| 1. |
- Arthur, Cecilia, et al.
(författare)
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Simultaneous Ultra-Sensitive Detection of Structural and Single Nucleotide Variants Using Multiplex Droplet Digital PCR in Liquid Biopsies from Children with Medulloblastoma
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma is one of the most common types of brain tumors in children. During and after treatment with surgery, chemotherapy, and/or radiotherapy, children with this disease are monitored with imaging and cerebrospinal fluid analysis for the detection of tumor cells. These methods are not always sensitive or specific enough to confirm or rule out residual disease. Here, we develop a laboratory test based on the genetic makeup of medulloblastomas in 12 children. We analyze liquid biopsies (cerebrospinal fluid and blood plasma) for specific genetic fragments leaking from the individual tumors and find molecular traces of disease in 75% (9/12) of children overall. None of the children had malignant cells in the cerebrospinal fluid. We propose that this test could open up new technical possibilities to track measurable residual disease in children with medulloblastoma in order to further risk-adapt treatment, but first, larger studies of the approach at standardized time points are warranted.Medulloblastoma is a malignant embryonal tumor of the central nervous system (CNS) that mainly affects infants and children. Prognosis is highly variable, and molecular biomarkers for measurable residual disease (MRD) detection are lacking. Analysis of cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) using broad genomic approaches, such as low-coverage whole-genome sequencing, has shown promising prognostic value. However, more sensitive methods are needed for MRD analysis. Here, we show the technical feasibility of capturing medulloblastoma-associated structural variants and point mutations simultaneously in cfDNA using multiplexed droplet digital PCR (ddPCR). Assay sensitivity was assessed with a dilution series of tumor in normal genomic DNA, and the limit of detection was below 100 pg of input DNA for all assays. False positive rates were zero for structural variant assays. Liquid biopsies (CSF and plasma, n = 47) were analyzed from 12 children with medulloblastoma, all with negative CSF cytology. MRD was detected in 75% (9/12) of patients overall. In CSF samples taken before or within 21 days of surgery, MRD was detected in 88% (7/8) of patients with localized disease and in one patient with the metastasized disease. Our results suggest that this approach could expand the utility of ddPCR and complement broader analyses of cfDNA for MRD detection.
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| 2. |
- Blomstedt, Patric, et al.
(författare)
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Deep brain stimulation in the posterior subthalamic area in the treatment of essential tremor
- 2010
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 25:10, s. 1350-1356
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the posterior subthalamic area (PSA) as a target for deep brain stimulation (DBS) in the treatment of essential tremor (ET). The ventral intermediate nucleus of the thalamus is the traditional target for DBS in the treatment of ET. Recent studies have presented beneficial effects of DBS in the PSA in the treatment of tremor. Twenty-one patients with ET were included in this study. All patients were evaluated before and 1 year after surgery, on and off stimulation, using the essential tremor rating scale (ETRS). A marked microlesional effect was noticed in 83%, in some cases obviating the need for electrical stimulation for many months. The total ETRS was reduced from 46.2 at baseline to 18.7 (60%). Item 5/6 (tremor of the upper extremity) was improved from 6.2 to 0.3 (95%), and items 11 to 14 (hand function) from 9.7 to 1.3 (87%) concerning the contralateral hand. Activities of daily living were improved by 66%. No severe complication occurred. Eight patients presented a postoperative mild dysphasia that regressed within days to weeks. DBS in the PSA resulted in a marked reduction of tremor.
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| 3. |
- Blomstedt, Patric, et al.
(författare)
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Deep brain stimulation of the subthalamic nucleus versus the zona incerta in the treatment of essential tremor
- 2011
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Ingår i: Acta Neurochirurgica. - Wien : Springer. - 0001-6268 .- 0942-0940. ; 153:12, s. 2329-2335
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Tidskriftsartikel (refereegranskat)abstract
- Background: Deep brain stimulation (DBS) is an effective treatment for essential tremor (ET). Currently the ventrolateral thalamus is the target of choice, but the posterior subthalamic area (PSA), including the caudal zona incerta (cZi), has demonstrated promising results, and the subthalamic nucleus (STN) has been suggested as a third alternative. The objective of the current study was to evaluate the effect of STN DBS in ET and to compare this to cZi DBS. Methods: Four patients with ET were implanted with two ipsilateral electrodes, one in the STN and one in the cZi. All contacts were evaluated concerning the acute effect on tremor, and the effect of chronic DBS in either target was analyzed. Results: STN and cZi both proved to be potent targets for DBS in ET. DBS in the cZi was more efficient, since the same degree of tremor reduction could here be achieved at lower energy consumption. Three patients became tremor-free in the treated hand with either STN or cZi DBS, while the fourth had a minor residual tremor after stimulation in either target. Conclusion: In this limited material, STN DBS was demonstrated to be an efficient treatment for ET, even though cZi DBS was more efficient. The STN may be an alternative target in the treatment of ET, pending further investigations to decide on the relative merits of the different targets.
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| 4. |
- Blomstedt, Patric, et al.
(författare)
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Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor
- 2011
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 17:8, s. 617-620
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures. Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11-14 (hand tremor and hand function) were selected for analysis of tremor outcome. The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.
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| 5. |
- Blomstedt, Patric, et al.
(författare)
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The posterior subthalamic area in the treatment of movement disorders : past, present, and future
- 2009
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Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 64:6, s. 1029-1038
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of thalamotomy in 1954 led naturally to exploration of the underlying subthalamic area, with the development of such procedures as campotomy and subthalamotomy in the posterior subthalamic area. The most popular of these procedures was the subthalamotomy, which was performed in thousands of patients for various movement disorders. Today, in the deep brain stimulation (DBS) era, subthalamic nucleus DBS is the treatment of choice for Parkinson's disease, whereas thalamic and pallidal DBS are mainly used for nonparkinsonian tremor and dystonia, respectively. The interest in DBS in the posterior subthalamic area has been quite limited, however, with a total of 95 patients presented in 14 articles. During recent years, interest has increased, and promising results have been published concerning both Parkinson's disease and nonparkinsonian tremor. We reviewed the literature to investigate the development of surgery in the posterior subthalamic area from the lesional era to the present.
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| 6. |
- Fytagoridis, Anders, et al.
(författare)
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Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor
- 2012
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 83:3, s. 258-262
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The ventral intermediate nucleus of thalamus is the standard target for deep brain stimulation (DBS) in essential tremor (ET). However, favourable data have recently highlighted the caudal zona incerta (cZi) as an alternative target. Reports concerning the long-term results are however lacking, and we have therefore evaluated the long-term effects in our patients with ET and cZi DBS. less thanbrgreater than less thanbrgreater thanMethods 18 patients were evaluated using the Essential Tremor Rating Scale (ETRS) before and on-/off-stimulation at 1 and 3-5 years after surgery (mean 48.5+/-10.6 months). Two patients were operated on bilaterally but all electrodes were evaluated separately. The stimulation parameters were recorded and the stimulation strength calculated. less thanbrgreater than less thanbrgreater thanResults A baseline total ETRS mean score of 46.0 decreased to 21.9 (52.4%) at the final evaluation. On the treated side, tremor of the upper extremity (item 5 or 6) improved from 6.1 to 0.5 (91.8%) and hand function (items 11-14) improved from 9.3 to 2.0 (78.0%). Activities of daily living improved by 65.8%. There was no increase in stimulation strength over time. less thanbrgreater than less thanbrgreater thanConclusion cZi DBS is a safe and effective treatment for the long term suppression of ET.
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| 7. |
- Hellsten, Ulrika, et al.
(författare)
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Self-assessment as a facilitator for learning
- 1999
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Ingår i: Proceedings of the 1999 ASQ's 53rd Annual Quality Congress. - : American Society for Quality. - 9789992892329 ; , s. 423-431
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Konferensbidrag (refereegranskat)abstract
- As a tool and as an approach, self-assessment supports organizational learning. For example, self-assessment is a tool in systematic problem solving and an approach in new experimentation. In addition to these two elements, a learning organization should be skilled in learning from the best practices and experience of others and in quickly and efficiency transferring knowledge throughout the organization. When based on total quality management (TQM), the best known self-assessment tools include the European Quality Award and the Malcolm Baldrige National Quality Award. The TQM perspective suggests a three-phase approach to self-assessment: preparation, accomplishment, and continuous improvement through generation and implementation of action plans. A pilot study of TQM-based self-assessment with about 25 employees at the Lule� University of Technology used a springboard assessment tool that covered four areas: customer cooperation, employee commitment, leadership, and process management. The springboard questionnaire analyzed employee opinions on the tool and approach of this self-assessment. For the preparation phase, the analysis suggested better reconciliation of improvement work with everyday tasks. For the accomplishment phase, the assessment demonstrated the useful but time consuming nature of teamwork. Meeting times needed to be better allocated. And for the continuous improvement phase, the self-assessment was incomplete as of this writing.
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| 8. |
- Jensdottir, Margret, et al.
(författare)
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Learning Curve Analysis and Adverse Events After Implementation of Neurosurgical Laser Ablation Treatment: A Population-Based Single-Institution Consecutive Series.
- 2023
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Ingår i: Neurosurgery clinics of North America. - : Elsevier BV. - 1558-1349 .- 1042-3680. ; 34:2, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a retrospective review of the first 30 patients treated with stereotactic laser ablation (SLA) at our institution since the introduction of the technique in September 2019. We aimed to analyze our initial results and potential learning curve by investigating precision and lesion coverage and assessing the frequency and nature of adverse events according to the Landriel-Ibanez classification for neurosurgical complications.Indications were de novo gliomas (23%), recurrent gliomas (57%), and epileptogenic foci (20%). There was a trend toward improvement of lesion coverage and target deviation, and a statistically significant improvement in entry point deviation, over time. Four patients (13.3%) experienced a new neurological deficit, where three patients had transient and one patient had permanent deficits, respectively. Our results show a learning curve on precision measures over the first 30 cases. Based on our results the technique can safely be implemented at centers with experience in stereotaxy.
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| 9. |
- Krynina, Olha, et al.
(författare)
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The potential of liquid biopsy for detection of the KIAA1549-BRAF fusion in circulating tumor DNA from children with pilocytic astrocytoma
- 2024
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Ingår i: Neuro-Oncology Advances. - : Oxford University Press. - 2632-2498. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLow-grade gliomas (LGGs) represent children’s most prevalent central nervous system tumor, necessitating molecular profiling to diagnose and determine the most suitable treatment. Developing highly sensitive screening techniques for liquid biopsy samples is particularly beneficial, as it enables the early detection and molecular characterization of tumors with minimally invasive samples.MethodsWe examined CSF and plasma samples from patients with pilocytic astrocytoma (PA) using custom multiplexed droplet digital polymerase chain reaction (ddPCR) assays based on whole genome sequencing data. These assays included a screening test to analyze BRAF duplication and a targeted assay for the detection of patient-specific KIAA1549::BRAF fusion junction sequences or single nucleotide variants.ResultsOur findings revealed that 5 out of 13 individual cerebrospinal fluid (CSF) samples tested positive for circulating tumor DNA (ctDNA). Among these cases, 3 exhibited the KIAA1549::BRAF fusion, which was detected through copy number variation (CNV) analysis (n = 1) or a fusion-specific probe (n = 2), while 1 case each displayed the BRAF V600E mutation and the FGFR1 N577K mutation. Additionally, a quantitative analysis of cell-free DNA (cfDNA) concentrations in PA CSF samples showed that most cases had low cfDNA levels, below the limit of detection of our assay (<1.9 ng).ConclusionsWhile CNV analysis of CSF samples from LGGs still has some limitations, it has the potential to serve as a valuable complementary tool. Furthermore, it can also be multiplexed with other aberrations, for example, to the BRAF V600 test, to provide important insights into the molecular characteristics of LGGs.
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| 10. |
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