Similar family-based cancer and genealogy data from Norway and Utah allowed comparisons of the incidence of testicular cancer (TC), and exploration of the role of Scandinavian ancestry and family history of TC in TC risk. Our study utilizes data from the Utah Population Database and Norwegian Population Registers. All males born during 1951–2015 were followed for TC until the age of 29 years. A total of 1,974,287 and 832,836 males were born in Norway and Utah, respectively, of whom 2,686 individuals were diagnosed with TC in Norway and 531 in Utah. The incidence per year of TC in Norway (10.6) was twice that observed in Utah (5.1) for males born in the last period (1980–1984). The incidence rates of TC in Utah did not differ according to the presence or absence of Scandinavian ancestry (p = 0.669). Having a brother diagnosed with TC was a strong risk factor for TC among children born in Norway and Utah, with HR = 9.87 (95% CI 5.68–17.16) and 6.02 (95% CI 4.80–7.55), respectively; with even higher HR observed among the subset of children in Utah with Scandinavian ancestry (HR = 12.30, 95% CI 6.78–22.31). A clear difference in TC incidence among individuals born in Norway and descendants of Scandinavian people born in Utah was observed. These differences in TC rates point to the possibility of environmental influence. Family history of TC is a strong risk factor for developing TC in both populations. 相似文献
Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI. 相似文献
Hypomineralized enamel may be found in connection with the condition molar incisor hypomineralization (MIH), which has a prevalence of around 15% in most parts of the world. Molar incisor hypomineralization is associated with extensive objective and subjective problems, such as hypersensitivity of the affected teeth, enamel breakdown, and problems with retention of restorations. The etiology behind MIH has not yet been elucidated, but a number of possible factors, which affect the same or different functions of ameloblasts during their different stages of maturation, have been suggested. The aim of this study was to utilize multi‐nuclear, solid‐state nuclear magnetic resonance (ss‐NMR) and time‐of‐flight secondary ion mass spectroscopy (ToF‐SIMS) to elucidate any differences, at a molecular level, between enamel powder prepared from normal, healthy teeth and enamel powder prepared from teeth diagnosed with MIH. 31P and 23Na ss‐NMR confirmed the presence of and two different Na+ sites in hypomineralized enamel, suggesting a heterogeneous chemical composition. The content of organic components was higher in hypomineralized enamel, as shown by both 13C ss‐NMR and ToF‐SIMS, indicating the presence of higher numbers of proteins and phospholipids. The interplay between both is necessary for the formation and mineralization of enamel, which might be disturbed or halted in hypomineralized enamel. 相似文献
Objective. Skeletal muscle perfusion during walking relies on complex interactions between cardiac activity and vascular control mechanisms, why cardiac dysfunction may contribute to intermittent claudication (IC) symptoms. The study aims were to describe cardiac function at rest and during stress in consecutive IC patients, to explore the relations between cardiac function parameters and treadmill performance, and to test the hypothesis that clinically silent myocardial ischemia during stress may contribute to IC limb symptomatology. Design. Patients with mild to severe IC (n?=?111, mean age 67 y, 52% females, mean treadmill distance 195 m) underwent standard echocardiography, dobutamine stress echocardiography (SE) and treadmill testing. The patient cohort was separated in two groups based on treadmill performance (HIGH and LOW performance). Results. Ten patients (9%) had regional wall motion abnormalities of which three had left ventricular ejection fraction <50% at standard echocardiography. A majority had lower than expected systolic- and diastolic ventricular volumes. LOW performers had smaller diastolic left ventricular volumes and lower global peak systolic velocity during dobutamine stress. No patient demonstrated significant cardiac dysfunction during dobutamine provocation that was not also evident at standard echocardiography. Conclusions. Most IC patients were without signs of ischemic heart disease or cardiac failure. The majority had small left ventricular volumes. The hypothesis that clinically silent myocardial ischemia impairing left ventricular function during stress may contribute to IC limb symptomatology was not supported.Trial registration:ClinicalTrials.gov identifier: NCT01219842.相似文献
Previous research suggests that prenatal maternal infections may be associated with increased odds of children having a neurodevelopmental disorder. However, little evidence exists on associations with broader child outcomes, especially subclinical symptoms. Participants were the N = 14,021 members of the population-representative UK Millennium Cohort Study. We examined associations between prenatal maternal infections, both maternal-reported and hospital-recorded, and children’s socioemotional development, using the Strengths and Difficulties Questionnaire (SDQ) at age three. Maternal-reported prenatal infections were associated with increased emotional symptoms, after adjusting for several potential confounds and covariates. Hospital-recorded prenatal infections were not associated with children’s socioemotional outcomes, after adjusting for potential confounding and covarying factors. Findings suggest that prenatal maternal infections, particularly those which the mothers remember months later, may be associated with increased emotional problems in early childhood. This emphasises the need for screening for and preventing infections during pregnancy. Further, the occurrence of prenatal infection indicates the potential need for early intervention for children’s emotional difficulties.
Intrathecal chemoprophylaxis is often administered to patients with diffuse large B-cell lymphoma (DLBCL) to lower the rates of central nervous system (CNS) relapse, although its benefit has not been well-described. Prognostic models, including the CNS-International Prognostic Index (IPI), have been developed to aid in identifying patients at highest risk for CNS relapse.
Patients and Methods
We evaluated 112 patients diagnosed with DLBCL from 2009 to 2016 at Emory Healthcare and classified them as high (n = 44) or low risk (n = 68) for CNS relapse and compared CNS prophylaxis rates and relapse rates between groups. The primary outcome was to compare the CNS relapse rate in high-risk patients who received intrathecal prophylaxis with patients who did not.
Results
Twenty-six patients (14 high-risk and 12 low-risk) received intrathecal prophylaxis. Only 4 of 112 patients experienced a CNS relapse, including 1 in the high-risk group and 3 in the low-risk group. Among 14 high-risk patients who received intrathecal prophylaxis, no patient experienced CNS relapse compared with 1 of 30 high-risk patients without prophylaxis (P = 1.0).
Conclusion
Given the low rates of CNS relapse in this series, it is difficult to discern the impact of current risk stratification combined with intrathecal prophylaxis on outcomes. Our observation that many high-risk patients did not receive prophylaxis, whereas many low-risk patients received prophylaxis emphasizes the need for a standardized approach. 相似文献