Background
Parkinson´s disease (PD) has a large phenotypic variability, which may, at least partly, be genetically driven including alterations of gene products. Candidates might not only be proteins ...associated with disease risk but also pathways that play a role in aging.
Objective
To evaluate phenotype‐modifying effects of genetic variants in Klotho, a longevity gene.
Methods
We analyzed two longitudinal cohorts: one local cohort comprising 459 PD patients who underwent genotyping for the KL‐VS haplotype in Klotho including a subgroup of 125 PD patients and 50 healthy controls who underwent biochemical cerebrospinal fluid (CSF) analyses of Klotho and fibroblast growth factor 23 as well as vitamin D metabolites. The second cohort comprised 297 patients from the Parkinsonʼs Progression Markers Initiative (PPMI) for validation of genetic−clinical findings.
Results
PD patients carrying the KL‐VS haplotype demonstrated a shorter interval between PD onset and onset of cognitive impairment (both cohorts) and higher Unified Parkinson´s Disease Rating Scale part III (UPDRS III) scores (PPMI). CSF protein levels of Klotho and fibroblast growth factor 23 were lower in PD patients irrespective of gender compared to controls. Moreover, low CSF levels of Klotho were associated with higher scores in the UPDRS III and Hoehn and Yahr Scale.
Conclusions
Our results indicate that genetic variants in Klotho together with its corresponding CSF protein profiles are associated with aspects of disease severity in PD. These findings suggest that pathways associated with aging might be targets for future biomarker research in PD.
Low CSF levels of the longevity protein Klotho were associated with higher scores in Unified Parkinson's Disease Rating scale part II (UPDRS III). Patients with Parkinson's disease (PD) carrying the genetic “KL‐VS”‐variant demonstrated a shorter interval between PD onset and onset of cognitive impairment and higher UPDRS III scores. Genetic variants in Klotho along with its corresponding CSF protein profiles are associated with aspects of disease severity in PD.
Mutations in the gene coding for glucocerebrosidase (GBA), which metabolizes glucosylceramide (a monohexosylceramide) into glucose and ceramide, is the most common genetic risk factor for sporadic ...Parkinson's disease (PD). GBA mutation carriers are more likely to have an earlier age of onset and to develop cognitive impairment and dementia. We hypothesized that plasma levels of lipids involved in ceramide metabolism would also be altered in PD non-GBA mutation carriers and associated with worse cognition.
Plasma ceramide, monohexosylceramide, and lactosylceramide levels in 26 cognitively normal PD patients, 26 PD patients with cognitive impairment or dementia, and 5 cognitively normal non-PD controls were determined by LC/ESI/MS/MS.
Levels of all lipid species were higher in PD patients versus controls. Among PD patients, levels of ceramide C16:0, C18:0, C20:0, C22:0, and C24:1 and monohexosylceramide C16:0, C20:0 and C24:0 species were higher (all P<0.05) in those with versus without cognitive impairment.
These results suggest that plasma ceramide and monohexosylceramide metabolism is altered in PD non-GBA mutation carriers and that higher levels are associated with worse cognition. Additional studies with larger sample sizes, including cognitively normal controls, are needed to confirm these findings.
Robotic surgery is increasingly gaining importance. While initial results suggest an advantage of the robotic over the minimally invasive approach in patients with gastric cancer, definitive proof of ...its superiority has yet to be provided. There are numerous approaches to recreate a gastric reservoir after a total gastrectomy. However, a major disadvantage of most conventional reconstructions are long term effects such as dumping syndrome, afferent loop syndrome and poor nutrition intake with severe impact on the patient quality of life. The jejunal pouch reconstruction is a beneficial reconstruction, which provides a larger reservoir capacity after gastrectomy and prevents anastomotic stenosis and dumping syndrome. The completely intercorporeal approach with a Pfannenstiel incision instead of an unfavorable midline incision can potentially decrease delayed complications such as incision hernias. With the increased deployment of robotic surgery, a complete intercorporeal reconstruction is now possible without major increase in operating time or further technical weak points. We provide for the first time a detailed technical explanation of the completely intercorporeal robotic jejunal pouch reconstruction after gastrectomy.
The health care situation of geriatric patients is often multifaceted, complex and often overlaps with social living conditions. Due to the lack of cross-sectoral and interprofessional health care ...geriatric patients often, receive insufficient care. Only a holistic view enables a comprehensive evaluation of the complex health risks, but also the potential to preserve the health of geriatric patients. The implementation of cross-sectoral, multi-professional case management could reduce the gaps in care, improve the autonomy of the geriatric patients in their own homes, and allow them to retain it as long as possible. The "RubiN" project examines the effects of multi-professional, cross-sectoral and assessment-based case management on the quality of the care of geriatric patients. The results of the study aim to show whether geriatric patients receive better care using case management than patients who receive standard health care. In addition, data on the effects of case management on practices of general practitioners (GP), the satisfaction with the care concept amongst the case managers, patients and relatives will be collected. Furthermore, a health economic analysis will be carried out.
The project is designed as a prospective controlled study and compares geriatric patients from practice networks in different regions in Germany. Inclusion criteria are: Age ≥ 70 years and care requirements from two different care complexes (identified with the screening instrument 'Angelina'-questionnaire). The intervention is the use of a geriatric case management, where health care is organised based on patient-specific care requirements. Five practice networks of physicians will implement the intervention (n = 3200 patients) and three practice networks will serve as the control group (n = 1200 patients). The primary endpoint is the ability to manage activities of daily living, measured using the Barthel Index. The patients in the intervention group receive geriatric case management and the patients in the control networks receive standard care ("care as usual"). The analysis of the primary data, which is pseudonymised, occurs according to the intention-to-treat principle. For this purpose, the endpoints will be analysed using a group comparison after 12 months. For the health economic analysis, secondary data from the statutory health insurance providers will be included in the analysis, in addition to the primary data. Data for the analysis of the effects the concept has on the GP practices as well as on the satisfaction of the project participants will be collected with questionnaires and interviews with experts.
The implementation of cross-sectoral and interdisciplinary geriatric case management has been a topic of discussion for years, whereby positive effects have already been-shown. This planned study will be the first evaluation of the effect of case management for geriatric patients with a very large sample. In addition, the effects of case management on the GP practices and also on the relatives of the geriatric patients will be shown. It is intended that the study results pave the way for a widespread implementation of this concept.
German Clinical Trials Register, ID: DRKS00016642 . Registered on 29 October 2019 - Retrospectively registered.
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