BACKGROUND AND OBJECTIVES: Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD. In this study, we sought to identify a distinctive metal deposition pattern in NWD using 7T SWI and investigate its diagnostic value and underlying pathophysiologic mechanism. METHODS: Patients with WD, healthy participants with monoallelic ATP7B variant(s) on a single chromosome, and health controls (HCs) were recruited. NWD and non-NWD (nNWD) were defined according to the presence or absence of neurologic symptoms during investigation. Patients with other diseases with comparable clinical or imaging manifestations, including early-onset Parkinson disease (EOPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and neurodegeneration with brain iron accumulation (NBIA), were additionally recruited and assessed for exploratory comparative analysis. All participants underwent 7T T1, T2, and high-resolution SWI scanning. Quantitative susceptibility mapping and principal component analysis were performed to illustrate metal distribution. RESULTS: We identified a linear signal intensity change consisting of a hyperintense strip at the lateral border of the globus pallidus in patients with NWD. We termed this feature "hyperintense globus pallidus rim sign." This feature was detected in 38 of 41 patients with NWD and was negative in all 31 nNWD patients, 15 patients with EOPD, 30 patients with MSA, 15 patients with PSP, and 12 patients with NBIA; 22 monoallelic ATP7B variant carriers; and 41 HC. Its sensitivity to differentiate between NWD and HC was 92.7%, and specificity was 100%. Severity of the hyperintense globus pallidus rim sign measured by a semiquantitative scale was positively correlated with neurologic severity (ρ = 0.682, 95% CI 0.467-0.821, p < 0.001). Patients with NWD showed increased susceptibility in the lenticular nucleus with high regional weights in the lateral globus pallidus and medial putamen. DISCUSSION: The hyperintense globus pallidus rim sign showed high sensitivity and excellent specificity for diagnosis and differential diagnosis of NWD. It is related to a special metal deposition pattern in the lenticular nucleus in NWD and can be considered as a novel neuroimaging biomarker of NWD. CLASSIFICATION OF EVIDENCE: The study provides Class II evidence that the hyperintense globus pallidus rim sign on 7T SWI MRI can accurately diagnose neurologic WD.
- MeSH
- ATPázy transportující měď metabolismus genetika MeSH
- dospělí MeSH
- globus pallidus diagnostické zobrazování metabolismus MeSH
- hepatolentikulární degenerace * diagnostické zobrazování metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- měď metabolismus MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozek diagnostické zobrazování metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.
- MeSH
- dospělí MeSH
- ganglioneurom * chirurgie MeSH
- lidé MeSH
- nádory měkkých tkání * MeSH
- neuroblastom * MeSH
- progrese nemoci MeSH
- retroperitoneální nádory * chirurgie MeSH
- retrospektivní studie MeSH
- sarkom * chirurgie patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: There are 20 million living US armed forces veterans; however, the organ donation attitudes of veterans have not been examined. METHODS: Over a 17-month period, a convenience sample of 1517 veterans in New England completed a survey to assess attitudes about organ, tissue, and vascularized composite allograft (VCA) donation. RESULTS: Most veterans (96%) supported the donation of organs and tissue for transplantation, and 59% were registered as an organ and tissue donor. Being younger (adjusted odds ratio [aOR]: 0.960.970.98; P = 0.01), female (aOR: 1.061.462.03; P = 0.02), non-Hispanic white (aOR: 1.302.073.30; P = 0.01), Hispanic (aOR: 1.282.434.61; P = 0.01), and having more trust that the transplant process is fair and equal (aOR: 1.191.401.65; P = 0.01) were predictive of donor registration. Also, most veterans were willing to donate their face (57%), hands/arms (81%), legs (81%), penis (men: 61%), and uterus (women: 76%) at time of death; donation willingness was higher for upper and lower limbs than for face or genitourinary organs (P < 0.001). Those unwilling to donate VCA organs expressed concerns about identity loss, psychological discomfort of self and others, body integrity, funeral presentation, and religious beliefs. Most (54%) felt that VCA donation should require permission of legal next-of-kin at the time of one's death, even if the decedent was a registered donor. CONCLUSIONS: There is a high level of support for organ, tissue, and VCA transplantation and donation among veterans, despite limited educational campaigns targeting this population. There is high potential among veterans to further increase donor registry enrollment and raise awareness about VCA benefits for severely injured service members.
- MeSH
- altruismus MeSH
- dárci tkání psychologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- náboženství a lékařství MeSH
- postoj ke smrti MeSH
- průzkumy a dotazníky MeSH
- transplantace orgánů * MeSH
- transplantace tkání * MeSH
- vaskularizovaná kompozitní alotransplantace MeSH
- veteráni váleční psychologie MeSH
- zdraví - znalosti, postoje, praxe * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- srovnávací studie MeSH
- Geografické názvy
- Nová Anglie MeSH
BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction <0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
- MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- infarkt myokardu genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 9 * MeSH
- nemoci koronárních tepen genetika patologie MeSH
- odds ratio MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
- MeSH
- dospělí MeSH
- koronární nemoc patologie MeSH
- kouření MeSH
- lidé středního věku MeSH
- lidé MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- rizikové faktory MeSH
- senioři MeSH
- sexuální faktory MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Face transplantation is a novel option for patients with severe facial disfigurement. Quality of life (QoL) outcomes of face transplantation remain poorly understood. OBJECTIVES: We sought to evaluate psychosocial functioning among 6 patients undergoing facial transplantation. METHODS: We prospectively assessed depressive symptoms, health status, mental and physical QoL, and self-esteem at 3-month intervals for 2 years. Social desirability was assessed pretransplant. RESULTS: On average, before transplantation, patients generally reported minimal to subthreshold depressive symptoms, normal to high health status, normal mental-health QoL, slightly below normal physical-health QoL, and normal to high self-esteem. Most endorsed high social desirability. As patients recovered from surgery, hospitalization, and immunosuppression induction, physical-health QoL generally deteriorated 3 months posttransplantation. Posttransplant trajectories show that perceived health state improved; health status and mental and physical health-related QoL slightly improved; self-esteem remained stable and high; and overall depressive symptoms remained stable but 3 patients experienced a depressive episode. CONCLUSIONS: Pretransplant ceiling effects may render improvements difficult to quantify. Future research should use mixed methods including population-specific measures with demonstrated sensitivity to change.
- Publikační typ
- časopisecké články MeSH
