X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort
    Wiley ; 2023
    In:  Movement Disorders Vol. 38, No. 2 ( 2023-02), p. 286-303
    Details
    In: Movement Disorders, Wiley, Vol. 38, No. 2 ( 2023-02), p. 286-303
    Abstract: As gene‐targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial‐ready cohorts is limited. Objective The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD‐linked variants; (2) provide harmonized and quality‐controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods We conducted a worldwide, systematic online survey to collect individual‐level data on individuals with PD‐linked variants in SNCA , LRRK2 , VPS35 , PRKN , PINK1 , DJ‐1 , as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2 , 115 SNCA , 23 VPS35 , 429 PRKN , 75 PINK1 , 13 DJ‐1 , and 1224 GBA ) and 703 were unaffected (ie, 328 LRRK2 , 32 SNCA , 3 VPS35 , 1 PRKN , 1 PINK1 , and 338 GBA ). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD‐linked variants; (2) provide harmonized and quality‐controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene‐targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v38.2
    DOI: 10.1002/mds.29288
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2041249-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 2
    Online Resource
    Online Resource
    Blood Markers of Inflammation, Neurodegeneration, and Cardiovascular Risk in Early Parkinson's Disease
    Wiley ; 2023
    In:  Movement Disorders Vol. 38, No. 1 ( 2023-01), p. 68-81
    Details
    In: Movement Disorders, Wiley, Vol. 38, No. 1 ( 2023-01), p. 68-81
    Abstract: Recent studies point toward a significant impact of cardiovascular processes and inflammation on Parkinson's disease (PD) progression. Objective The aim of this study was to assess established markers of neuronal function, inflammation, and cardiovascular risk by high‐throughput sandwich immune multiplex panels in deeply phenotyped PD. Methods Proximity Extension Assay technology on 273 markers was applied in plasma of 109 drug‐naive at baseline (BL) patients with PD (BL, 2‐, 4‐, and 6‐year follow‐up [FU]) and 96 healthy control patients (HCs; 2‐ and 4‐year FU) from the de novo Parkinson's cohort. BL plasma from 74 individuals (37 patients with PD, 37 healthy control patients) on the same platform from the Parkinson Progression Marker Initiative was used for independent validation. Correlation analysis of the identified markers and 6 years of clinical FU, including motor and cognitive progression, was evaluated. Results At BL, 35 plasma markers were differentially expressed in PD, showing downregulation of atherosclerotic risk markers, eg, E‐selectin and ß 2 ‐integrin. In contrast, we found a reduction of markers of the plasminogen activation system, eg, urokinase plasminogen activator. Neurospecific markers indicated increased levels of peripheral proteins of neurodegeneration and inflammation, such as fibroblast growth factor 21 and peptidase inhibitor 3. Several markers, including interleukin‐6 and cystatin B, correlated with cognitive decline and progression of motor symptoms during FU. These findings were independently validated in the Parkinson Progression Marker Initiative. Conclusions We identified and validated possible PD plasma biomarker candidates for state, fate, and disease progression, elucidating new molecular processes with reduced endothelial/atherosclerotic processes, increased thromboembolic risk, and neuroinflammation. Further investigations and validation in independent and larger longitudinal cohorts are needed. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v38.1
    DOI: 10.1002/mds.29257
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2041249-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 3
    Online Resource
    Online Resource
    Accurate Detection of α‐Synuclein Seeds in Cerebrospinal Fluid from Isolated Rapid Eye Movement Sleep Behavior Disorder and Patients with Parkinson's Disease in the DeNovo Parkinson (DeNoPa) Cohort
    Wiley ; 2023
    In:  Movement Disorders Vol. 38, No. 4 ( 2023-04), p. 567-578
    Details
    In: Movement Disorders, Wiley, Vol. 38, No. 4 ( 2023-04), p. 567-578
    Abstract: Misfolded α‐synuclein (αSyn) aggregates (αSyn‐seeds) in cerebrospinal fluid (CSF) are biomarkers for synucleinopathies such as Parkinson's disease (PD). αSyn‐seeds have been detected in prodromal cases with isolated rapid eye movement sleep behavior disorder (iRBD). Objectives The objective of this study was to determine the accuracy of the αSyn–seed amplification assay (αS‐SAA) in a comprehensively characterized cohort with a high proportion of PD and iRBD CSF samples collected at baseline. Methods We used a high‐throughput αS‐SAA to analyze 233 blinded CSF samples from 206 participants of the DeNovo Parkinson Cohort (DeNoPa) (113 de novo PD, 64 healthy controls, 29 iRBD confirmed by video polysomnography). Results were compared with the final diagnosis, which was determined after up to 10 years of longitudinal clinical evaluations, including dopamine‐transporter–single‐photon emission computed tomography (DAT‐SPECT) at baseline, CSF proteins, Movement Disorder Society–Unified Parkinson's Disease Rating Scale, and various cognitive and nonmotor scales. Results αS‐SAA detected αSyn‐seeds in baseline PD‐CSF with 98% accuracy. αSyn‐seeds were detected in 93% of the iRBD cases. αS‐SAA results showed higher agreement with the final than the initial diagnosis, as 14 patients were rediagnosed as non‐αSyn aggregation disorder. For synucleinopathies, αS‐SAA showed higher concordance with the final diagnosis than DAT‐SPECT. Statistically significant correlations were found between assay parameters and disease progression. Conclusions Our results confirm αS‐SAA accuracy at the first clinical evaluation when a definite diagnosis is most consequential. αS‐SAA conditions reported here are highly sensitive, enabling the detection of αSyn‐seeds in CSF from iRBD just months after the first symptoms, suggesting that αSyn‐seeds are present in the very early prodromal phase of synucleinopathies. Therefore, αSyn‐seeds are clear risk markers for synuclein‐related disorders, but not for time of phenoconversion. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v38.4
    DOI: 10.1002/mds.29329
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2041249-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 4
    Online Resource
    Online Resource
    Nephrectomy after response to immune checkpoint inhibitors for metastatic renal cell carcinoma (mRCC): A surgical challenge allowing favorable oncological outcomes.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e16557-e16557
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e16557-e16557
    Abstract: e16557 Background: In the current era of Immune checkpoint inhibitors (ICI), the role and timing of nephrectomy is still unknown. We aimed to evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) managed with nephrectomy for residual disease after complete response (CR) or major partial response (mPR defined as 〉 80%) on metastatic sites following ICI. Methods: Patients who underwent nephrectomy after prior ICI between 2015 and 2020 were retrospectively included and clinicopathological data were reviewed. Perioperative data, postoperative complications, toxicities related to ICI, continuation or discontinuation of systemic treatment following surgery, and 1-year oncological outcomes were recorded. Results: Twenty-five patients without initial cytoreductive nephrectomy at diagnosis underwent delayed nephrectomy after long ICI administration because of CR (or mPR) on metastatic sites. Median age was 62 years [38-79] . 88% of patients had clear cell RCC on the initial biopsy. IMDC prognostic group was intermediate (80%) or poor (20%). ICI was administered as first-line therapy in 56.0% of cases and as second-line option after TKI in 44.0% of cases. Treatments regimens were: nivolumab + ipilimumab (n = 12), nivolumab + tivozanib (n = 2) or nivolumab alone (n = 11). The mean duration of ICI treatment was 11.8 months (range: 3-38 months) and the mean number of cycles was 19 (range: 6-75). Twelve patients had a CR on metastatic sites while 13 patients had a mPR ( 〉 80%). Overall, 64% of patients experienced toxicities related to ICI treatment. Median operative time was 210 minutes [90-345] and mean blood loss was 558 cc [40-4000] . In 80.0% of cases, surgeons experienced difficulties in finding dissection plans due to adhesions and/or inflammatory infiltration. The 30-day Clavien-Dindo postoperative complication rate was 36.0%, including 1 surgery-related death. Pathological report showed lymphocyte and/or macrophage infiltration in 60% of cases and complete pathological response (pT0) in 3 cases (12%). After a mean follow-up of 19.4 months, 79.2% of the patients were free from progression and 70.8% free from systemic treatment. The recurrence-free survival (RFS) and overall survival (OS) at 1 year were 79.5% and 89.8% respectively. CR on metastatic sites was significantly associated with good RFS compared to mPR (1-year RFS = 100% vs. 56.8%, median RFS = 21.6 vs. 4.25 months, p = 0.006) while the duration of IO treatment exposure was not. Conclusions: Nephrectomy following ICI for mRCC can be a difficult procedure. However, it may provide good long-term RFS, with systemic treatment discontinuation following surgery in most cases. This strategy may be offered in well-selected patients, especially in case of CR on metastatic sites before surgery.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.e16557
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
Nothing or not found what you are looking for? Please check your search query or use the Interlibrary Loan Search.
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages