Sein Schmidt

Zusammenfassung: Hintergrund und Zielsetzung: Haarausfallerkrankungen beeinträchtigen die Lebensqualität weit über rein kosmetische Aspekte hinaus. Frühere Untersuchungen berichten meist von milder bis moderater Beeinträchtigung. Ziel dieser Studie war es, das Ausmaß der Lebensqualitätsbeeinträchtigung bei Patienten mit Haarausfall zu erfassen, dabei vernarbende und nicht vernarbende Formen zu vergleichen und mögliche Einflussfaktoren zu analysieren. Patienten und Methodik: In einer explorativen Querschnittstudie wurden 510 Patienten (281 mit nicht vernarbender und 229 mit vernarbender Alopezie) in der dermatologischen Ambulanz der Charité – Universitätsmedizin Berlin eingeschlossen. Die Lebensqualität wurde anhand des DLQI und ausgewählter PROMIS‐Instrumente erfasst. Zur Auswertung kamen t‐Tests, dreifaktorielle Varianzanalysen mit anschließenden Post‐hoc ‐Tests sowie Korrelationsanalysen zur Anwendung. Ergebnisse: Haarausfallerkrankungen können zur Beeinträchtigung der Lebensqualität führen, wobei das psychische Wohlbefinden am stärksten betroffen ist. Die DLQI‐Scores zeigten bei beiden Alopezie‐Typen moderate Einschränkungen. Die PROMIS‐Ergebnisse wiesen bei allen Patienten leichte Angstsymptome auf, bei der nicht vernarbenden Alopezie zusätzlich milde Depressivität. Betroffene mit nicht vernarbender Alopezie berichteten über stärkere psychische Belastung als jene mit vernarbender Alopezie. Patienten beider Gruppen sowie Frauen mit nicht vernarbender Alopezie zeigten teilweise ausgeprägtere Beeinträchtigungen. Schlussfolgerungen: Die Ergebnisse dieser explorativen Studie deuten darauf hin, dass Haarausfall mit deutlicher psychischer Belastung einhergehen kann. In der Behandlung sollte daher erwogen werden, psychologische Unterstützung in das Behandlungskonzept mit einzubeziehen.

Summary: Background and Objectives: Hair loss disorders impact quality of life (QoL) far beyond cosmetic issues, with previous studies showing mild to moderate impairment. This study aimed to assess QoL impairment in hair loss patients, comparing scarring and non‐scarring alopecia, and to analyze possibly related influencing factors. Patients and Methods: An exploratory cross‐sectional study of 510 patients (281 with non‐scarring and 229 with scarring alopecia) was conducted at the Charité –Universitätsmedizin Berlin's dermatology outpatient clinic. DLQI and PROMIS questionnaires were completed. T‐tests, three‐factor analysis of variance with post hoc tests, and correlation analyses were used for evaluation. Results: Hair loss disorders can lead to an impaired QoL, with psychological well‐being being the most affected. DLQI scores showed moderate impairment in both alopecia types. In addition, PROMIS indicated mild anxiety impairment in both, and mild depressive symptoms in non‐scarring alopecia. Subjects with non‐scarring type were more affected in their psychological well‐being than those with scarring alopecia. A greater impairment was partially observed at a younger age in both types of alopecia and in women with non‐scarring alopecia. Conclusions: This exploratory study suggests that hair loss may lead to a notable emotional burden; thus, psychological support could be considered beneficial in hair loss management.

Introduction The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations. Methods and analysis A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after ~90 days and includes assessments of the patient’s medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including ‘OMICs’ technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes. Ethics and dissemination The study was approved by the Charité—Universitätsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations. Study registration First study phase: Approved WHO primary register: German Clinical Trials Register: https://drks.de/search/de/trial/DRKS00016852; WHO International Clinical Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00016852. Recruitment started on July 18, 2017. Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL: http://www.drks.de/ DRKS00023323. Recruitment started on January 1, 2021.

Study Design.: Prospective quasi-experimental observational study. Objective.: The objective of this study was to evaluate whether duration of surgery is a modifiable risk factor for postoperative delirium (POD) after spine surgery and explore further modifiable risk factors. In addition, we sought to investigate the association between POD and postoperative cognitive dysfunction and persistent neurocognitive disorders. Summary of Background Data.: Advances in spine surgery enable technically safe interventions in elderly patients with disabling spine disease. The occurrence of POD and delayed neurocognitive complications (e.g. postoperative cognitive dysfunction/persistent neurocognitive disorder) remain a concern since these contribute to inferior functional outcomes and long-term care dependency after spine surgery. Materials and Methods.: This prospective single-center study recruited patients aged 60 years or above and scheduled for elective spine surgery between February 2018 and March 2020. Functional (Barthel Index, BI) and cognitive outcomes [Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test battery; telephone Montréal Cognitive Assessment] were assessed at baseline, three (V3), and 12 months postoperatively. The primary hypothesis was that the duration of surgery predicts POD. Multivariable predictive models of POD included surgical and anesthesiological parameters. Results.: Twenty-two percent of patients developed POD (n=22/99). In a multivariable model, duration of surgery [OR_adj=1.61/h (95% CI, 1.20–2.30)], age [OR_adj=1.22/yr (95% CI, 1.10–1.36)], and baseline deviations of intraoperative systolic blood pressure [25th percentile: OR_adj=0.94/mm Hg (95% CI, 0.89–0.99); 90th percentile: OR_adj=1.07/mm Hg (95% CI, 1.01–1.14)] were significantly associated with POD. Postoperative cognitive scores generally improved (V3, ΔCERAD total z-score: 0.22±0.63). However, this positive group effect was counteracted by POD [beta: −0.87 (95% CI, −1.31 to 0.42)], older age [beta: −0.03/yr (95% CI, −0.05 to 0.01)], and lack of functional improvement [ΔBI; beta: −0.04/point (95% CI, −0.06 to 0.02)]. Cognitive scores at twelve months remained inferior in the POD group, adjusted for baseline cognition/age. Conclusions.: This study identified distinct neurocognitive effects after spine surgery, which are influenced by perioperative risk factors. Potential cognitive benefits are counteracted by POD, rendering its prevention critical in an aging population.

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON’s goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36–62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON’s design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities. Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584

(1) Background: Headache disorders are among the most disabling medical conditions but the supply with experienced providers is outpaced by the demand for service. It is unclear to what extent particularly patients in rural regions are affected by limited access to comprehensive care. Furthermore, it is unknown what role general practitioners (GPs) play in headache care. (2) Methods: First-time consultations to a specialised headache clinic at a tertiary care centre were asked to participate. Their socio-demographic background, general and headache-specific medical history, disability and quality of life (QoL) were assessed. Additionally, 176 GPs in neighbouring districts were contacted regarding headache management. (3) Results: We assessed 162 patients with first-time consultations (age 46.1 ± 17.0 years, 78.1% female), who suffered from migraine (72%), tension type, cluster and secondary headaches (each 5–10%). About 50% of patients received a new headache-diagnosis and 60% had treatment inconsistent with national guidelines. QoL was significantly worse in all domains compared to the general population. About 75% of GPs see headache patients at least several times per week, and mostly treat them by themself. (4) Conclusions: More than every second headache patient was neither correctly diagnosed nor received guideline adherent treatment. Headache-related disability is inferior to what is expected from previous studies. Access to specialised health care is more limited in rural than in urban regions in Germany and GPs request more training.

Introduction Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%–60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity. Methods and analysis This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score Ethics and dissemination This protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226—EK 11) and by the relevant federal authority (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences. Trial registration numbers NCT04301271, DRKS00021119, EudraCT 2018-002947-27.

Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, in order to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions. Methods: Pa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charité - Universitätsmedizin Berlin. We collect data on epidemiology, demography, medical history, symptoms, clinical course, pathogen testing and treatment. Systematic, serial blood sampling will allow deep molecular and immunological phenotyping, transcriptomic profiling, and comprehensive biobanking. Longitudinal data and sample collection during hospitalization will be supplemented by long-term follow-up. Results: Outcome measures include the WHO clinical ordinal scale on day 15 and clinical, functional and health-related quality of life assessments at discharge and during follow-up. We developed a scalable dataset to ( i ) suit national standards of care ( ii ) facilitate comprehensive data collection in medical care facilities with varying resources and ( iii ) allow for rapid implementation of interventional trials based on the standardized study design and data collection. We propose this scalable protocol as blueprint for harmonized data collection and deep phenotyping in COVID-19 in Germany. Conclusion: We established a basic platform for harmonized, scalable data collection, pathophysiological analysis, and deep phenotyping of COVID-19, which enables rapid generation of evidence for improved medical care and identification of candidate therapeutic and preventive strategies. The electronic database accredited for interventional trials allows fast trial implementation for candidate therapeutic agents.

The clinical course of COVID-19 is highly variable, however, underlying host factors and determinants of severe disease are still unknown. Based on single-cell transcriptomes of nasopharyngeal and bronchial samples from clinically well-characterized patients presenting with moderate and critical severities, we reveal the different types and states of airway epithelial cells that are vulnerable for SARS-CoV-2 infection. In COVID-19 patients, we observed a two- to threefold increase of cells expressing the SARS-CoV-2 entry receptor ACE2 within the airway epithelial cell compartment. ACE2 is upregulated in epithelial cells through Interferon signals by immune cells suggesting that the viral defense system may increase the number of potentially susceptible cells in the respiratory epithelium. Infected epithelial cells recruit and activate immune cells by chemokine signaling. Recruited T lymphocytes and inflammatory macrophages were hyperactivated and showed a strong interaction with epithelial cells. In critical patients, increased expression of CCL2, CCL3, CCL5, CXCL9, CXCL10, IL8, IL1B and TNF in macrophages was identified as a likely cause of a hyperinflammatory lung pathology. Moreover, we observed exacerbated epithelial cell death, likely leading to lung injury and respiratory failure in fatal cases. Our study provides novel insights into the pathophysiology of COVID-19 and suggests an immunomodulatory therapy along the CCL2, CCL3/CCR1 axis as promising option to prevent and treat critical course of COVID-19.

Background: Elderly people are at particular high risk for postoperative delirium (POD) following spine surgery, which is associated with longer hospital stays, higher costs, risk for delayed complications, long-term care dependency, and cognitive dysfunction (POCD). It is insufficiently understood which mechanisms and risk factors contribute to the development of POD and POCD following these major but plannable surgeries. Objective: This study aims to identify modifiable risk factors in spine surgery. A better understanding thereof would help adapt medical management and surgical strategies to individual risk profiles. Methods: This is a single-center observational study jointly conducted by the departments of neurosurgery, neurology, and anesthesiology at a tertiary care hospital in Germany. All patients aged 60 years and older presenting to the neurosurgery outpatient clinic or ward for elective spine surgery are screened for eligibility. Exclusion criteria include presence of neurodegenerative or history of psychiatric disease and medication with significant central nervous system activity (eg, antidepressants, antipsychotics, sedatives). Surgical and anesthetic procedures including duration of surgery as primary end point of this study are thoroughly documented. All patients are furthermore evaluated for their preoperative cognitive abilities by a number of tests, including the Consortium to Establish a Registry for Alzheimer's Disease Plus test battery. Physical, mental, and social health and well-being are assessed using the Patient-Reported Outcome Measurement Information System Profile 29 and Hospital Anxiety and Depression Scale. Patients additionally receive preoperative cerebrovascular ultrasound and structural and functional brain imaging. The immediate postoperative period includes screening for POD using the Nursing Delirium Screening Scale and validation through Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, criteria. We furthermore investigate markers of (neuro)inflammation (eg, interleukins, C-reactive protein, tumor necrosis factor alpha). Preoperative examinations are repeated 3 months postoperatively to investigate the presence of POCD and its mechanisms. Statistical analyses will compare delirious and nondelirious patients for predictors of immediate (POD) and delayed (POCD) cognitive dysfunction. Results: This is the first study to prospectively evaluate risk factors for POD and POCD in spine surgery. Recruitment is ongoing, and data collection is estimated to be finished with the inclusion of 200 patients by mid-2020. Conclusions: The identification of mechanisms, possibly common, underlying POD and POCD would be a major step toward defining effective interventional strategies early in or even before the postoperative period, including the adaptation of surgical strategies to individual risk profiles. Trial Registration: ClinicalTrials.gov NCT03486288; https://clinicaltrials.gov/ct2/show/NCT03486288