| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
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| 4. |
- Oonk, M. H. M., et al.
(författare)
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Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 39:32
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (<= 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL. (C) 2021 by American Society of Clinical Oncology
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| 5. |
- Van der Kolk, W. L., et al.
(författare)
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Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe
- 2022
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 167:1, s. 3-10
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN.Methods. We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up.Results. Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was di-agnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor >= 30 mm. Bilateral ra-diotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence.Conclusion. The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
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| 6. |
- Oonk, Maaike H. M., et al.
(författare)
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Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node : Results of GROINSS-V II
- 2021
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Ingår i: Journal of Clinical Oncology. - : Lippincott, Williams & Wilkins. - 0732-183X .- 1527-7755. ; 39:32, s. 3623-3632
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (<= 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.
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| 7. |
- Steinthorsdottir, V, et al.
(författare)
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Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5976-
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.
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| 8. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
- 2023
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Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 55:11, s. 1807-19
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Tidskriftsartikel (refereegranskat)abstract
- A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n=65,405), maternal (n=61,228) and paternal (n=52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
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| 11. |
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| 12. |
- Vogelezang, Suzanne, et al.
(författare)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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| 13. |
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| 14. |
- Fadista, João, et al.
(författare)
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Genetic regulation of spermine oxidase activity and cancer risk : a Mendelian randomization study
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Spermine oxidase (SMOX) catalyzes the oxidation of spermine to spermidine. Observational studies have reported SMOX as a source of reactive oxygen species associated with cancer, implying that inhibition of SMOX could be a target for chemoprevention. Here we test causality of SMOX levels with cancer risk using a Mendelian randomization analysis. We performed a GWAS of spermidine/spermine ratio to identify genetic variants associated with regulation of SMOX activity. Replication analysis was performed in two datasets of SMOX gene expression. We then did a Mendelian randomization analysis by testing the association between the SMOX genetic instrument and neuroblastoma, gastric, lung, breast, prostate, and colorectal cancers using GWAS summary statistics. GWAS of spermidine/spermine ratio identified SMOX locus (P = 1.34 × 10–49) explaining 32% of the variance. The lead SNP rs1741315 was also associated with SMOX gene expression in newborns (P = 8.48 × 10–28) and adults (P = 2.748 × 10–8) explaining 37% and 6% of the variance, respectively. Genetically determined SMOX activity was not associated with neuroblastoma, gastric, lung, breast, prostate nor colorectal cancer (P > 0.05). A PheWAS of rs1741315 did not reveal any relevant associations. Common genetic variation in the SMOX gene was strongly associated with SMOX activity in newborns, and less strongly in adults. Genetic down-regulation of SMOX was not significantly associated with lower odds of neuroblastoma, gastric, lung, breast, prostate and colorectal cancer. These results may inform studies of SMOX inhibition as a target for chemoprevention.
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| 15. |
- Hill, Loreena, et al.
(författare)
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Integration of a palliative approach into heart failure care: aEuropean Society of Cardiology Heart Failure Associationposition paper
- 2020
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:12, s. 2327-2339
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Tidskriftsartikel (refereegranskat)abstract
- The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence-based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a good death. This new position paper aims to provide day-to-day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline-directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure.
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| 16. |
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| 17. |
- Selles, R. R., et al.
(författare)
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Avoidance, Insight, Impairment Recognition Concordance, and Cognitive-Behavioral Therapy Outcomes in Pediatric Obsessive-Compulsive Disorder
- 2020
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567. ; 59:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Insight and avoidance are commonly discussed factors in obsessive-compulsive disorder (OCD) that have demonstrated associations with increased severity as well as reduced treatment response in adults, but these factors have not been sufficiently examined in pediatric OCD. This study examined the impacts of avoidance, insight, and impairment recognition concordance on cognitive-behavioral therapy (CBT) outcomes as well as impacts of CBT on insight and avoidance in a large sample of youths affected by OCD. Method: Data from 573 OCD-affected youths enrolled in CBT trials were aggregated. Children's Yale-Brown Obsessive-Compulsive Scale items measured treatment response, insight, and avoidance. Standardized differences between child and parent ratings of impairment were used to calculate impairment recognition concordance. Binary logistic regression was used to identify variables associated with treatment response. Results: Greater avoidance, limited child recognition of impairment, older age, and lower baseline severity predicted reduced likelihood of treatment response, but insight did not. Both insight and avoidance improved significantly following CBT. Response rates were lower when posttreatment insight and avoidance were worse. Conclusion: Contrasting with prevailing belief, poor insight does not appear to limit CBT response potential in pediatric OCD. Avoidance and impairment recognition are understudied CBT response predictors and warrant further consideration in pediatric OCD. Clinicians should attend to these factors to optimize outcomes for children affected by this common, debilitating illness.
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| 18. |
- Smárason, Orri, et al.
(författare)
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Exploring latent clusters in pediatric OCD based on symptoms, severity, age, gender, and comorbidity.
- 2024
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Ingår i: European Child and Adolescent Psychiatry. - 1018-8827 .- 1435-165X.
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Tidskriftsartikel (refereegranskat)abstract
- Given diverse symptom expression and high rates of comorbid conditions, the present study explored underlying commonalities among OCD-affected children and adolescents to better conceptualize disorder presentation and associated features. Data from 830 OCD-affected participants presenting to OCD specialty centers was aggregated. Dependent mixture modeling was used to examine latent clusters based on their age- and gender adjusted symptom severity (as measured by the Children’s Yale-Brown Obsessive-Compulsive Scale; CY-BOCS), symptom type (as measured by factor scores calculated from the CY-BOCS symptom checklist), and comorbid diagnoses (as assessed via diagnostic interviews). Fit statistics favored a four-cluster model with groups distinguished primarily by symptom expression and comorbidity type. Fit indices for 3–7 cluster models were only marginally different and characteristics of the clusters remained largely stable between solutions with small clusters of distinct presentations added in more complex models. Rather than identifying a single classification system, the findings support the utility of integrating dimensional, developmental, and transdiagnostic information in the conceptualization of OCD-affected children and adolescents. Identified clusters point to the centrality of contamination concerns to OCD, relationships between broader symptom expression and higher levels of comorbidity, and the potential for complex/neurodevelopmental presentations.
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| 19. |
- Brogaard, K., et al.
(författare)
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Age and helium content of the open cluster NGC 6791 from multiple eclipsing binary members : III. Constraints from a subgiant
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649
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Tidskriftsartikel (refereegranskat)abstract
- Context. Models of stellar structure and evolution can be constrained using accurate measurements of the parameters of eclipsing binary members of open clusters. Multiple binary stars provide the means to tighten the constraints and, in turn, to improve the precision and accuracy of the age estimate of the host cluster. In the previous two papers of this series, we have demonstrated the use of measurements of multiple eclipsing binaries in the old open cluster NGC 6791 to set tighter constraints on the properties of stellar models than was previously possible, thereby improving both the accuracy and precision of the cluster age. Aims. We identify and measure the properties of a non-eclipsing cluster member, V56, in NGC 6791 and demonstrate how this provides additional model constraints that support and strengthen our previous findings. Methods. We analyse multi-epoch spectra of V56 from FLAMES in conjunction with the existing photometry and measurements of eclipsing binaries in NGC6971. Results. The parameters of the V56 components are found to be Mp = 1.103 ± 0.008 Mpdbl and Ms = 0.974 ± 0.007 Mpdbl, Rp = 1.764 ± 0.099 Rpdbl and Rs = 1.045 ± 0.057 Rpdbl, Teff,p = 5447 ± 125 K and Teff,s = 5552 ± 125 K, and surface [Fe/H] = +0.29 ± 0.06 assuming that they have the same abundance. Conclusions. The derived properties strengthen our previous best estimate of the cluster age of 8.3 ± 0.3 Gyr and the mass of stars on the lower red giant branch (RGB), which is MRGB = 1.15 ± 0.02 Mpdbl for NGC 6791. These numbers therefore continue to serve as verification points for other methods of age and mass measures, such as asteroseismology.
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| 20. |
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| 21. |
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| 22. |
- Hill, Loreena, et al.
(författare)
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Culture, ethnicity, and socio-economic status as determinants of the management of patients with advanced heart failure who need palliative care: A clinical consensus statement from the Heart Failure Association (HFA) of the ESC, the ESC Patient Forum, and the European Association of Palliative Care
- 2023
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 25:9, s. 1481-1492
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Tidskriftsartikel (refereegranskat)abstract
- The delivery of effective healthcare entails the configuration and resourcing of health economies to address the burden of disease, including acute and chronic heart failure, that affects local populations. Increasing migration is leading to more multicultural and ethnically diverse societies worldwide, with migration research suggesting that minority populations are often subject to discrimination, socio-economic disadvantage, and inequity of access to optimal clinical support. Within these contexts, the provision of person-centred care requires medical and nursing staff to be aware of and become adept in navigating the nuances of cultural diversity, and how that can impact some individuals and families entrusted to their care. This paper will examine current evidence, provide practical guidance, and signpost professionals on developing cultural competence within the setting of patients with advanced heart failure who may benefit from palliative care.
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| 23. |
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| 24. |
- Perotti, Daniela, et al.
(författare)
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Hallmark discoveries in the biology of Wilms tumour
- 2023
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Ingår i: Nature Reviews Urology. - 1759-4812.
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Forskningsöversikt (refereegranskat)abstract
- The modern study of Wilms tumour was prompted nearly 50 years ago, when Alfred Knudson proposed the ‘two-hit’ model of tumour development. Since then, the efforts of researchers worldwide have substantially expanded our knowledge of Wilms tumour biology, including major advances in genetics — from cloning the first Wilms tumour gene to high-throughput studies that have revealed the genetic landscape of this tumour. These discoveries improve understanding of the embryonal origin of Wilms tumour, familial occurrences and associated syndromic conditions. Many efforts have been made to find and clinically apply prognostic biomarkers to Wilms tumour, for which outcomes are generally favourable, but treatment of some affected individuals remains challenging. Challenges are also posed by the intratumoural heterogeneity of biomarkers. Furthermore, preclinical models of Wilms tumour, from cell lines to organoid cultures, have evolved. Despite these many achievements, much still remains to be discovered: further molecular understanding of relapse in Wilms tumour and of the multiple origins of bilateral Wilms tumour are two examples of areas under active investigation. International collaboration, especially when large tumour series are required to obtain robust data, will help to answer some of the remaining unresolved questions.
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| 25. |
- Saegerman, Claude, et al.
(författare)
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First Expert Elicitation of Knowledge on Possible Drivers of Observed Increasing Human Cases of Tick-Borne Encephalitis in Europe
- 2023
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis (TBE) is a viral disease endemic in Eurasia. The virus is mainly transmitted to humans via ticks and occasionally via the consumption of unpasteurized milk products. The European Centre for Disease Prevention and Control reported an increase in TBE incidence over the past years in Europe as well as the emergence of the disease in new areas. To better understand this phenomenon, we investigated the drivers of TBE emergence and increase in incidence in humans through an expert knowledge elicitation. We listed 59 possible drivers grouped in eight domains and elicited forty European experts to: (i) allocate a score per driver, (ii) weight this score within each domain, and (iii) weight the different domains and attribute an uncertainty level per domain. An overall weighted score per driver was calculated, and drivers with comparable scores were grouped into three terminal nodes using a regression tree analysis. The drivers with the highest scores were: (i) changes in human behavior/activities; (ii) changes in eating habits or consumer demand; (iii) changes in the landscape; (iv) influence of humidity on the survival and transmission of the pathogen; (v) difficulty to control reservoir(s) and/or vector(s); (vi) influence of temperature on virus survival and transmission; (vii) number of wildlife compartments/groups acting as reservoirs or amplifying hosts; (viii) increase of autochthonous wild mammals; and (ix) number of tick species vectors and their distribution. Our results support researchers in prioritizing studies targeting the most relevant drivers of emergence and increasing TBE incidence.
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