"I didn't even wonder why I was on the floor" - mixed methods exploration of stroke awareness and help-seeking behaviour at stroke symptom onset.

INTRODUCTION: To better target stroke awareness efforts (pre and post first stroke) and thereby decrease the time window for help-seeking, this study aims to assess quantitatively whether stroke awareness is associated with appropriate help-seeking at symptom onset, and to investigate qualitatively why this may (not) be the case. METHODS: This study conducted in a German regional stroke network comprises a convergent quantitative-dominant, hypothesis-driven mixed methods design including 462 quantitative patient questionnaires combined with qualitative interviews with 28 patients and seven relatives. Quantitative associations were identified using Pearson's correlation analysis. Open coding was performed on interview transcripts before the quantitative results were used to further focus qualitative analysis. Joint display analysis was conducted to mix data strands. Cooperation with the Patient Council of the Department of Neurology ensured patient involvement in the study. RESULTS: Our hypothesis that stroke awareness would be associated with appropriate help-seeking behaviour at stroke symptom onset was partially supported by the quantitative data, i.e. showing associations between some dimensions of stroke awareness and appropriate help-seeking, but not others. For example, knowing stroke symptoms is correlated with recognising one's own symptoms as stroke (r = 0.101; p = 0.030*; N = 459) but not with no hesitation before calling help (r = 0.003; p = 0.941; N = 457). A previous stroke also makes it more likely to recognise one's own symptoms as stroke (r = 0.114; p = 0.015*; N = 459), but not to be transported by emergency ambulance (r = 0.08; p = 0.872; N = 462) or to arrive at the hospital on time (r = 0.02; p = 0.677; N = 459). Qualitative results showed concordance, discordance or provided potential explanations for quantitative findings. For example, qualitative data showed processes of denial on the part of patients and the important role of relatives in initiating appropriate help-seeking behaviour on patients' behalf. CONCLUSIONS: Our study provides insights into the complexities of the decision-making process at stroke symptom onset. As our findings suggest processes of denial and inabilities to translate abstract disease knowledge into correct actions, we recommend to address relatives as potential saviours of loved ones, increased use of specific situational examples (e.g. lying on the bathroom floor) and the involvement of patient representatives in the preparation of informational resources and campaigns. Future research should include mixed methods research from one sample and more attention to potential reporting inconsistencies.

p37 regulates VCP/p97 shuttling and functions in the nucleus and cytosol.

The AAA+-ATPase valosin-containing protein (VCP; also called p97 or Cdc48), a major protein unfolding machinery with a variety of essential functions, localizes to different subcellular compartments where it has different functions. However, the processes regulating the distribution of VCP between the cytosol and nucleus are not understood. Here, we identified p37 (also called UBXN2B) as a major factor regulating VCP nucleocytoplasmic shuttling. p37-dependent VCP localization was crucial for local cytosolic VCP functions, such as autophagy, and nuclear functions in DNA damage repair. Mutations in VCP causing multisystem proteinopathy enhanced its association with p37, leading to decreased nuclear localization of VCP, which enhanced susceptibility to DNA damage accumulation. Both VCP localization and DNA damage susceptibility in cells with such mutations were normalized by lowering p37 levels. Thus, we uncovered a mechanism by which VCP nucleocytoplasmic distribution is fine-tuned, providing a means for VCP to respond appropriately to local needs.

Morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative patients with first unprovoked seizure.

OBJECTIVE: The aim of the study was to evaluate the benefits of morphometric magnetic resonance imaging (MRI) postprocessing in patients presenting with a first seizure and negative MRI results and to investigate these findings in the context of the clinical and electroencephalographic data, seizure recurrence rates, and epilepsy diagnosis in these patients. METHODS: We retrospectively reviewed 97 MRI scans of patients with first unprovoked epileptic seizure and no evidence of epileptogenic lesion on clinical routine MRI. Morphometric Analysis Program (MAP; v2018), automated postprocessing software, was used to identify subtle, potentially epileptogenic lesions in the three-dimensional T1-weighted MRI data. The resulting probability maps were examined together with the conventional MRI images by a reviewer who remained blinded to the patients' clinical and electroencephalographical data. Clinical data were prospectively collected between February 2018 and May 2023. RESULTS: Among the apparently MRI-negative patients, a total of 18 of 97 (18.6%) showed cortical changes suggestive of focal cortical dysplasia. Within the population with positive MAP findings (MAP+), seizure recurrence rates were 61.1% and 66.7% at 1 and 2 years after the first unprovoked seizure, respectively. Conversely, patients with negative MAP findings (MAP-) had lower seizure recurrence rates of 27.8% and 34.2% at 1 and 2 years after the first unprovoked seizure, respectively. Patients with MAP+ findings were significantly more likely to be diagnosed with epilepsy than those patients with MAP- findings (χ2 [1, n = 97] = 14.820, p < .001, odds ratio = 21.371, 95% CI = 2.710-168.531) during a mean follow-up time of 22.51 months (SD = 16.7 months, range = 1-61 months). SIGNIFICANCE: MRI postprocessing can be a valuable tool for detecting subtle epileptogenic lesions in patients with a first seizure and negative MRI results. Patients with first seizure and MAP+ findings had high seizure recurrence rates, meeting the criteria for beginning epilepsy.

[Comparison of acute stroke care pathways-A qualitative multicenter study in three referring hospitals of a stroke network]. / Vergleich von Behandlungspfaden beim akuten Schlaganfall ­ eine qualitative multizentrische Studie in drei zuweisenden Kliniken eines Schlaganfallnetzwerkes.

BACKGROUND: In stroke networks, hospitals that do not provide thrombectomy (referring hospitals) refer patients to specialized hospitals (receiving hospitals) for this specific intervention. In order to improve the access and management of thrombectomy, the focus of research needs to be not only on the receiving hospitals but also on the prior stroke care pathways in referring hospitals. OBJECTIVE: The purpose of this study was to investigate the stroke care pathways in different referring hospitals as well as the advantages and disadvantages associated with these pathways. METHODS: A qualitative multicenter study was carried out in three referring hospitals of a stroke network. Stroke care was assessed and analyzed by using non-participant observations and 15 semi-structured interviews with employees in various health professions. RESULTS: The following aspects were reported as advantageous within the stroke care pathways: (1) a structured and personal prenotification of the patient by the emergency medical service (EMS) members; (2) a more efficiently organized teleneurology workflow; (3) the provision of the secondary referral to thrombectomy by the same EMS members of the primary referral and (4) the integration of external neurologists into in-house structures. CONCLUSION: The study provides insights into different stroke care pathways of three different referring hospitals of a stroke network. The results can be used to derive potentials for improvement of other referring hospitals; however, this study is too small to provide reliable information about their potential effectiveness. Future studies should investigate whether implementation of these recommendations actually leads to improvements and under which conditions they are successful. To ensure patient-centeredness, the perspectives of patients and relatives should also be included.

Bilateral Change in Vertical Hoof Force Distribution in Horses with Unilateral Forelimb Lameness before and after Successful Diagnostic Anaesthesia.

Kinetic examinations of horses with induced lameness as well as the effect of perineural anaesthesia in sound horses have shown promise, but clinical studies regarding the effect of diagnostic anaesthesia during the different stance phases are rare. Fourteen horses with unilateral forelimb lameness were examined with the Hoof™ System during trot to assess vertical force distribution (in kg) affecting both front hooves before and after diagnostic anaesthesia during landing, midstance, and breakover. For statistical analysis, a covariance analysis with repeated measurements regarding the limb (lame/sound) as well as anaesthesia (before/after) and the covariable body weight was performed. The p-values for the pairwise comparisons were adjusted using the Bonferroni−Holm correction (p < 0.05). For all phases of the stance, a significant interaction between the factors limb and anaesthesia was shown. Before diagnostic anaesthesia, vertical force was significantly reduced on the lame limb compared to the sound limb during landing (−25%, p < 0.001), midstance (−20%, p < 0.001) and breakover (−27%, p < 0.001). After anaesthesia, the difference between both forelimbs was not significant anymore for all phases. The vertical force on the lame limb increased significantly after positive anaesthesia during the whole stance phase, with breakover being most affected (+27%, p = 0.001). Pressure measurements with the Hoof™ System can be used to evaluate the effect of diagnostic anaesthesia in a clinical setting with pain-related vertical force asymmetries being neutralised after diagnostic anaesthesia. Breakover is the main event influenced by lameness.

Patient Pathways During Acute in-Hospital Stroke Treatment: A Qualitative Multi-Method Study.

Introduction: Patients experiencing acute ischemic stroke should access treatment as soon as possible to increase their chances for survival without severe disability. Given the increased complexity of stroke treatment from the provider and patient perspective, this study provides an overview of the pathways followed by stroke patients during in-hospital treatment. Methods: This qualitative study combined twenty-seven observations and fifteen staff interviews at a German comprehensive stroke center providing endovascular treatment ("EVT hospital"). Analysis was based on the COMIC Model for the comprehensive evaluation of complex health care interventions and a grounded theory approach. Results: The patient pathways during in-hospital treatment span the phases (1) admission to hospital, (2) receiving recanalization therapies, and (3) in-patient treatment. Before admission to the EVT hospital, interactions between staff members from the EVT hospital and patients take place as part of the telestroke consultations during which the EVT hospital's ED neurologist meets the patient via a video- and audio-based connection. During the second phase, when IVT and/or EVT are provided to the patient, three teams (ED, neuroradiology and ICU team) with direct patient interactions intersect at the angiography suite until mechanical recanalisation treatment ends and the patient is transferred to the SU or ICU. In the third phase, the patients are treated on the SU or ICU and staff members interact with them according to a pre-defined schedule as well as based on individual needs. Discussion: Our results show that most direct staff-patient interactions are focussed within one phase, with a smaller number of interactions extending to other phases, and no professional (group) with direct patient interactions cover more than two phases of the acute stroke pathway. Future research should investigate how the pathways described here are experienced from the patient perspective, including how the organisation of visible care processes may influence patient satisfaction. Findings can be translated to accessible patient information resources as well as input for digitalisation efforts, provider orientation and training.

"But it's a nice compromise" - Qualitative multi-centre study of barriers and facilitators to acute telestroke cooperation in a regional stroke network.

BACKGROUND: Telemedical services can be used to complement on-site services when demand for specialists exceeds supply or when specialists are not evenly distributed across health systems. Using stroke as an example, this study aimed to explore how patients and staff experience telestroke cooperation in a stroke network in Germany. METHODS: We conducted a qualitative multi-method and multi-centre study combining 32 non-participant observations at one hub and four spoke hospitals with 26 semi-structured interviews with hub and spoke staff as well as stroke patients and relatives. Observation protocols and interview transcripts were analysed to identify barriers and facilitators to telestroke cooperation from the perspectives of staff, patients and relatives. RESULTS: In terms of barriers to telestroke cooperation, we found technological problems, providing the treatment for one patient from two sites, competing priorities between telestroke and in-house duties in the spoke hospitals, as well as difficulties in participating in the teleneurological examination via a videoconferencing system for older and disabled patients. In terms of facilitators, we found an overall very positive perception of telestroke provision by patients, good professional relationships within the network, and sharing of neurological expertise to be experienced as helpful for telestroke cooperation. CONCLUSIONS: We recommend better integration of telemedical services into the care pathway, fostering relationships within the network, improved technological support and resources, and more emphasis within networks, in public awareness efforts as well as in academia on the evaluation of telemedical services from the perspectives of patients and relatives, especially older patients and patients with disabilities.

Integrin αE(CD103)ß7 in Epithelial Cancer.

Interactions of both the innate and the adaptive immune system with tumors are complex and often influence courses and therapeutic treatments in unanticipated ways. Based on the concept that CD8+T cells can mediate important antitumor effects, several therapies now aim to amplify their specific activity. A subpopulation of CD8+ tissue-resident T lymphocytes that express the αE(CD103)ß7 integrin has raised particular interest. This receptor presumably contributes to the recruitment and retention of tumor-infiltrating immune cells through interaction with its ligand, E-cadherin. It appears to have regulatory functions and is thought to be a component of some immunological synapses. In TGF-rich environments, the αE(CD103)ß7/E-cadherin-interaction enhances the binding strength between tumor cells and infiltrating T lymphocytes. This activity facilitates the release of lytic granule contents and cytokines as well as further immune responses and the killing of target cells. Expression of αE(CD103)ß7 in some tumors is associated with a rather favorable prognosis, perhaps with the notable exception of squamous cell carcinoma of the skin. Although epithelial skin tumors are by far the most common tumors of fair-skinned people, there have been very few studies on the distribution of αE(CD103)ß7 expressing cells in these neoplasms. Given this background, we describe here that αE(CD103)ß7 is scarcely present in basal cell carcinomas, but much more abundant in squamous cell carcinomas with heterogeneous distribution. Notwithstanding a substantial number of studies, the role of αE(CD103)ß7 in the tumor context is still far from clear. Here, we summarize the essential current knowledge on αE(CD103)ß7 and outline that it is worthwhile to further explore this intriguing receptor with regard to the pathophysiology, therapy, and prognosis of solid tumors.

Effect of Perineural Anesthesia on the Centre of Pressure (COP) Path During Stance Phase at Trot in Sound Horses.

This study aimed to examine how short-term loss of proprioception in the equine foot influences the individual COP path during the stance phase of the trot in sound horses. Ten horses were evaluated to be objectively non-lame using the 'Equinosis Q System and subsequently examined using a portable pressure measuring system with pressure foils fixed directly underneath both front hooves prior to and after perineural anesthesia of the palmar digital nerves. The individual COP paths of both forelimbs was assessed prior to and after unilateral and bilateral abaxial sesamoid nerve blocks. COP from initial contact to mid stance and breakover as well as the inter-stride variability were descriptively evaluated for each horse and limb. The individual COP path for each horse and limb during stance was shown to be highly repeatable without significant inter-stride variability. Location of initial contact, COP during midstance and breakover are not affected by unilateral or bilateral short-term loss of sensory feedback from the foot after perineural anesthesia. Anesthesia of the foot with an abaxial sesamoid nerve block does not affect the foot's COP during stance at a trot, therefore, sudden changes in gait pattern after perineural anesthesia should be interpreted with caution and warrant further clinical investigation.

Effect of heel elevation on breakover phase in horses with laminitis.

BACKGROUND: In a laminitic horse, the maximal loading of the toe region occurs during the breakover phase. To date, no kinetic data demonstrates the effect of supportive orthopaedic therapy in horses with laminitis on breakover phase. Thus, the purpose of this study was to examine the effect of heel elevation on the breakover phase. Eight horses with acute laminitis treated medically as well as with application of a hoof cast with heel wedge (HCHW) were included in this study. Immediately following cessation of clinical signs of acute laminitis, two measurements using the Hoof™ System were taken: the first with HCHW and the second immediately following removal of the HCHW, i.e. in barefoot condition (BFC). The hoof print was divided into three regions: toe, middle hoof, and heel. Kinetic parameters included vertical force (VF), stance duration, contact area (CA) for all hoof regions during stance phase, duration of breakover, VF in the toe region at onset of breakover and location of centre of force. RESULTS: The VF and CA were higher in the heel region (63 and 61%, respectively) and decreased significantly after removal of the HCHW (43 and 28% after removal, respectively). The breakover phase in horses with HCHW lasted 2% of stance phase and was significantly shorter than that in BFC, which lasted 6% of stance phase. The VF at onset of breakover for the toe region in horses with HCHW was significantly lower than that in BFC. The centre of the force was located at the heel region in all horses with the HCHW, and at the middle the hoof region in BFC. CONCLUSIONS: Heel elevation in horses with laminitis as examined on a concrete surface significantly shortens breakover phase and decreases the vertical force in the toe region during breakover. HCHW provides adequate support to the palmar hoof structures by increasing the contact area in the heel region and incorporating the palmar part of frog and sole into weight bearing, thus decreasing the stress on the lamellae. Hoof cast with heel elevation could be a beneficial orthopaedic supportive therapy for horses suffering from acute laminitis.

Efficient removal of black henna tattoos.

BACKGROUND/OBJECTIVES: Para-phenylenediamine, a dye frequently added to henna tattoos to create the black color, is a potent contact allergen. Severe contact dermatitis may arise within days even after the first application. Our objective was to develop a method for rapid and complete removal of para-phenylenediamine-containing black henna tattoos from the skin, an important problem many physicians are confronted with, but for which no simple method exists. METHODS: A database search revealed polyethylene glycol 400, described in removal of ortho-phenylenediamine from contaminated skin. We therefore investigated its use in removal of the structurally related ortholog para-phenylenediamine present in black henna tattoos. RESULTS: A protocol was established involving repeated cycles of rinsing of the skin with polyethylene glycol 400 solution. In 5 patients, one of whom had already developed a severe blistering contact dermatitis and another a mild erosive dermatitis, black henna tattoos were successfully removed. Removal was completed in a single session of 1 hour or less, depending on tattoo size, with a maximum of 6 rinse cycles. CONCLUSIONS: We provide a simple and safe method for rapid and effective removal of black henna tattoos. This procedure requires no special equipment and can be applied in virtually any setting.

Acute Kidney Injury-Associated Systemic Inflammation Is Aggravated in Insulin-Dependent Diabetes Mellitus.

BACKGROUND: Acute kidney injury (AKI) significantly worsens the prognosis of hospitalized patients. Diabetes mellitus (DM) affects a growing number of individuals in the western world. DM subjects are at a higher risk for acquiring AKI during the stay at the hospital. The current study intended to quantify serum levels of specific immunomodulatory cytokines in diabetic mice suffering from AKI. METHODS: DM was induced in male C57/Bl6N mice by systemic injections of beta cell-toxic streptozotocin. Animals underwent bilateral renal ischemia (45 min) 6 weeks later. RESULTS: Post-ischemic diabetic mice showed significantly differing serum concentrations of the majority of all analytes as compared to untreated controls and non-diabetic (post-ischemic) animals. CONCLUSIONS: Together, our data suggest DM-associated immune activation in AKI. One may suppose that inadequate stimulation of the humoral/cellular immune response potentially contributes to the higher ischemia susceptibility of the organ in DM.

Cytokine profiling in anti neutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional cohort study.

ANCA-associated vasculitides (AAV) are severe diseases, potentially affecting lungs, kidney, and other organs. Nevertheless, risk profiling remains difficult. Aim of the current study was to analyze serological characteristics in AAV. The principal goal was to identify diagnostic markers that potentially allow a more sophisticated risk profiling in AAV. AAV subjects were recruited and evaluated for disease activity, disease stage, medication, and laboratory findings. Serum concentrations of the following parameters were measured: IL-1ß, IL-6, IL-17 A, IL-17 F, IL-21, IL-22, IL-23, TNF-α, sCD40L, IL-4, IL-10, IL-25, IL-31, IL-33, and INF-γ. A total number of 62 AAV subjects was included in the study (39 females; 23 males). Forty-five subjects were PR3+, 17 subjects showed ANCA specificity for MPO. The majority of all cytokines fell under the lower detection limit of the assay. Serum IL-10 was higher in both, AAV and SSc as compared to controls; it was also higher in early systemic AAV. Serum IL-33 was elevated in AAV and SSc; in AAV, higher levels were found in non-necrotizing GN and RTX untreated subjects. Serum CD40L was raised in AAV as well; higher concentrations were also found in PR3+ and MPO+ patients and early systemic, generalized, and refractory AAV. IL-10 may potentially serve as a marker of early systemic AAV. IL-33 may help to identify subjects with a higher risk for necrotizing GN in AAV.

Topical scabies therapy with permethrin is effective and well tolerated in infants younger than two months.

BACKGROUND AND OBJECTIVES: Proper management of infantile scabies is indispensable in order to prevent prolonged duration and spread of the disease. Data are still lacking that support topical treatment with permethrin 5 % cream in infants under two months of age, and application remains off-label for this age group. PATIENTS AND METHODS: We identified infants younger than two months who suffered from scabies in order to evaluate the safety and efficacy of topical treatment with permethrin cream in this age group. Diagnosis of scabies was based on the typical symptoms and pathognomonic features as determined with dermoscopy. We analyzed the efficacy and safety of the therapies that were applied. RESULTS: Seven scabies patients under two months of age were treated with permethrin 5 % cream. Topical therapy was repeated up to three times in four patients due to incomplete resolution or recurrence of skin lesions. CONCLUSIONS: Permethrin therapy was well tolerated in all seven infants, even when conducted several times. Our results confirm that the use of permethrin 5 % cream in children younger than two months of age is safe.

Patient safety - Development, implementation and evaluation of an interprofessional teaching concept.

Objective: Patient safety has high priority in health care. Since successful interprofessional collaboration is essential for patient safety, the topic should ideally be addressed interprofessionally in the curricula. The aim of the project was the development and implementation of an interprofessional teaching concept "patient safety" for medical students and students of health professions at the Medical Faculty Heidelberg. Methodology: The learning objectives were formulated on the basis of the "Patient Safety Learning Objective Catalog" ("Lernzielkatalog Patientensicherheit") of the Society for Medical Education (Gesellschaft für Medizinische Ausbildung, GMA) and on the basis of the American Interprofessional Competence Profile "Core Competencies for Interprofessional Collaborative Practice". Two courses were designed for interprofessional groups of approximately 15 participants. The learning content was designed interactively through the development of the project, its application and critical discussion of error reporting systems and security checklists as well as role-plays and video material. The evaluation was carried out by means of descriptive analysis of a structured course evaluation system, which was developed for this study. Results: 28 students took part in the courses. 82% of the students considered the topic "patient safety" to be relevant. In 82% of the cases, the participants rated the interprofessional aspect of the course as valuable. Overall, 73% of students whished for more interprofessional education. Conclusion: The results of the evaluation show that the teaching concept is well accepted by the students and encourage the implementation of further interprofessional courses with a thematic relevance.

Association between serum neuron-specific enolase, age, overweight, and structural MRI patterns in 901 subjects.

Serum neuron-specific enolase (sNSE) is considered a marker for neuronal damage, related to gray matter structures. Previous studies indicated its potential as marker for structural and functional damage in conditions with adverse effects to the brain like obesity and dementia. In the present study, we investigated the putative association between sNSE levels, body mass index (BMI), total gray matter volume (GMV), and magnetic resonance imaging-based indices of aging as well as Alzheimer's disease (AD)-like patterns. SUBJECTS/METHODS: sNSE was determined in 901 subjects (499 women, 22-81 years, BMI 18-48 kg/m2), participating in a population-based study (SHIP-TREND). We report age-specific patterns of sNSE levels between males and females. Females showed augmenting, males decreasing sNSE levels associated with age (males: p = 0.1052, females: p = 0.0363). sNSE levels and BMI were non-linearly associated, showing a parabolic association and decreasing sNSE levels at BMI values >25 (p = 0.0056). In contrast to our hypotheses, sNSE levels were not associated with total GMV, aging, or AD-like patterns. Pathomechanisms discussed are: sex-specific hormonal differences, neuronal damage/differentiation, or impaired cerebral glucose metabolism. We assume a sex-dependence of age-related effects to the brain. Further, we propose in accordance to previous studies an actual neuronal damage in the early stages of obesity. However, with progression of overweight, we assume more profound effects of excess body fat to the brain.