Risk of inflammatory bowel disease in patients with chronic obstructive pulmonary disease: A nationwide, population-based study

BACKGROUND There is a growing evidence regarding an increased risk of inflammatory bowel disease(IBD)among patients with airway diseases.AIM To investigate the influence of chronic obstructive pulmonary disease(COPD)on the risk of IBD.METHODS A nationwide,population-based study was conducted using data from the National Health Insurance Service database.A total of 1303021 patients with COPD and 6515105 non-COPD controls were identified.The COPD group was divided into the severe and the mild COPD group according to diagnostic criteria.The risk of IBD in patients with COPD compared to controls was analyzed by Cox proportional hazard regression models.The cumulative incidences of IBD were compared between the groups.RESULTS The COPD group had higher incidences of IBD compared to non-COPD controls(incidence rate,9.98 vs 7.18 per 100000 person-years,P<0.001).The risk of IBD in the COPD group was increased by 1.38(adjusted hazard ratio(HR);95%CI:1.25-1.52).The incidence rate of IBD was higher in the severe COPD group than in the mild COPD group(12.39 vs 9.77 per 100000 person-year,P<0.001).The severity of COPD was associated with an increased risk of IBD(adjusted HR 1.70 in severe COPD,95%CI:1.27-2.21 and adjusted HR 1.35 in mild COPD,95%CI:1.22-1.49)CONCLUSION The incidences of IBD were significantly increased in COPD patients in South Korea and the risk of developing IBD also increased as the severity of COPD increased.

Increased end-stage renal disease risk in patients with inflammatory bowel disease:A nationwide populationbased study

AIM To estimate the risk of end-stage renal disease(ESRD)in patients with inflammatory bowel disease(IBD).METHODS From January 2010 to December 2013, patients with Crohn's disease(CD) and ulcerative colitis(UC) were identified, based on both the International Classification of Diseases, 10 th revision(ICD-10) and the rare,intractable disease registration program codes from the National Health Insurance(NHI) database in South Korea. We compared 38812 patients with IBD to ageand sex-matched non-IBD controls with a ratio of 1:3.Patients newly diagnosed with ESRD were identified with the ICD-10 code.RESULTS During a mean follow-up of 4.9 years, ESRD was detected in 79(0.2%) patients with IBD and 166(0.1%)controls. The incidence of ESRD in patients with IBD was0.42 per 1000 person-years. Patients with IBD had a significantly higher risk of ESRD than controls [adjusted hazard ratio(HR) = 3.03; 95% confidence interval(CI):1.77-5.20; P < 0.001]. The incidences(per 1000 personyears)of ESRD were 0.51 in patients with CD and 0.13 in controls, respectively(adjusted HR = 6.33; 95%CI:2.75-14.56; P < 0.001). In contrast, the incidence of ESRD was similar between the UC and control groups(0.37 vs 0.37 per 1000 person-years; adjusted HR = 2.01;95%CI: 0.90-4.51; P = 0.089).CONCLUSION The risk of ESRD was elevated in patients with CD, but not UC. Patients with CD should be monitored carefully for signs of renal insufficiency.

Inverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serology

BACKGROUND Helicobacter pylori(H.pylori)infection is known to prevent the occurrence of gastroesophageal reflux disease(GERD)by inducing gastric mucosal atrophy.However,little is known about the relationship between atrophic gastritis(AG)and GERD.AIM To confirm the inverse correlation between AG and the occurrence and severity of GERD.METHODS Individuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included.The grade of reflux esophagitis was evaluated according to the Los Angeles classification.Endoscopic AG(EAG)was categorized into six grades.Serologic AG(SAG)was defined as pepsinogen I≤70 ng/m L and pepsinogen I/II ratio≤3.0.The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis.RESULTS In total,4684 individuals with GERD were compared with 21901 healthy controls.In multivariate logistic regression analysis,advanced age,male sex,body mass index>23 kg/m2,presence of metabolic syndrome,current smoking,and alcohol consumption were associated with an increased risk of GERD.Seropositivity for H.pylori immunoglobulin G antibodies was associated with a decreased risk of GERD.There was an inverse correlation between the extent of EAG and occurrence of GERD:Odds ratio(OR),1.01[95%confidence interval(CI):0.90-1.14]in C1,0.87(0.78-0.97)in C2,0.71(0.62-0.80)in C3,0.52(0.44-0.61)in O1,0.37(0.29-0.48)in O2,and 0.28(0.18-0.43)in O3.Additionally,the extent of EAG showed an inverse correlation with the severity of GERD.The presence of SAG was correlated with a reduced risk of GERD(OR=0.49,95%CI:0.28-0.87,P=0.014).CONCLUSION The extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD.AG followed by H.pylori infection may be independently protect against GERD.

Periodontitis combined with smoking increases risk of the ulcerative colitis: A national cohort study

BACKGROUND Periodontitis is a chronic inflammation of periodontal tissues.The effect of periodontitis on the development of inflammatory bowel disease(IBD)remains unclear.AIM To assessed the risk of IBD among patients with periodontitis,and the risk factors for IBD related to periodontitis.METHODS A nationwide population-based cohort study was performed using claims data from the Korean National Healthcare Insurance Service.In total,9950548 individuals aged≥20 years who underwent national health screening in 2009 were included.Newly diagnosed IBD[Crohn’s disease(CD),ulcerative colitis(UC)]using the International Classification of Disease 10th revision and rare intractable disease codes,was compared between the periodontitis and nonperiodontitis groups until 2017.RESULTS A total of 1092825 individuals(11.0%)had periodontitis.Periodontitis was significantly associated with older age,male gender,higher body mass index,quitting smoking,not drinking alcohol,and regular exercise.The mean age was 51.4±12.9 years in the periodontitis group and 46.6±14.2 years in the nonperiodontitis group(P<0.01),respectively.The mean body mass index was 23.9±3.1 and 23.7±3.2 in the periodontitis and non-periodontitis groups,respectively(P<0.01).Men were 604307(55.3%)and 4844383(54.7%)in the periodontitis and non-periodontitis groups,respectively.The mean follow-up duration was 7.26 years.Individuals with periodontitis had a significantly higher risk of UC than those without periodontitis[adjusted hazard ratio:1.091;95%confidence interval(CI):1.008-1.182],but not CD(adjusted hazard ratio:0.879;95%confidence interval:0.731-1.057).The risks for UC were significant in the subgroups of age≥65 years,male gender,alcohol drinker,current smoker,and reduced physical activity.Current smokers aged≥65 years with periodontitis were at a 1.9-fold increased risk of UC than non-smokers aged≥65 years without periodontitis.CONCLUSION Periodontitis was significantly associated with the risk of developing UC,but not CD,particularly in current smokers aged≥65 years.

Trends and risk factors of elderly-onset Crohn’s disease: A nationwide cohort study

BACKGROUND The incidence of inflammatory bowel disease(IBD)is increasing in Asia.Numerous risk factors associated with IBD development have been investigated.AIM To investigate trends and environmental risk factors of Crohn’s disease(CD)diagnosed in persons aged≥40 years in South Korea.METHODS Using the National Health Insurance Service database,a total of 14060821 persons aged>40 years who underwent national health screening in 2009 were followed up until December 2017.Patients with newly diagnosed CD were enrolled and compared with non-CD cohort.CD was identified according to the International Classification of Diseases 10th revision and the rare/intractable disease registration program codes from the National Health Insurance Service database.The mean follow-up periods was 7.39 years.Age,sex,diabetes,hypertension,smoking,alcohol consumption,regular exercise,body mass index,anemia,chronic kidney disease(CKD)and dyslipidemia were adjusted for in the multivariate analysis model.RESULTS During the follow-up,1337(1.33/100000)patients developed CD.Men in the middle-aged group(40-64 years)had a higher risk than women[adjusted hazard ratio(aHR)1.46,95%confidence interval(CI):1.29-1.66];however,this difference tended to disappear as the age of onset increases.In the middle-aged group,patients with a history of smoking[(aHR 1.46,95%CI:1.19-1.79)and anemia(aHR 1.85,95%CI:1.55-2.20)]had a significantly higher CD risk.In the elderly group(age,≥65 years),ex-smoking and anemia also increased the CD risk(aHR 1.68,95%CI:1.22-2.30)and 1.84(95%CI:1.47-2.30,respectively).Especially in the middle-aged group,those with CKD had a statistically elevated CD risk(aHR 1.37,95%CI:1.05-1.79).Alcohol consumption and higher body mass index showed negative association trend with CD incidence in both of the age groups.[Middle-aged:aHR 0.77(95%CI:0.66-0.89)and aHR 0.73(95% CI:0.63-0.84),respectively][Elderly-group:aHR 0.57(95% CI:0.42-0.78)and aHR 0.84(95%CI 0.67-1.04),respectively].For regular physical activity and dyslipidemia,negative correlation between CD incidences was proved only in the middle-aged group[aHR 0.88(95%CI:0.77-0.89)and aHR 0.81(95%CI:0.68-0.96),respectively].CONCLUSION History of cigarette smoking,anemia,underweight and CKD are possible risk factors for CD in Asians aged>40 years.

Ternary layered double hydroxide oxygen evolution reaction electrocatalyst for anion exchange membrane alkaline seawater electrolysis

Anion exchange membrane(AEM)water electrolyzers are promising energy devices for the production of clean hydrogen from seawater.However,the lack of active and robust electrocatalysts for the oxygen evolution reaction(OER)severely impedes the development of this technology.In this study,a ternary layered double hydroxide(LDH)OER electrocatalyst(NiFeCo-LDH)is developed for high-performance AEM alkaline seawater electrolyzers.The AEM alkaline seawater electrolyzer catalyzed by the NiFeCo LDH shows high seawater electrolysis performance(0.84 A/cm^(2)at 1.7 Vcell)and high hydrogen production efficiency(77.6%at 0.5 A/cm^(2)),thus outperforming an electrolyzer catalyzed by a benchmark IrO_(2)electrocatalyst.The NiFeCo-LDH electrocatalyst greatly improves the kinetics of the AEM alkaline seawater electrolyzer,consequently reducing its activation loss and leading to high performance.Based on the results,this NiFeCo-LDH-catalyzed AEM alkaline seawater electrolyzer can likely surpass the energy conversion targets of the US Department of Energy.

Deep Learning in DXA Image Segmentation

Many existing techniques to acquire dual-energy X-ray absorptiometry(DXA)images are unable to accurately distinguish between bone and soft tissue.For the most part,this failure stems from bone shape variability,noise and low contrast in DXA images,inconsistent X-ray beam penetration producing shadowing effects,and person-to-person variations.This work explores the feasibility of using state-of-the-art deep learning semantic segmentation models,fully convolutional networks(FCNs),SegNet,and U-Net to distinguish femur bone from soft tissue.We investigated the performance of deep learning algorithms with reference to some of our previously applied conventional image segmentation techniques(i.e.,a decision-tree-based method using a pixel label decision tree[PLDT]and another method using Otsu’s thresholding)for femur DXA images,and we measured accuracy based on the average Jaccard index,sensitivity,and specificity.Deep learning models using SegNet,U-Net,and an FCN achieved average segmentation accuracies of 95.8%,95.1%,and 97.6%,respectively,compared to PLDT(91.4%)and Otsu’s thresholding(72.6%).Thus we conclude that an FCN outperforms other deep learning and conventional techniques when segmenting femur bone from soft tissue in DXA images.Accurate femur segmentation improves bone mineral density computation,which in turn enhances the diagnosing of osteoporosis.

Midazolam dose is associated with recurrence of paradoxical reactions during endoscopy

BACKGROUND Midazolam is commonly used for sedation during gastrointestinal procedures.However,some patients experience paradoxical reactions characterized by excessive movement or excitement.AIM To investigate the rate of recurrence of paradoxical reactions to midazolam during an upper endoscopy.METHODS We retrospectively reviewed 122152 sedative endoscopies among a total of 58553 patients at the Seoul National University Hospital,Healthcare System Gangnam Center,from July 2013 to December 2018.Among them,361 patients with a history of paradoxical reaction during sedative upper endoscopy were enrolled.The characteristics of patients in the recurrent and non-recurrent groups were compared via multivariable analysis using logistic regression.RESULTS Paradoxical reactions occurred in 0.86%(1054/122152)of endoscopies,and in 1.51%(888/58553)of patients.Among the 361 subjects with previous paradoxical reactions in sedative endoscopies,111(30.7%)experienced further paradoxical reactions.Univariable analysis revealed that the total midazolam dose used was higher in the recurrent group(6.74±2.58 mg)than in the non-recurrent group(5.49±2.04 mg;P<0.0001).Patients were administered a lower dose of midazolam than previous doses:1 mg less in the recurrent group and 2 mg less in the non-recurrent group.Multivariable analysis showed that the midazolam dose difference was an independent risk factor for recurrent paradoxical reaction(odds ratio:1.213,95%CI:1.099-1.338,P=0.0001).CONCLUSION The rate of recurrence of paradoxical reactions is significantly associated with midazolam dosage.The dose of midazolam administered to patients with previous paradoxical reactions should be less than that previously used.

In-situ formation of MOF derived mesoporous Co3N/amorphous N-doped carbon nanocubes as an efficient electrocatalytic oxygen evolution reaction

The suitable materials,metal nitrides,are a promising class of electrocatalyst materials for a highly efficient oxygen evolution reaction (OER) because they exhibit superior intrinsic conductivity and have higher sustainability than oxide-based materials.To our knowledge,for the first time,we report a designable synthesis of three-dimensional (3D) and mesoporous Co3N@ amorphous N-doped carbon (AN-C) nanocubes (NCs) with well-controlled open-framework structures via monodispersed Co3[Co(CN)6]2 Prussian blue analogue (PBA) NC precursors using in situ nitridation and calcination processes.Co3N@AN-C NCs (2 h) demonstrate better OER activity with a remarkably low Tafel plot (69.6 mV-dec-1),low overpotential of 280 mV at a current density of 10 mA-crrf2.Additionally,excellent cycling stability in alkaline electrolytes was exhibited without morphological changes and voltage elevations,superior to most reported hierarchical structures of transition-metal nitride particles.The presented strategy for synergy effects of metal-organic frameworks (MOFs)-derived transition-metal nitrides-carbon hybrid nanostructures provides prospects for developing high-performance and advanced electrocatalyst materials.

Snail acetylation by autophagy-derived acetyl-coenzyme A promotes invasion and metastasis of KRAS-LKB1 co-mutated lung cancer cells

Background: Autophagy is elevated in metastatic tumors and is often associatedwith active epithelial-to-mesenchymal transition (EMT). However, the extent towhich EMT is dependent on autophagy is largely unknown. This study aimed toidentify the mechanisms by which autophagy facilitates EMT.Methods: We employed a liquid chromatography-based metabolomic approachwith kirsten rat sarcoma viral oncogene (KRAS) and liver kinase B1 (LKB1)gene co-mutated (KL) cells that represent an autophagy/EMT-coactivatedinvasive lung cancer subtype for the identification of metabolites linked to autophagy-driven EMT activation. Molecular mechanisms of autophagy-drivenEMT activation were further investigated by quantitative real-time polymerasechain reaction (qRT-PCR), Western blotting analysis, immunoprecipitation,immunofluorescence staining, and metabolite assays. The effects of chemicaland genetic perturbations on autophagic flux were assessed by two orthogonalapproaches: microtubule-associated protein 1A/1B-light chain 3 (LC3) turnoveranalysis by Western blotting and monomeric red fluorescent protein-greenfluorescent protein (mRFP-GFP)-LC3 tandem fluorescent protein quenchingassay. Transcription factor EB (TFEB) activity was measured by coordinatedlysosomal expression and regulation (CLEAR) motif-driven luciferase reporterassay. Experimental metastasis (tail vein injection) mouse models were used toevaluate the impact of calcium/calmodulin-dependent protein kinase kinase 2(CAMKK2) or ATP citrate lyase (ACLY) inhibitors on lung metastasis using IVISluciferase imaging system.Results: We found that autophagy in KL cancer cells increased acetyl-coenzymeA (acetyl-CoA), which facilitated the acetylation and stabilization of theEMT-inducing transcription factor Snail. The autophagy/acetyl-CoA/acetylSnail axis was further validated in tumor tissues and in autophagy-activatedpancreatic cancer cells. TFEB acetylation in KL cancer cells sustained prometastatic autophagy in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner. Pharmacological inhibition of this axis via CAMKK2inhibitors or ACLY inhibitors consistently reduced the metastatic capacity of KLcancer cells in vivo.Conclusions: This study demonstrates that autophagy-derived acetyl-CoA promotes Snail acetylation and thereby facilitates invasion and metastasis of KRASLKB1 co-mutated lung cancer cells and that inhibition of the autophagy/acetylCoA/acetyl-Snail axis using CAMKK2 or ACLY inhibitors could be a potentialtherapeutic strategy to suppress metastasis of KL lung cancer.