The role of autologous stem cell transplantation (ASCT) in aggressive B-cell lymphomas: real-world data from a retrospective single-center analysis.

Patients with high-risk or relapsed aggressive B-cell lymphomas are characterized by poor prognosis. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) can induce durable remissions in these patients and is potentially curative. Two hundred forty-seven patients with aggressive B-cell lymphomas treated with high-dose chemotherapy and ASCT, either as consolidation after first-line therapy or after salvage therapy for relapsed disease, between 2002 and 2019 at the University Hospital Muenster, were analyzed. The median follow-up of surviving patients was 36 months (range 0-163). Progression-free survival (PFS) and overall survival (OS) after 3 years was 63% and 68%, respectively. After ASCT, 28% of all patients experienced a relapse. The cumulative incidence of non-relapse mortality at day 100 after ASCT was 4%. Multivariate analysis identified remission status at ASCT, age at ASCT, and the numbers of infused CD34+ cells as independent prognostic factors for both PFS and OS. Patients with mantle cell lymphoma (MCL) or primary CNS lymphoma (PCNSL) treated with ASCT in first-line had a superior OS and PFS when compared to patients treated with ASCT in relapsed disease. For patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), early relapse (< 12 months) after first-line therapy showed a trend towards an inferior PFS and OS. Deaths after ASCT were predominantly caused by lymphoma relapse and/or progression (64%) or due to infections (23%). In conclusion, high-dose chemotherapy followed by ASCT in the era of novel targeted agents remains a feasible and effective approach for patients with high-risk or relapsed aggressive B-cell lymphomas. Remission status and age at ASCT, and the number of infused stem cells were of prognostic relevance.

[Evaluation of Short-term Psychoanalytic Child Therapy (PaCT) for Young Children with Depressive Disorders: Results from a Pilot Study]. / Evaluation der Psychoanalytischen Kurzzeittherapie (PaKT) für junge Kinder mit depressiven Störungen: Ergebnisse der Pilotstudie.

Depressive disorders in early childhood are associated with high psychosocial impairment and tend to remain stable over time without adequate treatment. Short-term psychoanalytic therapy is a common form of child psychotherapy, yet there is a lack of empirical evaluation of this approach for young children with depressive disorders. Therefore, this secondary evaluation of a study on the treatment of anxiety disorders used an uncontrolled pre-post design in a clinical setting to investigate whether children with depressive comorbidity would evidence significant diagnostic and symptomatic remission after treatment with manualized short-term Psychoanalytic Child Therapy (PaCT). Nineteen children who had an anxiety disorder and a (subclinical) depressive disorder (assessed with the Preschool Age Psychiatric Assessment using DSM-IV criteria) were treated with PaCT. After treatment, 15 of 19 children (78.94 %) were remitted and 15 of 17 children (88.24 %; 2 were lost to follow-up) were free of depressive disorders at the 6-month follow-up. Further analyses revealed significant effects for pre- to post and pre- to follow-up comparisons regarding internalizing symptoms and overall problems using parent- and (nursery-)teacher-ratings. These results suggest that short-term PaCT shows promise as a treatment for childhood depressive disorders.

Latent trajectories of internalizing symptoms from preschool to school age: A multi-informant study in a high-risk sample.

Recent proposals suggest early adversity sets in motion particularly chronic and neurobiologically distinct trajectories of internalizing symptoms. However, few prospective studies in high-risk samples delineate distinct trajectories of internalizing symptoms from preschool age onward. We examined trajectories in a high-risk cohort, oversampled for internalizing symptoms, several preschool risk/maintenance factors, and school-age outcomes. Parents of 325 children completed the Strengths and Difficulties Questionnaire on up to four waves of data collection from preschool (3-5 years) to school age (8-9 years) and Preschool Age Psychiatric Assessment interviews at both ages. Multi-informant data were collected on risk factors and symptoms. Growth mixture modelling identified four trajectory classes of internalizing symptoms with stable low, rising low-to-moderate, stable moderate, and stable high symptoms. Children in the stable high symptom trajectory manifested clinically relevant internalizing symptoms, mainly diagnosed with anxiety disorders/depression at preschool and school age. Trajectories differed regarding loss/separation experience, maltreatment, maternal psychopathology, temperament, and stress-hormone regulation with loss/separation, temperament, maternal psychopathology, and stress-hormone regulation (trend) significantly contributing to explained variance. At school age, trajectories continued to differ on symptoms, disorders, and impairment. Our study is among the first to show that severe early adversity may trigger a chronic and neurobiologically distinct internalizing trajectory from preschool age onward.

Commentary: The dynamic panel model: a promising approach to clarify sources of influence in developmental psychopathology - a commentary on Wichstrøm et al. (2017).

In their study, Wichstrøm et al. (2017) have proposed a novel groundbreaking approach for developmental psychopathology that undoubtedly will inspire other research. Applying the dynamic panel model (DPM), the authors were able to show that within-disorder (homotypic) and between-disorder (heterotypic) continuities of psychiatric symptoms are mostly due to unmeasured time-invariant factors while only few effects of earlier symptoms on later symptoms remained significant after accounting for these factors. The DPM calls for future applications of this approach to samples across different countries, diverse developmental phases, and in various settings - community samples and clinical samples alike.

Cause or consequence? Investigating attention bias and self-regulation skills in children at risk for obesity.

Impaired self-regulation, especially in food-specific situations, has been linked to childhood obesity. These deficits may be acquired during the development of obesity rather than being a prerequisite thereof. The current study, hence, focused on an at-risk population versus controls. Normal-weight children of obese and normal-weight parents were tested regarding attentional flexibility, emotion regulation, and inhibitory control. A sample of 50 preschoolers of obese parents (n=25) or normal-weight parents (n=25) participated in this study. Through eye-tracking, attentional bias for food cues was measured during a visual probe task using food and toy images. Emotion regulation was assessed during a distress-evoking task, and inhibitory control was examined through a delay-of-gratification task. Both tasks are standardized and were conducted in non-food contexts. Results showed no significant group differences in overall attentional bias to food images over toy images. However, children of normal-weight parents showed a preference for toy images. Regarding emotion regulation, children in the risk group expressed significantly less overall emotional distress. In addition, less gaze aversion and bodily sadness could be observed in this group. No differences were found for inhibitory control. Findings suggest that general deficits in self-regulation are not yet present in normal-weight children at risk for obesity. Instead, they might develop as a by-product of unhealthy weight gain. Results indicate, however, that children of obese parents are less emotionally expressive compared with children of normal-weight parents. Furthermore, children of normal-weight parents appeared to be more interested in toy images than in food images.

Recruitment strategies in a prospective longitudinal family study on parents with obesity and their toddlers.

BACKGROUND: Recruitment of participants with obesity is a real challenge. To reduce time and costs in similar projects, we investigated various recruiting strategies used in a longitudinal family study with respect to their enrolment yield and cost effectiveness. Results may help other research groups to optimize their recruitment strategies. METHODS: We applied different recruitment strategies to acquire families with children aged 6 to 47 months and at least one parent with obesity (risk group) or two parents of normal weight (control group) for a longitudinal non-interventional study. Based on four main strategies-via media, kindergartens, health professionals and focusing on the community-we examined 15 different subcategories of strategies. Based on enrolment yield and relative costs (e.g., material expenses, staff time) we analyzed the effectiveness of each recruitment strategy. RESULTS: Following different recruitment approaches, 685 families contacted us; 26% (n = 178) of these met the inclusion criteria. Of the four main strategies, the community-focused strategy was the most successful one (accounting for 36.5% of the sample) followed by contacts with kindergartens (accounting for 28.1% of the sample). Of the subcategories, two strategies were outstanding: Posters (community-focused strategies), and recruitment via kindergartens using phone contacts rather than emailing. Only a small number of participants were recruited via announcements in newspapers (lower cost strategy), advertisements on public transport or face-to-face recruitment at various places (higher cost strategies). CONCLUSIONS: Results revealed that only a combination of different active and passive methods and approaches led to a sufficient sample size. In this study, recruitment via posters and contacting kindergartens on the phone produced the highest numbers of participants (high enrolment yield) at moderate costs.

Maternal mentalization affects mothers' - but not children's - weight via emotional eating.

Previous research on childhood obesity has shown that maternal obesity is an important risk factor for this malady. Because biological and environmental factors are able to explain the transgenerational transmission of obesity only in part, psychological risk factors (e.g., emotional eating) have become more important in recent research. As maternal mentalization - which lays the foundation for the child's ability to regulate his/her emotions - has not yet been investigated, we examined the effects of mentalization on maternal and childhood obesity. By investigating groups of obese (n = 30) and normal-weight (n = 30) mothers and their children aged 18 to 55 months, we found, contrary to our expectations, that obese mothers' mentalization (Reflective Functioning Scale) was similar to that of mothers with normal weight and that mentalization showed no direct effect on the child's weight. However, we found hints of an indirect influence of mentalization via emotional eating on mothers' but not on children's weight and via mother-child attachment (Attachment Q-Set) on children's weight. Possible reasons for these inconclusive effects are discussed.

Insatiable insecurity: maternal obesity as a risk factor for mother-child attachment and child weight.

Childhood obesity has become a rising health problem, and because parental obesity is a basic risk factor for childhood obesity, biological factors have been especially considered in the complex etiology. Aspects of the family interaction, e.g., mother-child attachment, have not been the main focus. Our study tried to fill this gap by investigating whether there is a difference between children of obese and normal weight mothers in terms of mother-child attachment, and whether mother-child attachment predicts child's weight, in a sample of 31 obese and 31 normal weight mothers with children aged 19 to 58 months. Mother-child attachment was measured with the Attachment Q-Set. We found that (1) children of obese mothers showed a lower quality of mother-child attachment than children of normal weight mothers, which indicates that they are less likely to use their mothers as a secure base; (2) the attachment quality predicted child`s BMI percentile; and (3) the mother-child attachment adds incremental validity to the prediction of child's BMI beyond biological parameters (child's BMI birth percentile, BMI of the parents) and mother's relationship status. Implications of our findings are discussed.

Obese parents--obese children? Psychological-psychiatric risk factors of parental behavior and experience for the development of obesity in children aged 0-3: study protocol.

BACKGROUND: The incidences of childhood overweight and obesity have increased substantially and with them the prevalence of associated somatic and psychiatric health problems. Therefore, it is important to identify modifiable risk factors for early childhood overweight in order to develop effective prevention or intervention programs. Besides biological factors, familial interactions and parental behavioral patterns may influence children's weight development. Longitudinal investigation of children at overweight risk could help to detect significant risk and protective factors. We aim to describe infants' weight development over time and identify risk and protective factors for the incidence of childhood obesity. Based on our findings we will draw up a risk model that will lay the foundation for an intervention/prevention program. METHODS/DESIGN: We present the protocol of a prospective longitudinal study in which we investigate families with children aged from 6 months to 47 months. In half of the families at least one parent is obese (risk group), in the other half both parents are normal weight (control group). Based on developmental and health-psychological models, we consider measurements at three levels: the child, the parents and parent-child-relationship. Three assessment points are approximately one year apart. At each assessment point we evaluate the psychological, social, and behavioral situation of the parents as well as the physical and psychosocial development of the child. Parents are interviewed, fill in questionnaires, and take part in standardized interaction tasks with their child in a feeding and in a playing context in our research laboratory. The quality of these video-taped parent-child interactions is assessed by analyzing them with standardized, validated instruments according to scientific standards. DISCUSSION: Strengths of the presented study are the prospective longitudinal design, the multi-informant approach, including the fathers, and the observation of parent-child interaction. A limitation is the variation in children's age.

Maternal sensitivity and intrusiveness in early childhood as predictors of children's weight at school age.

BACKGROUND: While previous research indicates that low maternal sensitivity in mother-child interactions puts children at risk of overweight and obesity, maternal intrusiveness has rarely been investigated in association with children's weight. We investigated whether maternal sensitivity and intrusiveness in early childhood predict children's increased body mass index standard deviation scores (BMI-SDS) at school age. BMI-SDS are standardized for age and gender with respect to a reference standard. METHODS: At baseline (t1), we assessed maternal sensitivity and (non-)intrusiveness of 116 mothers with their children (48.3% female) aged 5-47 months (M = 24.00, SD = 11.36) using the emotional availability scales. We obtained anthropometric data for mothers at t1 by measuring height and weight in the laboratory and for children at birth assessed by medical staff. Six years later (t2) we obtained anthropometric data for children in the laboratory or based on parental report. Linear regression analyses were run with child BMI-SDS at t2 as outcome and sensitivity and (non-)intrusiveness as predictors, adjusting for confounders and exploring child age and gender as moderators. RESULTS: Maternal sensitivity only negatively predicted children's BMI-SDS in girls, while maternal intrusiveness predicted higher child BMI-SDS at school age regardless of child gender. The effect of maternal non-intrusiveness remained significant when controlling for confounders. CONCLUSION: Maternal intrusiveness in early childhood seems to represent a risk factor for increased BMI-SDS in children, while lower maternal sensitivity tends to be a risk factor for increased BMI-SDS in girls. This may have implications for prevention or intervention programmes.

[Fathers of children born to adolescent mothers and their interactive behavior]. / Väter von Kindern minderjähriger Mütter in der Interaktionsbeobachtung.

Adolescent mothers and their children received much scientific attention in the past. Some studies also looked at characteristics of the interaction between mother and child. However, little is known about the interaction between children of adolescent mothers and their fathers, as research to date has focussed on paternal psychosocial aspects. The present study examines 19 partners of adolescent mothers in the interaction with their four-months-old infants. Results indicate that fathers of this sample--despite a sufficiently large intuitive repertoire--mainly relate to their infants with tactile stimulation and behaviours that facilitate eye contact. Most fathers succeed in adjusting their behaviour to their child's state. Fathers who are able to adjust their behaviour to their child's state show a larger repertoire of intuitive capacity. The infant's readiness to interact is associated with successful paternal adjustment. We discuss implications for involving fathers in the clinical work with children of adolescent mothers.

Sandwich Immunoassay for Bioactive Plasma Adrenomedullin.

BACKGROUND: Adrenomedullin (ADM) is a circulating peptide known to regulate vasodilation and vascular integrity. Increased plasma ADM concentrations have been described for several life-threatening conditions, including cardiovascular diseases and septic shock. Reliable methods for the simple quantification of bioactive ADM (bio-ADM) are lacking. METHODS: Monoclonal antibodies against the amidated C-terminus and middle portion of bio-ADM were generated and used for the development of a 1-step immunometric assay for the specific quantification of bio-ADM in plasma. The assay was developed in a microtiter plate/chemiluminescence label format with a significantly reduced incubation time. Precision, linearity, specimen stability, and distribution of results in healthy subjects were evaluated. RESULTS: The use of monoclonal antibodies against predetermined epitopes of bio-ADM enabled the development of an assay for the determination of bio-ADM directly in EDTA plasma. Plasma samples were stable for up to 24 h at ambient temperature and over multiple freeze-thaw cycles without loss of immunoreactivity. The assay had a limit of detection of 3 pg/mL and a limit of quantification of 11 pg/mL. The assay exhibited acceptable linearity characteristics and was not influenced by complement factor H, a putative ADM-binding protein. In healthy subjects, bio-ADM concentrations were all above the limit of detection, and approximately half of them were above the limit of quantification. CONCLUSIONS: By using monoclonal antibodies with defined epitope specificities, we have developed a simple, rapid, accurate, and sensitive sandwich immunoassay for bio-ADM. The assay is a potentially novel tool to support patient management, particularly in acute care in the field of sepsis and other indications, which are currently being investigated, such as acute heart failure.

Breastfeeding in Obese versus Normal-Weight German Mothers of Various Socioeconomic Status.

BACKGROUND: To a large extent, breastfeeding practices depend on cultural norms. It is thus of particular importance to examine these practices in various settings, especially when considering the effect of complex factors, such as body mass index (BMI) or socioeconomic status. OBJECTIVE: This study aimed to compare the breastfeeding practices of obese mothers with those of normal weight, taking into account social and economic status. METHODS: Obese (BMI ≥ 30 kg/m(2)) and normal-weight (18.5 kg/m(2) ≤ BMI < 25 kg/m(2)) mothers with children between the ages of 6 months and 3 years were recruited for this study in Leipzig, Germany, via newspaper ads and other means. Kaplan-Meier curves for portraying breastfeeding over time were analyzed using Cox regression after checking the proportional hazards model. RESULTS: Eighty obese and 70 normal-weight mothers were recruited. Significantly fewer obese mothers breastfed (84%) than normal-weight mothers (96%) (95% confidence interval [CI] for the difference is 3 to 22 percentage points, P = .02). Even after adjusting for the level of education and family income, breastfeeding duration was significantly shorter (2.7 months; 95% CI, 0.8-4.6 months; P = .005) in the obese group than in the normal-weight group. CONCLUSION: Our findings demonstrate that even at the earliest stages, breastfeeding behavior of obese mothers differs from that of normal-weight mothers.

Maternal Weight Predicts Children's Psychosocial Development via Parenting Stress and Emotional Availability.

INTRODUCTION: Maternal obesity has been shown to be a risk factor for obesity in children and may also affect children's psychosocial outcomes. It is not yet clear whether there are also psycho-emotional mechanisms explaining the effects of maternal weight on young children's weight and psychosocial development. We aimed to evaluate whether maternal body mass index (BMI), mother-child emotional availability (EA), and maternal parenting stress are associated with children's weight and psychosocial development (i.e., internalizing/externalizing symptoms and social competence) and whether these predictors interact with each other. METHODS: This longitudinal study included three assessment points (~11 months apart). The baseline sample consisted of N = 194 mothers and their children aged 5-47 months (M = 28.18, SD = 8.44, 99 girls). At t 1, we measured maternal weight and height to calculate maternal BMI. We videotaped mother-child interactions, coding them with the EA Scales (fourth edition). We assessed maternal parenting stress with the Parenting Stress Index (PSI) short form. At t 1 to t 3, we measured height and weight of children and calculated BMI-SDS scores. Children's externalizing and internalizing problems (t 1-t 3) and social competence (t 3, N = 118) were assessed using questionnaires: Child Behavior Checklist (CBCL 1.5-5), Strengths and Difficulties Questionnaire (SDQ: prosocial behavior), and a checklist for behavioral problems at preschool age (VBV 3-6: social-emotional competence). RESULTS: By applying structural equation modeling (SEM) and a latent regression analysis, we found maternal BMI to predict higher BMI-SDS and a poorer psychosocial development (higher externalizing symptoms, lower social competence) in children. Higher parenting stress predicted higher levels of externalizing and internalizing symptoms and lower social competence. Better maternal EA was associated with higher social competence. We found parenting stress to serve as a mediator in the association between maternal weight and children's psychosocial outcomes. Moreover, children of mothers with an elevated BMI were at greater risk of lower social competence only when their mothers showed low levels of maternal EA (moderation). CONCLUSION: Interventional studies are needed that investigate the causal pathways between parenting stress, mother-child interaction quality and child outcomes. These aspects might be targets to improve the psychosocial development of the offspring of overweight or obese mothers.

Emotional availability, understanding emotions, and recognition of facial emotions in obese mothers with young children.

OBJECTIVE: Recent research has identified mother-child relationships of low quality as possible risk factors for childhood obesity. However, it remains open how mothers' own obesity influences the quality of mother-child interaction, and particularly emotional availability (EA). Also unclear is the influence of maternal emotional competencies, i.e. understanding emotions and recognizing facial emotions. This study aimed to (1) investigate differences between obese and normal-weight mothers regarding mother-child EA, maternal understanding emotions and recognition of facial emotions, and (2) explore how maternal emotional competencies and maternal weight interact with each other in predicting EA. A better understanding of these associations could inform strategies of obesity prevention especially in children at risk. METHODS: We assessed EA, understanding emotions and recognition of facial emotions in 73 obese versus 73 normal-weight mothers, and their children aged 6 to 47 months (Mchild age=24.49, 80 females). RESULTS: Obese mothers showed lower EA and understanding emotions. Mothers' normal weight and their ability to understand emotions were positively associated with EA. The ability to recognize facial emotions was positively associated with EA in obese but not in normal-weight mothers. Maternal weight status indirectly influenced EA through its effect on understanding emotions. CONCLUSION: Maternal emotional competencies may play an important role for establishing high EA in interaction with the child. Children of obese mothers experience lower EA, which may contribute to overweight development. We suggest including elements that aim to improve maternal emotional competencies and mother-child EA in prevention or intervention programmes targeting childhood obesity.

Freeze-drying of HESylated IFNα-2b: Effect of HESylation on storage stability in comparison to PEGylation.

A comparison of lyophilized PEGylated and HESylated IFNα was carried out to investigate the influence of protein conjugation, lyoprotectants as well as storage temperature on protein stability. Results show that PEG tends to crystallize during freeze-drying, reducing protein stability upon storage. In contrast, HESylation(®) drastically improved the stability over PEGylation by remaining totally amorphous during lyophilization, with and without lyoprotectants while providing a high glass transition temperature of the freeze-dried cakes.

Parent-child interaction during feeding or joint eating in parents of different weights.

The current study investigates parent-child interaction during feeding or during joint eating, and aimed to explore differences in feeding interactions between mothers and fathers, as well as between overweight, obese and not overweight parents. 148 mothers and 148 fathers with children aged between 7 and 47months were observed during feeding of or joint eating with their child in the laboratory. The videotaped mother-child and father-child dyads were coded using the Chatoor Feeding Scale. This scale consists of 5 subscales: Dyadic Reciprocity, Dyadic Conflict, Talk and Distraction during Feeding, Struggle for Control, and Non-Contingency. Compared to mothers, fathers showed higher readings on the Talk and Distraction scale; in all other subscales no differences were found. The comparison between overweight, obese and not overweight mother-child dyads revealed no significant differences. Differences in father-child dyads between overweight, obese and not overweight fathers were identified in the subscale Struggle for Control: overweight fathers were marked by a higher amount of Struggle for Control than obese and not overweight fathers. Taken together, differences found in the present observational study are small to moderate, and thus the current results support extant literature demonstrating that there are no differences in feeding behaviour between mothers and fathers or between obese and non-obese parents.