Ludwig-Maximilians-Universität München
Open Access LMU ( Ludwig-Maximilians-Univ. München)Not a member yet
40914 research outputs found
Sort by
Public health in Germany: structures, dynamics, and ways forward
No full textDespite Germany's robust economy, comprehensive social welfare system, and the country ranking third among Organisation for Economic Co-operation and Development countries in terms of per-capita health spending, its health indicators still lag behind those of other European nations. Germany also has one of the highest prevalences of major modifiable risk factors for non-communicable diseases within the EU. This Health Policy provides an overview of the development, structures, and actors in public health in Germany, highlighting possible explanations for the country's underperforming health indicators and suggesting a way forward. This Health Policy is structured along the essential public health operations. We identify the absence of a strong central institution for public health, inadequate funding for disease prevention and health promotion, and little interoperability in data collection as major challenges. The country's decentralised governance structure allows flexibility, especially at the community level, but leads to scattered responsibilities and little coordination between sectors. We also note the absence of a public health strategy. The current system's focus on curative care and individualised medicine has led to a neglect of disease prevention and health promotion. Furthermore, the country's strong economic interests and powerful lobbies have hindered the implementation of effective public health policies. To address these challenges, we recommend developing a public health identity, creating a comprehensive public health strategy, fostering a culture of health promotion and disease prevention that encompasses all areas and does not shy away from tackling the commercial determinants of health, and strengthening the connection between medicine, public health practice, and research
Thalamus involvement in genetic frontotemporal dementia assessed using structural and diffusion MRI: a GENFI study
Full text linkThalamic subregions are commonly, but variably, affected by different forms of frontotemporal dementia. We aimed to better characterize thalamic subregional involvement in genetic frontotemporal dementia with a recently published thalamus segmentation tool that utilizes structural and diffusion MRI, offering additional assessment of mean diffusivity and a more fine-grained analysis of the pulvinar specifically compared to previous studies. Using this tool, we performed thalamus segmentations in MRI scans from C9orf72, GRN and MAPT mutation carriers and mutation non-carriers with suitable 3-Tesla MRI cross-sectional data from the GENetic Frontotemporal dementia Initiative. Mutation carriers were divided according to their genetic group and Clinical Dementia Rating® Dementia Staging Instrument plus National Alzheimer’s Coordinating Center Behaviour and Language Domains global score (0 or 0.5: presymptomatic/prodromal stage, 1 or higher: symptomatic stage). Following stringent quality control and harmonization across sites and scanners, we compared volumes and mean diffusivity values of thalamic subregions in C9orf72 (47 presymptomatic, 10 symptomatic), GRN (57 presymptomatic, 11 symptomatic) and MAPT (31 presymptomatic, 12 symptomatic) mutation carriers to those in 109 mutation non-carriers with analyses of covariance including age and sex (and total intracranial volume for volumetric comparisons) as covariates. Presymptomatic C9orf72 expansion carriers showed smaller volumes (3–8% difference from non-carriers) and higher mean diffusivity (2–5% difference from non-carriers) for several thalamic subregions, including all pulvinar subdivisions. We found subtly larger volumes of the ventral anterior subregion and the non-medial pulvinar (3% difference from non-carriers for both) in presymptomatic GRN mutation carriers, and of the anteroventral subregion (5% difference from non-carriers) in presymptomatic MAPT mutation carriers. Symptomatic mutation carriers in all three genetic groups showed significantly smaller volumes and widespread higher mean diffusivity of thalamic subregions compared with non-carriers, which were overall most prominent in subregions involved in associative and limbic functions (the midline, medial pulvinar, anteroventral, mediodorsal, laterodorsal and lateral posterior subregions). Notably smaller volume (12–23% difference from non-carriers) and higher mean diffusivity (16–23% difference from non-carriers) of the most medial part of the medial pulvinar was a shared feature across the three genetic groups at the symptomatic stage. Overall, our study confirms that thalamic subregions are affected in genetic frontotemporal dementia and identifies prominent involvement of the most medial part of the medial pulvinar as a potential unifying feature in the variable pattern of thalamic subregional involvement across the main genetic groups
Predictive value of maximum tumor dissemination (Dmax) in lymphoma patients treated with CD19-specific CAR T-Cells
Full text linkObjectives
CD19-specific chimeric antigen receptor T-cell therapy (CART) has emerged as effective treatment for relapsed or refractory (r/r) lymphoma. The maximum distance (Dmax) of lymphoma lesions holds potential as prognostic imaging biomarker in lymphoma treated with conventional therapies, but evidence in the context of CART remains scarce and further studies are needed to clarify its clinical relevance. We evaluated Dmax at baseline imaging as a potential prognostic tool for assessment of metabolic and overall response, progression-free survival (PFS) and overall survival (OS).
Material & methods
Consecutive r/r lymphoma patients with (PET/)CT imaging at baseline (BL) before lymphodepletion and subsequent CAR T-cell transfusion were included. Dmax was measured in cm at BL. Patients were divided by tertiles into three equal sized groups according to Dmax. Ann Arbor stages were calculated at baseline and the sum of product diameters (SPD) was used to represent tumor burden (TB). Overall response according to Lugano criteria and the Deauville score were determined at day 90 PET/CT imaging.
Results
Thirty-nine patients met the inclusion criteria. Median Dmax was 40.0 cm (IQR: 16.4–70.3 cm) at BL. Median TB decreased from BL with 4,095 mm2 to 770 mm2 at FU imaging. Median TB at BL was significantly higher in the Dmax intermediate and high group compared to the Dmax low group (p = 0.005) with 7,222 mm2 (IQR: 3,355–11,941 mm2), 4,649 mm2 (IQR: 2,376–10,406 mm2) and 1,739 mm2 (IQR: 715–7,402 mm2), respectively. Dmax intermediate and high group showed significantly higher Ann Arbor stages (p < 0.001). The survival analysis revealed a significantly (p = 0.030) shorter PFS in the Dmax high group compared to the other patients (91 vs. 364 days), but no relevant differences in OS (p = 0.151).
Conclusions
Patients with high Dmax showed a shorter PFS, but no significant differences in OS. Dmax is a useful parameter for characterizing tumor dissemination, which could also be incorporated into scores due to its interval scale
Stroke risk associated with cold spells occurring during the warm season
Full text linkBackground: Recent climate changes have resulted in a rising frequency of extreme cold events that take place during the warm season. Few studies have investigated the impact of these warm-season cold spells on cardiovascular health. Here, we aimed to investigate the potential relationship between exposure to relatively low temperature exposure during the warm season and stroke risk.
Methods: We conducted a time-stratified case-crossover study using a validated, complete, and detailed registration of all stroke cases in the city of Augsburg, Germany, from 2006 to 2020 to assess the association between the occurrence of stroke and exposure to cold spell events during the warm season (May-October). Six cold spell definitions were created using different relative temperature thresholds (1st, 2.5th, and 5th percentiles) and durations (more than 1-2 consecutive days). Conditional logistic regression with distributed lag models was then applied to assess the accumulated effects of these warm-season cold spells on stroke risk over a lag period of 0-6 days, with adjustments for daily mean temperature.
Results: Results confirmed that warm-season cold spells were significantly linked to an elevated risk of stroke with effects that could persist three days after exposure. The cumulative odds ratio (OR) estimates for the cold spells using the 2.5th percentile as air temperature threshold reached 1.29 (95% confidence interval (CI): 1.09-1.53) and 1.23 (95%CI: 1.05-1.44) for durations more than one and two days, respectively. Warm-season cold spells also had significant associations with both transient ischemic attacks and ischemic strokes. The stratified analysis showed that the elderly population (aged ≥ 65 years), females, and stroke cases characterized by minor symptoms demonstrated a significantly increased stroke risk of the effects of warm season cold spells.
Conclusions: This study presents strong evidence for an overlooked association between warm-season cold spells and an increased risk of stroke occurrence. These findings further highlight the multifaceted ways in which climate change can affect human health
Cross-sectional study of health impairment related to post COVID-19 condition among participants of a large population-based cohort in Germany
Full text linkPost COVID-19 condition (PCC) is a substantial burden for patients, society, and the healthcare system. Participants of the German National Cohort (NAKO) were asked in an online survey about their self-perceived health, symptoms related to PCC, and infection status. PCC was defined as reporting symptoms for the time window 4-12 months after infection. Of 110,375 respondents (73% response), 86,833 were included in this analysis. Of these, 44,451 (51%) did not report a SARS-CoV-2 infection (no infection), 26,726 (31%) reported an infection but no symptoms 4-12 months after infection (infection/no PCC), and 15,656 (18%) reported an infection and symptoms (PCC). The median number of current symptoms at the time of the survey was two for the "no infection" and the "infection/no PCC" group, and five for the "PCC" group. Participants with PCC had a substantially higher probability of having worse self-perceived health (OR 1.84, 95% CI [1.75; 1.93] compared to the "no infection" group, adjusting for sex, age, education and chronic diseases with elevated risk for developing PCC. After adjusting for the number of current symptoms related to PCC, this difference disappeared, suggesting that the symptoms collected explain the impairment of self-perceived health in the PCC group
Entwicklung einer Checkliste zur Patient*innenbeteiligung in der Forschung – Eine qualitative Studie innerhalb eines Graduiertenkollegs zum Thema Depression
Full text linkHintergrund und Zielsetzung: Die Integration der Patient*innenperspektive in Forschungsprojekten ist essenziell, um die Relevanz und Qualität von Forschungsergebnissen zu stärken. Um den Mangel an strukturierten Vorgaben zur Patient*innenbeteiligung in deutschen Forschungsprojekten zu beheben, soll basierend auf einer Befragung von wissenschaftlichen Mitarbeiter*innen eine Checkliste als Implementierungshilfe entwickelt werden.
Methodik: Anhand von 13 halbstrukturierten qualitativen Interviews, durchgeführt mit Wissenschaftler*innen eines Graduiertenkollegs im Dezember 2022, wurden bereits erfolgte Patient*innenbeteiligung, sowie weitere Möglichkeiten und Barrieren erfragt. Die induktiv-deduktive Kodierung und die Analyse mit der Software MAXQDA führten zur Entwicklung einer standardisierten Checkliste für eine nahtlose Patient*innenintegration in die Forschung im Gesundheitswesen.
Ergebnisse: Von 13 Forscher*innen bezogen neun (69 %) die Erfahrungen der Patient*innen in ihre Arbeit ein, und zwar in Bezug auf Themen, Konzepte, Priorisierung von Schwerpunkten und Studienmaterialien. Vier Forscher*innen (31 %) sahen sich mit Hindernissen konfrontiert, weil es keine Leitlinien gab. Über 90 % erkannten das Potenzial der Einbeziehung von Patient*innen bei der Festlegung von Themenschwerpunkten, der Konzeptbildung, der Auswertung, Überprüfung und Interpretation von Ergebnissen. Die Forscher*innen wiesen auf Hindernisse hin, wie z. B. den eingeschränkten Zugang zu geeigneten Patient*innen, deren begrenzte wissenschaftliche Expertise und interaktionale Unsicherheiten auf beiden Seiten. Unter den Befragten verwiesen 56 % auf Schulungsbedarf und 44 % auf die Notwendigkeit struktureller Veränderungen hinsichtlich Arbeitsbelastung, Finanzierung, Leitlinienformulierung und Rekrutierungsstrategien. Die abgeleitete Checkliste umfasst sechs Unterkategorien mit jeweils durchschnittlich vier Unterpunkten, welche die Patient*innenbeteiligung im Forschungsprozess operationalisieren. Schlussfolgerung: In der aktuellen Forschung mangelt es an konkreten Vorgaben zur Einbeziehung von Patient*innen. Während einige Herausforderungen durch Schulungen sofort angegangen werden können, sind erforderliche Änderungen der Strukturen und der Finanzierung langfristig zu sehen. Die entstandene Checkliste ist ein Hilfsmittel, um die Patient*innenperspektive systematisch in Forschungsprojekte einbeziehen zu können.Objective: The integration of the patient perspective in research projects is essential to strengthen the relevance and quality of research results. To address the lack of structured procedures for patient integration in German research projects, this study summarises the existing knowledge in a simplified practice-oriented checklist for researchers.
Methodology: Through 13 semi-structured qualitative interviews conducted within a research group in December 2022, this study explored patient participation possibilities and barriers. The inductive-deductive coding and analysis in the software MAXQDA led to a standardized checklist development for seamless patient integration across similar contexts and research fields. Results: Of 13 experts, nine researchers (69%) incorporated patient insights into their work, covering topics, concepts, focus prioritization, and study materials. Four researchers (31%) faced barriers due to the absence of guidelines. More than 90% recognized potential for patient integration in topic prioritization, concept formation, evaluation, result review, and interpretation. Researchers highlighted barriers such as patient's limited scientific basis, restricted access, and knowledge gaps in patient interaction. Among the respondents, 56% pointed to training needs and 44% to structural barriers such as workload, unclear funding, guidelines and stakeholder involvement. The resulting checklist includes six sub-categories, each with an average of four sub-items, which operationalise the integration process.
Conclusion: Current research lacks effective patient inclusion processes due to inadequate access, tools, and knowledge. While immediate training can address some challenges, longer-term changes in policy and funding are necessary. With the new checklist researchers receive a support tool to integrate the patient perspective in their projects in a systematic manner
Alzheimer-Demenz bei Menschen mit einem Down-Syndrom
Full text linkHintergrund : Menschen mit einem Down-Syndrom (MmDS) haben ein genetisch bedingt stark erhöhtes Risiko, an einer früh beginnenden Alzheimer-Demenz zu erkranken. In einer Interviewstudie mit Ärzt:innen, Patientenvertretungen sowie Mitarbeitenden in Wohn- und Arbeitseinrichtungen wurden Defizite im medizinischen Versorgungsprozess und Lösungsansätze erhoben. Methodik : Es wurden 14 teilstrukturierte Interviews durchgeführt und über eine qualitative Inhaltsanalyse ausgewertet. Ergebnisse : Fehlende Kenntnisse und Erfahrungen von Ärzt:innen im Umgang mit sowie in der medizinischen Versorgung von MmDS zeigten sich als zentrale Herausforderung. Zudem ist die Diagnostik der Demenz bei MmDS aufgrund verschiedener Ursachen (u. a. Fehlen geeigneter Diagnostikinstrumente in der Regelversorgung, fehlende zeitliche/finanzielle Ressourcen) erschwert. Zweifel an der Wirksamkeit von Antidementiva wurden geäußert sowie Hintergründe für einen erhöhten Einsatz sedierender Medikamente diskutiert. Eine aufmerksame Verhaltensbeobachtung und eine Einbindung von Betreuenden, eine regelmäßige Überprüfung und Reduktion von Multimedikation sowie der Einsatz alternativer Verhaltensmodifikationstechniken wurden als Lösungsansätze genannt. Schlussfolgerung : Die identifizierten Defizite in der medizinischen Versorgung der Zielpopulation sowie die Lösungsansätze gehen in die Entwicklung gesundheitspolitischer Handlungsempfehlungen ein, um die Versorgungssituation nachhaltig zu optimieren.Background : People with Down syndrome have a genetically increased risk of developing early onset Alzheimer’s dementia. An interview study with healthcare providers, patient representatives and employees in residential and work facilities was conducted to identify deficits in the healthcare process and approaches to overcoming them. Method : In this study 14 semi-structured interviews were conducted and analyzed using qualitative content analysis. Results : A lack of knowledge and experience on the part of medical service providers in dealing with and providing medical care for people with Down syndrome was identified as a key challenge. In addition, the diagnosis of dementia in people with Down syndrome is difficult for various reasons (including lack of appropriate diagnostic tools in standard care and lack of time or financial resources). Doubts were expressed about the efficacy of antidementia medications and the reasons for the increased use of sedatives were discussed. Attentive observation of behavior and involvement of caregivers, regular review and reduction of polypharmacy and the use of alternative behavior modification techniques were mentioned as possible solutions. Conclusion : The identified deficits in the medical care of the target population and the approaches to solving them will be incorporated into the development of health policy recommendations in order to optimize the care situation of those affected in the long term
Proteomics Reveals Age as Major Modifier of Inflammatory CSF Signatures in Multiple Sclerosis
Full text linkBackground and Objectives : Multiple sclerosis (MS) can start as relapsing or progressive. While their clinical features and treatment responses are distinct, it has remained uncertain whether their pathomechanisms differ. A notable age-related effect on MS phenotype and response to immunotherapies is well acknowledged, but the underlying pathophysiologic reasons are yet to be fully elucidated. We aimed to identify disease-specific and age-related proteomic signatures using a comprehensive targeted proteomic analysis. Methods : In our retrospective cohort study, we analyzed the CSF and serum proteome of age-matched individuals with treatment-naïve relapsing-remitting and primary progressive MS, neurologic controls (NC), and individuals with neuroborreliosis using targeted proteomics and validated findings in an independent cohort. Proteomic results were integrated with clinical and laboratory covariates. Results : Among 2,500 proteins, 47 CSF proteins were distinct between individuals with MS (n = 60) and NC (n = 20), with a subset also differing from those with neuroborreliosis (n = 8). We identified MS-associated proteins, including novel candidate biomarkers such as LY9 and JCHAIN, and putative treatment targets, such as SLAMF7, BCMA, and IL5RA, for which drugs are already licensed in other indications. The CSF proteome differences between relapsing and progressive MS were minimal, but major changes were noted in individuals older than 50 years, indicating a shift from MS-associated inflammatory to age-related protein signature. NEFL was the only serum protein that differed between individuals with MS and controls. Discussion : This study unveils a unique CSF proteomic signature in MS, providing new pathophysiologic insights and identifying novel biomarker candidates and potential therapeutic targets. Our findings highlight similar immunologic mechanisms in relapsing and progressive MS and underscore aging's profound effect on the intrathecal immune response. This aligns with the observed lower efficacy of immunotherapies in the elderly, thus emphasizing the necessity for alternative therapeutic approaches in treating individuals with MS beyond the age of 50
Feasibility of a single-day protocol for SPECT and PET assessment of dopamine transporter availability, cardiac innervation and metabolic patterns in patients with movement disorders
Full text linkPurpose: Due to new advances in molecular and imaging biomarkers, a biological classification of Parkinson’s disease (PD) called SyNeurGe (Hoglinger et al. Lancet Neurol 2024;23:191-204) has been proposed for research use recently. [123I]ioflupane dopamine transporter single-photon-emission-computed tomography (DaT-SPECT) and cardiac [123I]meta-iodobenzylguanidine (MIBG) scintigraphy are included in this biological classification scheme together with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) as central imaging biomarkers for the assessment of dopaminergic function, cardiac sympathetic denervation, and metabolic patterns in brain. In order to facilitate this prospectively high imaging demand and optimize diagnostic workup in PD we propose a single-day protocol.
Methods: First, we excluded relevant binding of MIBG in the brain as well as DaT in the heart by acquisition of brain scans in patients that received MIBG as well as by acquisition of chest scans in patients that received DaT. Then, we performed a single-day protocol including DaT-SPECT and cardiac MIBG scintigraphy in ten patients with clinically suspected α-synucleinopathies (9 male, 1 female; 68.2 ± 7.3 years). Both radiotracers were injected simultaneously and cardiac imaging was performed at 3.5 h after injection followed by brain imaging at 4 h after injection using standard protocols for MIBG-scintigraphy and DaT-SPECT. Additionally, five patients of the dual tracer protocol group received brain FDG-PET after DaT and MIBG imaging.
Results: Single tracer imaging confirmed no relevant uptake of [123I]ioflupane in the heart or [123I]MIBG in the brain. Six out of the ten dual tracer protocol patients (PD or multiple system atrophy with Parkinsonian phenotype (MSA-P)) showed a significantly reduced DaT-SPECT binding (z-score < -2) in at least one hemisphere (mean putaminal z-score -4.01 ± 1.39) while seven patients had a pathological heart-to-mediastinum ratio in the MIBG scan (mean H/M-ratio: 1.12 ± 0.08). Both DaT and MIBG scans could visually be interpreted without any signs of image artifacts or decrease in imaging quality and also quantitatively did not reveal significant differences to the single tracer scans. FDG-PET brain scans of the triple tracer protocol patients also showed no relevant interference in regard to image quality as well was generation of surface projections and z-scores.
Conclusion: A single day protocol for DaT-SPECT, MIBG, and FDG-PET facilitates biomarker assessments needed for efficient biological characterization of Parkinsonian syndromes according to the SyNeurGe criteria