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- Tesi, Bianca, et al.
(author)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
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In: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
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Journal article (peer-reviewed)abstract
- BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
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| 2. |
- Tesi, Bianca, et al.
(author)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
-
In: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
-
Journal article (peer-reviewed)abstract
- Background: Childhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.Methods: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.Findings: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).Interpretation: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.Funding: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.
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| 3. |
- Dahlgren, David, et al.
(author)
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Ulcerative colitis progression : a retrospective analysis of disease burden using electronic medical records
- 2022
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In: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 127:1
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Journal article (peer-reviewed)abstract
- Background: Ulcerative colitis (UC) is a debilitating inflammatory bowel disease. Present knowledge regarding UC disease progression over time is limited.Objective: To assess UC progression to severe disease along with disease burden and associated factors.Methods: Electronic medical records linked with Swedish national health registries (2005-2015) were used to identify disease progression of UC. Odds of all-cause and disease-related hospitalization within 1 year were compared between patients with disease progression and those without. Annual indirect costs were calculated based on sick leave, and factors related to UC progression were examined.Results: Of the 1,361 patients with moderate UC, 24% progressed to severe disease during a median of 5.2 years. Severe UC had significantly higher odds for all-cause (OR [odds ratio] 1.47, 95% CI [confidence interval]: 1.12-1.94, P < 0.01) and UC-related hospitalization (OR 2.47, 95% CI: 1.76-3.47, P < 0.0001) compared to moderate disease. Average sick leave was higher in patients who progressed compared to those who did not (64.4 vs 38.6 days, P < 0.001), with higher indirect costs of 151,800 SEK (16,415 ) pound compared with 92,839 SEK (10,039 ) pound (P < 0.001), respectively. UC progression was related to young age (OR 1.62, 95% CI: 1.17-2.25, P < 0.01), long disease duration (OR 1.09, 95% CI: 1.03-1.15, P < 0.001), and use of corticosteroids (OR 2.49, 95% CI: 1.67-3.72, P < 0.001).Conclusion: Disease progression from moderate to severe UC is associated with more frequent and longer hospitalizations and sick leave. Patients at young age with long disease duration and more frequent gluco-corticosteroid medication are associated with progression to severe UC.
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| 5. |
- Morén, Staffan, et al.
(author)
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Speech in Adults Treated for Unilateral Cleft Lip and Palate as Rated by Naïve Listeners, Speech-Language Pathologists and Patients
- 2022
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In: Journal of Plastic, Reconstructive & Aesthetic Surgery. - : Elsevier. - 1748-6815 .- 1878-0539. ; 75:10
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Journal article (peer-reviewed)abstract
- Speech may be affected in patients with cleft lip and palate (CLP). Professional listeners, naïve listeners, and patients may perceive speech differently. The aim of the study was to assess speech among adults treated for unilateral CLP (UCLP) as rated by naïve listeners, speech-language pathologists (SLPs), and self-assessment and to evaluate how well these ratings correlate.All patients with complete UCLP treated at the Uppsala University Hospital, Uppsala, Sweden, in 1960–1987 were invited. A total of 73 of 109 patients (67%) participated, with a mean of 35 years since the initiation of treatment. The noncleft control group consisted of 55 volunteers. All participants answered questionnaires for self-rating of speech, and their speech was audio-recorded digitally. Fourteen naïve listeners and four SLPs rated the speech individually from blinded recordings.There were more speech abnormalities among patients compared to controls according to the ratings of naïve listeners and SLPs. In controls and patients, there were positive correlations between the speech ratings by naïve listeners and SLPs r = 0.44 to 0.71, p < 0.001, Spearman). The patients were less satisfied and rated to have more speech abnormalities than controls (p < 0.001).Although adults treated for UCLP considered their speech as fairly good, they were less satisfied than noncleft controls. The agreement between ratings by naïve listeners and SLPs were good, while the agreement between these ratings and self-assessment varied widely. When assessing speech in adults treated for UCLP, differences in perception of speech abnormalities by professionals, laymen, and patients should be considered.
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| 6. |
- Stålhammar, Jacob, 1967, et al.
(author)
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Neuropsychological Test Performance Among Native and Non-Native Swedes: Second Language Effects. : Neuropsykologisk testprestation hos infödda och icke infödda svensktalande: andraspråkseffekter
- 2022
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In: Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists. - : Oxford University Press (OUP). - 1873-5843. ; 37:4, s. 826-838
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Journal article (peer-reviewed)abstract
- We aimed to study second language effects on neuropsychological (NP) test performance.We administered an NP test battery in Swedish to 322 healthy community dwelling participants, recruited through the Gothenburg Pilot phase of the Swedish CArdioPulmonary BioImage Study (SCAPIS Pilot). All participants were conversationally fluent Swedish speakers (237 native, 85 non-native, mean age 61.1years). We compared the NP scores of native and non-native participants. We also investigated the influence of (a) age of arrival to Sweden, (b) majority language family of the birth country, and (c) proficiency in Swedish as assessed with a 30 item Boston naming test (BNT).Native speakers obtained better results on all NP tasks with a verbal component, whereas no significant differences were seen on completely nonverbal tasks (Rey complex figure). For non-native speakers, lower age at arrival to Sweden, arrival from a country where Swedish was also spoken, or arrival from a country with a majority language closer to Swedish, were all linked to better NP scores. Dichotomizing by BNT showed that normally-to-highly proficient non-native speakers obtained better scores.Second language effects may contribute to misclassification of non-native speakers. Assumptions of fluency based on short conversations may be misleading. A proficiency assessment with BNT may improve NP score interpretation among non-native speakers.
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