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.

Effects of Vortioxetine on Cognition and Fatigue in Patients with Multiple Sclerosis and Depression: A Case Series Study.

INTRODUCTION: Vortioxetine is a multimodal antidepressant drug that has been reported to have a positive impact on cognition, social function, and fatigue. Nevertheless, it has not been widely studied. Our objective was to explore the effects of vortioxetine on these and other parameters in patients with multiple sclerosis (MS) and depression. PATIENTS AND METHODOLOGY: This observational case series study included patients with MS and depression who received treatment with vortioxetine for at least 6 months. The patient history of depression and depressive symptoms was assessed. A neuropsychiatric evaluation was carried out using different scales, both before and after treatment. RESULTS: Of the 25 patients who enrolled in the study, 17 completed the treatment. Significant improvements were observed in health status (EQ-5D; p = 0.002), mood (Beck's Depression Inventory, BDI-II; p = 0.006), anxiety (State-Trait Anxiety Inventory, STAI-State; p = 0.021, and STAI-Trait; p = 0.011), and in the general health test (Short Form Health Survey, SF-36) for the vitality (p = 0.028) and mental health (p = 0.025) domains of the patients who completed the treatment. However, no statistically significant differences were observed in the cognitive tests related to attention, information processing speed, or fatigue. CONCLUSION: In this population, vortioxetine treatment was effective in reducing the symptoms of depression and improving anxiety, vitality, and mental health. In contrast, it did not produce any improvement in cognition or fatigue but an increase in sample size would be necessary to confirm these results.

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.

Protocolo de tratamiento con polietilenglicol 3350 con electrolitos para el estreñimiento en el niño crítico / Protocol for treatment of constipation with polyethylene glycol 3350 plus electrolytes in critically ill children

Introducción y objetivos: Ningún estudio ha analizado la efectividad del tratamiento del estreñimiento en niños críticamente enfermos. El objetivo de este estudio fue evaluar la implementación, la eficacia y la seguridad de un protocolo de tratamiento con polietilenglicol 3350 con electrolitos (PEG 3350+E) para el estreñimiento en niños en estado crítico. Métodos: Estudio prospectivo unicéntrico, incluyendo niños que ingresaron en cuidados intensivos pediátricos durante más de 72h y que desarrollaron estreñimiento. Se excluyeron los niños con trastornos o afecciones gastrointestinales previas. Los pacientes fueron tratados con enemas rectales o con PEG 3350+E oral a criterio del médico tratante. Se compararon variables clínicas, demográficas y efectos secundarios (diarrea, distensión abdominal y desequilibrio electrolítico). Resultados: Se estudiaron 56 pacientes de 48,2±11,9 meses de edad, siendo el 55,4% varones. Cuarenta y cuatro pacientes (78,6%) fueron tratados con PEG 3350+E y 12 pacientes (21,4%) con enemas rectales. El porcentaje de efectividad del PEG 3350+E (79,5%) fue mayor que el de los enemas (58,3%), pero la diferencia no fue estadísticamente significativa (p=0,151). No existieron diferencias significativas en ninguno de los efectos secundarios entre los 2 grupos. El PEG 3350+E fue más efectivo en los niños menores de 2 años (100%) que en los mayores de esa edad (65,4%), p<0,01, sin diferencias significativas en la aparición de efectos secundarios. Conclusiones: El tratamiento del estreñimiento en los niños en estado crítico con PEG 3350+E es eficaz y tiene pocos efectos secundarios, incluso en niños menores de 2 años. (AU)

Introduction and objectives: No studies have analysed the effectiveness of treatment for constipation in critically ill children. The aim of this study was to assess the implementation, efficacy and safety of a treatment protocol using polyethylene glycol 3350 with electrolytes (PEG 3350+E) for constipation in critically ill children. Methods: We conducted a single-centre prospective study in children admitted to the paediatric intensive care unit for a minimum of 72h and who developed constipation. Children with previous gastrointestinal disorders or diseases were excluded. The patients were treated with rectal enemas or with the oral PEG 3350+E protocol at the discretion of the treating physician. We compared clinical and demographic variables as well as adverse events (diarrhoea, abdominal distension and electrolyte imbalances). Results: The sample included 56 patients with a mean age of 48.2±11.9 months, of who 55.4% were male. Forty-four patients (78.6%) were treated with PEG 3350+E and 12 (21.4%) with rectal enemas. The proportion of patients who responded well to treatment was greater in the PEG 3350+E group (79.5%) compared to the enema group (58.3%), but the difference was not statistically significant (P=.151). There were no significant differences between the groups in any of the adverse effects. Treatment with PEG 3350+E was more effective in children aged less than 2 years (100%) compared to older children (100% vs. 65.4%; P<.01), with no significant differences in the development of adverse events. Conclusions: The PEG 3350+E treatment protocol for constipation in critically ill children was effective and associated with few adverse events, even in children aged less than 2 years. (AU)

Protocol for treatment of constipation with polyethylene glycol 3350 plus electrolytes in critically ill children.

INTRODUCTION AND OBJECTIVES: No studies have analysed the effectiveness of treatment for constipation in critically ill children. The aim of this study was to assess the implementation, efficacy and safety of a treatment protocol using polyethylene glycol 3350 with electrolytes (PEG 3350 + E) for constipation in critically ill children. METHODS: We conducted a single-centre prospective study in children admitted to the paediatric intensive care unit for a minimum of 72 h and who developed constipation. Children with previous gastrointestinal disorders or diseases were excluded. The patients were treated with rectal enemas or with the oral PEG 3350 + E protocol at the discretion of the treating physician. We compared clinical and demographic variables as well as adverse events (diarrhoea, abdominal distension and electrolyte imbalances). RESULTS: The sample included 56 patients with a mean age of 48.2 ±â€¯11.9 months, of who 55.4% were male. Forty-four patients (78.6%) were treated with PEG 3350 + E and 12 (21.4%) with rectal enemas. The proportion of patients that responded well to treatment was greater in the PEG 3350 + E group (79.5%) compared to the enema group (58.3%), but the difference was not statistically significant (P = .151). There were no significant differences between the groups in any of the adverse effects. Treatment with PEG 3350 + E was more effective in children aged less than 2 years (100%) compared to older children (100% vs 65.4%; P < .01), with no significant differences in the development of adverse events. CONCLUSIONS: The PEG 3350 + E treatment protocol for constipation in critically ill children was effective and associated with few adverse events, even in children aged less than 2 years.

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.

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.

Beef Nutritional Characteristics, Fat Profile and Blood Metabolic Markers from Purebred Wagyu, Crossbred Wagyu and Crossbred European Steers Raised on a Fattening Farm in Spain.

A high intramuscular fat content characterizes Wagyu (WY) cattle breed. Our objective was to compare beef from WY, WY-by-Angus, or Wangus (WN) steers with European, Angus-by-Charolais-Limousine crossbred steers (ACL), considering metabolic biomarkers pre-slaughtering and nutritional characteristics, including health-related indexes of the lipid fraction. The fattening system with olein-rich diets and no exercise restriction included 82 steers, 24 WY, 29 WN, and 29 ACL. The slaughter ages and weights were (median and interquartile range) 38.4 mo.-old (34.9-40.3 mo.) and 840 kg (785-895 kg) for WY; for WN, 30.6 mo. (26.9-36.5 mo.) and 832 kg (802-875 kg), and for ACL steers, 20.3 mo.-old (19.0-22.7 mo.) and 780 kg (715-852 kg). Blood lipid-related metabolites, except for non-esterified fatty acids (NEFA) and low-density level cholesterol (LDL), were higher in WY and WN than in ACL, while glucose was lower in WY and WN. Leptin was higher in WN than in ACL. Pre-slaughtering values of plasma HDL underscored as a possible metabolic biomarker directly related to beef quality. The amino-acid content in beef did not differ among experimental groups, except for more crude protein in ACL. Compared to ACL, WY steers showed higher intramuscular fat in sirloin (51.5 vs. 21.9%) and entrecote (59.6 vs. 27.6%), more unsaturated fatty acids in entrecote (55.8 vs. 53.0%), and more oleic acid in sirloin (46 vs. 41.3%) and entrecote (47.5 vs. 43.3%). Compared to ACL entrecote, WY and WN showed better atherogenic (0.6 and 0.55 vs. 0.69), thrombogenicity (0.82 and 0.92 vs. 1.1), and hypocholesterolemic/hypercholesterolemic index (1.9 and 2.1 vs. 1.7). Therefore, beef's nutritional characteristics depend on breed/crossbred, slaughtering age and cut, with WY and WN entrecote samples showing a healthier lipid fraction.

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.

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.

Comparison of Pure and Crossbred Japanese Black Steers in Growth Performance and Metabolic Features from Birth to Slaughter at a Spanish Fattening Farm.

Japanese Black (Wagyu) cattle produce high-quality beef. However, whether Wagyu steers can be profitably raised under conditions different than the traditional Japanese ones remains unclear. From 2018 to 2020, we raised 262 Wagyu purebred steers, 103 Wagyu-by-Angus (Wangus) crossbred steers, and 43 Angus-by-European (ACL) crossbred steers on a Spanish farm with high welfare standards and a locally sourced, high-olein diet. Factors and factors' interactions impacting steer growth were analyzed using generalized linear models. ACL steers grew faster than the other two groups, with Wangus showing intermediate fattening and muscle development. Average daily weight gains (kg/day) were 0.916 for Wagyu, 1.046 for Wangus, and 1.293 for ACL during the weaning to growing period, and 0.628 for Wagyu, 0.64 for Wangus, and 0.802 for ACL during the growing to fattening phase. ACL showed the lowest marbling rates. Wagyu and Wangus usually showed higher cholesterol, triglycerides, and high-density lipoprotein than ACL. ACL calves may experience greater stress at weaning, as suggested by higher glucose, lactate, and ß-hydroxybutyrate than the other groups. The results suggest that Wagyu and Wangus steers showed adequate growth, health, and metabolic development in this type of production system, with Wagyu purebreds probably being more profitable than Wangus crossbreeds.

Miltefosine and Benznidazole Combination Improve Anti-Trypanosoma cruzi In Vitro and In Vivo Efficacy.

Drug repurposing and combination therapy have been proposed as cost-effective strategies to improve Chagas disease treatment. Miltefosine (MLT), a synthetic alkylphospholipid initially developed for breast cancer and repositioned for leishmaniasis, is a promising candidate against Trypanosoma cruzi infection. This study evaluates the efficacy of MLT as a monodrug and combined with benznidazole (BZ) in both in vitro and in vivo models of infection with T. cruzi (VD strain, DTU TcVI). MLT exhibited in vitro activity on amastigotes and trypomastigotes with values of IC50 = 0.51 µM (0.48 µM; 0,55 µM) and LC50 = 31.17 µM (29.56 µM; 32.87 µM), respectively. Drug interaction was studied with the fixed-ration method. The sum of the fractional inhibitory concentrations (ΣFICs) resulted in ∑FIC= 0.45 for trypomastigotes and ∑FIC= 0.71 for amastigotes, suggesting in vitro synergistic and additive effects, respectively. No cytotoxic effects on host cells were observed. MLT efficacy was also evaluated in a murine model of acute infection alone or combined with BZ. Treatment was well tolerated with few adverse effects, and all treated animals displayed significantly lower mean peak parasitemia and mortality than infected non-treated controls (p<0.05). The in vivo studies showed that MLT led to a dose-dependent parasitostatic effect as monotherapy which could be improved by combining with BZ, preventing parasitemia rebound after a stringent immunosuppression protocol. These results support MLT activity in clinically relevant stages from T. cruzi, and it is the first report of positive interaction with BZ, providing further support for evaluating combined schemes using MLT and exploring synthetic alkylphospholipids as drug candidates.

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.

Doppler ultrasound in the assessment of renal perfusion before and during continuous kidney replacement therapy in the pediatric intensive care unit.

BACKGROUND: This study aimed to assess observer variability and describe renal resistive index (RRI) and pulsatility index (PI) before and after onset of continuous kidney replacement therapy (CKRT). A secondary objective was to correlate Doppler ultrasound findings with those from direct measurement of renal blood flow (RBF). METHODS: This is a prospective observational study in hemodynamically stable Maryland piglets with and without acute kidney injury (AKI) and in hemodynamically unstable critically ill children requiring CKRT. Doppler-based RRI and PI were assessed for each subject. Measurements were made by two different operators (pediatric intensivists) before and after CKRT onset. RESULTS: Observer variability assessment in the measurement of RRI and PI rendered a moderate correlation for both RRI (ICC 0.65, IQR 0.51-0.76) and PI (ICC 0.63, IQR 0.47-0.75). RRI and PI showed no correlation with RBF or urine output. Baseline RRI and PI were normal in control piglets [RRI 0.68 (SD 0.02), PI 1.25 (SD 0.09)] and those with AKI [RRI 0.68 (SD 0.03), PI 1.20 (SD 0.13)]. Baseline RRI and PI were elevated in critically ill children (RRI 0.85, PI 2.0). PI and RRI did not change with CKRT in any study group. CONCLUSIONS: Observer variability between inexperienced pediatric intensivists was comparable with that between senior and junior operators. Doppler-based calculations did not correlate with invasive measurements of RBF. RRI and PI were normal in hemodynamically stable piglets with and without AKI. RRI and PI were high in hemodynamically unstable patients requiring CKRT. RRI and PI did not change after CKRT onset, despite changes in hemodynamic status. A higher resolution version of the Graphical abstract is available as Supplementary information.

MOET Efficiency in a Spanish Herd of Japanese Black Heifers and Analysis of Environmental and Metabolic Determinants.

Multiple ovulation and embryo transfer (MOET) systems have been intensively implemented in Japanese Black cattle in Japan and to create Japanese Black herds out of these areas. Environmental conditions influence MOET efficiency. Thus, we describe results of 137 in vivo, non-surgical embryo flushings performed between 2016-2020, in a full-blood Japanese Black herd kept in Spain and the possible effects of heat, year, bull, donor genetic value, and metabolic condition. Additionally, 687 embryo transfers were studied for conception rate (CR) and recipient related factors. A total of 71.3% of viable embryos (724/1015) were obtained (5.3 ± 4.34/flushing). Donor metabolites did not affect embryo production (p > 0.1), although metabolite differences were observed over the years, and by flushing order, probably related to the donor age. CR was not affected by embryo type (fresh vs. frozen), recipient breed, and whether suckling or not suckling (p > 0.1). CR decreased significantly with heat (44.3 vs. 49.2%; (p = 0.042)) and numerically increased with recipient parity and ET-number. Pregnant recipients showed significantly higher levels of cholesterol-related metabolites, glucose, and urea (p < 0.05). Therefore, adequate MOET efficiency can be achieved under these conditions, and heat stress should be strongly avoided during Japanese Black embryo transfers. Moreover, recipients' metabolites are important to achieve pregnancy, being probably related to better nutrient availability during pregnancy.

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.

Effects of airway management and tidal volume feedback ventilation during pediatric resuscitation in piglets with asphyxial cardiac arrest.

To compare the effect on the recovery of spontaneous circulation (ROSC) of early endotracheal intubation (ETI) versus bag-mask ventilation (BMV), and expiratory real-time tidal volume (VTe) feedback (TVF) ventilation versus without feedback or standard ventilation (SV) in a pediatric animal model of asphyxial cardiac arrest. Piglets were randomized into five groups: 1: ETI and TVF ventilation (10 ml/kg); 2: ETI and TVF (7 ml/kg); 3: ETI and SV; 4: BMV and TVF (10 ml/kg) and 5: BMV and SV. Thirty breaths-per-minute guided by metronome were given. ROSC, pCO2, pO2, EtCO2 and VTe were compared among groups. Seventy-nine piglets (11.3 ± 1.2 kg) were included. Twenty-six (32.9%) achieved ROSC. Survival was non-significantly higher in ETI (40.4%) than BMV groups (21.9%), p = 0.08. No differences in ROSC were found between TVF and SV groups (30.0% versus 34.7%, p = 0.67). ETI groups presented lower pCO2, and higher pO2, EtCO2 and VTe than BMV groups (p < 0.05). VTe was lower in TVF than in SV groups and in BMV than in ETI groups (p < 0.05). Groups 1 and 3 showed higher pO2 and lower pCO2 over time, although with hyperventilation values (pCO2 < 35 mmHg). ETI groups had non significantly higher survival rate than BMV groups. Compared to BMV groups, ETI groups achieved better oxygenation and ventilation parameters. VTe was lower in both TVF and BMV groups. Hyperventilation was observed in intubated animals with SV and with 10 ml/kg VTF.

Hemodynamic disturbances and oliguria during continuous kidney replacement therapy in critically ill children.

BACKGROUND: About 1.5% of patients admitted to the Pediatric Intensive Care Unit (PICU) will require continuous kidney replacement therapy (CKRT)/renal replacement therapy (CRRT). Mortality of these patients ranges from 30 to 60%. CKRT-related hypotension (CKRT-RHI) can occur in 19-45% of patients. Oliguria after onset of CKRT is also common, but to date has not been addressed directly in the scientific literature. METHODS: A prospective observational study was conducted to define factors involved in the hemodynamic changes that take place during the first hours of CKRT, and their relationship with urinary output. RESULTS: Twenty-five patients who were admitted to a single-center PICU requiring CKRT between January 1, 2014, and December 31, 2018, were included, of whom 56.3% developed CKRT-RHI. This drop in blood pressure was transient and rapidly restored to baseline, and significantly improved after the third hour of CKRT, as core temperature and heart rate decreased. Urine output significantly decreased after starting CKRT, and 72% of patients were oliguric after 6 h of therapy. Duration of CKRT was significantly longer in patients presenting with oliguria than in non-oliguric patients (28.7 vs. 7.9 days, p = 0.013). CONCLUSIONS: The initiation of CKRT caused hemodynamic instability immediately after initial connection in most patients, but had a beneficial effect on the patient's hemodynamic status after 3 h of therapy, presumably owing to decreases in body temperature and heart rate. Urine output significantly decreased in all patients and was not related to negative fluid balance, patient's hemodynamic status, CKRT settings, or kidney function parameters.