Dysregulated innate and adaptive immune responses discriminate disease severity in COVID-19

The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive pro-inflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147 COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis reveals no specific inflammatory endotypes in COVID-19 patients. Functional assays reveal abrogated adaptive cytokine production (interferon-gamma, interleukin-17 and interleukin-22) and prominent T cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlight potential biomarkers of disease severity

Not only a matter of epilepsy: Early problems of cognition and behavior in children with "epilepsy only" - A prospective, longitudinal, controlled study starting at diagnosis

Objective. To understand early educational and behavioral predicament in childhood "epilepsy only." Methods. A multicenter, prospective, longitudinal study was conducted of 51 outpatient schoolchildren with newly diagnosed idiopathic or cryptogenic epilepsy and 48 sex-matched classmate control subjects. All children underwent neuropsychological assessment 3 times within the first year after diagnosis; parents and teachers completed behavior questionnaires, and patients' parents were interviewed to inventory contextual adversity. Principal components analysis of cognition and behavior disclosed 6 major components that were related with the interview data ( repeated measures analysis of variance). Results. Despite similar intelligence and educational background, significantly more patients (51%) than control subjects (27%) required special educational assistance. Patients obtained worse scores across components of cognition and behavior. Parents and teachers perceived patients to have more behavioral problems. Differences between groups existed at pretreatment baseline. Over time, notwithstanding stable percentages of poor scores in both groups, nonpersistence of poor scores was impressive ( each time other children scored poorly in other domains). Rather than epilepsy characteristics, contextual adversities were significant risk factors. Conclusion. Already in the earliest stage of the illness, children with epilepsy are liable to vicissitudes in cognitive and behavioral functioning. Contextual variables are all-important

Not only a Matter of Epilepsy: Early Problems of Cognition and Behavior in Children with "Epilepsy only" - A Prospective, Longitudinal, Controlled Study Starting at Diagnosis

Objective. To understand early educational and behavioral predicament in childhood "epilepsy only." Methods. A multicenter, prospective, longitudinal study was conducted of 51 outpatient schoolchildren with newly diagnosed idiopathic or cryptogenic epilepsy and 48 sex-matched classmate control subjects. All children underwent neuropsychological assessment 3 times within the first year after diagnosis; parents and teachers completed behavior questionnaires, and patients' parents were interviewed to inventory contextual adversity. Principal components analysis of cognition and behavior disclosed 6 major components that were related with the interview data (repeated measures analysis of variance). Results. Despite similar intelligence and educational background, significantly more patients (51%) than control subjects (27%) required special educational assistance. Patients obtained worse scores across components of cognition and behavior. Parents and teachers perceived patients to have more behavioral problems. Differences between groups existed at pretreatment baseline. Over time, notwithstanding stable percentages of poor scores in both groups, nonpersistence of poor scores was impressive (each time other children scored poorly in other domains). Rather than epilepsy characteristics, contextual adversities were significant risk factors. Conclusion. Already in the earliest stage of the illness, children with epilepsy are liable to vicissitudes in cognitive and behavioral functioning. Contextual variables are all-important

Treatment of cryptoglandular fistulas with the fistula tract laser closure (FiLaC™) method in comparison with standard methods: first results of a multicenter retrospective comparative study in the Netherlands

Background: Current surgical closure techniques for sphincter-sparing treatment of high cryptoglandular fistulas in the Netherlands include the mucosal advancement flap procedure (MAF) and ligation of the intersphincteric fistula tract (LIFT). A relatively novel treatment is the fistula tract laser closure (FiLaC™) method. The aim of this study was to investigate the differences in healing and recurrence rates between FiLaC™ and current standard practices. Methods: This multicenter retrospective cohort study included both primary and recurrent high cryptoglandular anorectal fistulas, treated with either FiLaC™ or standard methods (MAF or LIFT) between September 2015 and July 2020. Patients with extrasphincteric fistulas, Crohn’s disease, multiple fistulas, age < 18 years or missing data regarding healing time or recurrence were excluded. The primary outcomes were the clinical primary and secondary healing and recurrence rates. Primary healing was defined as a closed external opening without fluid discharge within 6 months of treatment on examination, while secondary healing was the same endpoint after secondary treatment. Secondary outcomes included healing time and complaints. Results: A total of 162 high fistulas from 3 Dutch hospitals were included. Ninety-nine high fistulas were treated with FiLaC™ and 63 with either MAF or LIFT. There were no significant differences between FiLaC™ and MAF/LIFT in terms of clinical healing (55.6% versus 58.7%, p =.601), secondary healing (70.0% versus 69.2%, p =.950) or recurrence rates (49.5% versus 54%, p =.420), respectively. Median follow-up duration was 7.1 months in the FiLaC™ group (interquartile range [IQR] 4.1–14.4 months) versus 6 months in the control group (IQR 3.5–8.1 months). Conclusions: FiLaC™ treatment of high anorectal fistulas does not appear to be inferior to MAF or LIFT. Based on these preliminary results, FiLaC™ can be considered as a worthwhile treatment option for high cryptoglandular fistulas. Prospective studies with a longer follow-up period and well-determined postoperative parameters such as complication rates, magnetic resonance imaging for confirmation of fistula healing, incontinence and quality of life are warranted

COVID-19 patients exhibit less pronounced immune suppression compared with bacterial septic shock patients

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