Random forest analysis of midbrain hypometabolism using [F]-FDG PET identifies Parkinson's disease at the subject-level.

Parkinson's disease (PD) is currently diagnosed largely on the basis of expert judgement with neuroimaging serving only as a supportive tool. In a recent study, we identified a hypometabolic midbrain cluster, which includes parts of the substantia nigra, as the best differentiating metabolic feature for PD-patients based on group comparison of [F]-fluorodeoxyglucose ([F]-FDG) PET scans. Longitudinal analyses confirmed progressive metabolic changes in this region and, an independent study showed great potential of nigral metabolism for diagnostic workup of parkinsonian syndromes.

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

Background And Objective: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied.

Combined Lanreotide Autogel and Temozolomide Treatment of Progressive Pancreatic and Intestinal Neuroendocrine Tumors: The Phase II SONNET Study.

Background: In advanced neuroendocrine tumors (NET), antiproliferative treatment options beyond somatostatin analogs remain limited. Temozolomide (TMZ) has shown efficacy in NET alone or combined with other drugs.

Materials And Methods: SONNET (NCT02231762) was an open, multicenter, prospective, phase II study to evaluate lanreotide autogel 120 mg (LAN) plus TMZ in patients with progressive advanced/metastatic grade 1/2 gastroenteropancreatic (GEP) NET or of unknown primary.

Normal organ dosimetry for thyroid cancer patients treated with radioiodine as part of the multi-centre multi-national Horizon 2020 MEDIRAD project.

Purpose: Dosimetry is rarely performed for the treatment of differentiated thyroid cancer patients with Na[I]I (radioiodine), and information regarding absorbed doses delivered is limited. Collection of dosimetry data in a multi-centre setting requires standardised quantitative imaging and dosimetry. A multi-national, multi-centre clinical study was performed to assess absorbed doses delivered to normal organs for differentiated thyroid cancer patients treated with Na[I]I.

Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study.

Background: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy.

Methods: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010.

Diacidic Motifs in the Carboxyl Terminus Are Required for ER Exit and Translocation to the Plasma Membrane of NKCC2.

Mutations in the apical Na-K-2Cl co-transporter, NKCC2, cause type I Bartter syndrome (BS1), a life-threatening kidney disease. We have previously demonstrated that the BS1 variant Y998X, which deprives NKCC2 from its highly conserved dileucine-like motifs, compromises co-transporter surface delivery through ER retention mechanisms. However, whether these hydrophobic motifs are sufficient for anterograde trafficking of NKCC2 remains to be determined.

Combined Focused Next-Generation Sequencing Assays to Guide Precision Oncology in Solid Tumors: A Retrospective Analysis from an Institutional Molecular Tumor Board.

Background: Increasing knowledge of cancer biology and an expanding spectrum of molecularly targeted therapies provide the basis for precision oncology. Despite extensive gene diagnostics, previous reports indicate that less than 10% of patients benefit from this concept.

Methods: We retrospectively analyzed all patients referred to our center's Molecular Tumor Board (MTB) from 2018 to 2021.

Vessel-Sparing Lymphadenectomy Should Be Performed in Small Intestine Neuroendocrine Neoplasms.

Introduction: The goal of primary tumor resection with lymphadenectomy (PTR) in small intestine neuroendocrine neoplasms (SI-NENs) is to avoid local recurrence while sparing as much of the small bowel as possible, even in the case of extensive mesenteric fibrosis. The results of PTR with retrograde vessel-sparing lymphadenectomy (VS-LA) were compared to those of conventional lymphadenectomy (Con-LA).

Methods: Prospectively collected clinical, surgical and pathological data of consecutive patients with SI-NENs who underwent small bowel resections were retrospectively analyzed regarding the resection technique performed.

Multicenter Analysis of Presacral Neuroendocrine Neoplasms-Clinicopathological Characterization and Treatment Outcomes of a Rare Disease.

Background And Aims: Neuroendocrine neoplasms (NENs) of the presacral space are an extremely rare disease entity with largely unknown outcome and no established standard of care treatment. Therefore, we wanted to analyze clinical presentation, histopathological findings, treatment outcomes, and prognosis in a multicentric patient cohort.

Methods: We searched local databases of six German NEN centers for patients with presacral NEN.

Treatment of advanced gastroenteropancreatic neuroendocrine neoplasia, are we on the way to personalised medicine?

Gastroenteropancreatic neuroendocrine neoplasia (GEPNEN) comprises clinically as well as prognostically diverse tumour entities often diagnosed at late stage. Current classification provides a uniform terminology and a Ki67-based grading system, thereby facilitating management. Advances in the study of genomic and epigenetic landscapes have amplified knowledge of tumour biology and enhanced identification of prognostic and potentially predictive treatment subgroups.

Degradation of integral membrane proteins modified with the photosensitive degron module requires the cytosolic endoplasmic reticulum-associated degradation pathway.

Protein quality mechanisms are fundamental for proteostasis of eukaryotic cells. Endoplasmic reticulum-associated degradation (ERAD) is a well-studied pathway that ensures quality control of secretory and endoplasmic reticulum (ER)-resident proteins. Different branches of ERAD are involved in degradation of malfolded secretory proteins, depending on the localization of the misfolded part, the ER lumen (ERAD-L), the ER membrane (ERAD-M), and the cytosol (ERAD-C).

A finite element updating approach for identification of the anisotropic hyperelastic properties of normal and diseased aortic walls from 4D ultrasound strain imaging.

Computational analysis of the biomechanics of the vascular system aims at a better understanding of its physiology and pathophysiology and eventually at diagnostic clinical use. Because of great inter-individual variations, such computational models have to be patient-specific with regard to geometry, material properties and applied loads and boundary conditions. Full-field measurements of heterogeneous displacement or strain fields can be used to improve the reliability of parameter identification based on a reduced number of observed load cases as is usually given in an in vivo setting.

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

Background: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa.

Methods: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo.

Method for aortic wall strain measurement with three-dimensional ultrasound speckle tracking and fitted finite element analysis.

Background: Aortic wall strains are indicators of biomechanical changes of the aorta due to aging or progressing pathologies such as aortic aneurysm. We investigated the potential of time-resolved three-dimensional ultrasonography coupled with speckle-tracking algorithms and finite element analysis as a novel method for noninvasive in vivo assessment of aortic wall strain.

Methods: Three-dimensional volume datasets of 6 subjects without cardiovascular risk factors and 2 abdominal aortic aneurysms were acquired with a commercial real time three-dimensional echocardiography system.