric CD patients.

Clinical practices among healthcare professionals concerning neonatal jaundice and pale stools.

Jaundice and pale stools are major indicators of neonatal liver disease. Prognosis depends on timely diagnosis and management. We evaluated the clinical practices among healthcare professionals concerning jaundiced newborns and their ability to recognize pale stools. We supplied a questionnaire and a panel with eight photographs of stools, both locally validated, to physicians and nurses of the National Healthcare Service. Analysis was conducted according to professional status, specialization and years of experience of professionals and level of healthcare. Questionnaires were administered to 266 participants (100 physicians, 166 nurses). The decision to send patients to medical observation depended on the intensity of jaundice for a significant percentage of nurses. Concerning jaundiced newborns breastfed and otherwise healthy, 28.9% of physicians would never request a conjugated bilirubin assay, and only 43.3% would request it after 14 days old; for those with other signs/symptoms of disease, only 69.1% of physicians would request it immediately. Multiple linear regression analysis identified specialization as an independent variable significantly associated with the ability to recognize pale stools. CONCLUSION: A significant percentage of healthcare professionals assumed clinical practices that preclude the timely recognition of cholestasis/pale stools, reinforcing the idea of educational needs. Specialization, rather than years of experience of professionals, was associated with better skills and practices. What is Known: • Neonatal cholestasis is a condition with some rare underlying entities having high mortality and morbidity. Early diagnosis is crucial to improve prognosis. Yet, many cases remain late recognized and referred. • Studies evaluating the ability of healthcare professionals to recognize neonatal cholestasis are scarce. What is New: • In this study, a significant percentage of professionals assumed clinical practices that preclude timely recognition of neonatal cholestasis and pale stools, reinforcing the idea of educational needs. • Specialization of professionals was associated with better skills and practices.

Distribution of the - 13910C>T polymorphism in the general population of Portugal and in subjects with gastrointestinal complaints associated with milk consumption.

BACKGROUND: The - 13910C>T polymorphism has been associated with lactase persistence (LP) in European populations. AIM: To assess - 13910C>T genotypes across Portugal and in adult individuals with unspecific gastrointestinal complaints associated with milk consumption. SUBJECTS AND METHODS: This study genotyped - 13910C>T in the general population from Northern (n = 64), Central (n = 70) and Southern (n = 65) Portugal and in 40 subjects with gastrointestinal symptoms. Additionally, the concordance was evaluated between breath-hydrogen test and - 13910C>T genotypes in 65 samples. RESULTS: An overall frequency of 0.349 for the LP - 13910*T allele was estimated in the general population, with a noticeable decrease in the South (0.269) compared with North (0.383) and Centre (0.393). Among the symptomatic group, the frequency of the - 13910*T allele (0.363) was not significantly different from the general population. A 94% concordance was found between the breath-hydrogen and the molecular tests. CONCLUSIONS: This study suggests that (i) the distribution of the LP polymorphism is not uniform across the country, (ii) genotyping - 13910C>T is a good diagnostic tool for lactase status in the Portuguese population and (iii) self-reported gastrointestinal complaints are not good predictors of the LP status, implying that a significant part of those complaints may not be related to hypolactasia.

Battery Ingestion in Children, an Ongoing Challenge: Recent Experience of a Tertiary Center.

Introduction: Morbidity related to childhood battery ingestions (BI) has increased recently due to the expanding use of larger lithium cells. A prompt endoscopic removal is vital to prevent severe complications in cases of esophageal batteries (EB). Materials and Methods: A retrospective, descriptive study of admissions for BI requiring endoscopic removal in a tertiary hospital's pediatric emergency department (Jan. 2011/Dec. 2020). Results: We had 35 cases, with an increasing incidence in the last 6 years; median age, 26 m (8 m-10 years), witnessed ingestion in 86%. On the X-ray: 14 (40%) had an EB, 21 (60%), a gastric battery (GB). Symptoms were present in 57% (100% EB/24% GB), and vomiting was the most frequent (50%). Endoscopy revealed: EB, 13 (37%); GB, 17 (49%); duodenal battery, 1 (3%); no battery, 4 (11%). Median time to removal: EB, 7 h (2 h-21days); GB, 12 h (2 h-3 days). All the patients with EB on the X-ray (14) had severe mucosal injury (Zargar classification): Grade IIIa, 7 (50%); IIIb, 5 (36%); IV, 2 (14%). CT-scan showed perforation in 2 patients (total, 4; 29% of EB). In patients with GB (21), 14 (67%) had mucosal damage; 13 (93%), mild (< Grade III, two esophageal erosions); 1 (7%) IIIa (esophageal ulceration). A statistically significant association between exposure time, younger age or battery size and severity of endoscopic lesions was found in EB location. There were no mortality cases. Acute complications occurred in 57% of EB: infection, 50%; perforation, 29%; pneumomediastinum/stridor, 14%; pneumothorax/subglottic stenosis/hemodynamic instability, 7 vs. 0% GB. Stenosis subsequently developed in 6 (43%) of EB: mild, 4 cases (29%); severe, 2 cases (14%, one resolved after endoscopic dilation; one needed a gastrostomy and esophagocoloplasty). Conclusion: We verified recent increase in admissions due to battery ingestions and associated complications, despite the availability of an emergency pediatric endoscopy team. The patients with EB had more severe mucosal injury and poorer short/long-term outcomes. Children with GB had milder lesions, although the presence of a GB did not exclude esophageal injury. The availability of actual data from national referral centers will support advocacy efforts among stakeholders, including industry representatives and policy makers, in preventing worldwide button battery injury.

Primary antibiotic resistance of Helicobacter pylori strains isolated from Portuguese children: a prospective multicentre study over a 10 year period.

OBJECTIVES: The aim of this study was to prospectively assess the pattern of evolution of primary resistance to antibiotics in Helicobacter pylori strains isolated from Portuguese children over a 10 year period (2000-09). METHODS: A total of 1115 H. pylori strains were tested for antibiotic susceptibility to clarithromycin, metronidazole, amoxicillin, ciprofloxacin and tetracycline. RESULTS: H. pylori strains were isolated from children and adolescents [ages 4 months-18 years (mean age 10.17 ±â€Š4.03 years)], comprising 562 (50.4%) boys and 553 (49.6%) girls. Overall, the primary resistance rate was 34.7% to clarithromycin, 13.9% to metronidazole and 4.6% to ciprofloxacin, while 6.9% were resistant to two of these antibiotics simultaneously. Resistance to amoxicillin and to tetracycline was not detected. In general, the resistance rate was not associated with gender or the children's age. European ethnicity, when compared with an African background, was associated with clarithromycin resistance [P = 0.002; odds ratio (OR) = 0.30; 95% confidence interval (CI) 0.14-0.66], while the inverse situation was observed for metronidazole (P < 0.001; OR = 3.50; 95% CI 1.90-6.45). No significant temporal trend was noticed for resistance to clarithromycin and metronidazole, whereas ciprofloxacin and double-resistance rates have significantly increased over time (P = 0.004 and P = 0.05, respectively). CONCLUSIONS: The primary resistance rate of H. pylori strains isolated from Portuguese children to the commonly used anti-H. pylori antibiotics used is high. Additionally, the increasing trend of ciprofloxacin-resistant and double-resistant strains may compromise H. pylori eradication in a high-prevalence population.

Prevalence and incidence of Helicobacter pylori Infection in a healthy pediatric population in the Lisbon area.

BACKGROUND: Helicobacter pylori is mainly acquired in childhood. Although adult studies reported a high prevalence of H. pylori infection in Portugal, the actual rate in children remains unknown. This study aimed to determine the prevalence and the incidence of H. pylori infection in an asymptomatic pediatric population of the Lisbon area and to correlate prevalence with sociodemographic determinants. MATERIALS AND METHODS: Helicobacter pylori infection was determined by stool antigen test in 844 asymptomatic children (age 0-15 years; 49.4% boys). For the incidence study, H. pylori-negative children in the prevalence study were followed-up every 6 months over a 3-year period. RESULTS: The global prevalence of H. pylori infection was 31.6%, increasing with age (19.9, 37.0 and 51.5%, in age groups 0-5, 6-10, and 11-15, respectively), but was similar among genders (34.5% in boys and 28.4% in girls). Older age and attendance of nursery/kindergarten during preschool constituted independent risk factors. The overall estimated incidence was 11.6 per 100 child-years (CY). Although 47.5% of children acquired H. pylori infection before 5 years of age, the mean age of acquisition was 6.3. The incidence of infection was similar among the three age groups (11.5, 13.0, and 10.5 per 100 CY, in age groups 0-5, 6-10, and 11-15, respectively). CONCLUSIONS: The prevalence of H. pylori infection in the Portuguese pediatric population is still high. Although this study confirmed that the highest acquisition rate occurs at young age, it showed that in high-prevalence populations, older children can also acquire H. pylori infection at a rate similar to that of young children.

The role of minor salivary glands' biopsy in the diagnosis of Sjögren's syndrome and other systemic diseases.

BACKGROUND: The minor salivary glands' biopsy is a minimally invasive procedure used for the diagnosis of Sjögren's syndrome. Its significance has also been reported in other inflammatory/infiltrative diseases. The objectives are to investigate its use in the diagnosis of Sjögren's syndrome, as well as to evaluate its role in the diagnosis of amyloidosis and sarcoidosis. METHODS: A retrospective analysis was carried out on patients who underwent minor salivary glands' biopsies between April of 2014 and December of 2017. RESULTS: A total of 173 patients were identified. Of the patients with suspected Sjögren's syndrome, in 40% of the cases there was evidence of lymphocytic sialadenitis. The antibodies against SSA, antinuclear antibodies and the Rheumatoid Factor correlated significantly with the presence of lymphocytic sialadenitis. The result of the minor salivary glands' biopsies allowed an increase of 12.4% of patients who met the criteria defined by the American - European Consensus Group. Of the patients with suspected amyloidosis (25%), the biopsies were positive in 4 patients. CONCLUSION: The minor salivary glands' biopsy is a simple procedure with effectiveness in the diagnosis of Sjögren's syndrome and amyloidosis. In this study, its use increased the number of patients who met the Sjögren's syndrome classification criteria. It also appears to be useful in the diagnosis of amyloidosis.

Neonatal Cholestasis Over Time: Changes in Epidemiology and Outcome in a Cohort of 154 Patients From a Portuguese Tertiary Center.

Introduction: In the last two decades there have been advances in the diagnosis and management of neonatal cholestasis, which may have changed its epidemiology, diagnostic accuracy, outcomes, and survival. Our goal was to characterize these changes over time in our setting. Methods: Retrospective cohort study in a tertiary center, enrolling patients born between January 1985 and October 2019. The cohort was divided into two periods, before (A; n = 67) and after (B; n = 87) the year 2000; and in two groups, according to patient's outcome (favorable, unfavorable). Overall survival and survival with and without orthotopic liver transplant (OLT) were evaluated in the two periods (A and B) and in different subgroups of underlying entities. Results: We found that the age of cholestasis recognition decreased significantly from period A to period B [median 43 days and 22 days, respectively, (p < 0.001)]; the changes in epidemiology were relevant, with a significant decrease in alpha-1-antitrypsin deficiency (p < 0.001) and an increase in transient cholestasis (p = 0.004). A next-generation sequencing (NGS) panel available since mid-2017 was applied to 13 patients with contributory results in 7, but, so far, only in 2 patients led to conclusive diagnosis of underlying entities. The number of cases of idiopathic cholestasis did not vary significantly. Over time there was no significant change in the outcome (p = 0.116). Overall survival and survival without OLT had no significant improvement during the period of observation (in periods A and B, 86 vs. 88%, and 85 vs. 87%, respectively). However, in period B, with OLT we achieved the goal of 100% of survival rate. Conclusions: Our data suggest that transient cholestasis became a very important subset of neonatal cholestasis, requiring specific guidance. The NGS panels can provide important inputs on disease diagnosis but, if applied without strict criteria and expertise, they can open a Pandora's box due to misinterpretation. Despite all the advances in accurate diagnosis and timely management-including early recognition of cholestasis-the improvement in patient outcomes and survival were still not significant.

Portuguese Consensus on Diagnosis, Treatment, and Management of Anemia in Pediatric Inflammatory Bowel Disease.

Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), both in pediatric and in adult patients. Iron deficiency is the main cause of anemia in patients with IBD. Anemia is a clinically relevant comorbidity, with impact on patients' quality of life and it should be timely diagnosed and adequately treated. Currently, an active treatment approach is the recommended strategy, with evidence showing efficacy and safety of intravenous iron formulations. However, evidence in pediatric age remains scarce and no clinical recommendations exist for the diagnosis and treatment of this particular age group. The present document represents the first national consensus on the management of anemia in pediatric IBD and is therefore particularly relevant. The authors anticipate that the proposed recommendations will be useful in daily clinical practice for diagnosing and managing iron deficiency and iron-deficiency anemia in the pediatric population with IBD.

A anemia é uma manifestação extra-digestiva frequente associada à doença inflamatória intestinal, tanto na população pediátrica como adulta, sendo a anemia por défice de ferro a sua forma mais frequente. Constitui uma comorbilidade clinicamente relevante, com repercussão na qualidade de vida. Deve ser atempadamente diagnosticada e adequadamente tratada. A estratégia terapêutica atualmente aceite preconiza uma atitude interventiva. Neste contexto, a evidência científica atual tem demonstrado a eficácia e segurança da utilização das formulações de ferro endovenoso. Contudo, em idade pediátrica a evidência ainda é insuficiente, não existindo orientações de abordagem diagnóstica ou terapêutica especificamente dirigidas a este grupo etário. Este é o primeiro consenso nacional sobre a abordagem da anemia na doença inflamatória intestinal pediátrica, revestindo-se por isso de particular relevância. Pretendese que este documento tenha utilidade e aplicabilidade na prática clínica na avaliação e seguimento do défice de ferro e anemia por défice de ferro em doentes pediátricos com doença inflamatória intestinal.

Incidence, predictors and validation of risk scores to predict postoperative mortality after noncardiac vascular surgery, a prospective cohort study.

BACKGROUND: Noncardiac vascular surgery (VS) patients have comorbidities that increase the risk of death after surgery. Assessing that risk is important to allocate the necessary resources and improve quality of care. We aimed to evaluate the incidence and predictors of 30-day post-operative mortality (POM) after VS and compare the performance of existing risk scores. MATERIALS AND METHODS: Prospective cohort study including consecutive patients submitted to elective VS at a tertiary university hospital. We collected patients' demographics/perioperative data and calculated Surgical Apgar, age-adjusted Charlson Comorbidity Index (CCI), Vascular-Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (V-POSSUM) and Preoperative Score to Predict Postoperative Mortality (POSPOM). We performed multivariate logistic regression to assess independent factors with Odds Ratio (OR) and 95% confidence interval (CI) calculation and Cox-regression for time-to-event analysis. We tested the predictive ability of the scores using the area under ROC curve (AUROC). RESULTS: POM was 6.2% (n = 19/306), not different from expected by V-POSSUM (6.5%) or POSPOM (5.6%). Post-operative myocardial infarction (MI) and acute kidney injury (AKI) were associated with higher POM (OR 4.8, p = 0.011 and OR 5.4, p = 0.001, respectively). On multivariate analysis, Chronic kidney disease (CKD) (OR 4.0, p = 0.021), Age (OR 1.1, p = 0.002), Peripheral arterial disease (PAD) (OR 8.0, p = 0.006), intra-operative red blood cells (RBC) Transfusion (OR 1.9, p < 0.001) and Atrial fibrillation (OR 8.4, p = 0.002) were considered independent predictors of POM (CAPTA score). The AUROC of our model was 0.882, better V-POSSUM (0.858), POSPOM (0.784), CCI (0.732) or Surgical Apgar (0.649). CONCLUSION: Observed POM was similar to predicted by V-POSSUM or POSPOM. Age, PAD, CKD, atrial fibrillation and intraoperative RBC transfusion were independent risk factors for POM. Score V-POSSUM performed better than POSPOM, CCI or Surgical Apgar.

Major Cardiac Events in Patients Admitted to Intensive Care After Vascular Noncardiac Surgery: A Retrospective Cohort.

Introduction. Patients proposed to vascular noncardiac surgery (VS) have several comorbidities associated with major adverse cardiac events (MACE). We evaluated incidence, predictors, and outcomes, and compared different scores to predict MACE after VS. Methods. We included all patients admitted from 2006 to 2013. Perioperative MACE included cardiac arrhythmias, myocardial infarction (MI), cardiogenic pulmonary edema (CPE), acute heart failure (AHF), and cardiac arrest (CA). Lee Revised Cardiac Risk Index (RCRI), Vascular Quality Initiative (VQI-CRI), Vascular Study Group of New England (VSG-CRI), and South African Vascular Surgical (SAVS-CRI) Cardiac Risk Indexes were calculated and analyzed. We performed multivariate logistic regression to assess independent predictors with calculation of odds ratio (OR) and 95% confidence interval (CI). To reduce overfitting, we used leave-one-out cross-validation approach. The Predictive ability of scores was tested using area under receiver operating characteristic curve (AUROC). Results. A total of 928 patients were included. We observed 81 MACE (28 MI, 22 arrhythmias, 10 CPE, 9 AHF, 12 CA) in 60 patients (6.5%): 3.3% in intermediate-risk surgery and 9.8% in high-risk surgery. Previous history of coronary artery disease (OR = 3.2, CI = 1.8-5.7), atrial fibrillation (OR = 5.1, CI = 2.4-11.0), insulin-treated diabetes mellitus (OR = 3.26, CI = 1.51-7.06), mechanical ventilation (OR = 2.75, CI = 1.41-4.63), and heart rate (OR = 1.02, CI = 1.01-1.03) at admission were considered independent risk factors in multivariate analysis. The AUROC of our model was 0.79, compared with RCRI (0.66), VSG-CRI (0.69), VQI-CRI (0.71), and SAVS-CRI (0.73). Conclusions. Observed MACE were within predicted range (1% to 5% after intermediate-risk surgery and >5% after high-risk surgery). SAVS-CRI and VQI-CRI had slightly better predictive capacity than VSG-CRI or RCRI.

Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients.

BACKGROUND: Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. OBJECTIVE: This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. METHODS: Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti-human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. RESULTS: The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. CONCLUSIONS: This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.