Early Enteral Nutrition and Gastrointestinal Complications in Pediatric Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: To assess the safety of enteral nutrition (EN) in children on extracorporeal membrane oxygenation (ECMO). To describe nutritional status and the characteristics of the nutritional support in this population. METHODS: A retrospective single-center analysis (2006-2016) including children <18 years on ECMO. Demographic data, nutritional status, characteristics of nutritional support, and development of gastrointestinal (GI) complications were recorded. RESULTS: One hundred children, with a median age of 9.7 months (interquartile range [IQR] 3.9-63.1) were enrolled. Undernutrition was prevalent among children on ECMO (33.3%) mainly in patients <2 years (P = 0.042). Most patients (64%) received EN at some point during ECMO therapy. EN was administered in the first 48 hours after ECMO initiation (48HEN) to 60.3% of the children.Mortality rate in the Pediatric Intensive Care Unit was lower in patients who received EN as the initial artificial nutrition support (ANS) (37.7 vs 51%, P = 0.005) and in children on 48HEN (34% vs 50%, P = 0.04). In the logistic regression analysis, duration of ECMO support and low cardiac output indication were the only factors associated with mortality.Although most patients on ECMO (45%) developed digestive complications, they were mostly mild, being constipation the most prevalent. In the logistic regression analysis, EN was not associated with an increase in GI complications (P = 0.09). Only three patients developed intestinal ischemia (one without EN and two on EN). CONCLUSIONS: Undernutrition is prevalent among children on ECMO, mainly in infants <2 years. EN is not associated with severe gastrointestinal complications or higher mortality in these children.

The clinical relevance of the microbiome when managing paediatric infectious diseases-Narrative review.

In recent years, the field of infectious diseases has been hit by the overwhelming amount of information generated while the human microbiome is being disentangled. Based on the interaction between the microbiota and the immune system, the implications regarding infectious diseases are probably major and remain a challenge. AIMS: This review was conceived as a comprehensive tool to provide an overview of the available evidence regarding the influence of the microbiome on infectious diseases in children. METHODS: We present the main findings aroused from microbiome research in prevention, diagnosis and treatment of infectious disease under a paediatric perspective, to inform clinicians of the potential relevance of microbiome-related knowledge for translation to clinical practice. RESULTS AND CONCLUSION: The evidence shown in this review highlights the numerous research gaps ahead and supports the need to move forward to integrating the so-called microbiome thinking into our routine clinical practice.

Hemodynamic impact of the connection to continuous renal replacement therapy in critically ill children.

BACKGROUND: Continuous renal replacement therapy (CRRT) is the treatment of choice for critically ill children with acute kidney injury. Hypotension after starting CRRT is frequent but very few studies have analyzed its incidence and clinical relevance. METHODS: A prospective, observational study was performed including critically ill children treated with CRRT between 2010 and 2014. Hemodynamic data and connection characteristics were collected before, during, and 60 min after CRRT circuit connection. Hypotension with the connection was defined as a decrease in > 20% of the mean arterial pressure from baseline or when intravenous fluid resuscitation or an increase in vasopressors was required. RESULTS: One hundred sixty-one connections in 36 children (median age 18.8 months) were analyzed. Twenty-eight patients (77.8%) were in the postoperative period of cardiac surgery, 94% had mechanical ventilation, and 86.1% had vasopressors. The heparinized circuit priming solution was discarded in 8.7% and infused to the patient in 18% of the connections. The circuit was re-primed in the remaining 73.3% using albumin (79.3%), red blood cells (4.5%), or another crystalloid solution without heparin (16.2%). Hypotension occurred in 49.7% of the connections a median of 5 min after the beginning of the therapy. Fluid resuscitation was required in 38.5% and the dose of vasopressors was increased in 12.4% of the connections. There was no relationship between hypotension and age or weight. Re-priming the circuit with albumin reduced the incidence of hypotension from 71.4 to 44.6% (p = 0.004). CONCLUSIONS: Hypotension after the connection to CRRT is very frequent in critically ill children. Re-priming the circuit with albumin could improve hemodynamics during connection.

Hemodynamic Effects of Connection to Continuous Renal Replacement Therapy in a Pediatric Animal Model.

To assess the hemodynamic effects of connection to continuous renal replacement therapy (CRRT) in a pediatric experimental animal model. Prospective experimental study was performed using piglets between 2 and 3 months of age and 9-11 kg. CRRT with a PrismaflexR monitor and HF20 filter (surface of 0.2 m2 ) was started after monitoring and anesthetic induction with an initial blood flow at 20 mL/min with 10 mL/min increases every minute until the goal flow of 5 mL/kg/min was achieved. Heart rate, blood pressure, central venous pressure, cardiac index, and renal blood flow were registered at baseline, 5, 15, 30, 60, 120, 180, 240, and 360 min. IBM SPSS Statistics 20.0 package was used for analysis. A P value of <0.05 was considered statistically significant. Thirty-four piglets were studied. Blood pressure, cardiac output, and systemic vascular resistance significantly decreased 5-min after CRRT connection (mean arterial pressure from 85.5 to 70.8 mm Hg, P < 0.001, cardiac index from 3.6 to 3.3 L/min/m2 P = 0.024, and systemic vascular resistance index from 1759 to 1607 dyn.s/cm5 P = 0.012). No significant changes were found in renal blood flow or central venous pressure. All parameters gradually increased at 15 and 30 min after connection but complete recovery was never achieved. Connection to CRRT produces a significant decrease in arterial pressure, cardiac index, and peripheral vascular resistances in hemodynamically stable piglets.

Evaluation of sublingual microcirculation in a paediatric intensive care unit: prospective observational study about its feasibility and utility.

BACKGROUND: Evaluation of the microcirculation in critically ill patients is usually done by means of indirect parameters. The aim of our study was to evaluate the functional state of the microcirculation by direct visualization of sublingual microcirculation using Sidestream Dark Field Imaging, to determine the correlation between these findings and other parameters that are commonly used in the clinical practice and to assess the applicability of the systematic use of this technique in critically ill children. METHODS: A prospective observational study was carried out in a Pediatric Intensive Care Unit (PICU) of a tertiary referral hospital. All patients admitted to the PICU during a three-month period were included in the study after obtaining the informed consent from the patient. Systematic evaluation of sublingual microcirculation was done in these patients (Total Vessel Density, Proportion of Perfused Vessels, Perfused Vessel Density, De Backer Score, Microvascular Flow Index, Heterogeneity Index) within the first day of admission (T1) and between the second and third day of admission (T2). Other clinical, hemodynamic, and biochemical parameters were measured and registered simultaneously. When the evaluation of the microcirculation was not feasible, the reason was registered. Descriptive analysis of our findings are expressed as means, medians, standard deviations and interquartile ranges. Mann-Whitney-Wilcoxon and Fisher tests were used to compare variables between patients with and without evaluation of the microcirculation. Pearson Correlation Coefficient (ρ) was used to evaluate the correlation between microcirculatory parameters and other clinical parameters. RESULTS: One hundred fine patients were included during the study period. Evaluation of the microcirculation was feasible in 18 patients (17.1%). 95.2% of them were intubated. The main reason for not evaluating microcirculation was the presence of respiratory difficulty or the absence of collaboration (95.1% on T1 and 68.9% on T2). Evaluated patients had a higher prevalence of intubation and ECMO at admission (72.2% vs. 14.9% and 16.6% vs. 1.1%, respectively), and longer median duration of mechanical ventilation (0 vs. 6.5 days), vasoactive drugs (0 vs. 3.5 days) and length of stay (3 vs. 16.5 days) than non-evaluated patients. There was a moderate correlation between microcirculatory parameters and systolic arterial pressure, central venous pressure, serum lactate and other biochemical parameters used for motoring critically ill children. CONCLUSIONS: Systematic evaluation of microcirculation in critically ill children is not feasible in the unstable critically ill patient, but it is feasible in stable critically ill children. Microcirculatory parameters show a moderate correlation with other parameters that are usually monitored in critically ill children.

Measurement of cardiac output in children by pressure-recording analytical method.

We evaluated two pressure-recording analytical method (PRAM) software versions (v.1 and v.2) to measure cardiac index (CI) in hemodynamically stable critically ill children and investigate factors that influence PRAM values. The working hypothesis was that PRAM CI measurements would stay within normal limits in hemodynamically stable patients. Ninety-five CI PRAM measurements were analyzed in 47 patients aged 1-168 months. Mean CI was 4.1 ± 1.4 L/min/m(2) (range 2.0-7.0). CI was outside limits defined as normal (3-5 L/min/m(2)) in 53.7% of measurements (47.8% with software v.1 and 69.2% with software v.2, p = 0.062). Moreover, 14.7% of measurements were below 2.5 L/min/m(2), and 13.6% were above 6 L/min/m(2). CI was significantly lower in patients with a clearly visible dicrotic notch than in those without (3.7 vs. 4.6 L/min/m(2), p = 0.004) and in children with a radial arterial catheter (3.5 L/min/m(2)) than in those with a brachial (4.4 L/min/m(2), p = 0.021) or femoral catheter (4.7 L/min/m(2), p = 0.005). By contrast, CI was significantly higher in children under 12 months (4.2 vs. 3.6 L/min/m(2), p = 0.034) and weighing under 10 kg (4.2 vs. 3.6 L/min/m(2), p = 0.026). No significant differences were observed between cardiac surgery patients and the rest of children. A high percentage of CI measurements registered by PRAM were outside normal limits in hemodynamically stable, critically ill children. CI measured by PRAM may be influenced by the age, weight, location of catheter, and presence of a dicrotic notch.

Population pharmacokinetics of omeprazole in critically ill pediatric patients.

BACKGROUND: To develop a population pharmacokinetic model for intravenous omeprazole in critically ill children. METHODS: One hundred eighty-six omeprazole concentration-time data from 40 critically ill children were analyzed using the nonlinear mixed-effects approach with the nonlinear mixed-effects modeling software, version 7.2 software. Patients were randomized into 2 groups and received intravenous omeprazole at a dose of 0.5 or 1 mg/kg twice daily. Blood samples were drawn at 0.5, 2, 6, 12, 24, and 48 hours after the first infusion. RESULTS: The pharmacokinetic profile was best described by a 2-compartment model with a first-order elimination process. Between-patient variability could only be associated with plasma clearance (CL). The typical values for plasma CL were 24.9 L·h·70 kg (10.08%), with a distributional clearance of 53.9 L·h·70 kg (11.00%) and central and peripheral compartment distribution volumes of 4.23 L/70 kg (19.62%) and 674 L/70 kg (0.89%), respectively. Allometric size models seemed to predict changes adequately in all the pharmacokinetic parameters. High values of between-patient variability of CL [75.50% (2.60%)] and residual variability [130.0% (5.26%)] were still found in the final model. Model-based simulations suggested that the most suitable dose was 1 mg/kg because this yielded similar exposure (defined by the area under the concentration-time curve) to that obtained in adults after a 20-mg dose of omeprazole intravenously. CONCLUSIONS: An allometric size model allows changes to be predicted in all the pharmacokinetic parameters, making dose adjustment by body weight important to achieve the most effective omeprazole exposure. This is the first step toward a population pharmacokinetic study, including more data to develop a predictable model to be used during therapeutic drug monitoring.

Relationship between hyperglycemia, hormone disturbances, and clinical evolution in severely hyperglycemic post surgery critically ill children: an observational study.

BACKGROUND: To study hormonal changes associated with severe hyperglycemia in critically ill children and the relationship with prognosis and length of stay in intensive care. METHODS: Observational study in twenty-nine critically ill children with severe hyperglycemia defined as 2 blood glucose measurements greater than 180 mg/dL. Severity of illness was assessed using pediatric index of mortality (PIM2), pediatric risk of mortality (PRISM) score, and pediatric logistic organ dysfunction (PELOD) scales. Blood glucose, glycosuria, insulin, C-peptide, cortisol, corticotropin, insulinlike growth factor-1, growth hormone, thyrotropin, thyroxine, and treatment with insulin were recorded. ß-cell function and insulin sensitivity and resistance were determined on the basis of the homeostatic model assessment (HOMA), using blood glucose and C-peptide levels. RESULTS: The initial blood glucose level was 249 mg/dL and fell gradually to 125 mg/dL at 72 hours. Initial ß-cell function (49.2%) and insulin sensitivity (13.2%) were low. At the time of diagnosis of hyperglycemia, 50% of the patients presented insulin resistance and ß-cell dysfunction, 46% presented isolated insulin resistance, and 4% isolated ß-cell dysfunction. ß-cell function improved rapidly but insulin resistance persisted. Initial glycemia did not correlate with any other factor, and there was no relationship between glycemia and mortality. Patients who died had higher cortisol and growth hormone levels at diagnosis. Length of stay was correlated by univariate analysis, but not by multivariate analysis, with C-peptide and glycemic control at 24 hours, insulin resistance, and severity of illness scores. CONCLUSIONS: Critically ill children with severe hyperglycemia initially present decreased ß-cell function and insulin sensitivity. Nonsurvivors had higher cortisol and growth hormone levels and developed hyperglycemia later than survivors.

Neurological symptoms in hospitalised patients: do we assess hyponatraemia with sufficient care?

AIM: To review the incidence of hyponatraemic encephalopathy in children treated in a tertiary care centre hospital, together with the clinical setting and clinical management of these cases. METHODS: Retrospective descriptive study by chart review of patients admitted to hospital during 2000-2010. Patients older than 1 month were included who had severe hyponatraemia (sodium concentration <125 mmol/L) on admission or during their hospital stay and co-incidental neurological symptoms. Epidemiological, clinical, laboratory and therapeutic data were collected. RESULTS: We analysed 41 cases of severe hypotonic hyponatraemia and neurological symptoms compatible with hyponatraemic encephalopathy. Boys accounted for 56.1% patients, and the median age was 1 year. Hyponatraemia was acquired in hospital by 61% of the patients, and 88% of those patients were receiving intravenous hypotonic fluids. The most frequent neurological symptom was seizures. The most common therapeutic strategy was sodium supplementation and antiepileptic drugs. Hypertonic fluids were only used in the initial treatment of 16 patients. There were two deaths related to hyponatraemic encephalopathy. CONCLUSION: Hyponatraemia should always be considered a cause of neurological symptoms in hospitalised patients. Treatment should be prompt to prevent neurological sequelae and death. Current recommendations for fluid management in hospitalised children should be reviewed.

Can Glatiramer Acetate Prevent Cognitive Impairment by Modulating Oxidative Stress in Patients with Multiple Sclerosis?

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and neuroinflammation, often accompanied by cognitive impairment. This study aims (1) to investigate the potential of glatiramer acetate (GA) as a therapy for preventing cognitive decline in patients with MS (pwMS) by modulating oxidative stress (OS) and (2) to seek out the differences in cognition between pwMS in a cohort exhibiting good clinical evolution and control subjects (CS). An exploratory, prospective, multicentre, cross-sectional case-control study was conducted, involving three groups at a 1:1:1 ratio-41 GA-treated pwMS, 42 untreated pwMS, and 42 CS. The participants performed a neuropsychological battery and underwent venepuncture for blood sampling. The inclusion criteria required an Expanded Disability Status Scale score of ≤3.0 and a minimum of 5 years of MS disease. Concerning cognition, the CS had a better performance than the pwMS (p = <0.0001), and between those treated and untreated with GA, no statistically significant differences were found. Regarding oxidation, no statistically significant differences were detected. Upon categorizing the pwMS into cognitively impaired and cognitively preserved groups, the lactate was elevated in the pwMS with cognitive preservation (p = 0.038). The pwMS exhibited a worse cognitive performance than the CS. The pwMS treated with GA did not show an improvement in oxidation. Lactate emerged as a potential biomarker for cognitive preservation.

0.5 mg/kg versus 1 mg/kg of intravenous omeprazole for the prophylaxis of gastrointestinal bleeding in critically ill children: a randomized study.

OBJECTIVE: To compare the effect of 2 doses of intravenous omeprazole on gastric pH, gastrointestinal bleeding, and adverse effects in critically ill children. STUDY DESIGN: We undertook a prospective randomized clinical trial in critically ill children at risk of gastrointestinal bleeding. The effect of 2 intravenous omeprazole regimens (0.5 or 1 mg/kg every 12 hours) on the gastric pH and incidence of gastrointestinal hemorrhage was compared. The efficacy criteria were a gastric pH >4 and the absence of clinically significant gastrointestinal bleeding. RESULTS: Forty patients, 20 in each treatment group, were studied. Overall, the gastric pH was greater than 4 for 57.8% of the time, with no difference between the doses (P = .66). The percentage of time with a gastric pH > 4 increased during the study (47.8% between 0 and 24 hours vs 76% between 24 and 48 hours, P = .001); the greater dose showed a greater increase in the percentage of time with a pH > 4: between hours 24 and 48 of the study, the gastric pH was greater than 4 for 84.5% of the time with the 1 mg/kg dose and for 65.5% of the time with the 0.5 mg/kg dose (P = .036). Plasma omeprazole levels were greater with 1 mg/kg dose, but no correlation was found between omeprazole plasma levels and gastric pH. No toxic adverse effects were detected, and there was no clinically significant bleeding. CONCLUSION: Neither of the 2 omeprazole regimens achieved adequate alkalinization of the gastric pH during the first 24 hours. Between 24 and 48 hours, the 1 mg/kg dose maintained the gastric pH greater than 4 for a greater percentage of the time.

Prevalence, Risk Factors and Impact of Nutrition Interruptions in Critically Ill Children.

Background: Enteral nutrition interruptions (ENI) are prevalent in the pediatric intensive care unit (PICU), but there is little evidence of their characteristics. Methods: This is a cross-sectional multicenter study including critically ill children on enteral nutrition. ENIs were classified as PICU procedures, procedures performed outside the PICU (PPOP), feeding intolerance and other criteria. The number and features of ENIs were collected. Results: A total of 75 children were enrolled. There were 41 interruptions affecting 37.3% of the patients with a median duration of 5 ± 9.4 h. The most common reason for ENI was PPOP (41.5%), followed by other criteria. Interruptions were considered preventable in 24.4% of the cases, but only eight were compensated. ENIs were more prevalent among children with cardiac disease (p = 0.047), higher PRISM (p = 0.047) and longer PICU stay (p = 0.035). There was association between PRISM and total interruption time (p = 0.02) and lower caloric intake (p = 0.035). Patients with respiratory illness (p = 0.022) and on noninvasive ventilation (p = 0,028) had fewer ENIs. ENI total time was associated with lower caloric (p = 0.001) and protein (p = 0.02) intake. Conclusions: ENIs are prevalent in PICU, especially in children with higher PRISM, longer PICU stays and cardiac disease, and result in lower caloric and protein intake.

A prospective study of cellular immune response to booster COVID-19 vaccination in multiple sclerosis patients treated with a broad spectrum of disease-modifying therapies.

BACKGROUND: Most people with Multiple Sclerosis (pwMS) are subjected to immunomodulatory disease-modifying treatments (DMTs). As a result, immune responses to COVID-19 vaccinations could be compromised. There are few data on cellular immune responses to the use of COVID-19 vaccine boosters in pwMS under a broad spectrum of DMTs. METHODS: In this prospective study, we analysed cellular immune responses to SARS-CoV-2 mRNA booster vaccinations in 159 pwMS with DMT, including: ocrelizumab, rituximab, fingolimod, alemtuzumab, dimethyl fumarate, glatiramer acetate, teriflunomide, natalizumab and cladribine. RESULTS: DMTs, and particularly fingolimod, interact with cellular responses to COVID-19 vaccination. One booster dose does not increase cellular immunity any more than two doses, except in the cases of natalizumab and cladribine. SARS-CoV-2 infection combined with two doses of vaccine resulted in a greater cellular immune response, but this was not observed after supplementary booster jabs. Ocrelizumab-treated pwMS who had previously received fingolimod did not develop cellular immunity, even after receiving a booster. The time after MS diagnosis and disability status negatively correlated with cellular immunity in ocrelizumab-treated pwMS in a booster dose cohort. CONCLUSIONS: After two doses of SARS-CoV-2 vaccination, a high response yield was achieved, except in patients who had received fingolimod. The effects of fingolimod on cellular immunity persisted for more than 2 years after a change to ocrelizumab (which, in contrast, conserved cellular immunity). Our results confirmed the need to find alternative protective measures for fingolimod-treated people and to consider the possible failure to provide protection against SARS-CoV-2 when switching from fingolimod to ocrelizumab.

Early vs late enteral nutrition in pediatric intensive care unit: Barriers, benefits, and complications.

BACKGROUND: This study aimed to define the existing barriers for early enteral nutrition (EEN) in critically ill children and to analyze the differences in nutrient supply, complications, and outcomes between EEN and late EN (LEN). METHODS: This is a secondary analysis of a multicenter observational, prospective study including critically ill children receiving EN. Variables analyzed included demographic and anthropometric features, caloric and nutrient supply, outcomes, and complications according to the EN onset. Patients were classified into two groups according to the start of EN: 24-EEN vs EN started after 24 h (24-LEN) and 48-EEN vs EN started after 48 h (48-LEN). RESULTS: Sixty-eight children were enrolled; 22.1% received 24-EEN, and 67.6% received 48-EEN. EN was most frequently delayed in patients older than 12 months, in patients with cardiac disease, and in those requiring mechanical ventilation (MV). Children in the 24-EEN group had shorter duration of MV compared with those in the 24-LEN group (P = 0.04). The 48-EEN group received a higher caloric intake (P = 0.04), reached the caloric target earlier (P < 0.01), and had lower incidence of constipation (P = 0.01) than the 48-LEN group. There was a positive correlation between the time required to reach the maximum caloric intake and the length of pediatric intensive care stay (r = 0.46; P < 0.01). CONCLUSION: EEN may improve nutrient delivery, reduce time on MV, and prevent constipation in critically ill children. No relevant differences between 24-EEN and 48-EEN were found. Cardiac disease, MV, and age older than 12 months were risk factors associated with LEN.

Volumetric capnography and return of spontaneous circulation in an experimental model of pediatric asphyxial cardiac arrest.

A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation (CPR) and to analyze the ability of these parameters to predict the return of spontaneous circulation (ROSC) in a pediatric animal model of asphyxial cardiac arrest (CA). Asphyxial CA was induced by sedation, muscle relaxation and extubation. CPR was started 2 min after CA occurred. Airway management was performed with early endotracheal intubation or bag-mask ventilation, according to randomization group. CPR was continued until ROSC or 24 min of resuscitation. End-tidal carbon dioxide (EtCO2), CO2 production (VCO2), and EtCO2/VCO2/kg ratio were continuously recorded. Seventy-nine piglets were included, 26 (32.9%) of whom achieved ROSC. EtCO2 was the best predictor of ROSC (AUC 0.72, p < 0.01 and optimal cutoff point of 21.6 mmHg). No statistical differences were obtained regarding VCO2, VCO2/kg and EtCO2/VCO2/kg ratios. VCO2 and VCO2/kg showed an inverse correlation with PCO2, with a higher correlation coefficient as resuscitation progressed. EtCO2 also had an inverse correlation with PCO2 from minute 18 to 24 of resuscitation. Our findings suggest that EtCO2 is the best VCAP-derived parameter for predicting ROSC. EtCO2 and VCO2 showed an inverse correlation with PCO2. Therefore, these parameters are not adequate to measure ventilation during CPR.

Seroprevalence of SARS-CoV-2 in Patients with Multiple Sclerosis under Disease-Modifying Therapies: A Multi-Centre Study.

BACKGROUND: The EMCOVID project conducted a multi-centre cohort study to investigate the impact of COVID-19 on patients with Multiple Sclerosis (pwMS) receiving disease-modifying therapies (DMTs). The study aimed to evaluate the seroprevalence and persistence of SARS-CoV-2 antibodies in MS patients enrolled in the EMCOVID database. The DMTs were used to manage MS by reducing relapses, lesion accumulation, and disability progression. However, concerns arose regarding the susceptibility of pwMS to COVID-19 due to potential interactions between SARS-CoV-2 and the immune system, as well as the immunomodulatory effects of DMTs. METHODS: This prospective observational study utilized data from a Multiple Sclerosis and COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data, SARS-CoV-2 serology, and symptoms of COVID-19 were extracted for pwMS receiving any type of DMT. The relationship between demographics, MS phenotype, DMTs, and COVID-19 was evaluated. The evolution of SARS-CoV-2 antibodies over a 6-month period was also assessed. RESULTS: The study included 709 pwMS, with 376 patients providing samples at the 6-month follow-up visit. The seroprevalence of SARS-CoV-2 antibodies was higher among pwMS than the general population, with Interferon treatment being significantly associated with greater seroprevalence (16.9% vs. 8.4%; p 0.003). However, no other specific DMT showed a significant association with antibody presence. A total of 32 patients (8.5%) tested positive for IgG, IgM, or IgA antibodies against SARS-CoV-2 at baseline, but then tested negative at 6 months. Most of the pwMS in the cohort were asymptomatic for COVID-19 and, even among symptomatic cases, the prognosis was generally favourable. CONCLUSION: pwMS undergoing DMTs exhibited a higher seroprevalence of COVID-19 than the general population. Interferon treatment was associated with a higher seroprevalence, suggesting a more robust humoral response. This study provides valuable insights into the seroprevalence and persistence of SARS-CoV-2 antibodies in pwMS and contributes to our understanding of the impact of COVID-19 amongst this population.

Seroprevalence of SARS-CoV-2 in a Cohort of Patients with Multiple Sclerosis under Disease-Modifying Therapies.

Background: Disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS) alter the immune system and therefore increase the risk of infection. There is growing concern about the impact of COVID-19 on patients with MS (pwMS), especially those treated with DMTs. Methods: This is a single-center prospective observational study based on data from the Esclerosis Múltiple y COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data and SARS-CoV-2 serology, and symptoms of COVID-19 in pwMS treated with any DTM were extracted. The relationship among demographics, MS status, DMT, and COVID-19 was evaluated. Results: A total of 259 pwMS were included. The administration of interferon was significantly associated with the presence of SARS-CoV-2 antibodies (26.4% vs. 10.7%, p = 0.006). Although patients taking interferon were significantly older (49.1 vs. 43.5, p = 0.003), the association of interferon with the presence of SARS-CoV-2 antibodies was still significant in the multivariate analysis (OR 2.99 (1.38; 6.36), p = 0.006). Conclusions: According to our data, pwMS present a higher risk of COVID-19 infection compared with results obtained from the general population. There is no evidence of a worse COVID-19 outcome in pwMS. DMTs did not significantly change the frequency of COVID-19, except for interferon; however, these findings must be interpreted with caution given the small sample of pwMS taking each DMT.

Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.

OBJECTIVE: To compare a standard diet and a protein-enriched diet in critically ill children. STUDY DESIGN: In this prospective randomized controlled trial in critically ill children, all patients received enteral nutrition exclusively and were randomly assigned to a standard diet or a protein-enriched diet (1.1 g protein/100 mL of feeding formula). Blood and urine tests, nitrogen balance assessment, and energy expenditure testing by indirect calorimetry were performed before the beginning of the nutrition regimen and at 24 hours, 72 hours, and 5 days after initiation. Demographic data and pediatric mortality risk scores were recorded. RESULTS: Fifty-one children were randomized, and 41 completed the study. Of these, 21 patients received standard formula and 20 received a protein-enriched formula. There were no between-group differences in terms age, sex, diagnosis, or mortality risk scores. There was a greater positive trend in levels of prealbumin, transferrin, retinol-binding protein, and total protein in the protein-enriched diet group. These differences were significant only for retinol-binding protein. The positive nitrogen balance trend was also higher in the protein-enriched diet group; however, this difference did not reach statistical significance. No adverse effects or hyperproteinemia were detected in the protein-enriched diet group. CONCLUSIONS: The standard diet provides insufficient protein delivery to critically ill children. Enteral protein supplementation is safe and can improve some biochemical parameters of protein metabolism.

Relationship between energy expenditure, nutritional status and clinical severity before starting enteral nutrition in critically ill children.

The objective of the present study was to investigate the relationship between energy expenditure (EE), biochemical and anthropometric nutritional status and severity scales in critically ill children. We performed a prospective observational study in forty-six critically ill children. The following variables were recorded before starting nutrition: age, sex, diagnosis, weight, height, risk of mortality according to the Paediatric Risk Score of Mortality (PRISM), the Revised Paediatric Index of Mortality (PIM2) and the Paediatric Logistic Organ Dysfunction (PELOD) scales, laboratory parameters (albumin, total proteins, prealbumin, transferrin, retinol-binding protein, cholesterol and TAG, and nitrogen balance) and EE measured by indirect calorimetry. The results showed that there was no relationship between EE and clinical severity evaluated using the PRISM, PIM2 and PELOD scales or with the anthropometric nutritional status or biochemical alterations. Finally, it was concluded that neither nutritional status nor clinical severity is related to EE. Therefore, EE must be measured individually in each critically ill child using indirect calorimetry.

Neostigmine in the treatment of refractory constipation in critically ill children.

Constipation is a common complication in critically ill children and it is occasionally resistant to the drugs typically used in treatment. Neostigmine has been used in some cases of refractory constipation in critically ill adults. There is no reference to its use in critically ill children. We describe 3 cases of refractory constipation in critically ill children treated with intravenous neostigmine by continuous infusion. Two patients responded well. There were no adverse effects. We conclude that continuous intravenous neostigmine can be effective in critically ill children with refractory constipation. Further studies are necessary to determine the dose and safety of the treatment.