[Medical nutrition therapy in amyotrophic lateral sclerosis - Do we act or react? A case report and multidisciplinary review]. / Tratamiento médico nutricional en la esclerosis lateral amiotrófica: ¿Actuamos o reaccionamos? Un caso clínico y revisión multidisciplinar.

BACKGROUND: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a progressive course. The current prevalence is between 3 and 6 cases/100,000. Malnutrition is closely related to patient prognosis in ALS. The implications of this conditions have been that we should recommend patient care in a multidisciplinary unit. CASE REPORT: the case presented shows the evolution of a patient with ALS. The patient was referred to different clinical departments after neurological evaluation and her nutritional, functional and respiratory status were assessed. There was no nutritional deterioration at diagnosis; however, intake was below energy-protein requirements. The clinical evolution of the patient showed a decrease in muscle mass with preservation of weight and fat mass. "Aggressive" measures to control nutritional status such as gastrostomy were rejected in the initial stages of the disease, but had to be carried out after development of dysphagia and associated malnutrition. This situation of progressive morphofunctional deterioration and the development of disease-related complications made essential the participation of different health services and professionals in its control. DICUSSION: the management of ALS in a multidisciplinary manner allows to improve the course of the disease and the quality of life of both the patients and their families. Patient follow-up is based on the adjustment and management of complications. The basis of the relationship with these patients includes maintaining an adequate communication with them and their families, and ensuring joint decision-making about their condition.

Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis.

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.

Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population.

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

A Simplified Screening Model to Predict the Risk of Gestational Diabetes Mellitus in Caucasian and Latin American Pregnant Women.

The pathophysiology of gestational diabetes mellitus (GDM) comprises clinical and genetic factors. In fact, GDM is associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, including 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT) individuals, and 255 (16.1%) had GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed via IPLEX Mass ARRAY PCR, selecting 110 SNPs based on literature references. SNPs showing the strongest likelihood of developing GDM were rs10830963, rs7651090, and rs1371614 in CAU and rs1387153 and rs9368222 in LAT. Clinical variables, including age, pre-pregnancy body mass index, and fasting plasma glucose (FPG) at 12 gestational weeks, predicted the risk of GDM (AUC 0.648, 95% CI 0.601-0.695 in CAU; AUC 0.688, 95% CI 0.628-9.748 in LAT), and adding SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95% CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women.

Effect of a nutritional intervention based on an energy-reduced Mediterranean diet on environmental impact.

OBJECTIVE: To estimate the environmental impact of a dietary intervention based on an energy-reduced Mediterranean diet (MedDiet) after one year of follow-up. METHODS: Baseline and 1-year follow-up data were used for 5800 participants aged 55-75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT-Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate to what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact. RESULTS: We observed a significant reduction in the intervention group compared to the control group in acidification levels (-13.3 vs. -9.9 g SO2-eq), eutrophication (-5.4 vs. -4.0 g PO4-eq) and land use (-2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %. CONCLUSIONS: A nutritional intervention based on consumption of an energy-reduced MedDiet for one year was associated with an improvement in different environmental quality parameters.

[Consenso del grupo de trabajo de los trastornos de la conducta alimentaria de SENPE (GTTCA-SENPE). Evaluación y tratamiento médico-nutricional en la anorexia nerviosa. Actualización 2023]. / Consenso del grupo de trabajo de los trastornos de la conducta alimentaria de SENPE (GTTCA-SENPE). Evaluación y tratamiento médico-nutricional en la anorexia nerviosa. Actualización 2023.

Anorexia nervosa (AN) is a multifactorial disorder. A possible role of the social network and the gut microbiota in pathogenesis has been added. Exogenous shocks such as the COVID19 pandemic have had a negative impact on patients with AN. The potential medical and nutritional impact of malnutrition and/or compensatory behaviors gives rise to a complex disease with a wide range of severity, the management of which requires a multidisciplinary team with a high level of subject matter expertise. Coordination between levels of care is necessary as well as understanding how to transition the patient from pediatric to adult care is essential. A proper clinical evaluation can detect possible complications, as well as establish the organic risk of the patient. This allows caregivers to tailor the medical-nutritional treatment for each patient. Reestablishing adequate nutritional behaviors is a fundamental pillar of treatment in AN. The design of a personalized nutritional treatment and education program is necessary for this purpose. Depending on the clinical severity, artificial nutrition may be necessary. Although the decision regarding the level of care necessary at diagnosis or during follow-up depends on a number of factors (awareness of the disease, medical stability, complications, suicidal risk, outpatient treatment failure, psychosocial context, etc.), outpatient treatment is the most frequent and most preferred choice. However, more intensive care (total or partial hospitalization) may be necessary in certain cases. In severely malnourished patients, the appearance of refeeding syndrome should be prevented during renourishment. The presence of AN in certain situations (pregnancy, vegetarianism, type 1 diabetes mellitus) requires specific care. Physical activity in these patients must also be addressed correctly.

Nutritional and Morphofunctional Assessment of Post-ICU Patients with COVID-19 at Hospital Discharge: NutriEcoMuscle Study.

This paper presents baseline results from the NutriEcoMuscle study, a multicenter observational study conducted in Spain which focused on changes in nutritional status, body composition, and functionality in post-intensive care unit (ICU) COVID-19 patients following a nutritional intervention. Assessments at hospital discharge included Subjective Global Assessment (SGA), Global Leadership Initiative on Malnutrition (GLIM) criteria, the Barthel index, handgrip strength (HGS) and the Timed Up-and-Go test, bioelectrical impedance analysis (BIA), and nutritional ultrasound (US). The study involved 96 patients (71.9% male, mean age 58.8 years, mean BMI 28.8 kg/m2, 36.5% obese). All patients were malnourished at discharge according to GLIM and SGA. Functional status declined from admission up to hospital discharge. A total of 33.3% of patients had a low fat-free mass index (FFMI) and 29.5% had a low phase angle (PhA). Myosteatosis was observed in 83.7% of the population. There was a positive correlation between rectus femoris cross-sectional area, PhA, FFMI, and HGS. In conclusion, post-critically ill COVID-19 patients commonly suffer from malnutrition and reduced muscle mass, causing a loss of independence at hospital discharge. BIA and US could be valuable tools for assessing body composition in these patients. The NutriEcoMuscle study highlights the need for a thorough nutritional and morphofunctional status assessment of post-ICU patients.

The inflammatory spectrum of cardiomyopathies.

Infiltration of the myocardium with various cell types, cytokines and chemokines plays a crucial role in the pathogenesis of cardiomyopathies including inflammatory cardiomyopathies and myocarditis. A more comprehensive understanding of the precise immune mechanisms involved in acute and chronic myocarditis is essential to develop novel therapeutic approaches. This review offers a comprehensive overview of the current knowledge of the immune landscape in cardiomyopathies based on etiology. It identifies gaps in our knowledge about cardiac inflammation and emphasizes the need for new translational approaches to improve our understanding thus enabling development of novel early detection methods and more effective treatments.

Consenso del Grupo de Trabajo de los Trastornos de la Conducta Alimentaria de SENPE (GTTCA-SENPE). Evaluación y tratamiento médico-nutricional en la anorexia nerviosa.Actualización 2023 / A consensus report by the Working Group on Eating Disorders of Sociedad Española de Nutrición Clínica y Metabolismo (GTTCA-SENPE). Evaluation, medical and nutritional management of anorexia nervosa. Update 2023

La anorexia nerviosa (AN) es una enfermedad de origen multifactorial. Recientemente se ha sumado el papel de las redes sociales y la microbiota intestinal en la patogenia. La pandemia por COVID-19 ha tenido un impacto negativo en los pacientes con AN. La potencial afectación médica y nutricional derivada de la desnutrición o las conductas compensatorias dan lugar a una compleja enfermedad de gravedad variable, cuyo manejo precisa un equipo multidisciplinar con elevado nivel de conocimientos en la materia. Es fundamental la coordinación entre niveles asistenciales y en la transición de pediatría a adultos. Una adecuada valoración clínica permite detectar eventuales complicaciones, así como establecer el riesgo orgánico del paciente y, por tanto, adecuar el tratamiento médico-nutricional de forma individualizada. El restablecimiento de un apropiado estado nutricional es un pilar fundamental del tratamiento en la AN. Para ello es necesario diseñar una intervención de renutrición individualizada que incluya un programa de educación nutricional. Según el escenario clínico puede ser necesaria la nutrición artificial. Aunque la decisión de qué nivel de atención escoger al diagnóstico o durante el seguimiento depende de numerosas variables (conciencia de enfermedad, estabilidad médica, complicaciones, riesgo autolítico, fracaso del tratamiento ambulatorio o contexto psicosocial, entre otros), el tratamiento ambulatorio es de elección en la mayoría de las ocasiones. No obstante, puede ser necesario un escenario más intensivo (hospitalización total o parcial) en casos seleccionados. En pacientes gravemente desnutridos debe prevenirse la aparición de un síndrome de alimentación cuando se inicia la renutrición. La presencia de una AN en determinadas situaciones (gestación, vegetarianismo, diabetes mellitus de tipo 1, etc.) exige un manejo particular. En estos pacientes también debe abordarse de forma correcta el ejercicio físico.(AU)

Anorexia nervosa (AN) is a multifactorial disorder. A possible role of the social network and the gut microbiota in pathogenesis has been added.Exogenous shocks such as the COVID19 pandemic have had a negative impact on patients with AN.The potential medical and nutritional impact of malnutrition and/or compensatory behaviors gives rise to a complex disease with a wide range ofseverity, the management of which requires a multidisciplinary team with a high level of subject matter expertise. Coordination between levelsof care is necessary as well as understanding how to transition the patient from pediatric to adult care is essential. A proper clinical evaluationcan detect possible complications, as well as establish the organic risk of the patient. This allows caregivers to tailor the medical-nutritionaltreatment for each patient.Reestablishing adequate nutritional behaviors is a fundamental pillar of treatment in AN. The design of a personalized nutritional treatment andeducation program is necessary for this purpose. Depending on the clinical severity, artificial nutrition may be necessary. Although the decisionregarding the level of care necessary at diagnosis or during follow-up depends on a number of factors (awareness of the disease, medical stability,complications, suicidal risk, outpatient treatment failure, psychosocial context, etc.), outpatient treatment is the most frequent and most preferredchoice. However, more intensive care (total or partial hospitalization) may be necessary in certain cases. In severely malnourished patients, theappearance of refeeding syndrome should be prevented during renourishment.The presence of AN in certain situations (pregnancy, vegetarianism, type 1 diabetes mellitus) requires specific care. Physical activity in thesepatients must also be addressed correctly.(AU)

[A consensus report by the Working Group on Eating Disorders of Sociedad Española de Nutrición Clínica y Metabolismo (GTTCA-SENPE). Evaluation, medical and nutritional management of anorexia nervosa. Update 2023]. / Consenso del grupo de trabajo de los trastornos de la conducta alimentaria de SENPE (GTTCA-SENPE). Evaluación y tratamiento médico-nutricional en la anorexia nerviosa. Actualización 2023.

Introduction: Anorexia nervosa (AN) is a multifactorial disorder. A possible role of the social network and the gut microbiota in pathogenesis has been added. Exogenous shocks such as the COVID19 pandemic have had a negative impact on patients with AN. The potential medical and nutritional impact of malnutrition and/or compensatory behaviors gives rise to a complex disease with a wide range of severity, the management of which requires a multidisciplinary team with a high level of subject matter expertise. Coordination between levels of care is necessary as well as understanding how to transition the patient from pediatric to adult care is essential. A proper clinical evaluation can detect possible complications, as well as establish the organic risk of the patient. This allows caregivers to tailor the medical-nutritional treatment for each patient. Reestablishing adequate nutritional behaviors is a fundamental pillar of treatment in AN. The design of a personalized nutritional treatment and education program is necessary for this purpose. Depending on the clinical severity, artificial nutrition may be necessary. Although the decision regarding the level of care necessary at diagnosis or during follow-up depends on a number of factors (awareness of the disease, medical stability, complications, suicidal risk, outpatient treatment failure, psychosocial context, etc.), outpatient treatment is the most frequent and most preferred choice. However, more intensive care (total or partial hospitalization) may be necessary in certain cases. In severely malnourished patients, the appearance of refeeding syndrome should be prevented during renourishment. The presence of AN in certain situations (pregnancy, vegetarianism, type 1 diabetes mellitus) requires specific care. Physical activity in these patients must also be addressed correctly.

Introducción: La anorexia nerviosa (AN) es una enfermedad de origen multifactorial. Recientemente se ha sumado el papel de las redes sociales y la microbiota intestinal en la patogenia. La pandemia por COVID-19 ha tenido un impacto negativo en los pacientes con AN. La potencial afectación médica y nutricional derivada de la desnutrición o las conductas compensatorias dan lugar a una compleja enfermedad de gravedad variable, cuyo manejo precisa un equipo multidisciplinar con elevado nivel de conocimientos en la materia. Es fundamental la coordinación entre niveles asistenciales y en la transición de pediatría a adultos. Una adecuada valoración clínica permite detectar eventuales complicaciones, así como establecer el riesgo orgánico del paciente y, por tanto, adecuar el tratamiento médico-nutricional de forma individualizada. El restablecimiento de un apropiado estado nutricional es un pilar fundamental del tratamiento en la AN. Para ello es necesario diseñar una intervención de renutrición individualizada que incluya un programa de educación nutricional. Según el escenario clínico puede ser necesaria la nutrición artificial. Aunque la decisión de qué nivel de atención escoger al diagnóstico o durante el seguimiento depende de numerosas variables (conciencia de enfermedad, estabilidad médica, complicaciones, riesgo autolítico, fracaso del tratamiento ambulatorio o contexto psicosocial, entre otros), el tratamiento ambulatorio es de elección en la mayoría de las ocasiones. No obstante, puede ser necesario un escenario más intensivo (hospitalización total o parcial) en casos seleccionados. En pacientes gravemente desnutridos debe prevenirse la aparición de un síndrome de alimentación cuando se inicia la renutrición. La presencia de una AN en determinadas situaciones (gestación, vegetarianismo, diabetes mellitus de tipo 1, etc.) exige un manejo particular. En estos pacientes también debe abordarse de forma correcta el ejercicio físico.

Timing of Kidney Replacement Therapy Initiation and Survival during Pediatric Extracorporeal Membrane Oxygenation: An Extracorporeal Life Support Organization Registry Study.

To characterize kidney replacement therapy (KRT) and pediatric extracorporeal membrane oxygenation (ECMO) outcomes and to identify the optimal timing of KRT initiation during ECMO associated with increased survival. Observational retrospective cohort study using the Extracorporeal Life Support Organization Registry database in children (0-18 yo) on ECMO from January 1, 2016, to December 31, 2020. Of the 14,318 ECMO runs analyzed, 26% of patients received KRT during ECMO. Patients requiring KRT before ECMO had increased mortality to ECMO decannulation (29% vs. 17%, OR 1.97, P < 0.001) and to hospital discharge (58% vs. 39%, OR 2.16, P < 0.001). Patients requiring KRT during ECMO had an increased mortality to ECMO decannulation (25% vs. 15%, OR 1.85, P < 0.001) and to hospital discharge (56% vs. 34%, OR 2.47, P < 0.001). Multivariable logistic regression demonstrated that the need for KRT during ECMO was an independent predictor for mortality to ECMO decannulation (OR 1.49, P < 0.001) and to hospital discharge (OR 2.02, P < 0.001). Patients initiated on KRT between 24 and 72 hours after cannulation were more likely to survive to ECMO decannulation and showed a trend towards survival to hospital discharge as compared to those initiated before 24 hours and after 72 hours.

"Extracorporeal membrane oxygenation outcomes in multisystem inflammatory syndrome of childhood - An extracorporeal life support organization registry study".

Multisystem inflammatory disease in childhood (MIS-C) is a novel pediatric syndrome after a COVID-19 infection that causes systemic injury, with potential life-threatening hemodynamic compromise requiring Extracorporeal Membrane Oxygenation (ECMO) support. We performed an observational retrospective cohort study in children aged 0-18 years with MIS-C and non-MIS-C myocarditis on ECMO between January 2020 and December 2021, using the ELSO Registry database. We aimed to compare the outcomes of both populations and to identify factors for decreased survival in MIS-C patients on ECMO. The Extracorporeal Life Support Organization (ELSO) Registry reported 310 pediatric ECMO patients with MIS-C (56.1%) and non-MIS-C myocarditis (43.9%). No difference was found in survival to hospital discharge between groups (67.2% for MIS-C vs 69.1% for non-MIS-C myocarditis, p 0.725). Multivariable analysis demonstrated that ECPR and co-infection were significantly associated with decreased survival to hospital discharge in MIS-C patients (OR 0.138, p 0.01 and OR 0.44, p 0.02, respectively). Outcomes of children with MIS-C on ECMO support are similar to those of non-MIS-C myocarditis despite higher infectious, multiorgan dysfunction and respiratory complications accompanying COVID-19 infections. The use of ECMO for MIS-C patients seems to be feasible and safe. Prospective studies on the use of ECMO support in MIS-C patients may improve outcomes in this pediatric population.

Apolipoprotein E-ε2 and Resistance to Atherosclerosis in Midlife: The PESA Observational Study.

BACKGROUND: APOE is a known genetic contributor to cardiovascular disease, but the differential role APOE alleles play in subclinical atherosclerosis remains unclear. METHODS: The PESA (Progression of Early Subclinical Atherosclerosis) is an observational cohort study that recruited 4184 middle-aged asymptomatic individuals to be screened for cardiovascular risk and multiterritorial subclinical atherosclerosis. Participants were APOE-genotyped, and omics data were additionally evaluated. RESULTS: In the PESA study, the frequencies for APOE -ε2, -ε3, and -ε4 alleles were 0.060, 0.844, and 0.096, respectively. This study included a subcohort of 3887 participants (45.8±4.3 years of age; 62% males). As expected, APOE-ε4 carriers were at the highest risk for cardiovascular disease and had significantly greater odds of having subclinical atherosclerosis compared with ε3/ε3 carriers, which was mainly explained by their higher levels of low-density lipoprotein (LDL)-cholesterol. In turn, APOE-ε2 carriers were at the lowest risk for cardiovascular disease and had significantly lower odds of having subclinical atherosclerosis in several vascular territories (carotids: 0.62 [95% CI, 0.47-0.81]; P=0.00043; femorals: 0.60 [0.47-0.78]; P=9.96×10-5; coronaries: 0.53 [0.39-0.74]; P=0.00013; and increased PESA score: 0.58 [0.48-0.71]; P=3.16×10-8). This APOE-ε2 atheroprotective effect was mostly independent of the associated lower LDL-cholesterol levels and other cardiovascular risk factors. The protection conferred by the ε2 allele was greater with age (50-54 years: 0.49 [95% CI, 0.32-0.73]; P=0.00045), and normal (<150 mg/dL) levels of triglycerides (0.54 [0.44-0.66]; P=4.70×10-9 versus 0.90 [0.57-1.43]; P=0.67 if ≥150 mg/dL). Omics analysis revealed an enrichment of several canonical pathways associated with anti-inflammatory mechanisms together with the modulation of erythrocyte homeostasis, coagulation, and complement activation in ε2 carriers that might play a relevant role in the ε2's atheroprotective effect. CONCLUSIONS: This work sheds light on the role of APOE in cardiovascular disease development with important therapeutic and prevention implications on cardiovascular health, especially in early midlife. REGISTRATION: URL: https://www.clinicaltrials.gov: NCT01410318.

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults.

Importance: In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown. Objective: To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90). Design, Setting, and Participants: This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023. Exposure: The primary exposure was time to CRRT initiation from intensive care unit admission. Main Outcomes and measures: The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]). Results: Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio, 1.03 [95% CI, 1.02-1.04]). Conclusions and Relevance: In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.

Update on the role of T cells in cognitive impairment.

The central nervous system (CNS) has long been considered an immune-privileged site, with minimal interaction between immune cells, particularly of the adaptive immune system. Previously, the presence of immune cells in this organ was primarily linked to events involving disruption of the blood-brain barrier (BBB) or inflammation. However, current research has shown that immune cells are found patrolling CNS under homeostatic conditions. Specifically, T cells of the adaptive immune system are able to cross the BBB and are associated with ageing and cognitive impairment. In addition, T-cell infiltration has been observed in pathological conditions, where inflammation correlates with poor prognosis. Despite ongoing research, the role of this population in the ageing brain under both physiological and pathological conditions is not yet fully understood. In this review, we provide an overview of the interactions between T cells and other immune and CNS parenchymal cells, and examine the molecular mechanisms by which these interactions may contribute to normal brain function and the scenarios in which disruption of these connections lead to cognitive impairment. A comprehensive understanding of the role of T cells in the ageing brain and the underlying molecular pathways under normal conditions could pave the way for new research to better understand brain disorders. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

Modifiable Risk Factors and Trends in Changes in Glucose Regulation during the First Three Years Postdelivery: The St Carlos Gestational Diabetes Mellitus Prevention Cohort.

OBJECTIVE: Evaluation of the influence of potential risk factors (RFs) on glycemic changes at 3 years postpartum. METHODS: The glycemic status of 1400 women, in absence of a new pregnancy, was evaluated at 3 months (3 m) and 3 years (3 y) postpartum, after participation in the St. Carlos Gestational Study (2228 normoglycemic pregnant women followed from before gestational week 12 to delivery, from 2015-2017). Abnormal glucose regulation (AGR) was defined as fasting serum glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% and/or 2 h 75 g OGTT glucose ≥ 140 mg/dL. In total, 12 modifiable and 3 unmodifiable RFs were analyzed. RESULTS: 3 m postpartum, 110/1400 (7.9%) women had AGR; 3 y postpartum, 137 (9.8%) women exhibited AGR (110 with 3 m normal glucose tolerance [NGT]); 1263 (90.2%) had NGT (83 with 3 m AGR). More women with gestational diabetes mellitus (GDM) progressed to AGR at 3 y (OR: 1.60 [1.33-1.92]) than women without GDM. Yet, most women with 3 m and/or 3 y AGR had no GDM history. Having ≥2 unmodifiable RFs was associated with increased risk for progression to AGR (OR: 1.90 [1.28-2.83]) at 3 y postpartum. Having >5/12 modifiable RFs was associated with increased progression from NGT to AGR (OR: 1.40 [1.00-2.09]) and AGR persistence (OR: 2.57 [1.05-6.31]). Pregestational BMI ≥ 25 kg/m2 (OR: 0.59 [0.41-0.85]), postdelivery weight gain (OR: 0.53 [0.29-0.94]), and waist circumference > 89.5 cm (OR: 0.54 [0.36-0.79]) reduced the likelihood of NGT persisting at 3 y. CONCLUSIONS: 3-month and/or 3-year postpartum AGR can be detected if sought in women with no prior GDM. Modifiable and unmodifiable RF predictors of AGR at 3 y postpartum were identified. Universal screening for glycemic alterations should be considered in all women following delivery, regardless of prior GDM. These findings could be useful to design personalized strategies in women with risk factors for 3 y AGR.

DECTIN-1: A modifier protein in CTLA-4 haploinsufficiency.

Autosomal dominant loss-of-function (LoF) variants in cytotoxic T-lymphocyte associated protein 4 (CTLA4) cause immune dysregulation with autoimmunity, immunodeficiency and lymphoproliferation (IDAIL). Incomplete penetrance and variable expressivity are characteristic of IDAIL caused by CTLA-4 haploinsufficiency (CTLA-4h), pointing to a role for genetic modifiers. Here, we describe an IDAIL proband carrying a maternally inherited pathogenic CTLA4 variant and a paternally inherited rare LoF missense variant in CLEC7A, which encodes for the ß-glucan pattern recognition receptor DECTIN-1. The CLEC7A variant led to a loss of DECTIN-1 dimerization and surface expression. Notably, DECTIN-1 stimulation promoted human and mouse regulatory T cell (Treg) differentiation from naïve αß and γδ T cells, even in the absence of transforming growth factor-ß. Consistent with DECTIN-1's Treg-boosting ability, partial DECTIN-1 deficiency exacerbated the Treg defect conferred by CTL4-4h. DECTIN-1/CLEC7A emerges as a modifier gene in CTLA-4h, increasing expressivity of CTLA4 variants and acting in functional epistasis with CTLA-4 to maintain immune homeostasis and tolerance.

Cardiovascular toxicity of checkpoint inhibitors: review of associated toxicity and design of the Spanish Immunotherapy Registry of Cardiovascular Toxicity

Immune checkpoint inhibitors (ICI) have changed the prognosis of many tumors. However, concerning associated cardiotoxicity has been reported. Little is known about the real-life incidence-specific surveillance protocols or the translational correlation between the underlying mechanisms and the clinical presentation of ICI-induced cardiotoxicity. The lack of data from prospective studies led us to review the current knowledge and to present the creation of the Spanish Immunotherapy Registry of Cardiovascular Toxicity (SIR-CVT), a prospective registry of patients receiving ICI that aims to examine the role of hsa-miR-Chr8:96, (a specific serum biomarker of myocarditis) in the early diagnosis of ICI-induced myocarditis. An exhaustive prospective cardiac imaging study will be performed before and during the first 12 months of treatment. The correlation between clinical, imaging, and immunologic parameters may improve our understanding of ICI-induced cardiotoxicity and enable simpler surveillance protocols. We assess ICI-induced cardiovascular toxicity and describe the rationale of the SIR-CVT (AU)

Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort.

BACKGROUND: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. METHODS: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. RESULTS: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. CONCLUSIONS: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19. TRIAL REGISTRATION: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 ).