Background:The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in ...debate.Methods and Results:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m2); moderate CKD (60>eGFR≥30 mL/min/1.73 m2); and severe CKD (eGFR <30 mL/min/1.73 m2). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788–0.841) to 0.831 (0.806–0.857), as well as 0.731 (0.708–0.755) to 0.740 (0.717–0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement NRI 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively.Conclusions:CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.
Background:The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in ...debate.Methods and Results:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m2); moderate CKD (60>eGFR≥30 mL/min/1.73 m2); and severe CKD (eGFR <30 mL/min/1.73 m2). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788–0.841) to 0.831 (0.806–0.857), as well as 0.731 (0.708–0.755) to 0.740 (0.717–0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement NRI 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively.Conclusions:CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.
Purpose
This study was conducted to identify the maximum-tolerated dose (MTD) of fixed-dose-rate gemcitabine (FDR-gem) administered concurrently with S-1 and radical radiation for locally advanced ...pancreatic cancer (LAPC) and to provide efficacy and safety data.
Methods
Patients with unrespectable pancreatic cancer confined to the pancreatic region were treated with FDR-gem (300–400 mg/m
2
, 5 mg/m
2
/min) on days 1, 8, 22, and 29 and 60 mg/m
2
of S-1 orally on days 1–14, 22–35. A total radiation dose of 50.4 Gy (1.8 Gy/day, 28 fractions) was delivered concurrently.
Results
Twenty-five patients were enrolled; all were evaluable for toxicity assessment. In phase I, eight patients were treated in sequential cohorts of three to five patients per dose level. The MTD was reached at level 2, and dose-limiting toxicities were neutropenia and thrombocytopenia. The recommended doses were 300 mg/m
2
of gemcitabine and 60 mg/m
2
of S-1 daily. The overall response rate was 25 % and disease control rate (partial response plus stable disease) was 92 %. The progression-free survival was 11.0 months. The median overall survival and 1-year survival rates were 16.0 months and 73 %, respectively.
Conclusion
The combination of FDR-gem and S-1 with radiation is a feasible regimen that shows favorable antitumor activity with an acceptable safety profile in patients with LAPC.
Abstract
Background
Rectal neuroendocrine tumors (NETs) are the most common of GI NETs, growing in incidence. Though NETs are capable of invasion and metastasis regardless of size, currently there is ...no molecular marker to predict them. Accumulating evidence indicates that miRNAs have been implicated as key regulators of carcinogenesis. Aim: We sought to develop a miRNA-based signature to predict rectal NETs invasion and metastasis using comprehensive miRNA-based analysis and examined its performance. We also analyzed associated mechanisms. Methods: We performed miRNA microarray using small (≤1cm) rectal NETs tissues resected endoscopically to compare lymphovascular invasion (LVI)(+) (n = 7) vs. LVI(-) (n = 7). Candidate miRNAs were assessed by qRT-PCR in an independent cohort (n = 10). We then evaluated the diagnostic performance of the marker by qRT-PCR for the other independent cohort (n = 22). Finally, we examined its metastasis-promoting mechanisms by pathway analysis program and in-vitro experiments using NET cell line H727. Results: Initially, we identified 5 most over-expressed miRNAs in LVI, of which miR-144/451 were successfully validated in an alternative cohort. The miRNA signature (miR-144/451) was able to accurately discriminate LVI patients (AUC=0.75; Sens:80%, Spec:82%). Mechanistically, we revealed miR-144/451 directly targeted PTEN/p19 and validated by immunohistochemistry. Transfection of miR-144/451 mimics into NET cells significantly increased invasion and migration. Similarly, knockdown of PTEN/p19 with siRNAs in NET cells significantly increased them. Conclusion: Using systematic and comprehensive biomarker discovery approach, we have developed and successfully validated the first novel and robust miRNA signature to detect rectal NETs invasion and metastasis and demonstrated the underlying mechanisms for invasion and metastasis. These data highlights great potential for not only the biomarker-guided treatment strategy, but therapeutic targets for rectal NET.
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