| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Krauss, Tobias, et al.
(författare)
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Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors
- 2018
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Ingår i: Endocrine-Related Cancer. - : BIOSCIENTIFICA LTD. - 1351-0088 .- 1479-6821. ; 25:9, s. 783-793
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were >= 2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off >= 2.8 cm, 44% and 91% for TVDT cut-off of <= 24 months). In 117 of 273 patients, PanNETs > 1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs < 2.8 cm vs >= 2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.
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| 6. |
- Bausch, Birke, et al.
(författare)
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Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention
- 2017
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Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 3:9, s. 1204-1212
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P amp;lt; .001). CONCLUSIONS AND RELEVANCE The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.
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| 7. |
- Duygu, K., et al.
(författare)
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Association of dietary and gut microbiota-related metabolites with calcific aortic stenosis
- 2021
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Ingår i: Acta Cardiologica. - : Informa UK Limited. - 0001-5385 .- 0373-7934. ; 76:5, s. 544-522
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Tidskriftsartikel (refereegranskat)abstract
- Background Histopathological changes in calcific aortic stenosis (CAS) resemble changes in coronary atherosclerosis. Concerning recent evidence on dietary and gut microbiota-related metabolites representing players in atherosclerosis, we aimed to investigate the link between dietary and gut microbiota-derived metabolites and CAS. Methods We consecutively recruited eligible subjects with moderate-severe CAS (n = 60), aortic sclerosis (ASc) (n = 49) and age and gender-matched control subjects (n = 48) in May 2016-December 2016. Plasma dietary and gut microbiota-related metabolite levels, namely choline, betaine, and trimethylamine N-oxide (TMAO), were measured using ultra-performance liquid chromatography-tandem mass spectroscopy method. Histopathological examinations were performed in patients that underwent aortic valve surgery. Results Prevalence of traditional cardiovascular risk factors or co-morbidities did not differ among groups (all p > 0.05). CAS patients had higher plasma choline levels compared to both control (p < 0.001) and ASc (p = 0.006). Plasma betaine and TMAO levels were similar (both p > 0.05). Compared to the lowest quartile choline levels (<11.15 mu M), patients with the highest quartile choline levels (>= 14.98 mu M) had higher aortic valvular (p < 0.001) and mitral annular (p = 0.013) calcification scores. Plasma choline levels were independently associated with aortic peak flow velocity (B +/- SE:0.165 +/- 0.060, p = 0.009). Choline levels were elevated in subjects who had aortic valves with denser lymphocyte infiltration (p < 0.001), neovascularization (p = 0.011), osseous metaplasia (p = 0.004), more severe tissue remodelling (p = 0.002) and calcification (p = 0.002). Conclusion We found a significant association between choline levels and CAS presence and severity depicted on imaging modalities and histopathological examinations. Our study may open new horizons for prevention of CAS.
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| 8. |
- Kocyigit, D., et al.
(författare)
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Cholesterol efflux promoting function of high-density lipoproteins in calcific aortic valve stenosis
- 2021
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Ingår i: Atherosclerosis Plus. - : Elsevier BV. - 2667-0909 .- 2667-0895. ; 44:October, s. 18-24
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Cholesterol efflux capacity is a functional property of high-density lipoproteins (HDL) reflecting the efficiency of the atheroprotective reverse cholesterol transport process in humans. Its relationship with calcific aortic valve stenosis (CAVS) has not been fully assessed yet. Methods: We evaluated HDL-CEC in a patient population with varying degrees of aortic valvular calcific disease, assessed using echocardiography and cardiac computed tomography. Measurement of biomarkers that reflect osteogenic and tissue remodeling, along with dietary and gut microbiota-derived metabolites were performed. Results: Patients with moderate-severe CAVS had significantly lower HDL-CEC compared to both control and aortic sclerosis subjects (mean: 6.09%, 7.32% and 7.26%, respectively). HDL-CEC displayed negative correlations with peak aortic jet velocity and aortic valve calcium score, indexes of CAVS severity (ρ = -0.298, p = 0.002 and ρ = -0.358, p = 0.005, respectively). In multivariable regression model, HDL-CEC had independent association with aortic valve calcium score (B: -0.053, SE: 0.014, p < 0.001), GFR (B: -0.034, SE: 0.012, p = 0.007), as well as with levels of total cholesterol (B: 0.018, SE: 0.005, p = 0.002). Conclusion: These results indicate an impairment of HDL-CEC in moderate-severe CAVS and may contribute to identify potential novel targets for CAVS management. © 2021 The Authors
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| 9. |
- Ortiz-Fernandez, Lourdes, et al.
(författare)
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Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study
- 2021
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Ingår i: American Journal of Human Genetics. - CAMBRIDGE, MA USA : Cell Press. - 0002-9297 .- 1537-6605. ; 108:1, s. 84-99
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Tidskriftsartikel (refereegranskat)abstract
- Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.
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| 10. |
- Young, Susan, et al.
(författare)
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Guidelines for identification and treatment of individuals with attention deficit/hyperactivity disorder and associated fetal alcohol spectrum disorders based upon expert consensus
- 2016
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Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association of attention deficit/hyperactivity disorder (ADHD) and fetal alcohol spectrum disorders (FASD) results in a complex constellation of symptoms that complicates the successful diagnosis and treatment of the affected individual. Current literature lacks formal guidelines, randomized control trials, and evidence-based treatment plans for individuals with ADHD and associated FASD. Therefore, a meeting of professional experts was organized with the aim of producing a consensus on identification and treatment guidelines that will aid clinicians in caring for this unique patient population. Methods: Experts from multiple disciplines in the fields of ADHD and FASD convened in London, United Kingdom, for a meeting hosted by the United Kingdom ADHD Partnership (UKAP; www.UKADHD.com) in June 2015. The meeting provided the opportunity to address the complexities of ADHD and FASD from different perspectives and included presentations, discussions, and group work. The attendees worked towards producing a consensus for a unified approach to ADHD and associated FASD. Results: The authors successfully came to consensus and produced recommended guidelines with specific regards to identification and assessment, interventions and treatments, and multiagency liaisons and care management, highlighting that a lifespan approach to treatment needs to be adopted by all involved. Included in the guidelines are: 1) unique 'red flags', which when identified in the ADHD population can lead to an accurate associated FASD diagnosis, 2) a treatment decision tree, and 3) recommendations for multiagency care management. Conclusions: While clinically useful guidelines were achieved, more research is still needed to contribute to the knowledge base about the diagnosis, treatment, and management of those with ADHD and associated FASD.
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