Association of smoking cessation after atrial fibrillation diagnosis on the risk of cardiovascular disease: a cohort study of South Korean men

While smoking elevates the risk for cardiovascular disease (CVD) among atrial fibrillation (AF) patients, whether smoking cessation after AF diagnosis actually leads to reduced CVD risk is unclear. We aimed to determine the association of smoking cessation after AF diagnosis with subsequent CVD Risk among South Korean men. This retrospective cohort study included 2372 newly diagnosed AF male patients during 2003–2012 from the Korean National Health Insurance Service database. Self-reported smoking status within 2 years before and after diagnosis date were determined, after which the participants were divided into continual smokers, quitters (smokers who quit after AF diagnosis), sustained-ex smokers (those who quit prior to AF diagnosis), and never smokers. Participants were followed up from 2 years after AF diagnosis until 31 December 2015 for CVD. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for CVD according to the change in smoking habits before and after AF diagnosis. The mean (standard deviation, minimum-maximum) age of the study subjects was 62.5 (8.6, 41–89) years. Among AF patients, quitters had 35% reduced risk (aHR 0.65, 95% CI 0.44–0.97) and never smokers had 32% reduced risk (aHR 0.68, 95% CI 0.52–0.90) for CVD compared to continual smokers (p for trend 0.020). Similarly, compared to continual smokers, quitters had 41% risk-reduction (aHR 0.59, 95% CI 0.35–0.99) and never smokers 34% risk-reduction (aHR 0.66, 95% CI 0.46–0.93) for total stroke (p for trend 0.047). Quitters had 50% reduction (aHR 0.50, 95% CI 0.27–0.94), sustained ex-smokers had 36% reduction (aHR 0.64, 95% CI 0.42–0.99), and never smokers had 39% reduction (aHR 0.61, 95% CI 0.41–0.91) in ischemic stroke risk (p for trend 0.047). The risk-reducing effect of quitting on CVD risk tended to be preserved regardless of aspirin or warfarin use. Smoking cessation after AF diagnosis was associated with reduced CVD, total stroke, and ischemic stroke risk

Non-sequential protein structure alignment by conformational space annealing and local refinement.

Protein structure alignment is an important tool for studying evolutionary biology and protein modeling. A tool which intensively searches for the globally optimal non-sequential alignments is rarely found. We propose ALIGN-CSA which shows improvement in scores, such as DALI-score, SP-score, SO-score and TM-score over the benchmark set including 286 cases. We performed benchmarking of existing popular alignment scoring functions, where the dependence of the search algorithm was effectively eliminated by using ALIGN-CSA. For the benchmarking, we set the minimum block size to 4 to prevent much fragmented alignments where the biological relevance of small alignment blocks is hard to interpret. With this condition, globally optimal alignments were searched by ALIGN-CSA using the four scoring functions listed above, and TM-score is found to be the most effective in generating alignments with longer match lengths and smaller RMSD values. However, DALI-score is the most effective in generating alignments similar to the manually curated reference alignments, which implies that DALI-score is more biologically relevant score. Due to the high demand on computational resources of ALIGN-CSA, we also propose a relatively fast local refinement method, which can control the minimum block size and whether to allow the reverse alignment. ALIGN-CSA can be used to obtain much improved alignment at the cost of relatively more extensive computation. For faster alignment, we propose a refinement protocol that improves the score of a given alignment obtained by various external tools. All programs are available from http://lee.kias.re.kr

Exploring the Folding Mechanism of Small Proteins GB1 and LB1

The computational atomistic description of the folding reactions of the B1 domains, GB1 and LB1, of protein G and protein L, respectively, is an important challenge in current protein folding studies. Although the two proteins have overall very similar backbone structures (β-hairpin-α-helix-β-hairpin), their apparent folding behaviors observed experimentally were remarkably different. LB1 folds in a two-state manner with the single-exponential kinetics, whereas GB1 folds in a more complex manner with an early stage intermediate that may exist on the folding pathway. Here, we used a new method of all-atom molecular dynamics simulations to investigate the folding mechanisms of GB1 and LB1. With the Lorentzian energy term derived from the native structure, we successfully observed frequent folding and unfolding events in the simulations at a high temperature (414 K for GB1 or 393 K for LB1) for both the proteins. Three and two transition-state structures were predicted for the GB1 and LB1 folding, respectively, at the high temperature. Two of the three transition-state structures of GB1 have a better formed second β-hairpin. One of the LB1 transition states has a better formed first hairpin, and the other has both hairpins equally formed. The structural features of these transition states are in good agreement with experimental transition-state analysis. At 300 K, more complex folding processes were observed in the simulations for both the proteins. Several intermediate structures were predicted for the two proteins, which led to the conclusion that both the proteins folded through similar mechanisms. However, the intermediate state accumulated in a sufficient amount only in the GB1 folding, which led to the double-exponential feature of its folding kinetics. On the other hand, the LB1 folding kinetics were well fitted by a single-exponential function. These results are fully consistent with those previously observed experimentally

Intravitreal dexamethasone implant therapy for the treatment of cystoid macular Oedema due to hydroxychloroquine retinopathy: a case report and literature review

Abstract Background Cystoid macular oedema (CMO) is an uncommon complication associated with hydroxychloroquine (HCQ) retinopathy threatening central vision. We report a patient with HCQ retinopathy and CMO, for which an intravitreal dexamethasone implant was used, which led to complete resolution of oedema. Case presentation A 57-year-old woman with systemic lupus erythematosus (SLE) complaining of blurred vision in both eyes was diagnosed with bilateral HCQ retinopathy and CMO based on characteristic photoreceptor defects and cystoid spaces on optical coherence tomography, hypo-autofluorescence on fundus autofluorescence, and corresponding visual field defects. After treatment with systemic acetazolamide and topical dorzolamide, CMO showed partial resolution in the right eye. Owing to worsening renal function, an intravitreal dexamethasone implant was placed in the right eye, which resulted in resolution of CMO and visual improvement from 20/50 to 20/30. Conclusion Intravitreal dexamethasone implant may be effective for the treatment of CMO in HCQ retinopathy, particularly for the cases refractory to systemic or topical carbonic anhydrase inhibitors

Association of the presence of allergic disease with subsequent risk of liver cancer in a nationwide retrospective cohort among Koreans

A number of studies have proposed an inverse association between allergic diseases and risk of cancer, but only a few studies have specifically investigated the risk of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the association of allergic diseases with risk of primary liver cancer. We conducted a retrospective cohort study of the Korean National Health Insurance Service database consisted of 405,512 Korean adults ages 40 and above who underwent health screening before January 1st, 2005. All participants were followed up until the date of liver cancer, death, or December 31st, 2013, whichever happened earliest. Those who died before the index date or had pre-diagnosed cancer were excluded from the analyses. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of primary liver cancer according to the presence of allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis. The aHR (95% CI) for overall liver cancer among allergic patients was 0.77 (0.68-0.87) compared to those without allergic disease. Allergic patients had significantly reduced risk of HCC (aHR, 0.72; 95% CI 0.62-0.85) but not ICC (aHR, 0.95; 95% CI 0.73-1.22). The presence of allergies was associated with significantly lower risk of liver cancer among patients whose systolic blood pressure is lower than 140 mmHg (aHR, 0.64; 95% CI 0.62-0.78 for overall liver cancer; aHR, 0.64; 95% CI 0.52-0.78 for HCC) but this effect was not observed among patients whose systolic blood pressure is higher than 140 mmHg (aHR, 0.91; 95% CI 0.71-1.18 for overall liver cancer; aHR, 0.91; 95% CI 0.71-1.18 for HCC) The aHR (95% CI) for overall liver cancer of allergic patients with and without chronic hepatitis virus infection were 0.60 (95% CI 0.44-0.81) and 0.77 (95% CI 0.64-0.93), respectively. In addition, allergic patients without cirrhosis showed significantly lower risk of overall liver cancer (aHR, 0.73; 95% CI 0.63-0.83). Patients with allergic diseases have significantly lower risk of primary liver cancer compared to those without allergic diseases, which supports the rationale for immunotherapy as an effective treatment for liver cancer.N

Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study

(1) Background: The association between proton pump inhibitor (PPI) use and hepatocellular carcinoma (HCC) has been controversial, especially in the general population. We aimed to determine the impact of PPI on HCC risk in participants without liver cirrhosis or chronic hepatitis virus infection. (2) Methods: We assessed 406,057 participants from the Korean National Health Insurance Service database who underwent health screening from 2003 to 2006. We evaluated exposure to PPI before the index date using a standardized daily defined dose (DDD) system. The association of proton pump inhibitor use with the risk of HCC was evaluated using multivariable-adjusted Cox proportional hazards regression. (3) Results: Compared with non-users, PPI use was not associated with the HCC risk in low (<30 DDDs; aHR, 1.07; 95% CI, 0.91–1.27), intermediate (30 ≤ PPI < 60 DDDs; aHR, 0.96; 95% CI, 0.73–1.26), and high (≥60 DDDs; aHR, 0.86; 95% CI, 0.63–1.17) PPI groups in the final adjustment model. In addition, risks of cirrhosis-associated HCC and non-cirrhosis-associated HCC were not significantly associated with PPI use. The results remained consistent after excluding events that occurred within 1, 2, and 3 years to exclude pre-existing conditions that may be associated with the development of HCC. We also found no PPI-associated increase in HCC risk among the selected population, such as those with obesity, older age, and chronic liver diseases. (4) Conclusions: PPI use may not be associated with HCC risk regardless of the amount. We call for future studies conducted in other regions to generalize our findings

Estimating Risk of Cardiovascular Disease Among Long-Term Colorectal Cancer Survivors: A Nationwide Cohort Study

BackgroundConcerns about a growing number of colorectal cancer survivors have emerged regarding cardiovascular disease (CVD) risks. However, there is not yet a predictive tool that can estimate CVD risk and support the management of healthcare as well as disease prevention in terms of CVD risk among long-term colorectal cancer survivors. AimTo develop predictive tools to estimate individualized overall and each subtype of CVD risk using a nationwide cohort in South Korea. Methods and ResultsA total of 4,709 newly diagnosed patients with colorectal cancer who survived at least 5 years in the National Health Insurance System were analyzed. Cox proportional hazard regression was used for the identification of independent risk factors for the derivation of predictive nomograms, which were validated in an independent cohort (n = 3,957). Age, fasting serum glucose, gamma-glutamyl transpeptidase, Charlson comorbidity index, household income, body mass index, history of chemotherapy, cigarette smoking, and alcohol consumption were identified as independent risk factors for either overall CVD or each subtype of CVD subtype. Based on the identified independent risk factors, six independent nomograms for each CVD category were developed. Validation by an independent cohort demonstrated a good calibration with a median C-index of 0.687. According to the nomogram-derived median score, relative risks of 2.643, 1.821, 4.656, 2.629, 4.248, and 5.994 were found for overall CVD, ischemic heart disease, myocardial infarction, total stroke, ischemic stroke, and hemorrhage stroke in the validation cohort. ConclusionsThe predictive tools were developed with satisfactory accuracy. The derived nomograms may support the estimation of overall and individual CVD risk for long-term colorectal cancer survivors.N

Combined Associations of Physical Activity and Particulate Matter With Subsequent Cardiovascular Disease Risk Among 5-Year Cancer Survivors

Background The combined associations of physical activity and particulate matter (PM) with subsequent cardiovascular disease (CVD) risk is yet unclear. Methods and Results The study population consisted of 18 846 cancer survivors who survived for at least 5 years after initial cancer diagnosis from the Korean National Health Insurance Service database. Average PM levels for 4 years were determined in administrative district areas, and moderate-to-vigorous physical activity (MVPA) information was acquired from health examination questionnaires. A multivariable Cox proportional hazards model was used to evaluate the risk for CVD. Among patients with low PM with particles &lt;= 2.5 mu m (PM2.5; (19.8-25.6 mu g/m(3)) exposure, &gt;= 5 times per week of MVPA was associated with lower CVD risk (adjusted hazard ratio [aHR], 0.77; 95% CI, 0.60-0.99) compared with 0 times per week of MVPA. Also, a higher level of MVPA frequency was associated with lower CVD risk (P for trend=0.028) among cancer survivors who were exposed to low PM2.5 levels. In contrast, &gt;= 5 times per week of MVPA among patients with high PM2.5 (25.8-33.8 mu g/m(3)) exposure was not associated with lower CVD risk (aHR, 0.98; 95% CI, 0.79-1.21). Compared with patients with low PM2.5 and MVPA &gt;= 3 times per week, low PM2.5 and MVPA &lt;= 2 times per week (aHR, 1.26; 95% CI, 1.03-1.55), high PM2.5 and MVPA &gt;= 3 times per week (aHR, 1.34; 95% CI, 1.07-1.67), and high PM2.5 and MVPA &lt;= 2 times per week (aHR, 1.38; 95% CI, 1.12-1.70) was associated with higher CVD risk. Conclusions Cancer survivors who engaged in MVPA &gt;= 5 times per week benefited from lower CVD risk upon low PM2.5 exposure. High levels of PM2.5 exposure may attenuate the risk-reducing effects of MVPA on the risk of CVD.N