University and Rehabilitation Clinics Ulm

Childhood maltreatment and FKBP5 CATT haplotypes increase identity dissociation risk. While maltreatment often fosters disorganized attachment, the specific role of the FKBP5 CATT haplotype within this developmental pathway remains unknown. In 310 trauma-exposed adults, we assessed childhood maltreatment, disorganized attachment, and identity dissociation. FKBP5 CATT haplotype status was dichotomized (present/absent). Regression models were estimated to examine the pathway Childhood Maltreatment → Disorganized Attachment → Identity Dissociation, comparing two competing hypotheses: 1) The Formation Hypothesis (Maltreatment × CATT → Disorganization), and 2) The Translation Hypothesis (Disorganization × CATT → Identity Dissociation). Model fit was compared using BIC, and simple slopes were examined. Disorganized attachment predicted identity dissociation (β = 0.143, z = 3.83, p < .001), and childhood maltreatment predicted disorganization (β = 0.007, z = 4.46, p < .001). The Formation hypothesis was not supported, as the Maltreatment × CATT interaction did not predict disorganization (β = -0.004, z = -1.18, p = .24). However, the Translation hypothesis was supported by three pieces of evidence: a significant Disorganization × CATT interaction predicting identity dissociation (β = 0.133, z = 2.22, p = .027), model fit (∆BIC = 265.3), and simple slopes showing a strong effect of disorganization on identity dissociation for CATT carriers (β = 0.15, p < .001; +16.5 % per unit) but not for non-carriers (β = 0.02, p = .65). The FKBP5 CATT haplotype does not promote disorganized attachment but amplifies the translation of disorganized attachment into identity dissociation. This result highlights a genetically influenced failure of identity development following disorganized attachment.

Cytoplasmic TDP-43 pathology is a pathological sign of ALS/ALS-FTD and a converging disease event across different genotypes, phenotypes and CNS areas. To understand this process and target it therapeutically, we need to define which cell types are affected and which cell-type specific effects make them particularly vulnerable. We coupled flow-cytometry nuclear sorting and sequencing with single-nucleus multi-omic ATAC-seq and RNA-seq and spatial transcriptomics to define the transcriptional cell type of affected neurons in the post-mortem ALS/ALS-FTD motor cortex (30 ALS, 20 ALS-FTD & 32 control samples). Here, we show that mainly excitatory cortical neurons are affected by TDP-43 pathology and define the cell types that are affected the most: intratelencephalic L2-L3-LINC00507-FREM3, L3-L5-RORB-LNX2, L3-L5-RORB-ADGRL4 & L6-THEMIS-LINC00343 neurons and extratelencephalic L5-FEZF2-NTNG1 neurons. Transcriptional aberrations by TDP-43 pathology, like cryptic exon inclusion, are cell-type specific and affect distinct gene sets in each cell type, highlighting the need to address TDP-43 pathology in a cell-type specific manner.

Spinal cord injury (SCI) incidence is rising among the elderly, yet the relationship between age and recovery remains controversial. The aim of this study was to evaluate the relationship between age and neurologic and functional outcomes and to identify an age cutoff associated with a decline in recovery. We conducted a prospective cohort study using data from patients with traumatic and ischemic SCI enrolled in the European Multicenter Study about Spinal Cord Injury between 2001 and 2022. Linear regression models assessed the relationship between age and changes from baseline to 1 year after SCI in the total motor score (TMS) of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and in the Spinal Cord Independence Measure (SCIM) total score. Additional analyses examined the relationship between age and the evolution of ISNCSCI light-touch and pinprick scores, as well as ambulation parameters (6-minute walking test, 10-meter walking test, and Walking Index for Spinal Cord Injury). Models were adjusted for baseline scores, sex, year of injury, American Spinal Injury Association Impairment Scale (AIS) grade, and level of injury. The age cutoff was determined using a change-point model. A total of 2,171 patients (median age 47 years, 77.9% male, 51.9% injured at the cervical level, and 50.0% with a motor complete injury [AIS-A and AIS-B]) were included in the analysis. Increased age was not associated with changes in TMS (p = 0.896) but was significantly associated with reduced SCIM improvement (p < 0.001), with an estimated decline of 4.3 SCIM points per decade of age. Sensory outcomes were not significantly affected by age (Δlight-touch: p = 0.273; Δpinprick: p = 0.520) while ambulation recovery declined with increasing age (all outcomes p < 0.01). A noticeable reduction in functional recovery was observed in patients older than 70 years. Older age does not seem to affect neurologic recovery but is linked to poorer functional and ambulation outcomes. These findings, including the identified age cutoff, should inform future clinical trial design and guide tailored care strategies for older adults with SCI. ClinicalTrials.gov Identifier NCT01571531.

BackgroundTo date, there is no framework for actively involving people living with dementia, individuals from their social networks and healthcare professionals in systematic reviews (SRs). Additionally, no SRs have been planned or partially carried out with the active involvement of these individuals. For these reasons, a framework and a review protocol for a planned SR were developed as part of the federal-funded DECIDE-SR project, in which the abovementioned groups were actively involved as coresearchers. The purpose of this paper is to provide an overview of the project and to illustrate the lessons learned from conducting active research involving this case example.MethodsA framework for actively involving coresearchers in SRs was developed via the synthesis of theoretical and empirical findings from a previous research project. The coresearchers participated in meetings and one workshop, which were planned on the basis of the INVOLVE criteria and the ACTIVE framework model, to test and reflect on the previously developed framework. Additionally, an SR protocol was jointly planned during these meetings, and individual SR steps were conducted (e.g., development of the research question). The lessons learned were drawn from the workshop with the coresearchers, who were clustered using the Engaging with Purpose Patient Engagement Framework (EwPPEF).ResultsEight coresearchers were actively involved in 15 meetings and one workshop to test and reflect on the framework. The framework allows coresearchers to individually choose their own level of involvement (where the levels are nonhierarchical), and the individual support needs at each step of an SR are considered. Additionally, an SR protocol was developed together with the research question "What is the effect of hospital treatment provided in one’s own living place on people living with dementia?". The lessons learned provide information on all aspects of the EwPPEF (e.g., cobuilding, impact, and inclusiveness) and include implications for conducting SRs that actively involve the public.ConclusionsThe framework and the SR protocol can now be used for further tests and to gain initial experience in conducting SRs that actively involve the public. Furthermore, the lessons learned can provide other project groups with important insights into actively planning and conducting SRs.

BackgroundSynovial leukocyte cell count (LC) and polymorphonuclear percentage (PMN%) are key parameters in the diagnostic workup of periprosthetic joint infection (PJI). Despite ongoing debates regarding optimal thresholds—particularly for reliably excluding low-grade infections—no study has investigated potential confounders such as intra-individual, time-dependent variability of LC and PMN% in patients with PJI following total knee arthroplasty (TKA).MethodsWe conducted a retrospective, double-centre study using prospectively collected data from 35 consecutive patients with confirmed knee PJI, each of whom underwent two joint aspirations at different time points (t1 and t2; mean interval 33 ± 31 days, range 0–111 days; total 70 samples). We analysed absolute and percentage changes in LC and PMN% between t1 and t2 and identified the number of “false-negative” results potentially caused by this variability. A subset analysis was performed on cases exhibiting more than 20% variability to minimize methodological bias. Additionally, we compared LC and PMN% levels between infections caused by low- vs. high-virulence pathogens.ResultsMean LC among all samples was 19.969 n/µl ± 27.035 n/µl [300–135.000 n/µl], mean PMN% was 65%±28% [6-97%]. Seven (20%) of the LC results and four (11%) of the PMN% results exhibited discrepant values, either falling below or exceeding the threshold depending on the timepoint of aspiration. Regarding the time-dependent variability, there was a trend to higher percentual change for LC compared to PMN% (58% ± vs. 11%; p = 0.062). Synovial analyses of low-virulent bacteria showed significantly decreased overall LC- and PMN%-values compared to high virulent pathogen associated PJI (p < 0.001).ConclusionLC values exhibit significant intra-individual variability of up to 58% over time, which could lead to false-negative exclusion of PJI in up to 20% of cases if only a single aspiration were performed. In contrast, PMN% is less affected by timing, showing a variability of just 11%. Notably, in PJI caused by low-virulence pathogens, both LC and PMN% show approximately 80% variability, whereas PMN% variability in high-virulence infections is only 22%. LC, in particular, demonstrates a high degree of independent variability. These findings suggest that synovial LC—especially—is less reliable diagnostically than previously assumed. PMN%, on the other hand, appears to be less influenced by timing and pathogen virulence, and may therefore be the more robust parameter. In addition to timing, future research should explore other potential confounders that may impact the diagnostic reliability of both LC and PMN%.Level of evidenceIII.

To investigate the professional dementia experts' understanding of a dementia-friendly hospital to identify its characteristics. We used a qualitative design embedded in a case study. A total of 16 semi-structured expert interviews were conducted with 17 professional dementia experts. Using inductive content analysis, the interviews were analysed in a participatory manner involving a group of researchers and dementia experts. We identified six characteristics of dementia-friendly hospitals: Proud to be dementia-friendly-That's what we want; Seeing the human being-Taking care of everyone; Having everyone on board-It's a collective task; Being professional-It takes more than being nice and kind; Rethinking the 'running' system-We have to change, not them; and Being part of the community-Thinking beyond the hospital. The concept of a dementia-friendly hospital seems complex and requires a rethinking of the traditional hospital. For a conceptualisation, the involvement of people with dementia and their relatives is important to gain a comprehensive understanding. A dementia-friendly hospital is characterised by professional care that comprises a safe, familiar and supportive environment, is prepared but also flexible, has everyone on board, and sees the human being. To become dementia-friendly, individual interventions such as training courses can be a starting point. However, an overall concept is required that also includes components that contribute to successful implementation and a welcoming culture of people with dementia. Our findings on the perspective of professional dementia experts contribute to the conceptualisation of dementia-friendly hospitals. We reported our study according to the COREQ checklist. The investigation of the perspective of professional dementia experts is one part of a larger study. In this overall DEMfriendlyHospital study, we interviewed professional dementia experts, people with dementia and their relatives and also involved them in a participatory manner in various stages of the research process.

Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is aneed for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94 cmH2O ± 26.12 standard deviation (SD) to 21.07 cmH2O ± 17.32 SD (P < 0.001, n = 34). Maximum bladder pressure (MBC) increased by 34% from 260.45 ml ± 200.26 SD to 348.45 ml ± 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be auseful alternative for patients who do not respond to other therapies or suffered side effects.

StudyHigh-frequency ultrasound in auricular skin cancer surgery: a precise, in vivo tool for identification of a potential cartilage infiltration and planning the therapeutic approach Dear Editor, Auricular basal (BCC) and squamous cell carcinomas (SCC) represent 6-10% of cutaneous head and neck malignancies. 1umors located in the facial "H-zone" are considered high risk, as a result of the increased invasion and metastatic risk, particularly due to the thin skin layer and lymphatic proximity. 2The therapy of choice in auricular BCCs and SCCs is surgery;hence, the preoperative assessment of tumor extent, especially a potential infiltration into deeper structures, is essential for therapeutic guidance.High-frequency ultrasound (HFUS) is an optimal pretherapeutic tool for assessing operability and potential neurovascular, cartilaginous, and bony infiltration, and it is increasingly Figure 1 (A) Squamous cell carcinoma (SCC) of the helix and antihelix (a); high-frequency ultrasound (HFUS) depicting an intact cartilaginous framework as marked by "ca" (b); Second-intention healing at 1 week (c) and 12 weeks postsurgery (d); (B) basal cell carcinoma (BCC) of the concha (e); HFUS showing intact conchal cartilage as marked by "ca" (f); complete tumor resection (g) and reconstruction with a tunneled flap (h); (C) SCC of the tragus and preauricular area (i); HFUS showing no cartilage infiltration as marked by "ca" (j); surgical site prior (k) and 6 weeks after transposition flap reconstruction (l).

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. 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. 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. 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 was provided by the International Centre for Missing and Exploited Children.