Tract-based spatial statistics to assess the neuroprotective effect of early erythropoietin on white matter development in preterm infants

In a randomized double-blind placebo-controlled trial, O'Gorman et al. show that administration of erythropoietin within the first 42 hours after preterm birth improves white matter development in preterm infants. Improvements are seen in the corpus callosum, the anterior and posterior limbs of the internal capsule, and the corticospinal tract bilaterall

Effect of Early High-Dose Recombinant Human Erythropoietin on Behavior and Quality of Life in Children Aged 5 Years Born Very Preterm: Secondary Analysis of a Randomized Clinical Trial

IMPORTANCE In light of the promising neuroprotective properties of recombinant human erythropoietin (RHEpo), the Swiss EPO Neuroprotection Trial was started to investigate its effect on neurodevelopment in very preterm infants. The results of the primary and secondary outcome analysis did not show any effect of RHEpo on cognitive performance, neuromotor outcomes, or somatic growth of the study participants at ages 2 or 5 years. OBJECTIVE To investigate whether early high-dose RHEpo improves behavioral outcomes and health-related quality of life (HRQoL) at age 5 years. DESIGN, SETTING, AND PARTICIPANTS This was a prespecified secondary analysis of the double-blind, placebo-controlled, multicenter Swiss EPO Neuroprotection randomized clinical trial, which was conducted at 5 level-III perinatal centers in Switzerland. Infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were recruited between 2005 and 2012 and followed-up until age 5 years (last follow-up in 2018). Data were analyzed from January 6 to December 31, 2021. INTERVENTIONS Infants were assigned to receive either RHEpo (3000 IU/kg) or placebo (saline, 0.9%) intravenously 3 times within the first 42 hours after birth. MAIN OUTCOMES AND MEASURES The prespecified parent-reported measures of behavioral outcomes and health-related quality of life (HRQoL) of their children at the age of 5 years were assessed by two standardized questionnaires: the Strengths and Difficulties Questionnaire (behavioral outcomes) and the KIDSCREEN-27 (HRQoL). RESULTS Among 448 randomized infants, 228 infants were assigned to the RHEpo group and 220 infants were assigned to the placebo group. Questionnaire data were available for 317 children (71%) at a mean (SD) age of 5.8 (0.4) years (mean [SD] gestational age at birth, 29.3 [1.6] weeks; mean [SD] birth weight 1220 [340] grams; 128 [40%] female infants). At the age 5 years follow-up, the mean (SD) total difficulties score in the RHEpo group (8.41 [5.60] points) was similar to that of the placebo group (7.76 [4.81]) (P = .37). There were no statistically significant differences between the groups in any other outcome measures. CONCLUSIONS AND RELEVANCE This secondary analysis of a randomized clinical trial showed no evidence for an effect of early high-dose RHEpo administration on behavioral outcomes or HRQoL in children born very preterm at early school age. TRIAL REGISTRATION - ClinicalTrials.gov Identifier: NCT00413946

Uptake of Radionuclides by Bryophytes in the Chornobyl Exclusion Zone

The “Chernobyl nuclear disaster” released huge amounts of radionuclides, which are still detectable in plants and sediments today. Bryophytes (mosses) are primitive land plants lacking roots and protective cuticles and therefore readily accumulate multiple contaminants, including metals and radionuclides. This study quantifies 137Cs and 241Am in moss samples from the cooling pond of the power plant, the surrounding woodland and the city of Prypiat. Activity concentrations of up to 297 Bq/g (137Cs) and 0.43 Bq/g (241Am) were found. 137Cs contents were significantly higher at the cooling pond, where 241Am was not detectable. Distance to the damaged reactor, amount of original fallout, presence of vascular tissue in the stem or taxonomy were of little importance. Mosses seem to absorb radionuclides rather indiscriminately, if available. More than 30 years after the disaster, 137Cs was washed out from the very top layer of the soil, where it is no more accessible for rootless mosses but possibly for higher plants. On the other hand, 137Cs still remains solved and accessible in the cooling pond. However, 241Am remained adsorbed to the topsoil, thus accessible to terrestrial mosses, but precipitated in the sapropel of the cooling pond

A Balanced Risk–Benefit Analysis to Determine Human Risks Associated with Pyrrolizidine Alkaloids (PA)—The Case of Tea and Herbal Infusions

Humans are exposed to pyrrolizidine alkaloids (PA) through different sources, mainly from contaminated foodstuff. Teas and herbal infusions (T&HI) can be contaminated by PA producing weed. PA can possess toxic, mutagenic, genotoxic, and carcinogenic properties. Thus, possible health risks for the general population are under debate. There is a strong safety record for T&HI and additionally epidemiological evidence for the preventive effects of regular tea consumption on cardiovascular events and certain types of cancer. There is no epidemiological evidence, however, for human risks of regular low dose PA exposure. Recommended regulatory PA-threshold values are based on experimental data only, accepting big uncertainties. If a general risk exists through PA contaminated T&HI, it must be small compared to other frequently accepted risks of daily living and the proven health effects of T&HI. Decision making should be based on a balanced riskbenefit analysis. Based on analyses of the scientific data currently available, it is concluded that the benefits of drinking T&HI clearly outweigh the negligible health risk of possible PA contamination. At the same time, manufacturers must continue their efforts to secure good product quality and to be transparent on their measures of quality control and risk communication

A Balanced Risk-Benefit Analysis to Determine Human Risks Associated with Pyrrolizidine Alkaloids (PA)-The Case of Herbal Medicinal Products Containing St. John's Wort Extracts (SJW)

Objectives: Pyrrolizidine alkaloids (PA) exist ubiquitously in our environment. More than 6000 plants, about 3% of the world's flowering plants, are known to synthesize PA. As a consequence, many herbal ingredients, including St. John's wort (SJW), are contaminated with PA that can possess acute and subchronic toxic effects as well as mutagenic and genotoxic properties. Therefore, the possible benefits of SJW as an herbal remedy against depression need to be weighed against the possible risks of unwanted PA intake. Methods: We searched the literature regarding the current knowledge on PA and evaluated the evidence on the antidepressant effects of quantified SJW extract based on a Cochrane Review and the current practice guidelines on depression. Risks are depicted in form of a risk ladder and benefits in form of an icon array. Results: Evidence from clinical studies indicates that quantified SJW extract is an effective treatment option for mild to moderate depression with fewer side effects than conventional antidepressants. Health statistics from different countries do not quantify cases of death caused by PA intake. However, deaths due to suicide, often triggered by depression, are common (11 in 1000 in Germany in 2015) and rank between fatalities due to liver diseases (16 in 1000) and household accidents (10 in 1000). Conclusions: Quantified SJW extract is a safe and effective treatment option, and its potential of treating depression outweighs the (hypothetical) risk of unwanted PA intake

Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial

BACKGROUND: In light of declining autopsy rates around the world, post-mortem MR imaging is a promising alternative to conventional autopsy in the investigation of infant death. A major drawback of this non-invasive autopsy approach is the fact that histopathological and microbiological examination of the tissue is not possible. The objective of this prospective study is to compare the performance of minimally invasive, virtual autopsy, including CT-guided biopsy, with conventional autopsy procedures in a paediatric population. METHODS/DESIGN: Foetuses, newborns and infants that are referred for autopsy at three different institutions associated with the University of Zurich will be eligible for recruitment. All bodies will be examined with a commercial CT and a 3 Tesla MRI scanner, masked to the results of conventional autopsy. After cross-sectional imaging, CT-guided tissue sampling will be performed by a multifunctional robotic system (Virtobot) allowing for automated post-mortem biopsies. Virtual autopsy results will be classified with regards to the likely final diagnosis and major pathological findings and compared to the results of conventional autopsy, which remains the diagnostic gold standard. DISCUSSION: There is an urgent need for the development of alternative post-mortem examination methods, not only as a counselling tool for families and as a quality control measure for clinical diagnosis and treatment but also as an instrument to advance medical knowledge and clinical practice. This interdisciplinary study will determine whether virtual autopsy will narrow the gap in information between non-invasive and traditional autopsy procedures. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01888380

Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients

Narcissism and the strategic pursuit of short-term mating : universal links across 11 world regions of the International Sexuality Description Project-2.

Previous studies have documented links between sub-clinical narcissism and the active pursuit of short-term mating strategies (e.g., unrestricted sociosexuality, marital infidelity, mate poaching). Nearly all of these investigations have relied solely on samples from Western cultures. In the current study, responses from a cross-cultural survey of 30,470 people across 53 nations spanning 11 world regions (North America, Central/South America, Northern Europe, Western Europe, Eastern Europe, Southern Europe, Middle East, Africa, Oceania, Southeast Asia, and East Asia) were used to evaluate whether narcissism (as measured by the Narcissistic Personality Inventory; NPI) was universally associated with short-term mating. Results revealed narcissism scores (including two broad factors and seven traditional facets as measured by the NPI) were functionally equivalent across cultures, reliably associating with key sexual outcomes (e.g., more active pursuit of short-term mating, intimate partner violence, and sexual aggression) and sex-related personality traits (e.g., higher extraversion and openness to experience). Whereas some features of personality (e.g., subjective well-being) were universally associated with socially adaptive facets of Narcissism (e.g., self-sufficiency), most indicators of short-term mating (e.g., unrestricted sociosexuality and marital infidelity) were universally associated with the socially maladaptive facets of narcissism (e.g., exploitativeness). Discussion addresses limitations of these cross-culturally universal findings and presents suggestions for future research into revealing the precise psychological features of narcissism that facilitate the strategic pursuit of short-term mating

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among comorbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. Conclusions: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event. Clinical trial registration: NCT02350348

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

BACKGROUND: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. METHODS: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. RESULTS: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1–6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among co-morbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. CONCLUSIONS: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event