| 1. |
- Arthur, Cecilia, et al.
(författare)
-
Simultaneous Ultra-Sensitive Detection of Structural and Single Nucleotide Variants Using Multiplex Droplet Digital PCR in Liquid Biopsies from Children with Medulloblastoma
- 2023
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:7
-
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.
|
|
| 2. |
- Jensdottir, Margret, et al.
(författare)
-
Learning Curve Analysis and Adverse Events After Implementation of Neurosurgical Laser Ablation Treatment: A Population-Based Single-Institution Consecutive Series.
- 2023
-
Ingår i: Neurosurgery clinics of North America. - : Elsevier BV. - 1558-1349 .- 1042-3680. ; 34:2, s. 259-267
-
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.
|
|
| 3. |
- Krynina, Olha, et al.
(författare)
-
The potential of liquid biopsy for detection of the KIAA1549-BRAF fusion in circulating tumor DNA from children with pilocytic astrocytoma
- 2024
-
Ingår i: Neuro-Oncology Advances. - : Oxford University Press. - 2632-2498. ; 6:1
-
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.
|
|
| 4. |
|
|
| 5. |
- Uche, E. O., et al.
(författare)
-
Global neurosurgery over a 60-year period : Conceptual foundations, time reference, emerging Co-ordinates and prospects for collaborative interventions in low and middle income countries
- 2022
-
Ingår i: BRAIN AND SPINE. - : Elsevier BV. - 2772-5294. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: We evaluated salient initiatives invested in global neurosurgery over a 60-year period.Research question: What are the Phases, Achievements, Challenges, and Lessons of Global Neurosurgery.Methods: A 60-year retrospective study from 1960 to 2020 analyzing the major phases, lessons, and progress notes. We reviewed the foundational need questions and innovated tools used to answer them.Results: Three phases defining our study period were identified. In the early phase, birthing academic units and the onset of individual volunteerism were dominant concepts. The 2nd phase is summarized by the rise of volunteerism and surgical camps. The third phase is heralded by advocacy and strategies for achieving care equity.The defining moment is the Lancet commission for global surgery summit in 2015. Lessons include the need for evaluation of the resources of recipient and donor locations using novel global surgery tools.Conclusion: Global neurosurgery over the 60-year study period is summarized by indelible touchstones of personal and group efforts as well as triumphs derived from innovations in the face of formidable challenges.
|
|
| 6. |
- Uche, Enoch Ogbonnaya, et al.
(författare)
-
Pilot application of Lecture-Panel-Discussion Model (LPDM) in global collaborative neurosurgical education : a novel training paradigm innovated by the Swedish African Neurosurgery Collaboration
- 2022
-
Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 164:4, s. 967-972
-
Tidskriftsartikel (refereegranskat)abstract
- Background Disruptions in global surgery educational routines by the COVID-19 pandemic have elicited demands for alternative formats for rendering qualitative neurosurgical education. This study presents application of a novel model of online neurosurgical course, the Lecture-Panel-Discussion Model (LPDM). Methods This is a cross-sectional survey of participants who attended the Swedish African Neurosurgery Collaboration (SANC)-100A course. Participants evaluated the course through an online self-administered questionnaire using a 5-point Likert scale ranging from very poor-1, poor-2, average (fair)-3, good-4, to excellent-5. SANC-100A comprises a tripod of Lectures, Panel review, and interactive case Discussion. This model (LPDM) was innovated by SANC and applied at the Enugu International Neurosurgery course in February 2021. Results There were 71 attendees, 19 were course faculty, while 52 were participants. Thirty-five attended from Nigeria, 11 from Sweden, 3 from Malawi, 2 from Senegal, and 1 from the UK. Among 44 participants who completed the questionnaire, there were 9 fellows and 35 residents. The overall median course Likert rating was 4.65 +/- 0.1. The median overall rating for course events was similar between day 1 (Likert score = 4.45) and day 2 (Likert score = 4.55), U = 55, Z score = 1.10, P = 0.27. The median rating for lectures was 4.50 +/- 0.2 and varied from 4.40 on day 1 to 4.55 on day 2. The median rating for panel review was 4.60 +/- 0.1 and varied from 4.55 on day 1 to 4.65 on day 2. Interactive case discussions were rated 4.80 on both course days. There was a significant variability in the rating profiles of the course tripod: U = 24.5, P = 0.03. Fifty-one (98%) participants believe LPDM was COVID-19-compliant, while 90% believe the course was beneficial to training and practice. Conclusion Initial application of LPDM is rewarded with both high acceptance and high rating among participants.
|
|
| 7. |
- Windahl, Ulrika, et al.
(författare)
-
Alpha-chloralose poisoning in cats in three Nordic countries-the importance of secondary poisoning
- 2022
-
Ingår i: BMC Veterinary Research. - : Springer Nature. - 1746-6148. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Alpha-chloralose (AC) is a compound known to be toxic to various animal species and humans. In 2018 and 2019 an increase in suspected cases of AC poisoning in cats related to the use of AC as a rodenticide was reported to national veterinary and chemical authorities in Finland, Norway and Sweden by veterinarians working in clinical practices in respective country. The aims of this study were to prospectively investigate AC poisoning in cats, including possible secondary poisoning by consuming poisoned mice, and to study metabolism and excretion of AC in cats through analysis of feline urine. Methods Data on signalment, history and clinical findings were prospectively collected in Finland, Norway and Sweden from July 2020 until March of 2021 using a questionnaire which the attending veterinarian completed and submitted together with a serum sample collected from suspected feline cases of AC-poisoning. The diagnosis was confirmed by quantification of AC in serum samples. Content of AC was studied in four feline urine samples, including screening for AC metabolites by UHPLC-HRMS/MS. Bait intake and amount of AC consumed by mice was observed in wild mice during an extermination of a rodent infestation. Results In total, 59 of 70 collected questionnaires and accompanying serum samples were included, with 127 to 70 100 ng/mL AC detected in the serum. Several tentative AC-metabolites were detected in the analysed feline urine samples, including dechlorinated and oxidated AC, several sulfate conjugates, and one glucuronic acid conjugate of AC. The calculated amount of AC ingested by each mouse was 33 to 106 mg with a mean of 61 mg. Conclusions Clinical recognition of symptoms of AC poisoning in otherwise healthy cats roaming free outdoors and known to be rodent hunters strongly correlated with confirmation of the diagnosis through toxicological analyses of serum samples. The collected feline exposure data regarding AC show together with the calculation of the intake of bait and subsequent AC concentrations in mice that secondary poisoning from ingestion of mice is possible. The results of the screening for AC metabolites in feline urine confirm that cats excrete AC both unchanged and metabolized through dechlorination, oxidation, glucuronidation and sulfatation pathways.
|
|
