| 1. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 2. |
- Scheer, Monika, et al.
(författare)
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Low-grade fibromyxoid sarcoma : A report of the Cooperative Weichteilsarkom Studiengruppe (CWS)
- 2020
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Ingår i: Pediatric Blood & Cancer. - : WILEY. - 1545-5009 .- 1545-5017. ; 67:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue tumor with benign histologic appearance, though fully malignant behavior is possible.Methods: Patients with LGFMS<21 years registered in Cooperative Weichteilsarkom Studiengruppe trials until 2017 were analyzed. Firstline treatment consisted of complete surgical resection whenever possible.Results: Median age of 31 patients was 10.9 years (first month to 17.1 years). Twenty-six tumors were confirmed to the tissue of origin (T1), four invaded contiguous structures (T2), one was TX. Eight were >5 cm. The best surgical result was resection with free margins (R0) in 24 and microscopic residuals (R1) in seven. Five-year event-free (EFS), 5-year local-relapse-free (LRFS), and 5-year overall-survival were 71 +/- 18.6% confidence interval (CI) 95%, 76 +/- 17.6% CI 95%, and 100%, respectively. Six patients suffered local relapse in a median of 1 year, one combined within 1.3 year and one metastatic relapse with lesions in the lung, back muscles, and thigh discovered in whole-body imaging 6 years after the first diagnosis. In univariate analysis, T status correlated with EFS (T1 79.6 +/- 18.6%, T2 50.0 +/- 49.0%, P = .038). Resection with free margins tends to be associated with better LRFS (R0 82.4 +/- 18.6%, R1 53.6 +/- 39.4%, P = .053). Among 24 patients with R0 resection, five (21%) suffered relapse, thereof three local, one metastatic, and one combined. Among seven patients with R1-resection, three (43%) suffered local relapse.Conclusion Special caution is advisable in T2 tumors. The metastatic potential with lesions in unusual sites indicates that affected patients need to be informed. If long-term follow-up with whole-body imaging is beneficial, it may be addressed in larger intergroup analyses. Further research in disease biology is essential for optimal treatment and follow-up care.
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| 3. |
- Scheer, Monika, et al.
(författare)
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Synovial sarcoma disease characteristics and primary tumor sites differ between patient age groups : a report of the Cooperative Weichteilsarkom Studiengruppe (CWS)
- 2020
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : SPRINGER. - 0171-5216 .- 1432-1335. ; 146:4, s. 953-960
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Tidskriftsartikel (refereegranskat)abstract
- Background: Older age is associated with worse outcome in synovial sarcoma (SS) patients. Differences in disease presentation among distinct age groups, however, are currently unknown.Methods: SS patients < 21 years registered in consecutive CWS trials over the period of 1981-2018 were evaluated. Characteristics were analyzed according to age groups using the Fisher's exact test.Results: The study population included 432 SS patients. Disease characteristics differed according to age groups of children (0-12 years, n = 176), adolescents (13-16 years, n = 178), and young adults (17-21 years, n = 78). The proportion of invasive tumors (T2) was significantly higher in older patients: children 33%, adolescents 39% and young adults 54%, p = 0.009805. Similarly, the proportion of tumors > 10 cm was higher (13%, 21%, 31%; p = 0.005657) whereas conversely, the proportion of small tumors < 3 cm was lower in older patients (29%, 24%, 6%; p = 0.000104). The presence of metastases at first diagnosis was also highest in older patients (6%, 10%, 21%, p = 0.000963). Notably, the proportion of thigh tumors was higher in older patients (p = 0.04173), whereas the proportion of head-neck tumors was lower in older patients (p = 0.08896).Conclusions The rates of large, invasive tumors and the presence of metastases are significantly associated with older patient age. Localization to the thigh is more frequent in older patients.Discussion The causes for these variations require further exploration.
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| 4. |
- Sparber-Sauer, Monika, et al.
(författare)
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The impact of local control in the treatment of children with advanced infantile and adult-type fibrosarcoma : Experience of the cooperative weichteilsarkom studiengruppe (CWS)
- 2020
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Ingår i: Journal of Pediatric Surgery. - : W B SAUNDERS CO-ELSEVIER INC. - 0022-3468 .- 1531-5037. ; 55:9, s. 1740-1747
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: This study aims at examining the potential survival benefits of primary versus secondary surgery of children diagnosed with advanced infantile (iFS) and adult-type fibrosarcoma (aFS). Methods: Treatment and outcome of 89 children with FS treated within prospective Cooperative Studiengruppe (CWS) trials (1981-2016) were analyzed retrospectively. Results: Localized disease (LD) was diagnosed in 87 patients: 64/66 patients with iFS (<= 2 years) and 23 with aFS (>2 <= 18 years). Two patients (iFS) had metastatic disease. Resection was the mainstay of therapy of patients with LD resulting in microscopically complete (R0, IRS group I) (n = 29/87, 33%), microscopically incomplete (R1, IRS group II) (n = 17/87, 20%) and macroscopically incomplete (R2, IRS group III) (n = 41/87, 47%). Advanced LD (IRS group Ill) was present in 32/64 (50%) palieras with iFS and in 9/23 (39%) with aFS. Chemotherapy was added predominantly in patients with advanced disease and an assessable objective response to CHT was seen in 71% iFS and 75% aFS. The 5 -year event-free survival (EFS) of patients with iFS and aFS was 81% (+/- 10, 95% Cl) and 70% (+/- 19, 95% Cl) (p = 0.24); the 5 -year overall survival (OS) was 98% (+/- 3, 95% Cl) and 82% (+/- 16, 95% Cl) (p = 0.02). Primary resection was no prognostic factor. Secondary R0/R1 resection in patients with advanced disease improved 5-year EFS and OS in aFS (p = 0.002 and p = 0.000) but not in infants. Conclusions: Secondary resection improves outcome in advanced aFS but not in infants. Mutilating surgery in infants should be avoided. (C) 2019 Elsevier Inc. All rights reserved.
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