Partial hepatectomy accelerates colorectal metastasis by priming an inflammatory premetastatic niche in the liver.

Background: Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression. Methods: CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry. Results: Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in de novo liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding. Conclusions: Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.

Clinical care of childhood sexual abuse: a systematic review and critical appraisal of guidelines from European countries.

Background: The clinical management of Child sexual abuse (CSA) demands specialised skills from healthcare professionals due to its sensitivity, legal implications, and serious physical health and mental health effects. Standardised, comprehensive clinical practice guidelines (CPGs) may be pivotal. In this systematic review, we examined existing CSA national CPGs (NCPGs) from European countries to assess their quality and reporting. Methods: We systematically searched six international databases and multiple grey literature sources, reporting by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Eligible guidelines were CSA guidance from national health agencies or societies in 34 COST Action 19106 Network Countries (CANC), published between January 2012 and November 2022. Two independent researchers searched, screened, reviewed, and extracted data. NCPGs were compared for completeness with reference WHO 2017 and 2019 guidelines. We used the Appraisal of Guidelines for Research and Evaluation (AGREE II) to appraise quality and reporting. PROSPERO: CRD42022320747. Findings: Of 2919 records identified by database searches, none met inclusion criteria. Of 4714 records identified by other methods, 24 NCPGs from 17 (50%) of CANC countries were included. In 17 (50%) of eligible countries, no NCPGs were found. Content varied significantly within and between countries. NCPGs lacked many components in state-of-the art clinical practice compared to WHO reference standards, particularly in safety and risk assessment, interactions with caregivers, and mental health interventions. Appraisal by AGREE II revealed shortcomings in NCPG development, regarding scientific rigour, stakeholder involvement, implementation and evaluation. Interpretation: A notable number of European countries lack an NCPG; existing NCPGs often fall short. The healthcare response to CSA in Europe requires a coordinated approach to develop and implement high-quality CPGs. We advocate for a multidisciplinary team to develop a pan-European CSA guideline to ensure quality care for survivors. Funding: Funding was provided by the International Centre for Missing and Exploited Children.

Abusive head trauma: The body of the iceberg - A population-based survey on prevalence and perpetrators.

BACKGROUND: Research on abusive head trauma (AHT) is usually research on clinically identified cases, while population-based studies, having the potential to identify cases of shaking that did not end with hospital admission, are missing to date. OBJECTIVE: Thus, we aimed to assess the prevalence of AHT and associated risk factors in a representative sample of the German population. PARTICIPANTS AND SETTING: We conducted a cross-sectional, observational study in Germany from July to October 2021. Using different sampling steps including a random route procedure, a probability sample of the German population was generated. The final sample consisted of 2503 persons (50.2 % female, mean age: 49.5 years). METHODS: Participants were asked about sociodemographic information in a face-to-face interview and whether they had been ever responsible for the care of an infant and whether they had ever performed potential harmful methods including shaking to calm it, intimate partner violence (IPV) and adverse childhood experiences (ACEs) using a questionnaire. RESULTS: In total, 1.4 % of women (N = 18) and 1.1 % of men (N = 13) reported to have at least once shaken an infant to calm it. Ever having used a potential harmful parenting method in calming an infant was reported by 4.9 % of women (N = 61) and 3.1 % (N = 39) of men. No gender differences were seen. A low income, living with someone under 16 in the household and victimization and perpetration of IPV and ACEs are associated with increased risks of shaking and other potential harmful methods to calm an infant. CONCLUSIONS: Our data suggest that despite better knowledge on the dangers of shaking, the percentage of women that shake infants might be higher than previously thought. Also, intimate partner violence and ACEs are key risk factor for shaking and harmful parenting behaviors in general. This has important implications for future prevention programs.

[Sexualized Violence Toward Children and Adolescents: The Visibility and Implementation of Safeguarding Concepts in Sports, Music, and Church]. / Sexualisierte Gewalt an Kindern und Jugendlichen: Sichtbarkeit und Umsetzung von institutionellen Schutzkonzepten in den Bereichen Sport, Musik und Kirche.

Sexualized Violence Toward Children and Adolescents: The Visibility and Implementation of Safeguarding Concepts in Sports, Music, and Church Abstract: Objective: In 2010, the disclosure of sexualized violence in educational organizations led to a public debate and calls for safeguarding concepts against sexualized violence toward children and adolescents. However, there have been few efforts to systematically record the visibility, availability, and implementation of such concepts. We used a broad Google search and a telephone survey as an initial approach to close this research gap. Method: In a systematic Google search and a telephone survey (N = 50), we identified and examined safeguarding concepts against sexualized violence toward children and adolescents in the context of religious organizations, sports, and musical education regarding its visibility, availability, and implementation level. Results: The results of our systematic internet research show a low hit rate of identified safeguarding concepts in all contexts. The low number of search hits indicates that the issue of sexualized violence toward children and adolescents has been inadequately addressed in many institutions, and that protective measures have been neglected. The supplementary results of the telephone survey suggest a low implementation level within organizations and a low availability of existing safeguarding concepts.

Consensus building on definitions and types of child maltreatment to improve recording and surveillance in Europe: protocol for a multi-sectoral, European, electronic Delphi study.

INTRODUCTION: Child maltreatment (CM) is a complex global public health issue with potentially devastating effects on individuals' physical and mental health and well-being throughout the life course. A lack of uniform definitions hinders attempts to identify, measure, respond to, and prevent CM. The aim of this electronic Delphi (e-Delphi) study is to build consensus on definitions and types of CM for use in surveillance and multi-sectoral research in the 34 countries in the Euro-CAN (Multi-Sectoral Responses to Child Abuse and Neglect in Europe) project (COST Action CA19106). METHODS AND ANALYSIS: The e-Delphi study will consist of a maximum of three rounds conducted using an online data collection platform. A multi-disciplinary expert panel consisting of researchers, child protection professionals (health and social care), police, legal professionals and adult survivors of CM will be purposefully recruited. We will approach approximately 100 experts, with between 50 and 60 of these anticipated to take part. Participants will rate their agreement with a range of statements relating to operational definitions and types of CM, and free-text comments on each of the statements to give further detail about their responses and areas of uncertainty. Consensus has been defined a priori as ≥70% of the panel agreeing or disagreeing with the statement after the final round. The responses to the open-ended questions will be analysed using a 'codebook' approach to thematic analysis, and used to refine the statements between rounds where no consensus is reached. ETHICS AND DISSEMINATION: Ethical approval has been granted from the Cardiff University School of Medicine ethics committee (reference number SMREC22/96). Results will be submitted for publication in a peer-reviewed journal and presented at workshops (including for the participants) and international academic conferences. The Euro-CAN network will also be used to disseminate the results, with results briefings and presentations to key public health and other relevant organisations in the field.

Single-cell deconvolution reveals high lineage- and location-dependent heterogeneity in mesenchymal multivisceral stage 4 colorectal cancer.

Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in Union for International Cancer Control (UICC) stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analyzed the transcriptome of single cells derived from murine multivisceral CRC and delineated the intermetastatic cellular heterogeneity regarding tumor epithelium, stroma, and immune cells. Interestingly, we found an intercellular site-specific network of cancer-associated fibroblasts and tumor epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell-dependent antigen presentation and consecutive effector T cell exhaustion. Furthermore, we demonstrated major similarities of this murine metastatic CRC model with human disease and - based on the results of our analysis - provided an auspicious site-specific immunomodulatory treatment approach for stage IV CRC by intraperitoneal checkpoint inhibition.

Hospitalization for physical child abuse: Associated medical factors and medical history since birth.

BACKGROUND: Physical abuse often begins at a very young age and sometimes results in serious or fatal injuries. It is crucial to diagnose physical abuse as early as possible to protect this vulnerable population. OBJECTIVE: To study the factors associated with the first hospitalization for physical abuse from birth to the infant's first birthday in France. PARTICIPANTS AND SETTING: We included all singleton children born in a hospital setting in France between 2009 and 2013, who were identified from the French national information system database (SNDS). METHODS: To study factors associated with the first hospitalization for physical abuse during the first year after birth, we used the Fine and Gray regression model. Factors included in the multivariate model were the infant's sex, prematurity, neonatal conditions, the number of hospitalizations (at least two), medical consultations and complementary universal health insurance (proxy for family precariousness and socio-economic vulnerability). RESULTS: Over the 2009-2013 period, among 3,432,921 newborn singletons, 903 (0.026 %) were hospitalized for physical abuse in the year following birth. Among the factors associated with physical abuse, such as prematurity (aHR = 2.2[1.8-2.7]), male sex (aHR = 1.3[1.2-1.5]), or having had at least two hospitalizations (aHR = 1.7[1.4-2.1]), we found that complementary universal health insurance coverage was the factor most associated (aHR = 4.1[3.5-4.7]) with being hospitalized for physical abuse. CONCLUSION: These findings could help introduce preventative measures for infant protection in certain groups, such as parents of infants born prematurely, especially if they are in a precarious situation. This study also suggests that particular attention should be paid to infants who have been hospitalized at least two times in the first year of life, whatever the reason.

Adverse childhood experiences increase the risk for low perceived social participation and health-related quality of life in a large-scale population-based study in Germany.

BACKGROUND: Adverse childhood experiences (ACEs) are highly prevalent and increase the risk for long-term adverse health outcomes. Next to well-known ACE-associated risks for morbidity, recent research is increasingly invested in exploring pathways towards health, overall functioning, and partaking in society following early adversity. OBJECTIVES: Thus, this study aims to assess the association between latent classes of ACEs with perceived social participation and health-related Quality of Life (QoL) in a large population-based sample and to explore potential moderators of these associations. METHOD: A representative sample of the German population (N = 2531; Mage = 48.7; 51 % women) was cross-sectionally investigated for ACEs, social participation (KsT-5), and health-related QoL (EuroQol-5D-5L). Latent Class Analysis (LCA) was performed to derive groups with similar ACE patterns. Multiple regression analyses were used to investigate the association of latent classes of ACEs with social participation and health-related QoL and to explore potential moderators. RESULTS: Four distinct latent classes of ACEs were identified; "no/low ACEs" (N = 1968, 77.8 %); "household-dysfunction" (N = 259, 10.2 %), "child abuse and neglect" (N = 188, 7.4 %), and "polyadversity" (N = 116, 4.6 %). Compared to participants in the no/low ACE class, those in the ACE-exposed classes showed overall lower levels of perceived social participation and health-related QoL. The polyadversity class showed lower levels of social participation compared to the two other ACE-exposed classes. Chronic stress, living with a partner, education, current job/educational involvement, and gender were found to moderate these associations in exploratory analyses. CONCLUSIONS: This study shows people exposed to ACEs to have a higher risk for lower perceived social participation and lower health-related QoL - an increased risk, however, is not a deterministic uninventable fortune. Reduction of chronic stress, fostering of social support, and educational and vocational paths as interventional targets are discussed to enable those with precarious starting conditions to partake in society.

Current issues and challenges in the definition and operationalization of child maltreatment: A scoping review.

BACKGROUND: Studies show considerable variability in the definitions and operationalization of child maltreatment (CM), which limits research, policy formation, surveillance, and cross-country and cross-sector comparisons. OBJECTIVE: To review the recent literature (2011-2021) to understand current issues and challenges in defining CM, to assist in the planning, testing and implementing of CM conceptualizations. METHODS: We searched eight international databases. Articles were included if the substantive content was related to issues, challenges, and debates in defining CM, and the article was an original study, review, commentary, report, or guideline. The review followed methodological guidance for the conduct of scoping reviews and was reported in accordance with the PRISMA-ScR checklist. Four experts in CM conducted a thematic analysis to summarize findings. Methodological rigor of the included studies was not formally assessed. RESULTS: We identified 7372 potentially relevant articles; 55 full-text studies were assessed for eligibility, 25 satisfied the inclusion criteria. We identified three themes: 1) strategies to define CM, including the integration of child and victim perspectives; 2) difficulties in defining specific CM types; and 3) real-world implications for research, prevention and policy. CONCLUSIONS: Despite longstanding concerns, challenges regarding the definitions of CM persist. A small minority of studies have tested and implemented CM definitions and operationalizations in practice. The findings will inform international multi-sectoral processes to develop uniform definitions of CM, for example by highlighting the need to acknowledge challenges in defining some CM types and emphasizing the importance of considering the perspectives of children and CM survivors.

Appraisal of published guidelines in European countries addressing the clinical care of childhood sexual abuse: protocol for a systematic review.

INTRODUCTION: Childhood sexual abuse (CSA) is a global public health problem with potentially severe health and mental health consequences. Healthcare professionals (HCPs) should be familiar with risk factors and potential indicators of CSA, and able to provide appropriate medical management. The WHO issued global guidelines for the clinical care of children with CSA, based on rigorous review of the evidence base. The current systematic review identifies existing CSA guidelines issued by government agencies and academic societies in the European Region and assesses their quality and clarity to illuminate strengths and identify opportunities for improvement. METHODS AND ANALYSIS: This 10-database systematic review will be conducted according to the Centre for Reviews and Dissemination guidelines and will be reported according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Guidance for HCPs regarding CSA, written by a national governmental agency or academic society of HCPs within 34 COST Action 19106 Network Countries (CANC) and published in peer-reviewed or grey literature between January 2012 and November 2022, is eligible for inclusion. Two independent researchers will search the international literature, screen, review and extract data. Included guidelines will be assessed for completeness and clarity, compared with the WHO 2017/2019 guidelines on CSA, and evaluated for consistency between the CANC guidelines. The Appraisal of Guidelines for Research and Evaluation II tool and Grading of Recommendations Assessment, Development and Evaluation methodology will be used to evaluate CANC guidelines. Descriptive statistics will summarise content similarities and differences between the WHO guidelines and national guidelines; data will be summarised using counts, frequencies, proportions and per cent agreement between country-specific guidelines and the WHO 2017/2019 guidelines. ETHICS AND DISSEMINATION: There are no individuals or protected health information involved and no safety issues identified. Results will be published in a peer-reviewed medical journal. PROSPERO REGISTRATION NUMBER: CRD42022320747.

Epidemiology of intimate partner violence perpetration and victimisation in a representative sample.

AIMS: Intimate partner violence (IPV) is a major global public health problem. Although IPV is known to be frequent and perpetration and victimisation often co-occur, large representative samples assessing both, male and female IPV perpetration and victimisation and overlaps are missing to date. Thus, we aimed to assess victimisation and perpetration and its overlap in physical, sexual, psychological and economic IPV in a representative sample of the German population. METHODS: We conducted a cross-sectional, observational study in Germany from July to October 2021. Using different sampling steps including a random route procedure, a probability sample of the German population was generated. The final sample consisted of 2503 persons (50.2% female, mean age: 49.5 years). Participants were asked about socio-demographic information in a face-to-face interview and experience of physical, psychological, sexual and economic IPV using a questionnaire. RESULTS: A significant proportion of persons in Germany reporting IPV are both perpetrator and victim for each IPV form. The biggest overlap between perpetration and victimisation was seen for psychological IPV. Major risk factors for IPV perpetration only were male gender and adverse childhood experiences (ACEs) while major risk factors for IPV victimisation only comprised of female gender, low household income and ACEs. In the perpetration and victimisation group, gender differences were less significant; older age and lower household income did increase the likelihood of combined perpetration and victimisation. CONCLUSIONS: We have identified a significant overlap of perpetration and victimisation of IPV in the German population for men and women. However, men are at much higher risk to perpetrate IPV without being a victim. Further research and the development of adapted approaches for contexts of overlapping IPV are necessary.

Widening epidemiological data on the prevalence of child maltreatment: Validation of the German ICAST-R in a student sample and national household survey.

BACKGROUND: A number of instruments for measuring child maltreatment (CM) prevalence have repeatedly been used across different countries. Although they hold the potential for providing benchmarks to tackle the gap of lacking comparability of CM prevalence across countries, contextual information about the adverse experiences such as perpetrator, chronicity, frequency, or severity are rarely covered. The ISPCAN Child Abuse Screening Tool - Retrospective (ICAST-R) covers these important dimensions. The German version increases the number of available versions to 21 different languages. Spoken by about 120 million people, German is one of the 20 most prevalent languages around the world. Moreover, the ICAST-R is intended to be used with young adults. This study further aims at adding towards the gap of psychometrics in older age groups. METHODS: Analyses are based on both a sample of German students (n = 333) and a nationally representative household survey (n = 2515). The validation process covered six steps: (1) Analyses of missing data on single items, (2) calculation of descriptive statistics to estimate the prevalence CM as well as subjective severity and main perpetrators. (3) Structural validity of the four conceptualized subtypes of CM (neglect, physical abuse, emotional abuse and sexual abuse) was tested using confirmatory factor analyses (CFA). Next (4), equivalence testing by multigroup confirmatory factor analyses (MGCFA) on age groups was conducted within the representative sample; (5) reliability was tested by determining internal consistencies for each subscale via the McDonald's Omega, Kuder-Richardson 20 (KR-20), and Cronbach's alpha. Lastly (6), criterion validity was tested in regression models comparing depressive/anxious symptomatology for single victimization and polyvictimization. RESULTS: The German ICAST-R yielded low missing values items in both samples. 16 % of the participants in the national household survey reported neglect, 20.3 % physical abuse, 22.2 % emotional abuse, and 8.6 % sexual abuse. Polyvictimization was prevalent with 20.6 % of subjects reporting >2 types of CM. Students in the pilot-survey reported much higher prevalence estimates than participants in the nationally representative sample. The types of CM subjectively rated as most harmful were emotional abuse and sexual abuse. In both samples, structural validity was similarly confirmed as CFA was reproducing the four conceptualized subtypes of CM with adequate fit (household survey: CFI 0.919, TLI 0.907, RMSEA 0.017, SRMR 0.046). Internal consistency achieved acceptable and comparable values for all three types of coefficients; criterion validity was established with a significant dose-response effect of CM experiences on both anxiety and depressive symptoms/diagnoses. Age dependent analyses on structural validity (MGCFA) and reliability in the household survey revealed potential weaknesses of items. CONCLUSION: The German version of the ICAST-R both widens the possibility of international CM prevalence comparison and provides novel epidemiological data for Germany on subjective severity of CM and CM perpetrators. Even in the presence of a marked selection bias, the ICAST-R had similarly good psychometric properties in the student and nationally representative household sample. Except for issues with two items, equivalence testing was comparable across age groups.

Prevalence and Predictors of Affirmations of Intimate Partner Violence in Germany: A First Nationwide Study on Victimization in Women and Men.

Large-size studies on the prevalence of female intimate partner violence (IPV) victimization in Germany are rare and partly outdated; representative data on male IPV victimization are lacking altogether. The present survey addresses these gaps. For this study, the instrument of the WHO Multi-country study on women's health and domestic violence has been translated to German and adapted to be used with females and males. A random route procedure in selecting household addresses has been used to gather data on IPV in combination with an omnibus survey on (mental) health issues. A total 2,503 respondents with a minimum age of 14 years have participated (response rate=44.1%). The resulting distribution of age and gender was representative for the German population above the age of 14 years. A total of 57.6% of female participants and 50.8% of male participants have reported victimization by intimate partners during their lifespan; gender distribution differs significantly (Chi2=43.43; p<0.001). Out of the different documented subtypes, psychological IPV was most prevalent (53.6% in females, 48.0% in males). Other forms ranged between 15.2% (physical IPV) and 18.6% (sexual IPV) for females, and 5.5% (sexual IPV) and 10.8% (physical IPV) for males. All forms of victimization regularly coincided, both in females and males. Experiencing any IPV was not only significantly associated with female gender, but also with older age, periods of unemployment, poverty, and IPV perpetration. The findings highlight the still much needed global efforts to prevent IPV against women - and in general. They further support previous research in underlining that fighting poverty might also be instrumental in reducing the likelihood of IPV. The discussion further addresses the issues of reciprocity in IPV.

Survey on Reporting of Child Abuse by Pediatricians: Intrapersonal Inconsistencies Influence Reporting Behavior More than Legislation.

Background: Internationally, various laws govern reporting of child abuse to child protection services by medical professionals. Whether mandatory reporting laws are in place or not, medical professionals need internal thresholds for suspicion of abuse to even consider a report ("reasonable suspicion" in US law, "gewichtige Anhaltspunkte" in German law). Objective: To compare internal thresholds for suspicion of abuse among US and German pediatricians, i.e., from two countries with and without mandatory reporting laws. Participants and Setting: In Germany, 1581 pediatricians participated in a nationwide survey among child health professionals. In the US, a survey was mailed to all Pennsylvania pediatricians, and 1249 participated. Methods: Both samples were asked how high in their rank order of differential diagnoses child abuse would have to be when confronted with a child's injuries to qualify for reasonable suspicion/gewichtige Anhaltspunkte (differential diagnosis scale, DDS). In a second step, both had to mark a 10-point likelihood scale (0-100%) corresponding to reasonable suspicion/gewichtige Anhaltspunkte (estimated probability scale, EPS). Results: While for almost two-thirds of German pediatricians (62.4%), child abuse had to be among the top three differential diagnoses for gewichtige Anhaltspunkte, over half of the US respondents (48.1%) had a lower threshold for reasonable suspicion. On the estimated probability scale, over 65% in both samples indicated that the probability of abuse had to exceed 50% for reasonable suspicion/gewichtige Anhaltspunkte. There was great variability between the two countries. Conclusions: There are similar uncertainties in assessing cases of suspected child abuse in different legal systems. There is a need for debates on thresholds among medical professionals in both countries.

Can You Sleep? - Effect of Retrospective Recall of Child Maltreatment on Sleep Parameters and the Mediating Role of Psychological Distress Among Students of Two German Universities.

Purpose: Child maltreatment may be linked with long-term sleeping disorders and limited coping with stress. Yet, the potential relationships are only marginally studied. Patients and Methods: Based on a sample of young adults (n = 312) this study aims at exploring the effects of child maltreatment and the experience of threat to personal safety and life in childhood on sleep disturbances in early adulthood. Data were collected at the two study sites, Ulm University and Bielefeld University, by an online survey. For both risk factors, child maltreatment and the experience of threat to personal safety and life in childhood, a direct impact on sleep disturbances and an indirect path via psychological distress were tested using Structural Equation Modelling (SEM). Results: In these models, the direct path to sleep disturbances turned out to be significant for the experience of threat to personal safety and life (Path C: b = 0.18, p = 0.013), but not for child maltreatment (Path C: b = 0.05, p = 0.491). However, the current level of psychological distress was found to have a mediating effect on sleep disturbances for both risk factors, thereby confirming indirect significant effects. Conclusion: Considering that the etiological pathway of child maltreatment on sleeping disturbances is mediated via psychological distress, this provides a venue to test in future research whether stress reduction interventions can reduce the negative consequences of child maltreatment on sleep disorders.

COVID-19-What Price Do Children Pay? An Analysis of Economic and Social Policy Factors.

Numerous studies have addressed the indirect consequences of the COVID-19 pandemic for children such as social isolation or increases in reported child maltreatment. Research on the economic and sociopolitical consequences is scarce as they can only be evaluated with a time lag. To improve our understanding of future, long-term developments in the context of the COVID-19 pandemic, we gathered findings from the still unexploited empirical literature on the aftermath of earlier pandemics, epidemics, and other infectious disease outbreaks. On top of this, we scrutinized research on past economic crises to interpret the link between changes in the economy and the health of children. Many of the side effects of battling the spread of the current pandemic, such as school closures, the stigma of infection, or conflicts about vaccines, are not novel and have already been documented in connection with previous infectious disease outbreaks. Results highlight that changes in the financial situation of families and socio-political challenges affect the situation and daily routine of children and youth in the long term. In consequence, the already pronounced socioeconomic inequalities will likely further increase. On top of this, due to reduced revenues, child protective services are likely to face challenges in the availability of human and financial resources.

Proteome biology of primary colorectal carcinoma and corresponding liver metastases.

Colorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compared to non-metastasized CRC patients. The metastasis process and metastasis-promoting factors in patients with CRC are under intensive debate. However, CRC studies investigating the proteome biology are lacking. Formalin-fixed paraffin-embedded (FFPE) tissue specimens provide a valuable resource for comprehensive proteomic studies of a broad variety of clinical malignancies. The presented pilot study compares the proteome of primary CRC and patient-matched CRC-LM. The applied protocol allows a reproducible and straightforward identification and quantification of over 2,600 proteins within the dissected tumorous tissue. Subsequent unsupervised clustering reveals distinct proteome biologies of the primary CRC and the corresponding CRC-LM. Statistical analysis yields multiple differentially abundant proteins in either primary CRC or their corresponding liver metastases. A more detailed analysis of dysregulated biological processes suggests an active immune response in the liver metastases, including several proteins of the complement system. Proteins with structural roles, e.g. cytoskeleton organization or cell junction assembly appear to be less prominent in liver metastases as compared to primary CRC. Immunohistochemistry corroborates proteomic high expression levels of metabolic proteins in CRC-LM. We further assessed how the in vitro inhibition of two in CRC-LM enriched metabolic proteins affected cell proliferation and chemosensitivity. The presented proteomic investigation in a small clinical cohort promotes a more comprehensive understanding of the distinct proteome biology of primary CRC and their corresponding liver metastases.

Physical abuse of young children during the COVID-19 pandemic: Alarming increase in the relative frequency of hospitalizations during the lockdown period.

BACKGROUND: In France, the COVID-19 pandemic led to a general lockdown from mid-March to mid-May 2020, forcing families to remain confined. We hypothesized that children may have been victims of more physical abuse during the lockdown, involving an increase in the relative frequency of hospitalization. METHODS: Using the national administrative database on all admissions to public and private hospitals (PMSI), we selected all children aged 0-5 years hospitalized and identified physically abused children based on ICD-10 codes. We included 844,227 children hospitalized in March-April 2017-2020, of whom 476 (0.056%) were admitted for physical abuse. Relative frequency of hospitalization for physical abuse observed in March to April 2020 were compared with those from the same months in the three previous years (2017-2019). FINDINGS: Even if absolute number of children exposed to physical abuse did not fluctuate significantly, we found a significant increase in the relative frequency of young children hospitalized for physical abuse from 2017 (0.053%) to 2020 (0.073%). Compared with the 2017-2019 period, and considering the observed decrease in the number of overall hospital admissions during the first lockdown, the number of children exposed to physical violence was 40% superior to what would be expected. INTERPRETATION: The sharp increase in the relative frequency of hospitalizations for physical abuse in children aged 0-5 years in France is alarming. As only the most severe cases were brought to the hospital for treatment during the lockdown, our figures probably only represent the tip of the iceberg of a general increase of violence against young children.

[Reporting "Reasonable Suspicion" of Child Abuse - A Survey among Physicians and Psychotherapists in Germany]. / "Gewichtige Anhaltspunkte" bei Verdacht auf Kindesmisshandlung ­ eine Befragung in Deutschland tätiger Ärzte und Psychotherapeuten.

BACKGROUND: There is evidence that health care professionals are uncertain about the legal framework when suspicion of child abuse or neglect is raised. This could result in inconsistent handling of such cases, putting children at risk in further danger. The present study was intended to provide an empirical basis for examining the knowledge of the legal framework among health care professionals. METHODS: A survey of child and youth physicians, child surgeons, child and adolescent psychiatrists as well as psychotherapists working in Germany was carried out to obtain information on the general conditions. RESULTS: In all occupational groups, a majority of respondents feel insecure about the application of the legal framework on particular cases. Only a minority can correctly reflect the legal regulations of the Federal Child Protection Act ("Bundeskinderschutzgesetz"). Experience with child abuse cases doubled the odds to correctly understanding legal frameworks. Having attended training courses showed no impact. CONCLUSION: There is little knowledge of the legal framework in child protection. There is a need to improve training and provide low-threshold counselling services, especially for professionals with little experience in child protection cases.