Genomics-based Approach and Prognostic Stratification Significance of Gene Mutations in Intermediate-risk Acute Myeloid Leukemia

Objective:

Intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML cases, is highly heterogeneous. We systematically summarize the latest research progress on the significance of gene mutations for prognostic stratification of IR-AML.

Data Sources:

We conducted a systemic search from the PubMed database up to October, 2014 using various search terms and their combinations including IR-AML, gene mutations, mutational analysis, prognosis, risk stratification, next generation sequencing (NGS).

Study Selection:

Clinical or basic research articles on NGS and the prognosis of gene mutations in IR-AML were included.

Results:

The advent of the era of whole-genome sequencing has led to the discovery of an increasing number of molecular genetics aberrations that involved in leukemogenesis, and some of them have been used for prognostic risk stratification. Several studies have consistently identified that some gene mutations have prognostic relevance, however, there are still many controversies for some genes because of lacking sufficient evidence. In addition, tumor cells harbor hundreds of mutated genes and multiple mutations often coexist, therefore, single mutational analysis is not sufficient to make accurate prognostic predictions. The comprehensive analysis of multiple mutations based on sophisticated genomic technologies has raised increasing interest in recent years.

Conclusions:

NGS represents a pioneering and helpful approach to prognostic risk stratification of IR-AML patients. Further large-scale studies for comprehensive molecular analysis are needed to provide guidance and a theoretical basis for IR-AML prognostic stratification and clinical management.     

Oncologic impact of preoperative prognostic nutritional index change in resected pancreatic cancer following neoadjuvant chemotherapy

BackgroundAlthough several studies have focused on the oncologic impact of the preoperative prognostic nutritional index (PNI), there is no study correlating the preoperative PNI changes with the oncologic outcome of resected pancreatic cancer following neoadjuvant chemotherapy (NAC).MethodsWe retrospectively analyzed 107 pancreatic ductal adenocarcinoma patients who underwent NAC followed by surgical resection. ΔPNI was defined as post-NAC PNI subtracted from pre-NAC PNI. Patients were divided into high (≥-1.94, n = 54) and low ΔPNI groups (<-1.94, n = 53). Long-term oncologic outcomes, such as overall survival (OS) and disease-free survival (DFS), were compared. Univariate and multivariate analysis were used to identify independent prognostic factors.ResultsThe high ΔPNI group correlated with lower pre-NAC PNI (46.96 ± 4.68 vs. 51.77 ± 5.63, p < 0.001) and higher post-NAC PNI (50.05 ± 4.80 vs. 42.56 ± 7.44, p < 0.001) more than the low ΔPNI group. The high ΔPNI group was also associated with longer OS compared with the low ΔPNI group (mean OS: 63.97 months [95% CI: 49.95–77.99] vs. 41.16 months [95% CI: 27.66–54.66], p = 0.003); there was no significant difference in DFS (p > 0.05). Multivariate analysis revealed that low ΔPNI was an independent risk factor for OS (HR, 3.516; 95% CI, 1.885–6.558; p < 0.001), but not for DFS (p > 0.05).ConclusionsLow ΔPNI (<-1.94) was an independent risk factor for the overall survival of resected pancreatic cancer patients following NAC. In the preoperative setting, improving the PNI can better the long-term oncologic outcome of this condition.     

Impact of chronic kidney disease definition on assessment of its incidence and risk factors in patients with newly diagnosed type 1 and type 2 diabetes in the UK: A cohort study using primary care data from the United Kingdom

AimTo estimate the incidence and risk factors of chronic kidney disease (CKD) in patients with newly-diagnosed diabetes using different CKD definitions.MethodsUsing UK primary care data, patients with diabetes (type 1, 4691; type 2, 109,365) and no CKD were followed to identify newly-diagnosed CKD, classified by a broad and narrow CKD definition (to capture diabetes-induced CKD, termed diabetic kidney disease, DKD). Adjusted incidence rates of CKD/DKD were calculated, and risk factors identified using Cox regression.ResultsThere were 404 CKD cases and 147 DKD cases among patients with type 1 diabetes (T1D), and 29,104 CKD cases, 9284 DKD cases among patients with type 2 diabetes (T2D). Adjusted incidence rates of CKD per 100 years were 5.4 (T1D) and 5.5 (T2D); for DKD they were 1.9 and 1.5, respectively. Risk factors for CKD/DKD were older age, high social deprivation, obesity, cardiovascular disease, hypertension and smoking. Poor glycaemic control in the year after diabetes diagnosis was a strong predictor of CKD/DKD occurrence beyond this first year, and a risk factor for CKD/DKD in T2D.ConclusionsCKD and DKD remain common in diabetics in the decade after diagnosis. Early prevention of T2D and aggressive treatment of risk factors is urgent.