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Article ; Online: Being the Pillar for Children with Rare Diseases—A Systematic Review on Parental Quality of Life

Johannes Boettcher / Michael Boettcher / Silke Wiegand-Grefe / Holger Zapf

International Journal of Environmental Research and Public Health, Vol 18, Iss 4993, p

2021 Volume 4993

Abstract: Parents caring for children with rare diseases fear the long-term progression of the child’s disease. The current study aims to systematically investigate the quality of life (QoL) in parents of children with different rare diseases. We performed a ... ...

Abstract	Parents caring for children with rare diseases fear the long-term progression of the child’s disease. The current study aims to systematically investigate the quality of life (QoL) in parents of children with different rare diseases. We performed a systematic literature search including quantitative studies on QoL of parents caring for children and adolescents with rare diseases in five databases (APA PsycArticles, APA PsycInfo, MEDLINE, PSYNDEXplus, and PubMed) published between 2000–2020. Of the 3985 titles identified, 31 studies met the inclusion criteria and were selected for narrative review. Studies were included if they investigated predictors of parental QoL or reported QoL compared to normative samples, parents of healthy children, or children with other chronic diseases. We used the Newcastle–Ottawa Scale to assess methodological quality. The systematic review revealed that parents of children with rare diseases experience reduced QoL compared to parents with healthy children and norm values. Psychosocial factors, beyond disease-specific predictors, were shown to influence parental QoL substantially and may thus present an essential aspect within interventions for this highly burdened group. Health care professionals should consider and address the impairment of parental QoL due to the child’s rare disease. We discuss insights into existing research gaps and improvements for subsequent work.
Keywords	quality of life ; parents ; rare diseases ; systematic review ; caregivers ; Medicine ; R
Subject code	360 ; 610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Development of CAR T Cell Therapy in Children—A Comprehensive Overview

Michael Boettcher / Alexander Joechner / Ziduo Li / Sile Fiona Yang / Patrick Schlegel

Journal of Clinical Medicine, Vol 11, Iss 8, p

2022 Volume 2158

Abstract: CAR T cell therapy has revolutionized immunotherapy in the last decade with the successful establishment of chimeric antigen receptor (CAR)-expressing cellular therapies as an alternative treatment in relapsed and refractory CD19-positive leukemias and ... ...

Abstract	CAR T cell therapy has revolutionized immunotherapy in the last decade with the successful establishment of chimeric antigen receptor (CAR)-expressing cellular therapies as an alternative treatment in relapsed and refractory CD19-positive leukemias and lymphomas. There are fundamental reasons why CAR T cell therapy has been approved by the Food and Drug administration and the European Medicines Agency for pediatric and young adult patients first. Commonly, novel therapies are developed for adult patients and then adapted for pediatric use, due to regulatory and commercial reasons. Both strategic and biological factors have supported the success of CAR T cell therapy in children. Since there is an urgent need for more potent and specific therapies in childhood malignancies, efforts should also include the development of CAR therapeutics and expand applicability by introducing new technologies. Basic aspects, the evolution and the drawbacks of childhood CAR T cell therapy are discussed as along with the latest clinically relevant information.
Keywords	evolution of CAR T cells ; FDA-approved CAR products ; TcR versus CAR ; limitations and complications of CAR T cell therapy ; future directions of CAR T cell therapy ; Medicine ; R
Subject code	380
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Radiomics-Assisted Computed Tomography-Based Analysis to Evaluate Lung Morphology Characteristics after Congenital Diaphragmatic Hernia

Silviu-Viorel Virlan / Matthias F. Froelich / Greta Thater / Neysan Rafat / Julia Elrod / Michael Boettcher / Stefan O. Schoenberg / Meike Weis

Journal of Clinical Medicine, Vol 12, Iss 24, p

2023 Volume 7700

Abstract: Purpose: Children with congenital diaphragmatic hernia suffer from long-term morbidity, including lung function impairment. Our study aims to analyze lung morphology characteristics via radiomic-assisted extraction of lung features in patients after ... ...

Abstract	Purpose: Children with congenital diaphragmatic hernia suffer from long-term morbidity, including lung function impairment. Our study aims to analyze lung morphology characteristics via radiomic-assisted extraction of lung features in patients after congenital diaphragmatic hernia repair. Materials and Methods: 72 patients were retrospectively analyzed after approval by the local research ethics committee. All the image data were acquired using a third-generation dual-source CT (SOMATOM Force, Siemens Healthineers, Erlangen, Germany). Dedicated software was used for image analysis, segmentation, and processing. Results: Radiomics analysis of pediatric chest CTs of patients with status after CDH was possible. Between the ipsilateral (side of the defect) and contralateral lung, three shape features and two higher-order texture features were considered statistically significant. Contralateral lungs in patients with and without ECMO treatment showed significant differences in two shape features. Between the ipsilateral lungs in patients with and without the need for ECMO 1, a higher-order texture feature was depicted as statistically significant. Conclusions: By adding quantitative information to the visual assessment of the radiologist, radiomics-assisted feature analysis could become an additional tool in the future to assess the degree of lung hypoplasia in order to further improve the therapy and outcome of CDH patients.
Keywords	congenital diaphragmatic hernia ; radiomics ; ECMO ; pulmonary hypoplasia ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fetal MRI-Based Mediastinal Shift Angle (MSA) and Percentage Area of Left Ventricle (pALV) as Prognostic Parameters for Congenital Diaphragmatic Hernia

Greta Thater / Lara Angermann / Silviu-Viorel Virlan / Christel Weiss / Neysan Rafat / Michael Boettcher / Julia Elrod / Tom Bayer / Oliver Nowak / Stefan O. Schönberg / Meike Weis

Journal of Clinical Medicine, Vol 13, Iss 1, p

2024 Volume 268

Abstract: Objective: Fetal magnetic resonance imaging (MRI) is broadly used as a method for assessing prognosis in congenital diaphragmatic hernia (CDH). In addition to the extent of lung hypoplasia, determined by measuring the lung volume, cardiac impairment due ... ...

Abstract	Objective: Fetal magnetic resonance imaging (MRI) is broadly used as a method for assessing prognosis in congenital diaphragmatic hernia (CDH). In addition to the extent of lung hypoplasia, determined by measuring the lung volume, cardiac impairment due to pulmonary hypertension and left cardiac hypoplasia is decisive for the prognosis. The percentage area of left ventricle (pALV) describes the percentage of the inner area of the left ventricle in relation to the total area, whereas the mediastinal shift angle (MSA) quantifies the extent of cardiac displacement. The prognostic value of pALV and MSA should be evaluated in terms of survival, the need for extracorporeal membrane oxygenation (ECMO) therapy, and the development of chronic lung disease (CLD). Methods: In a total of 122 fetal MRIs, the MSA and pALV were measured retrospectively and complete outcome parameters were determined regarding survival for all 122 subjects, regarding ECMO therapy in 109 cases and about the development of CLD in 78 cases. The prognostic value regarding the endpoints was evaluated using logistic regression and ROC analysis. Results: The MSA was significantly higher in children who received ECMO therapy ( p = 0.0054), as well as in children who developed CLD ( p = 0.0018). ROC analysis showed an AUC of 0.68 for ECMO requirement and 0.77 with respect to CLD development. The pALV showed a tendency towards higher levels in children who received ECMO therapy ( p = 0.0824). The MSA and the pALV had no significant effect on survival (MSA: p = 0.4293, AUC = 0.56; pALV: p = 0.1134, AUC = 0.57). Conclusions: The MSA determined in fetal MRI is a suitable prognostic parameter for ECMO requirement and CLD development in CDH patients and can possibly be used as a supplement to the established parameters.
Keywords	congenital diaphragmatic hernia (CDH) ; mediastinal shift angle (MSA) ; percentage area of left ventricle (pALV) ; prenatal diagnosis of CDH ; prognostic parameters CDH ; fetal MRI ; Medicine ; R
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification of X-chromosomal genes that drive sex differences in embryonic stem cells through a hierarchical CRISPR screening approach

Oriana Genolet / Anna A. Monaco / Ilona Dunkel / Michael Boettcher / Edda G. Schulz

Genome Biology, Vol 22, Iss 1, Pp 1-

2021 Volume 41

Abstract: Abstract Background X-chromosomal genes contribute to sex differences, in particular during early development, when both X chromosomes are active in females. Double X-dosage shifts female pluripotent cells towards the naive stem cell state by increasing ... ...

Abstract	Abstract Background X-chromosomal genes contribute to sex differences, in particular during early development, when both X chromosomes are active in females. Double X-dosage shifts female pluripotent cells towards the naive stem cell state by increasing pluripotency factor expression, inhibiting the differentiation-promoting MAP kinase (MAPK) signaling pathway, and delaying differentiation. Results To identify the genetic basis of these sex differences, we use a two-step CRISPR screening approach to comprehensively identify X-linked genes that cause the female pluripotency phenotype in murine embryonic stem cells. A primary chromosome-wide CRISPR knockout screen and three secondary screens assaying for different aspects of the female pluripotency phenotype allow us to uncover multiple genes that act in concert and to disentangle their relative roles. Among them, we identify Dusp9 and Klhl13 as two central players. While Dusp9 mainly affects MAPK pathway intermediates, Klhl13 promotes pluripotency factor expression and delays differentiation, with both factors jointly repressing MAPK target gene expression. Conclusions Here, we elucidate the mechanisms that drive sex-induced differences in pluripotent cells and our approach serves as a blueprint to discover the genetic basis of the phenotypic consequences of other chromosomal effects.
Keywords	X chromosome ; Gene dosage ; Embryonic stem cells ; Sex differences ; Pluripotency ; MAPK signaling ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
Subject code	570
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Feasibility of using breath sampling of non-volatiles to estimate the prevalence of illicit drug use among nightlife attendees

Kristin Feltmann / Tobias H. Elgán / Michael Böttcher / Stefan Lierheimer / Sigurd Hermansson / Olof Beck / Johanna Gripenberg

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 9

Abstract: Abstract The prevalence of drug use among nightlife attendees needs to be accurately estimated to, for example, evaluate preventive interventions. This study tested the feasibility of using a breath-sampling device to estimate the prevalence of drug use ... ...

Abstract	Abstract The prevalence of drug use among nightlife attendees needs to be accurately estimated to, for example, evaluate preventive interventions. This study tested the feasibility of using a breath-sampling device to estimate the prevalence of drug use among nightlife attendees. The study was conducted at five nightclubs and a large music festival in Stockholm, Sweden. Participants were invited to participate and microparticles in exhaled breath were sampled and analyzed for 47 compounds using a state-of-the-art analytic method that follows forensic standards. In addition, participants’ breath alcohol concentration was measured and they were interviewed about demographics, drinking habits, and drug use. Of the people invited, 73.7% (n = 1223) agreed to participate, and breath samples were collected from 1204 participants. Breath sampling was fast and well-accepted by participants. 13 percent of participants tested positive for an illicit drug, but only 4.3% self-reported drug use during the last 48 h. The most common substances detected were cocaine, amphetamine, and MDMA. There was no agreement between self-reported and measured use of any drug. Breath sampling is a convenient method to test illicit drug use among a large number of participants at events, and can be used as an estimate of drug use prevalence.
Keywords	Medicine ; R ; Science ; Q
Subject code	150
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: cfDNA and DNases

Moritz Lenz / Thomas Maiberger / Lina Armbrust / Antonia Kiwit / Axel Von der Wense / Konrad Reinshagen / Julia Elrod / Michael Boettcher

Cells, Vol 11, Iss 192, p

New Biomarkers of Sepsis in Preterm Neonates—A Pilot Study

2022 Volume 192

Abstract: Introduction: An early and accurate diagnosis of early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) is essential to improve the outcome of this devastating conditions. Especially, preterm infants are at risk. Reliable biomarkers are ...

Abstract	Introduction: An early and accurate diagnosis of early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) is essential to improve the outcome of this devastating conditions. Especially, preterm infants are at risk. Reliable biomarkers are rare, clinical decision-making depends on clinical appearance and multiple laboratory findings. Markers of NET formation and NET turnover might improve diagnostic precision. Aim of this study was to evaluate the diagnostic value of NETs in sepsis diagnosis in neonatal preterm infants. Methods: Plasma samples of neonatal preterm infants with suspected sepsis were collected. Blood samples were assayed for markers of NET formation and NET turnover: cfDNA, DNase1, nucleosome, NE, and H3Cit. All clinical findings, values of laboratory markers, and epidemiological characteristics were collected retrospectively. Two subpopulations were created to divide EONS from LONS. EMA sepsis criteria for neonatal sepsis were used to generate a sepsis group (EMA positive) and a control group (EMA negative). Results: A total of 31 preterm neonates with suspected sepsis were included. Out of these, nine patients met the criteria for sepsis according to EMA. Regarding early onset neonatal sepsis (3 EONS vs. 10 controls), cfDNA, DNase I, nucleosome, and CRP were elevated significantly. H3Cit and NE did not show any significant elevations. In the late onset sepsis collective (6 LONS vs. 12 controls), cfDNA, DNase I, and CRP differed significantly compared to control group.
Keywords	sepsis ; NETs ; extracellular DNA ; neutrophil extracellular traps ; preterm infants ; early onset neonatal sepsis ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Midgut Volvulus Adds a Murine, Neutrophil-Driven Model of Septic Condition to the Experimental Toolbox

Julia Elrod / Antonia Kiwit / Moritz Lenz / Holger Rohde / Daniela Börnigen / Malik Alawi / Christoph Mohr / Laia Pagerols Raluy / Magdalena Trochimiuk / Jasmin Knopf / Konrad Reinshagen / Martin Herrmann / Michael Boettcher

Cells, Vol 12, Iss 366, p

2023 Volume 366

Abstract: Background: Severe infections that culminate in sepsis are associated with high morbidity and mortality. Despite continuous efforts in basis science and clinical research, evidence based-therapy is mostly limited to basic causal and supportive measures. ... ...

Abstract	Background: Severe infections that culminate in sepsis are associated with high morbidity and mortality. Despite continuous efforts in basis science and clinical research, evidence based-therapy is mostly limited to basic causal and supportive measures. Adjuvant therapies often remain without clear evidence. The objective of this study was to evaluate the septic volvulus ischemia-reperfusion model in comparison to two already established models and the role of neutrophil extacellular traps (NETs) in this model. Methods: The technique of the murine model of midgut volvulus was optimized and was compared to two established models of murine sepsis, namely cecal ligation and puncture (CLP) and intra-peritoneal (i.p.) injection of lipopolysaccharide (LPS). Results: Midgut volvulus for 15 min caused a comparable mortality (38%) as CLP (55%) and peritoneal LPS injection (25%) at 48 h. While oxidative stress was comparable, levels of circulating free DNA (cfDNA), and splenic/hepatic and pulmonary translocation of bacteria were decreased and increased, respectively at 48 h. DNases were increased compared to the established models. Proteomic analysis revealed an upregulation of systemic Epo, IL-1b, Prdx5, Parp1, Ccl2 and IL-6 at 48 h in comparison to the healthy controls. Discussion and Conclusion: Midgut volvulus is a stable and physiological model for sepsis. Depending on the duration and subsequent tissue damage, it represents a combination of ischemia-reperfusion injury and hyperinflammation.
Keywords	sepsis ; extracellular DNA ; sepsis model ; volvulus ; CLP ; LPS ; Biology (General) ; QH301-705.5
Subject code	630
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Perceived mental health in parents of children with rare congenital surgical diseases

Johannes Boettcher / Holger Zapf / Mareike Fuerboeter / Rojin Nazarian / Konrad Reinshagen / Silke Wiegand-Grefe / Michael Boettcher

Orphanet Journal of Rare Diseases, Vol 16, Iss 1, Pp 1-

a double ABCX model considering gender

2021 Volume 10

Abstract: Abstract Background Previous research has supported the utility of the Double ABCX model of family adaptation for parents in various diseases. Nonetheless, it remains unclear how raising a child with rare congenital surgical diseases impacts the mental ... ...

Abstract	Abstract Background Previous research has supported the utility of the Double ABCX model of family adaptation for parents in various diseases. Nonetheless, it remains unclear how raising a child with rare congenital surgical diseases impacts the mental health of both mothers and fathers. Methods The potential predictors of maternal and paternal mental health in a German sample of 210 parents of children with rare congenital surgical diseases were investigated. Parents were investigated cross-sectionally utilizing standardized psychometric questionnaires that assessed factors attributed to parental adaptation within the Double ABCX model. Results Stressor pile-up, family functioning, perceived stress, and mental health were positively associated with mothers and fathers. However, further analyses revealed that family functioning, social support, and perceived stress fully mediated the positive association between stressor pile-up and mental health in mothers, but not fathers. Conclusion Our findings suggest that parental adaptation to a rare congenital surgical disease in their children may be improved by increased intra- and extrafamilial resources and decreased perceived family-related stress in mothers, but not fathers. Our results may help to identify gender-specific factors that may guide clinicians and future interventions.
Keywords	Mental health ; Rare diseases ; Parents ; Pediatric surgery ; Double ABCX model ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Time- and dose-dependent inhibition of neutrophil extracellular trap formation by blocking of the interleukin-1 receptor

Hannah Wadehn / Laia Pagerols Raluy / Jan Kolman / Charlotte Duecker / Magdalena Trochimiuk / Birgit Appl / Michael Boettcher / Konrad Reinshagen / Julian Trah

Central European Journal of Immunology, Vol 46, Iss 4, Pp 419-

2021 Volume 426

Abstract: Besides performing phagocytosis and degranulation, neutrophils are capable of eliminating microorganisms by releasing neutrophil extracellular traps (NETs). NET formation was found to be associated with increased mortality in sepsis. During sepsis levels ...

Abstract	Besides performing phagocytosis and degranulation, neutrophils are capable of eliminating microorganisms by releasing neutrophil extracellular traps (NETs). NET formation was found to be associated with increased mortality in sepsis. During sepsis levels of interleukin 1 (IL-1), a cytokine, increases significantly and also was associated with increased mortality. Blocking of the interleukin 1 (IL-1) receptor by anakinra leads to less NET formation in gout patients. However, NET formation is crucial during infection by trapping pathogens and thereby slowing the process. Total or early blocking of cascades leading to NETs may lead to aggravation of infection in otherwise mild cases. The dose- and time-dependent effect of the IL-1 receptor antagonist anakinra was tested on spontaneous, lipopolysaccharide (LPS)-induced and phorbol-12-myristate 13-acetate (PMA)-induced formation of NETs in vitro . Quantitative detection of NETs was performed for NETspecific proteins and cell-free DNA. Immunostained microscopy imaging was used for visualization. Our study shows a dose- and time-dependent inhibitory effect of anakinra that involves the change of intracellular calcium mobilization on the formation of NETs in vitro for PMA-stimulated neutrophils but not for LPS-stimulated neutrophils. It may be useful for treatment of sepsis as part of a multimodal treatment concept, but it seems that timing and dose need to be carefully chosen.
Keywords	neutrophil granulocytes ; neutrophil extracellular traps ; interleukin-1 receptor antagonist ; anakinra ; sepsis ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Termedia Publishing House
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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