Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

IMPORTANCE: Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE: To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized. INTERVENTIONS: Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group). MAIN OUTCOMES AND MEASURES: The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months. RESULTS: Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053). CONCLUSIONS AND RELEVANCE: Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00879892

Effects of hormonal contraception on systemic metabolism : cross-sectional and longitudinal evidence

Background: Hormonal contraception is commonly used worldwide, but its systemic effects across lipoprotein subclasses, fatty acids, circulating metabolites and cytokines remain poorly understood. Methods: A comprehensive molecular profile (75 metabolic measures and 37 cytokines) was measured for up to 5841 women (age range 24-49 years) from three population-based cohorts. Women using combined oral contraceptive pills (COCPs) or progestin-only contraceptives (POCs) were compared with those who did not use hormonal contraception. Metabolomics profiles were reassessed for 869 women after 6 years to uncover the metabolic effects of starting, stopping and persistently using hormonal contraception. Results: The comprehensive molecular profiling allowed multiple new findings on the metabolic associations with the use of COCPs. They were positively associated with lipoprotein subclasses, including all high-density lipoprotein (HDL) subclasses. The associations with fatty acids and amino acids were strong and variable in direction. COCP use was negatively associated with albumin and positively associated with creatinine and inflammatory markers, including glycoprotein acetyls and several growth factors and interleukins. Our findings also confirmed previous results e.g. for increased circulating triglycerides and HDL cholesterol. Starting COCPs caused similar metabolic changes to those observed cross-sectionally: the changes were maintained in consistent users and normalized in those who stopped using. In contrast, POCs were only weakly associated with metabolic and inflammatory markers. Results were consistent across all cohorts and for different COCP preparations and different types of POC delivery. Conclusions: Use of COCPs causes widespread metabolic and inflammatory effects. However, persistent use does not appear to accumulate the effects over time and the metabolic perturbations are reversed upon discontinuation. POCs have little effect on systemic metabolism and inflammation.Peer reviewe

Pediatricians and nutritionists knowledge about treatment of cow milk allergy in infants

OBJECTIVE: Evaluate the knowledge of pediatricians and nutritionists regarding the exclusion diet of cow milk and derivates, with emphasis on questions related to the nutrition of children submitted to such diet. METHODS: Cross-sectional study that enrolled pediatricians (n=53) and nutritionists (n=29) from public hospitals in São Paulo, Brazil, during 2005. Data was collected through self-administered questionnaires. RESULTS: The age of the professionals varied from 21 to 50 years old. Regarding professional experience, 41.2% were graduated for less than five years and 91.6% had a specialization course, masters and/or PhD degree. The vast majority of professionals (97.5%) confirmed that they regularly evaluated the diet of children that needed exclusion of cow milk. However, only 48% of the professionals conducted a more detailed evaluation of the diet, including calculations of food ingestion. Only 38.7% of the professionals compared child s food ingestion with some recommended pattern. Recommendations for daily ingestion of calcium by children up to the age of 36 months were properly mentioned by 22% of the pediatricians and 60.7% of the nutritionists (p=0.001). Inadequate cow milk substitute products were recommended by 66% of the pediatricians and by 48.3% of the nutritionists. Regarding labels of industrialized products, 81.6% of the pediatricians and 96.4% of the nutritionists advised the parents to look for all terms that could indicate the presence of cow milk protein. CONCLUSIONS: Pediatricians and nutritionists made conceptual errors in their main recommendations regarding the treatment of cow milk protein allergy.OBJETIVO: Avaliar o conhecimento de pediatras e nutricionistas sobre a dieta de exclusão do leite de vaca e seus derivados, com ênfase em questões relacionadas à nutrição da criança. MÉTODOS: Estudo transversal descritivo, do qual participaram pediatras (n=53) e nutricionistas (n=29), vinculados a hospitais públicos do Município de São Paulo, no ano de 2005. Os dados foram coletados por questionário auto-administrado. RESULTADOS: A idade dos profissionais variou de 21 a 50 anos. Quanto ao tempo de graduação, 41,2% eram formados a menos de cinco anos e 91,6% possuíam especialização, mestrado e/ou doutorado. A maioria (97,5%) afirmou avaliar a dieta de crianças submetidas à exclusão do leite de vaca, entretanto, somente 48% o faziam de forma mais detalhadas, incluindo o cálculo da ingestão alimentar. Apenas 38,7% comparam a ingestão alimentar da criança com algum padrão de recomendação. A recomendação diária da ingestão de cálcio para crianças com até 36 meses foi corretamente assinalada por 22% dos pediatras e 60,7% dos nutricionistas (p=0,001). Produtos não adequados como substitutos do leite de vaca seriam recomendados por 66% dos pediatras e 48,3% dos nutricionistas. Com relação à leitura de rótulos de produtos industrializados, 81,6% dos pediatras e 96,4% dos nutricionistas orientam os pais a ler todos os termos que indicam a presença das proteínas do leite de vaca. CONCLUSÕES: Os pediatras e nutricionista demonstraram erro conceitual no que se refere às principais recomendações terapêuticas na alergia às proteínas do leite de vaca.Universidade Federal de São Paulo (UNIFESP)UNIFESPUNIFESPSciEL

Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA

Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health-care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Associations of subjective and objective cognitive functioning after COVID-19 : A six-month follow-up of ICU, ward, and home-isolated patients

Publisher Copyright: © 2023 The AuthorsBackground: Subjective and objective cognitive dysfunction are reported after COVID-19 but with limited data on their congruence and associations with the severity of the acute disease. The aim of this cohort study is to describe the prevalence of subjective and objective cognitive dysfunction at three and six months after COVID-19 and the associations of subjective cognitive symptoms and psychological and disease-related factors. Methods: We assessed a cohort of 184 patients at three and six months after COVID-19: 82 patients admitted to the Intensive Care Unit (ICU), 53 admitted to regular hospital wards, and 49 isolated at home. A non-COVID control group of 53 individuals was included. Demographic and clinical data were collected. Subjective cognitive symptoms, objective cognitive impairment, and depressive and post-traumatic stress disorder (PTSD) symptoms were assessed. Results: At six months, subjective cognitive impairment was reported by 32.3% of ICU-treated, 37.3% of ward-treated, and 33.3% of home-isolated patients and objective cognitive impairment was observed in 36.1% of ICU-treated, 34.7% of ward-treated, and 8.9% of home-isolated patients. Subjective cognitive symptoms were associated with depressive and PTSD symptoms and female sex, but not with objective cognitive assessment or hospital metrics. Conclusions: One-third of COVID-19 patients, regardless of the acute disease severity, reported high levels of subjective cognitive dysfunction which was not associated with results from objective cognitive screening but with psychological and demographic factors. Our study stresses the importance of thorough assessment of patients reporting long-term subjective symptoms, screening for underlying mental health related factors such as PTSD or depression.Peer reviewe