Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation,Stemness, and BrafV600E-Induced Tumorigenesis

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Comparison of normal saline versus Lactated Ringer's solution for fluid resuscitation in patients with mild acute pancreatitis,A randomized controlled trial

Background/Objectives

Aggressive fluid resuscitation is recommended for initial management of acute pancreatitis. However, there are few studies which focus on types of fluid therapy.

Prognostic importance of DNA repair gene polymorphisms of <Emphasis Type="Italic">XRCC1</Emphasis> Arg399Gln and <Emphasis Type="Italic">XPD</Emphasis> Lys751Gln in lung cancer patients from India

Purpose Inter individual variation in lung cancer susceptibility may be modulated in part through genetic polymorphisms in the DNA repair genes, especially the genes involved in the Base Excision Repair (BER) and nucleotide excision repair (NER) pathway. Two of the genetic polymorphisms, XRCC1Arg399Gln and XPD Lys751Gln have been extensively studied in the association with lung cancer risk, although published studies have been inconclusive. Methods In order to verify the role of the common variant alleles in the XPD gene, we have genotyped 211 lung cancer patients and 211 healthy controls using PCR-RFLP assays in a hospital based, case-control study in an Indian population. Logistic regression models were fit to examine the relationship between the log odds of lung cancer and each covariate. Overall Survival in relation to various genotypes and clinicopathological factors were analyzed using Kaplan Meier estimates and hazard ratios were calculated using Cox Regression analysis. Results The carriers of XRCC1 399 AA genotypes were at higher risk of lung cancer (OR = 2.1, 95% CI:1.224–3.669, P = 0.007) than carriers of GG genotype. Subjects carrying 751 AC genotype were at an increased risk of carcinoma of the lung (OR = 1.8; 95% CI:1.233–2.807, P = 0.003) than subjects with AA genotypes. Compared to the XRCC1 399 GG/ XPD 751 AA reference genotype, the combined variants, XRCC1 399 GG/ XPD 751 AC+CC (OR = 1.9, 95% CI: 1.037–3.481), P = 0.03), XRCC1 399 GA+AA/ XPD 751 AA (OR = 1.7, 95% CI: 1.020–2.833, P = 0.04), XRCC1 399 GA+AA/XPD 751 AC+CC (OR = 2.7, 95% CI: 1.582–4.864, P = 0.01), had significantly higher odds ratios. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival, the risk being significant for the XRCC1 gene polymorphism (P = 0.01 by log-rank test). The hazard of dying was significant for the XRCC1 399 AA genotype (HR = 3.04, 95%CI: 1.393–6.670, P = 0.005). Higher tumour stage also came out as significant predictors of patient death. Conclusions These findings suggest that genetic polymorphisms in the DNA repair genes may modulate overall lung cancer susceptibility and that pathological stage and XRCC1 Arg399Gln independently predicted overall survival among Indian lung cancer patients.     

Postoperative atrial fibrillation and mortality after coronary artery bypass surgery

OBJECTIVES: We sought to determine if the occurrence of postoperative atrial fibrillation (AF) affects early or late mortality following coronary artery bypass surgery (CABG). BACKGROUND: Atrial fibrillation is the most common arrhythmia seen following CABG. METHODS: The Texas Heart Institute Cardiovascular Research Database was used to identify all patients that developed AF after isolated initial CABG from January 1993 to December 1999 (n = 994). This population was compared with patients who underwent CABG during the same period but did not develop AF (n = 5,481). In-hospital end points were adjusted using logistic regression models to account for baseline differences. Long-term survival was evaluated using a retrospective cohort design, where Cox proportional hazards methods were used to adjust for baseline differences, and with case-matched populations (n = 390, 195 per arm). RESULTS: Atrial fibrillation was diagnosed in 16% of the population. Postoperative AF was associated with greater in-hospital mortality (odds ratio [OR] 1.7, p = 0.0001), more strokes (OR 2.02, p = 0.001), prolonged hospital stays (14 vs. 10 days, p < 0.0001), and a reduced incidence of myocardial infarction (OR 0.62, p = 0.01). At four to five years, survival was worse in patients who developed postoperative AF (74% vs. 87%, p < 0.0001 in the retrospective cohort; 80% vs. 93%, p = 0.003 in the case-matched population). On multivariate analysis, postoperative AF was an independent predictor of long-term mortality (adjusted OR 1.5, p < 0.001 in the retrospective cohort; OR 3.4, p = 0.0018 in the case-matched population). CONCLUSIONS: The occurrence of AF following CABG identifies a subset of patients who have a reduced survival probability following CABG. The impact of various strategies, such as antiarrhythmics and warfarin, aimed at reducing AF and its complications deserves further study.     

Mechanism of recurrence after radiofrequency catheter ablation of atrial fibrillation guided by complex fractionated atrial electrograms

Background A better understanding of the mechanisms of recurrent atrial fibrillation (AF) after radiofrequency ablation of complex, fractionated atrial electrograms (CFAEs) may be helpful for refining AF ablation strategies. Methods and results Electrogram-guided ablation (EGA) was repeated in 30 consecutive patients (mean age = 59 ± 8 years) for recurrent paroxysmal AF, 10 ± 4 months after the first ablation. During the first procedure, CFAEs were targeted without isolating all pulmonary veins (PVs). During repeat ablation, all PVs and the superior vena cava (SVC) were mapped with a circular catheter and the left atrium was mapped for CFAEs. EGA was performed until AF was rendered noninducible or all identified CFAEs were eliminated. During repeat ablation, ≥1 PV tachycardia was found in 83 PVs in 29 of the 30 patients (97%). Among these 83 PVs, 63 (76%) had not been completely isolated previously. During repeat ablation, drivers originating in a PV or PV antrum were identified only after infusion of isoproterenol (20 μg/min) in 12 patients (40%). At 9 ± 4 months of follow-up after the repeat ablation procedure, 21 of the 30 patients (70%) were free from recurrent AF and flutter without antiarrhythmic drugs. Conclusions Recurrence of AF after EGA is usually due to PV tachycardias. Therefore, it may be preferable to systematically map and isolate all PVs during the first procedure. High-dose isoproterenol may be helpful to identify AF drivers.     

The dietary inflammatory index,obesity, type 2 diabetes,and cardiovascular risk factors and diseases

An unhealthy diet is a recognized risk factor in the pathophysiology of numerous chronic noncommunicable diseases (NCD), including obesity, type 2 diabetes (T2DM), and cardiovascular diseases (CVD). This is, at least in part, due to unhealthy diets causing chronic low-grade inflammation in the gut and systemically. To characterize the inflammatory potential of diet, we developed the Dietary Inflammatory Index (DII®). Following this development, around 500 papers have been published, which examined the association between the DII, energy-adjusted DII (E-DII?), and the children's DII (C-DII?) and many chronic NCDs including obesity and cardiometabolic diseases. Although a previous narrative review published in 2019 briefly summarized the evidence in this area, there was a significant increase in papers on this topic since 2020. Therefore, the purpose of this narrative review is to provide an in-depth updated review by including all papers until July 2021 on DII and its relationship with obesity, T2DM, and CVD. Furthermore, we aim to identify potential gaps in the literature and provide future directions for research. Most studies found that DII was associated with an increased risk of obesity, T2DM, and CVD with some relationships being sex-specific. However, we identified the paucity of papers describing associations between dietary inflammation and T2DM and its risk factors. Few studies used gold-standard measures of cardiometabolic risk factors. We also identified the lack of interventional studies designed to change the inflammatory potential of diets and study its effect on cardiometabolic risk factors and diseases. We recommend that such interventional studies are needed to assess if changes in DII, representing the inflammatory potential of diet, independently of changes in body composition can modulate cardiometabolic risk factors and diseases.