Sugar-Sweetened Beverage Intake and Cancer Recurrence and Survival in CALGB 89803 (Alliance)

Background: In colon cancer patients, obesity, sedentary lifestyle, and high dietary glycemic load have been associated with increased risk of cancer recurrence. High sugar-sweetened beverage intake has been associated with obesity, diabetes, and cardio-metabolic diseases, but the influence on colon cancer survival is unknown. Methods: We assessed the association between sugar-sweetened beverage consumption on cancer recurrence and mortality in 1,011 stage III colon cancer patients who completed food frequency questionnaires as part of a U.S. National Cancer Institute-sponsored adjuvant chemotherapy trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazard models. Results: Patients consuming ≥2 servings of sugar-sweetened beverages per day experienced an adjusted HR for disease recurrence or mortality of 1.67 (95% CI, 1.04–2.68), compared with those consuming <2 servings per month (Ptrend = 0.02). The association of sugar-sweetened beverages on cancer recurrence or mortality appeared greater among patients who were both overweight (body mass index ≥25 kg/m2) and less physically active (metabolic equivalent task-hours per week <18) (HR = 2.22; 95% CI, 1.29–3.81, Ptrend = 0.0025). Conclusion: Higher sugar-sweetened beverage intake was associated with a significantly increased risk of cancer recurrence and mortality in stage III colon cancer patients

KRAS Mutation in Stage III Colon Cancer and Clinical Outcome Following Intergroup Trial CALGB 89803

Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts resistance to anti-EGFR targeted therapy (cetuximab or panitumumab). However, it remains uncertain whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy

Predictive and Prognostic Roles of BRAF Mutation in Stage III Colon Cancer: Results from Intergroup Trial CALGB 89803

Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers in colon and rectal carcinogenesis. In colorectal cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer

Relationship Between Statin Use and Colon Cancer Recurrence and Survival: Results From CALGB 89803

Although preclinical and epidemiological data suggest that statins may have antineoplastic properties, the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown

In Situ NMR Spectroscopy of Supercapacitors: Insight into the Charge Storage Mechanism

Electrochemical capacitors, commonly known as supercapacitors, are important energy storage devices with high power capabilities and long cycle lives. Here we report the development and application of in situ nuclear magnetic resonance(NMR) methodologies to study changes at the electrode−electrolyte interface in working devices as they charge and discharge. For a supercapacitor comprising activated carbon electrodes and an organic electrolyte, NMR experiments carried out at different charge states allow quantification of the number of charge storing species and show that there are at least two distinct charge storage regimes. At cell voltages below 0.75 V, electrolyte anions are increasingly desorbed from the carbon micropores at the negative electrode, while at the positive electrode there is little change in the number of anions that are adsorbed as the voltage is increased. However, above a cell voltage of 0.75 V, dramatic increases in the amount of adsorbed anions in the positive electrode are observed while anions continue to be desorbed at the negative electrode. NMR experiments with simultaneous cyclic voltammetry show that supercapacitor charging causes marked changes to the local environments of charge storing species, with periodic changes of their chemical shift observed. NMR calculations on a model carbon fragment show that the addition and removal of electrons from a delocalized system should lead to considerable increases in the nucleus-independent chemical shift of nearby species, in agreement with our experimental observations

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council