Analysis of routine blood parameters in patients with amyotrophic lateral sclerosis and evaluation of a possible correlation with disease progression—a multicenter study

ObjectiveAmyotrophic lateral sclerosis (ALS) pathogenesis is still unclear, its course is considerably variable, and prognosis is hard to determine. Despite much research, there is still a lack of easily accessible markers predicting prognosis. We investigated routine blood parameters in ALS patients regarding correlations with disease severity, progression rate, and survival. Additionally, we analyzed disease and patients' characteristics relating to baseline blood parameter levels.MethodsWe analyzed creatine kinase (CK), albumin (ALB), creatinine (CREA), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG) levels around time of diagnosis in 1,084 ALS patients. We carried out linear regression analyses including disease and patients' characteristics with each blood parameter to detect correlations with them. Linear regression models were performed for ALSFRS-R at study entry, its retrospectively defined rate of decay and prospectively collected progression rate. Different survival analysis methods were used to examine associations between blood parameters and survival.ResultsWe found higher CK (p-value 0.001), ALB (p-value <0.001), CREA (p-value <0.001), and HDL levels (p-value 0.044) at time of diagnosis being associated with better functional status according to ALSFRS-R scores at study entry. Additionally, higher CREA levels were associated with lower risk of death (p-value 0.003).ConclusionsOur results indicate potential of CK, ALB, CREA, and HDL as disease severity or progression markers, and may also provide clues to ALS pathogenesis. However, these values are highly dependent on other variables, and further careful, longitudinal analyses will be necessary to prove the relevance of our findings

Families’ Worries during the First and Second COVID-19 Wave in Germany: Longitudinal Study in Two Population-Based Cohorts

This study aimed to compare worries related to the Coronavirus disease 2019 (COVID-19) in families with young children in two regions in Germany differently affected by the pandemic (Regensburg in Southeast Germany, Leipzig in Eastern Germany) during the first and the second waves of the COVID-19 pandemic. 720 parents participating in the KUNO Kids health study in Regensburg (n = 507) or the LIFE Child study in Leipzig (n = 213) answered questions regarding COVID-19-related worries and trust in anti-pandemic policy measures during the first wave (spring 2020) and during the second wave (winter 2020/2021) of the pandemic. Ordinal mixed-effects models were performed to assess differences depending on region and time, adjusting for education and migration background. Participants worried most about the general economic situation and their family and least about their own health or financial situation. Worries about oneself, family, friends, hometown, and country were stronger during the second than during the first wave. In regional comparisons, worries about family, friends, and hometown increased more pronouncedly from wave 1 to wave 2 in Leipzig (OR ranging from 2.67 (95% CI 1.71–4.19) to 3.01 (95% CI 1.93–4.71), all p < 0.001) than in Regensburg (OR ranging from to 1.38 (95% CI 1.08–1.78) to 1.72 (95% CI 1.33–2.21), all p < 0.05), running parallel with the increase in SARS-CoV-2 infections. Trust in anti-pandemic policy measures, in contrast, decreased significantly between wave 1 and wave 2, with a stronger decrease in Regensburg (OR = 0.30 (95% CI 0.22–0.39), p < 0.001) than in Leipzig (OR = 0.91 (95% CI 0.59–1.41), n.s.). The degree of families’ COVID-19-related worries differs by region and time, which might be related to differences in infection rates and public interest. Regional differences should be taken into account when developing communication strategies and policy measures during the COVID-19 pandemic

Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85610 x 10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84 x 10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at similar to 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults

Soil conditions and phylogenetic relatedness influence total community trait space during early plant succession

This study is part of the Transregional Collaborative Research Centre 38 (SFB/TRR 38: ecosystem assembly and succession). The authors thank the working group Z1 (monitoring) members of the SFB/TRR 38 who helped us to perform this study and the Vattenfall Europe Mining A.G. for providing the research site.Aims The total space of traits covered by the members of plant com- munities is an important parameter of ecosystem functioning and complexity. We trace the variability of trait space during early plant succession and ask how trait space co-varies with phylogenetic community structure and soil conditions. Particularly, we are inter - ested in the small-scale variability in trait space and the influence of biotic and abiotic filters. Methods We use data on species richness and soil conditions from the first 7 years of initial succession of an artificial catchment in north-east- ern Germany. Total functional attribute diversity serves as a proxy to total trait space. Important Findings Total trait space steadily increased during succession. We observed high small-scale variability in total trait space that was positively cor - related with species richness and phylogenetic segregation and nega- tively correlated with total plant cover. Trait space increased with soil carbonate content, while pH and the fraction of sandy material behaved indifferently. Our results indicate that during early succession, habitat filtering processes gain importance leading to a lesser increase in trait space than expected from the increase in species richness alone

Peanut‐induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. Results 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). Conclusions The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model

Summary Background Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive, fatal motor neuron disease with a variable natural history. There are no accurate models that predict the disease course and outcomes, which complicates risk assessment and counselling for individual patients, stratification of patients for trials, and timing of interventions. We therefore aimed to develop and validate a model for predicting a composite survival endpoint for individual patients with ALS. Methods We obtained data for patients from 14 specialised ALS centres (each one designated as a cohort) in Belgium, France, the Netherlands, Germany, Ireland, Italy, Portugal, Switzerland, and the UK. All patients were diagnosed in the centres after excluding other diagnoses and classified according to revised El Escorial criteria. We assessed 16 patient characteristics as potential predictors of a composite survival outcome (time between onset of symptoms and non-invasive ventilation for more than 23 h per day, tracheostomy, or death) and applied backward elimination with bootstrapping in the largest population-based dataset for predictor selection. Data were gathered on the day of diagnosis or as soon as possible thereafter. Predictors that were selected in more than 70% of the bootstrap resamples were used to develop a multivariable Royston-Parmar model for predicting the composite survival outcome in individual patients. We assessed the generalisability of the model by estimating heterogeneity of predictive accuracy across external populations (ie, populations not used to develop the model) using internal–external cross-validation, and quantified the discrimination using the concordance (c) statistic (area under the receiver operator characteristic curve) and calibration using a calibration slope. Findings Data were collected between Jan 1, 1992, and Sept 22, 2016 (the largest data-set included data from 1936 patients). The median follow-up time was 97·5 months (IQR 52·9–168·5). Eight candidate predictors entered the prediction model: bulbar versus non-bulbar onset (univariable hazard ratio [HR] 1·71, 95% CI 1·63–1·79), age at onset (1·03, 1·03–1·03), definite versus probable or possible ALS (1·47, 1·39–1·55), diagnostic delay (0·52, 0·51–0·53), forced vital capacity (HR 0·99, 0·99–0·99), progression rate (6·33, 5·92–6·76), frontotemporal dementia (1·34, 1·20–1·50), and presence of a C9orf72 repeat expansion (1·45, 1·31–1·61), all p<0·0001. The c statistic for external predictive accuracy of the model was 0·78 (95% CI 0·77–0·80; 95% prediction interval [PI] 0·74–0·82) and the calibration slope was 1·01 (95% CI 0·95–1·07; 95% PI 0·83–1·18). The model was used to define five groups with distinct median predicted (SE) and observed (SE) times in months from symptom onset to the composite survival outcome: very short 17·7 (0·20), 16·5 (0·23); short 25·3 (0·06), 25·2 (0·35); intermediate 32·2 (0·09), 32·8 (0·46); long 43·7 (0·21), 44·6 (0·74); and very long 91·0 (1·84), 85·6 (1·96). Interpretation We have developed an externally validated model to predict survival without tracheostomy and non-invasive ventilation for more than 23 h per day in European patients with ALS. This model could be applied to individualised patient management, counselling, and future trial design, but to maximise the benefit and prevent harm it is intended to be used by medical doctors only. Funding Netherlands ALS Foundation

Extended winters entail long-term costs for insect offspring reared in an overwinter burrow

International audienceWinter imposes an ecological challenge to animals living in colder climates, especially if these adverse conditions coincide with reproduction and offspring rearing. To overcome this challenge, some insects burrow in the soil to protect adults, larvae, or eggs from negative effects of winter. However, whether this protection is effective against any long-term consequences of changes in winter duration is unclear. Here, we investigated the long-term effects of winter length variation on eggs of the European earwig Forficula auricularia. In this insect, females construct and maintain a burrow between late autumn and spring, in which they provide extensive forms of care to their eggs and then juveniles. We experimentally maintained earwig females under two winter durations of either four or six weeks and examined the resulting effects in terms of 1) hatching date, 2) developmental time of juveniles until adulthood, 3) adult mass at emergence, and 4) investment of adult offspring females in three key immune parameters: hemocyte concentration, phenoloxidase, and prophenoloxidase activities. Because earwigs' resistance against pathogens relies on their social environment, effects of winter length on immunity were tested on females exposed to different social environments: with familiar conspecifics, unfamiliar conspecifics, or in isolation. Our results reveal that after the winter treatments, eggs reared in short winters hatched earlier and the emerging juveniles reached adulthood faster than juveniles from eggs exposed to long winters. We also showed that prophenoloxidase was 30% higher in females from the long compared to short winter treatment, regardless of social environment. Finally, we found that hemocyte counts where twice as high in short compared to long winter females, but only with unfamiliar conspecifics. Overall, our study reveals that maintaining and caring for eggs in a burrow does not prevent the costs associated with increased winter duration