ObjectivesRare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their potential impact on the age of disease onset and clinical outcomes, as well as their potential interactions with environmental risk factors, remain unclear. These issues are addressed here in a large Chinese CP cohort.MethodsWe performed targeted next-generation sequencing of the four CP-associated genes in 1061 Han Chinese CP patients and 1196 controls. To evaluate gene–environment interactions, the patients were divided into three subgroups, idiopathic CP (ICP; n = 715), alcoholic CP (ACP; n = 206), and smoking-associated CP (SCP; n = 140). The potential impact of rare pathogenic variants on the age of onset of CP and clinical outcomes was evaluated using the Kaplan–Meier model.ResultsWe identified rare pathogenic genotypes involving the SPINK1, PRSS1, CTRC, and/or CFTR genes in 535 (50.42%) CP patients but in only 71 (5.94%) controls (odds ratio = 16.12; P < 0.001). Mutation-positive patients had significantly earlier median ages at disease onset and at diagnosis of pancreatic stones, diabetes mellitus and steatorrhea than mutation-negative ICP patients. Pathogenic genotypes were present in 57.1, 39.8, and 32.1% of the ICP, ACP, and SCP patients, respectively, and influenced age at disease onset and clinical outcomes in all subgroups.ConclusionsWe provide evidence that rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes significantly influence the age of onset and clinical outcomes of CP. Extensive gene–environment interactions were also identified.
The aim of this study was to investigate the relationship between the tumor uptake of 16a-18 F-fluoro-17b-estradiol ( 18 F-FES) and 18 F-FDG using PET and expressions of sex hormone receptors, such as estrogen receptor (ER), as well as glucose transporter 1 (GLUT-1) and Ki-67 analyzed by the immunohistochemistry method in mesenchymal uterine tumors. Methods: Forty-seven patients with mesenchymal uterine tumors were studied with 18 F-FES and 18 F-FDG PET. Postoperative pathologic diagnosis revealed 33 uterine leiomyomas and 14 uterine sarcomas. Tissue samples were assayed for expression of ERa, ERb, progesterone receptor (PR), PR-B, GLUT-1, and Ki-67 by an immunohistochemistry method. Standardized uptake values (SUVs) for 18 F-FES and 18 F-FDG were compared with the semiquantitative immunoreactive score (0-12) and quantitative labeling index (LI) for Ki-67 in immunohistochemistry. Results: 18 F-FES uptake was significantly lower (P , 0.001) and the 18 F-FDG uptake and SUV ratio of 18 F-FDG to 18 F-FES ( 18 F-FDG/ 18 F-FES ratio) (P , 0.005 and P , 0.001, respectively) were significantly higher in uterine sarcomas than in leiomyomas. Immunohistochemistry analysis showed significantly higher expressions of ERa, PR, and PR-B in uterine leiomyomas than in sarcomas. The Ki-67 LI was significantly greater in uterine sarcomas than in leiomyomas. Correlation analysis for all tumors showed positive correlations between 18 F-FES SUV and immunohistochemistry scores of ERa, PR (P , 0.001), and PR-B (P , 0.005) as well as between 18 F-FDG SUV and GLUT-1 and Ki-67 (P , 0.001). However, the 18 F-FDG/ 18 F-FES ratio showed significantly negative correlations with ERa, PR (P , 0.001), and PR-B (P , 0.005) and a positive correlation with Ki-67 LI (P , 0.001). In uterine sarcomas, ERa and 18 F-FES SUV showed a positive correlation (P , 0.001) in a low SUV range, and the 18 F-FDG/ 18 F-FES ratio showed positive correlations with ERb and GLUT-1 expression (P , 0.005). Conclusion: 18 F-FES and 18 F-FDG PET showed correlations between tracer uptake and expressions of sex hormone receptors, GLUT-1, and Ki-67 in mesenchymal uterine tumors. The 18 F-FDG/ 18 F-FES ratio was correlated with Ki-67, GLUT-1, and ERb in uterine sarcoma. Functional PET imaging and PET parameters would be useful noninvasive biomarkers for the assessment of tumor hormone receptor expression, glucose metabolism, and proliferation and for differential diagnosis of uterine leiomyoma and sarcoma.
Studies have shown inflammation is involved in the development of acute aortic dissection (AAD). The hypothesis that white blood cell count (WBCc) on admission may have an impact on the short- and long-term outcomes of type A AAD was tested in a large-scale, prospective observational cohort study.From 2008 to 2010, a total of 570 consecutive patients with type A AAD in Fuwai hospital were enrolled and were followed up. Baseline characteristics and WBCc on admission were collected. The primary outcomes were 30-day and long-term all-cause mortality.During a median of 1.89 years of follow-up, the 30-day and long-term all-cause mortality were 10.7% and 6.5%, respectively. Univariate Cox regression analysis identified admission WBCc as an independent predictor of 30-day mortality when considered as a continuous variable or as a categorical variable using the cutoff of 11.0 × 109 cells/L (all P < 0.05). After adjustment for age, sex, C-reactive protein, d-dimer, and surgical intervention, elevated admission WBCc (>11.0 × 109 cells/L) remained an independent predictor of 30-day mortality of AAD (hazard ratio = 3.31, 95% confidence interval 1.38–7.93, P = 0.007). No impact of admission WBCc was observed on the long-term all-cause mortality.In conclusion, elevated admission WBCc may be valuable as a predictor of 30-day mortality, and may be useful in the risk stratification of type A AAD during hospitalization.
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