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Hai-Sheng You,1,* Chun-Xia Gao,1,* Hai-Bin Wang,2 Sai-Sai Luo,1 Si-Ying Chen,1 Ya-Lin Dong,1 Jun Lyu,3 Tao Tian4 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Hangzhou Cognitive N&T. Co., Ltd, Hangzhou, Zhengjiang, People’s Republic of China; 3Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao TianDepartment of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86-13572206784Fax +86-29-85324086Email tiantao0607@163.comJun LyuClinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86 29 8532 3614Fax +86 29 8532 3473Email lujun2006@xjtu.edu.cnObjective: The disease complexity of metastatic non-small-cell lung cancer (mNSCLC) makes it difficult for physicians to make clinical decisions efficiently and accurately. The Watson for Oncology (WFO) system of artificial intelligence might help physicians by providing fast and precise treatment regimens. This study measured the concordance of the medical treatment regimens of the WFO system and actual clinical regimens, with the aim of determining the suitability of WFO recommendations for Chinese patients with mNSCLC.Methods: Retrospective data of mNSCLC patients were input to the WFO, which generated a treatment regimen (WFO regimen). The actual regimen was made by physicians in a medical team for patients (medical-team regimen). The factors influencing the consistency of the two treatment options were analyzed by univariate and multivariate analyses.Results: The concordance rate was 85.16% between the WFO and medical-team regimens for mNSCLC patients. Logistic regression showed that the concordance differed significantly for various pathological types and gene mutations in two treatment regimens. Patients with adenocarcinoma had a lower rate of “recommended” regimen than those with squamous cell carcinoma. There was a statistically significant difference in EGFR-mutant patients for “not recommended” regimens with inconsistency rate of 18.75%. In conclusion, the WFO regimen has 85.16% consistency rate with medical-team regimen in our treatment center. The different pathological type and different gene mutation markedly influenced the agreement rate of the two treatment regimens.Conclusion: WFO recommendations have high applicability to mNSCLC patients in our hospital. This study demonstrates that the valuable WFO system may assist the doctors better to determine the accurate and effective treatment regimens for mNSCLC patients in the Chinese medical setting.Keywords: metastatic non-small-cell lung cancer, Watson for Oncology, concordance, artificial intelligence, treatment recommendations

Lina Tang,1,* Chunling Zhang,2,* Hairong He,3 Zhenyu Pan,3,4 Di Fan,1 Yinli He,1 Haisheng You,1 Yuanjie Li5 1Department of Pharmacy, The First Affiliated Hospital, Xi’an Jiao Tong University, Xi’an, China; 2Department of Pharmacy, Hong-Hui Hospital, Xi’an Jiao Tong University College of Medicine, Xi’an, China; 3Clinical Research Center, The First Affiliated Hospital, Xi’an Jiao Tong University, Xi’an, China; 4Department of Pharmacy, Xi’an Jiao Tong University Affiliated Children’s Hospital, Xi’an, China; 5Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiao Tong University Health Science Center, Xi’an, China *These authors contributed equally to this work Background: Gefitinib is frequently used to treat patients with non-small cell lung cancer (NSCLC) and is excreted out from cells via the ATP-binding cassette transporter ABCG2. ABCG2 gene polymorphisms have been suggested to be associated with ABCG2 protein expression and function and may influence the risk of gefitinib toxicity in NSCLC patients. Previous studies on the associations between ABCG2 gene polymorphisms and the toxicity of gefitinib in NSCLC patients have produced conflicting results. The aim of this meta-analysis was to determine whether ABCG2 gene polymorphisms are associated with the risk of gefitinib-induced toxicity in NSCLC patients.Methods: The PubMed and EMBASE databases were searched systematically for all eligible studies. A relative risk with corresponding 95% CI was calculated to evaluate the associations between ABCG2 gene polymorphisms and gefitinib-induced toxicity.Results: Data were finally extracted from seven studies and 515 patients were found to meet the inclusion criteria of the meta-analysis. A dominant model showed that there was no significant association between the ABCG2 C421A polymorphism and the risk of gefitinib-induced toxicity, while the ABCG2 G34A polymorphism might be associated with an increased risk of skin toxicity in gefitinib therapy (relative risk =1.54, 95% CI 1.08–2.21, P=0.02). However, more reliable data are required to confirm the associations between the ABCG2 C421A and ABCG2 G34A polymorphisms and the toxicity of gefitinib in NSCLC patients.Conclusion: While the ABCG2 C421A polymorphism might not be a reliable marker of gefitinib-related toxicity, the ABCG2 G34A genotype may be predictive of the skin toxicity of gefitinib in NSCLC patients. These conclusions need to be verified in further large-scale studies. Keywords: gefitinib, ABCG2, meta-analysis, polymorphism, toxicity, NSCLC

The association between human metabolites and the environmental microbiome has primarily been investigated in relation to disease. In this study, the associations between environmental conditions and microbial communities on the surface of bloodstains were analyzed from a forensic science approach. The composition of microbial communities can be affected by numerous variables. After exposing bloodstains to two different environments with limited airflow and human interference, the microbial communities of the bloodstain surfaces were subjected to longitudinal analysis. Various microbes showed increasing or decreasing trends at the phylum and species level. The microbes identified in this study are usually found in soil, freshwater, and seawater and are known to exhibit unique properties, such as sporulation. Longitudinal variation in temperature and humidity were associated with various changes and correlations with the blood surface microbial community. Understanding these changes could introduce a new perspective to forensic science and could be used to develop a forensic tool used at crime scenes to analyze blood stains in more detail., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: Recent research has increasingly focused on the role of the gastric microbiome in the development of gastric cancer. We aimed to investigate the changes in the microbiome during gastric carcinogenesis in structural and functional aspects, with a specific focus on the association between oral and gastric microbiomes., Methods: We collected saliva, gastric juice, and gastric tissue samples from 141 patients at different stages of gastric carcinogenesis and processed them for microbiome analysis using 16S rRNA gene profiling. The alpha and beta diversities were analyzed, and the differences in microbiome composition and function profiles were analyzed among the groups, as well as the correlation between changes in the oral and gastric microbiomes during carcinogenesis., Results: We observed significant differences in microbial diversity and composition between the disease and control groups, primarily in the gastric juice. Specific bacterial strains, including Schaalia odontolytica, Streptococcus cristatus, and Peptostreptococcus stomatis, showed a significant increase in abundance in the gastric juice in the low-grade dysplasia and gastric cancer groups. Notably, the correlation between the oral and gastric microbiota compositions, increased as the disease progressed. Predictive analysis of the metagenomic functional profiles revealed changes in functional pathways that may be associated with carcinogenesis (ABC transport and two-component systems)., Conclusion: During gastric carcinogenesis, the abundance of oral commensals associated with cancer increased in the stomach. The similarity in microbial composition between the stomach and oral cavity also increased, implying a potential role of oral-gastric bacterial interactions in gastric cancer development.

Objective: To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD)., Methods: We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery., Results: In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54)., Conclusion: Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery., Competing Interests: Declaration of conflicting interestsThe authors declare that they have no conflicting interests.

Purpose: To assess the effects of intravenous tranexamic acid (TXA) on visual clarity at various surgical stages and the correlation between the severity of synovitis and bursitis and the grade of visual clarity in patients undergoing arthroscopic shoulder surgery under an interscalene brachial plexus block., Methods: This double-blind, randomized controlled study included patients undergoing arthroscopic rotator cuff repair. The TXA group underwent injection of a 100-mL mixture of 1,000 mg of TXA and normal saline solution intravenously whereas the control group was administered the same volume of normal saline solution at 10 minutes preoperatively. Visual clarity was rated according to a 3-grade visual clarity scoring system from grade 1 (clear) to grade 3 (poor) at 4 surgical stages (I, intra-articular soft-tissue procedures including synovectomy; II, acromioplasty; III, bursectomy; and IV, greater tuberoplasty). The primary outcome was arthroscopic visual clarity. The secondary outcomes were medications administered for hemodynamic stability, length of hospital stay, and thromboembolic events., Results: Altogether, 63 patients were included in the study; they were divided into the TXA group, comprising 32 patients, and the control group, comprising 31 patients. The TXA group showed significantly better visual clarity than the control group (median [interquartile range], 1 [1-2] vs 2 [1-2]; P = .027) during stage I but not during stages II through IV. Spearman correlation analysis revealed a significant correlation between synovitis and visual clarity grade during synovectomy (correlation coefficient, 0.393; P = .001) but not between bursitis and visual clarity grade during bursectomy. Deep vein thrombosis and pulmonary embolism did not occur in either group., Conclusions: Intravenous TXA can improve visual clarity during intra-articular soft-tissue procedures, including synovectomy. However, it does not have a significant effect during acromioplasty, bursectomy, and greater tuberoplasty. TXA can be used to improve visual clarity in patients with suspected severe synovitis., Level of Evidence: Level I, randomized controlled trial., Competing Interests: Disclosures The authors report no conflicts of interest in the authorship and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (Copyright © 2024. Published by Elsevier Inc.)

Importance: Cardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear., Objective: To investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes., Design, Setting, and Participants: This cohort study analyzed data from the Korean National Health Insurance Service-Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females., Exposures: Habitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking., Main Outcomes and Measures: The primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death., Results: Of the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants., Conclusions and Relevance: Results of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

Aims: Heavy alcohol consumption is an established risk factor for atrial fibrillation (AF). However, the association between habitual changes in heavy habitual drinkers and incident AF remains unclear. The aim of this study was to evaluate whether absolute abstinence or reduced drinking decreases incident AF in heavy habitual drinkers., Methods and Results: Atrial fibrillation-free participants with heavy alcohol consumption registered in the Korean National Health Insurance Service database between 2005 and 2008 were enrolled. Habitual changes in alcohol consumption between 2009 and 2012 were classified as sustained heavy drinking, reduced drinking, and absolute abstinence. The primary outcome measure was new-onset AF during the follow-up. To minimize the effect of confounding variables on outcome events, inverse probability of treatment weighting (IPTW) analysis was performed. Overall, 19 425 participants were evaluated. The absolute abstinence group showed a 63% lower incidence of AF (IPTW hazard ratio: 0.379, 95% confidence interval: 0.169-0.853) than did the sustained heavy drinking group. Subgroup analysis identified that abstinence significantly reduced incident AF in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease (all P-value <0.05). There was no statistical difference in incident AF in participants with reduced drinking compared with sustained heavy alcohol group., Conclusion: Absolute abstinence could reduce the incidence of AF in heavy alcohol drinkers. Comprehensive clinical measures and public health policies are warranted to motivate alcohol abstinence in heavy drinkers., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background/aims: Colonic diverticular bleeding (CDB) is a common cause of acute lower gastrointestinal bleeding. Patients with CDB are at increased risk for recurrence. Here, we aimed to evaluate the clinical course of patients with CDB and identify risk factors for recurrent CDB (rCDB)., Methods: We included patients who were hospitalized at a single tertiary center for management of CDB between January 2005 and March 2020. A Cox proportional hazards regression analysis was performed to evaluate the risk factors of patients with rCDB as follows: model 1 adjusted by age, Charlson comorbidity index (CCI), and presence of bilateral colon diverticula; model 2 adjusted by age, CCI, and presence of left side colon diverticula; model 3 adjusted by age, CCI, and presence of sigmoid colon diverticula., Results: Among 219 patients (mean age, 68.0 years; 55 females), 56 and 163 had definite and presumptive CDB, respectively. During the median period of 506 days, 62 patients (28.3%) experienced rCDB. CCI score ≥ 4 was independently associated with rCDB in models 1, 2 and 3 (all p  < 0.05). Age ≥ 75 years was independently associated with rCDB in models 1 and 2 (both p  < 0.05). The presence of bilateral colon and sigmoid colon diverticula were independently associated with rCDB in models 1 and 3, respectively (both p  < 0.05)., Conclusion: rCDB frequently occurred at any time in patients with previous CDB. High CCI scores and distribution of colon diverticula were associated with rCDB. Clinicians should consider a possible rCDB for a patient considering age, comorbidity, and distribution of colon diverticula., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 You, Kim, Cho, Park, Park, Kim and Choi.)

Competing Interests: The authors have nothing to disclose.

Background: Polycythemia, a state in which the hematocrit or hemoglobin (Hb) concentration in the peripheral blood increases, is associated with several thrombosis-related diseases, of which cerebral infarction is relatively common. This study aimed to investigate the association between ischemic stroke and polycythemia, as a potential risk factor., Research Design and Methods: This study included men who had undergone national health checkups between 2002 and 2003; the data were extracted from the Korean National Health Insurance Service-Health Screening database. The primary outcome was the risk ischemic stroke; adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for ischemic stroke were calculated using Cox proportional hazards regression models., Results: In total, 207,737 male participants aged 40-79 years were included in this study. At the baseline, 13972 (6.7%) participants met the polycythemia criteria (Hb >16.5 g/dL). During the study period, 897 and 12,440 cases of ischemic stroke occurred in the polycythemia and normocythemia (13.0 g/dL ≤ Hb ≤16.5 g/dL) groups, respectively. Compared with the normocythemia group, the polycythemia group showed an adjusted HR (95% CI) for ischemic stroke of 1.12 (1.04-1.20)., Conclusions: The risk of ischemic stroke was higher in participants with polycythemia than in those with normocythemia.

Background and Objectives: Triptans and ergotamine are commonly used to treat migraine, a risk factor for ischemic stroke. This study aimed to investigate the association between migraine and ischemic cardio-cerebrovascular disease (CCVD). Further analyses were performed to examine whether symptom-relieving treatment of migraine with triptans and ergotamine reduces ischemic CCVD in migraineurs., Methods: Participants from the Korean NHIS-HEALS cohort database were divided into patients reporting headache without migraine (HA), migraineurs who received at least one prescription for triptans or ergotamine (TE), and migraineurs who were prescribed neither triptans nor ergotamine (NTNE). Ischemic CCVDs comprised ischemic cerebrovascular diseases and cardiovascular diseases. Using cox proportional hazards regression models, primary and secondary analysis for risk of ischemic CCVDs was compared., Results: Among 62,272 patients diagnosed with migraine or HA, men with migraine or HA numbered 14,747 and 8935, respectively, while the numbers of women were 27,836 and 10,754, respectively. The median follow-up was 6.65 years. The overall incidence rate of CCVDs was 4728/38,590 (12.25%) in females and 3158/23,682 (13.33%) in males. Compared with the HA group, the hazard ratios (HRs) (95% CIs) of the TE and NTNE groups for ischemic CCVDs were 1.18 (1.01-1.39) and 1.39 (1.28-1.50), respectively, in males, and 1.22 (1.09-1.37) and 1.53 (1.42-1.65), respectively, in females, after full adjustment for confounding variables. Compared with the NTNE group, the HRs (95% CIs) of the TE group for ischemic CCVDs were 0.86 (0.73-0.999) in males and 0.80 (0.72-0.88) in females., Conclusions: Migraine increased the risk of ischemic CCVDs in both sexes, and migraineurs treated with triptans and ergotamine were at lower risk of ischemic CCVDs than migraineurs who did not take those medications, especially in women., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background/aims: Gastrointestinal (GI) bezoars are relatively rare diseases with clinical characteristics and treatment modalities that depend on the location of the bezoars. This study evaluated the clinical characteristics and treatment outcomes in patients with GI bezoars., Methods: Seventy-five patients diagnosed with GI bezoars were enrolled in this study. Data were collected on the demographic and clinical characteristics and the characteristics of the bezoars, such as type, size, location, treatment modality, and clinical outcomes., Results: Among the 75 patients (mean age 71.2 years, 38 males), 32 (42.6%) had a history of intra-abdominal surgery. Hypertension (43%) and diabetes (30%) were common morbidities. The common location of the bezoars was the stomach in 33 (44%) and the small intestine in 33 (44%). Non-surgical management, including adequate hydration, chemical dissolution, and endoscopic removal, was successful in 2/2 patients with esophageal bezoars, 26/33 patients with gastric bezoars, 7/9 patients with duodenal bezoars, and 20/33 patients with small intestinal bezoars. The remaining patients had undergone surgical management., Conclusions: The management of GI bezoars requires multidisciplinary approaches, including the appropriate correction of fluid and electrolyte imbalances, chemical dissolution, and endoscopic and surgical treatments.

Introduction: Identification of key microbiome components has been suggested to help address the maintenance of oral and intestinal health in humans. The core microbiome is similar in all individuals, whereas the diverse microbiome varies across individuals, based on their unique lifestyles and phenotypic and genotypic determinants. In this study, we aimed to predict the metabolism of core microorganisms in the gut and oral environment based on enterotyping and orotyping., Materials and Methods: Gut and oral samples were collected from 83 Korean women aged 50 years or older. The extracted DNA was subjected to next-generation sequencing analysis of 16S rRNA hypervariable regions V3-V4., Results: Gut bacteria were clustered into three enterotypes, while oral bacteria were clustered into three orotypes. Sixty-three of the core microbiome between the gut and oral population were correlated, and different metabolic pathways were predicted for each type. Eubacterium &#95;g11, Actinomyces , Atopobium , and Enterococcus were significantly positively correlated between the gut and oral abundance. The four bacteria were classified as type 3 in orotype and type 2 in enterotype., Conclusion: Overall, the study suggested that collapsing the human body's multidimensional microbiome into a few categories may help characterize the microbiomes better and address health issues more deeply., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Lee, You, Sung and Hyun.)

Introduction: Underwater endoscopic mucosal resection (UEMR) is effective for treating intermediate-sized colorectal polyps. However, it is sometimes difficult to obtain visibility in underwater conditions., Methods: This prospective, observational, single-center study included consecutive patients with intermediate-sized (10-20 mm) sessile colorectal polyps. Modified UEMR method was used to initially snare the lesion without injection or water infusion. Thereafter, water was infused until the lesion was submerged, then it was resected using electrocautery. We also evaluated the rates of complete resection and procedure-related complications., Results: Forty-two patients with 47 polyps were enrolled in the study. The median procedure time and fluid infusion were 71 s (42-607) and 50 mL (30-130), respectively. The rates of R0 resection and en bloc resection were 80.9 and 97.9%, respectively, with 100% technical success. R0 resection was observed in 42.9% of polyps sized ≥15 mm and 87.5% sized <15 mm ( p  < 0.01). Muscle entrapment was found in 71.4% of patients with polyps sized ≥15 mm and 10% <15 mm ( p  < 0.01). Immediate bleeding occurred in 12.8% of cases and was controlled using a snare tip or hemostatic forceps. Snare-tip ablation and hemostatic forceps ablation were performed in 27.7 and 6.4% of patients, respectively. No delayed bleeding, perforation, or any other complications were reported., Conclusion: Modified UEMR can be used in cases in which securing visibility or performing the existing UEMR is challenging. Careful treatment is required when removing polyps >15 mm in size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Park, You, Jung, Joo, Myung, Kim, Kim, Kim and Ju.)

Age-related diseases represent the largest threat to public health. Aging is a degenerative, systemic, multifactorial and progressive process, coupled with progressive loss of function and eventually leading to high mortality rates. Excessive levels of both pro- and anti-oxidant species qualify as oxidative stress (OS) and result in damage to molecules and cells. OS plays a crucial role in the development of age-related diseases. In fact, damage due to oxidation depends strongly on the inherited or acquired defects of the redox-mediated enzymes. Molecular hydrogen (H 2 ) has recently been reported to function as an anti-oxidant and anti-inflammatory agent for the treatment of several oxidative stress and aging-related diseases, including Alzheimer's, Parkinson's, cancer and osteoporosis. Additionally, H 2 promotes healthy aging, increases the number of good germs in the intestine that produce more intestinal hydrogen and reduces oxidative stress through its anti-oxidant and anti-inflammatory activities. This review focuses on the therapeutic role of H 2 in the treatment of neurological diseases. This review manuscript would be useful in knowing the role of H 2 in the redox mechanisms for promoting healthful longevity.

Background: Tailored therapy has been widely used for patients with Helicobacter pylori ( H. pylori ) infection in South Korea. Herein, we evaluated the treatment outcomes of tailored clarithromycin-based triple therapy (TT) in patients infected with H. pylori ., Methods: We enrolled 460 patients without A2142G and A2143G point mutations by dual priming oligonucleotide-based polymerase chain reaction who had taken TT and undergone the urease breath test to evaluate eradication in clinical practice. Eradication rates according to the treatment duration and dose of clarithromycin were analyzed., Results: Among 460 patients (164 women, median age 63.0 years), 250 patients underwent TT with full-dose clarithromycin (TT-full CLA), and 216 patients underwent TT with half-dose clarithromycin (TT-half CLA). The eradication rates were 88.0% (220/250) in patients with TT-full CLA and 85.2% (179/210) in patients with TT-half CLA. In 250 patients with TT-full CLA, the eradication rates were 86.8% (33/38) in patients with 7-day TT-full CLA and 88.2% (187/212) in patients with 10-day or 14-day TT-full CLA ( P = 0.788). In 210 patients with TT-half CLA, the eradication rates were 84.2% (139/165) in those with a 7-day TT-half CLA and 88.9% (40/45) in those with a 10-day or 14-day TT-half CLA ( P = 0.436)., Conclusion: For patients with H. pylori infection without A2142G and A2143G point mutations by DPO-PCR in clinical practice, treatment extension above 7-day TT with full CLA did not improve the eradication rates. Future studies on the treatment outcomes of TT-half CLA considering effectiveness and compliance are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cho, Park, Park, Kim, You and Kim.)

Background: Elderly patients with hip fractures frequently receive perioperative transfusions, which are associated with increased morbidity and mortality. This study aimed to evaluate the impact of a patient blood management (PBM) program on the appropriateness of red blood cell (RBC) transfusion and clinical outcomes in geriatric patients undergoing hip fracture surgery., Methods: In 2018, the revised PBM program was implemented at the Korea University Anam Hospital, Seoul, Republic of Korea. Elderly patients aged ≥ 65 years who underwent hip fracture surgery from 2017 to 2020 were evaluated. Clinical characteristics and outcomes were analyzed according to the timing of PBM implementation (pre-PBM, early-PBM, and late-PBM). Multiveriate regression analysis was used to evaluate the risk factors of the adverse outcomes, such as in-hospital mortality or 30-day readmission., Results: A total of 884 elderly patients were included in this study. The proportion of patients who received perioperative RBC transfusions decreased significantly (43.5%, 40.1%, and 33.2% for pre-PBM, early-PBM, and late-PBM, respectively; P = 0.013). However, the appropriateness of RBC transfusion significantly increased (54.0%, 60.1%, and 94.7%, respectively; P < 0.001). The duration of in-hospital stay and 30-day readmission rates significantly decreased. Multivariable regression analysis revealed that RBC transfusion (odds ratio, 1.815; 95% confidence interval, 1.137-2.899; P = 0.013) was significantly associated with adverse outcomes., Conclusion: Implementing the PBM program increased the appropriateness of RBC transfusion without compromising transfusion quality and clinical outcomes. Therefore, adopting the PBM program may improve the clinical management of elderly patients following hip fracture surgery., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

There is limited evidence of a natural course of an upper gastrointestinal (UGI)-subepithelial lesion (SEL) of 2 cm or less in size. This study aims to determine the natural course of UGI-SELs and find the risk factors of the endoscopic and endoscopic ultrasonography (EUS) findings associated with an increase in size. The medical records of 2539 patients with UGI-SELs between 2004 and 2016 were reviewed retrospectively. A total of 672 SELs of 2 cm or less in size were analyzed through EUS and followed up for at least 36 months. The mean follow-up duration was 68 months (range: 36-190 months), and 97 SELs (14.4%) showed an increase in size with a mean increase rate of 1.2 mm/year. Initial size (aOR 1.03, 95% confidence interval (CI) 1.01-1.06), an endoscopic finding of a hemorrhagic spot (aOR 3.13, 95% CI 1.14-8.60), and an EUS finding of a lesion in the fourth layer (aOR 1.87, 95% CI (1.21-2.88) were related to an increase in size. An endoscopic finding of translucidity (aOR 0.28, 95% CI (0.10-0.76) and an EUS finding of calcification (aOR 0.30, 95% CI 0.09-0.95) were inversely related to an increase in size. There was no death related to UGI-SELs during the follow-up. While most UGI-SELs of 2 cm or less in size showed no significant size change and favorable prognosis, an individualized follow-up strategy needs to be considered in case of the presence of hemorrhagic spots and lesions in the fourth layer., Competing Interests: The authors declare no conflicts of interest.

Mulberry is a rich source of anthocyanins (ACNs) known to possess biological activities. However, these ACNs are unstable in high pH, heat, and aqueous environments with a low bioavailability. In this study, a colloidal dispersion was prepared by hot melt extrusion with proper excipients. In this process, a hydrophilic polymer matrix was used to confirm the stability of the compound in high pH, high temperature, and aqueous media. It was confirmed that the particle size and the polydispersity index value were reduced, thereby improving the solubility. In vitro release studies revealed that the extrudate had a sustained release compared to a non-extruded product. As a result of measuring changes of intestinal microorganisms ( Lacticaseibacillus rhamnosus , Pediococcus pentosaceus , Escherichia coli, Enterococcus faecalis , and Staphylococcus aureus ), contents of probiotics were found to be increased whereas contents of pathogenic microorganisms were decreased. Thus, hot-melt extrusion could enhance the stability of ACN with prolonged release. The processed formulation exhibited probiotic properties and antimicrobial activities against pathogenic intestinal microflora.

Next-generation sequencing (NGS) technology has led to innovations in environmental metagenomics and investigations involving humans and microbes. However, it is necessary to analyze the components that will affect analysis of the method upon processing a large amount of information. In particular, the processing method after sample collection affects the NGS results, and it is necessary to check for inaccurate results. Here, we show that the microbial communities obtained from fingertip samples differ from those obtained from fingertips remaining on mobile phones and desks, when cultured or not for 24 h. We also confirmed changes in microbial communities in fingertip samples from desks incubated for 2, 4, 8, 16, and 24 h. Samples of prints from mobile phones that are considerably vulnerable to external factors were not analyzed. Ratios of Firmicutes and Bacillus were, respectively, increased in cultures at the phylum and species levels. Collectively, we identified bacterial species that can aid in determining whether a sample has been cultured. In addition, although microbial communities differed depending on sample types, we confirmed changes after culture for 4 and 8 h. However, since this study is a sample limited to three types, it is necessary to analyze other types of samples in the same way and check whether they are applicable to all types. This strategy can verify the suitability of samples for deriving informative results from cultured or uncultured bacterial communities., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Opioids are prescribed to treat moderate to severe pain. We investigated recent trends in opioid (morphine, oxycodone, fentanyl, and hydromorphone) prescriptions using data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2015., Methods: The morphine milligram equivalent (MME) was calculated to standardize the relative potency of opioids. The number (cases) or amount (MME) of annual opioid prescriptions per 10,000 registrants was computed to analyze trends in opioid prescriptions after age standardization. Joinpoint regression analysis was conducted to calculate the annual percentage change and average annual percentage change (AAPC)., Results: The number (cases) of prescriptions per 10,000 registrants increased from 0.07 in 2002 to 41.23 in 2015 (AAPC, 76.0%; 95% confidence interval [CI], 61.6 to 91.7). The MME per 10,000 registrants increased from 15.06 in 2002 to 40,727.80 in 2015 (AAPC, 103.0%; 95% CI, 78.2 to 131.3). The highest AAPC of prescriptions and MME per 10,000 registrants were observed in the elderly (60-69 years) and in patients treated at general hospitals. Fentanyl prescriptions increased most rapidly among the 4 opioids., Conclusions: Consumption of opioids greatly increased in Korea over the 14-year study period.

Aging has become a global problem, and the interest in healthy aging is growing. Healthy aging involves a focus on the maintenance of the function and well-being of elderly adults, rather than a specific disease. Thus, the management of frailty, which is an accumulated decline in function, is important for healthy aging. The adaptation method was used to develop clinical practice guidelines on frailty management that are applicable in primary care settings. The guidelines were developed in three phases: preparation (organization of committees and establishment of the scope of development), literature screening and evaluation (selection of the clinical practice guidelines to be adapted and evaluation of the guidelines using the Korean Appraisal of Guidelines for Research and Evaluation II tool), and confirmation of recommendations (three rounds of Delphi consensus and internal and external reviews). A total of 16 recommendations (five recommendations for diagnosis and assessment, 11 recommendations for intervention of frailty) were made through the guideline development process. These clinical practice guidelines provide overall guidance on the identification, evaluation, intervention, and monitoring of frailty, making them applicable in primary care settings. As aging and "healthy aging" become more and more important, these guidelines are also expected to increase in clinical usefulness.

Background and Objective: The programmed death 1 and ligand (PD-1/PD-L1) inhibitors have significantly altered therapeutic perspectives on non-small-cell lung cancer (NSCLC). However, their efficacy and safety are unknown since direct clinical trials have not yet been performed on them. It is also necessary to determine the economics of PD-1/PD-L1 inhibitors due to their high cost. The aim was to evaluate the efficacy, safety, and cost-effectiveness of PD-1/PD-L1 inhibitor monotherapy for advanced NSCLC patients in China with high PD-L1 expression as first-line treatment., Methods: From the PubMed, Cochrane, and Web of Science databases, we retrieved survival, progression, and safety data on PD-1/PD-L1 inhibitor monotherapy for advanced NSCLC patients. A network meta-analysis (NMA) was performed to consider PD-1/PD-L1 inhibitors in efficacy and safety. A Markov model with a full-lifetime horizon was adopted. Clinical and utility data were collected through the trial. The cost per quality-adjusted life year (QALY) was as incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed., Results: This study included five phase III clinical trials using four drugs: nivolumab, pembrolizumab, atezolizumab, and durvalumab. The NMA demonstrated that the four drugs had similar efficacy and safety, while pembrolizumab and atezolizumab were better for than for nivolumab (hazard ratio (HR) = 0.66, 95% confidence intervals (CIs): 0.46-0.95 and HR = 0.59, 95%CI: 0.37-0.94) in progression-free survival (PFS), and the risk of a severe adverse event was higher for atezolizumab than for nivolumab and pembrolizumab. Compared with nivolumab, durvalumab, pembrolizumab, and atezolizumab had QALY of 0.19, 0.38, and 0.53, respectively, which induced ICERs of $ 197,028.8/QALY, $ 111,859.0/QALY, and $ 76,182.3/QALY, respectively., Conclusion: The efficacy and safety are similar among types of PD-1/PD-L1-inhibitor monotherapy. The cost-effectiveness of nivolumab appears optimal, but the other PD-1/PD-L1 inhibitors are not as cost-effective for the first-line treatment of advanced NSCLC in China., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Dyslipidemia is nephrotoxic and can result in the development of chronic kidney disease (CKD). The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG/HDL-C ratio) is well-correlated with insulin resistance and cardiovascular events. The aim of this study is to examine the association between the TG/HDL-C ratio and CKD in Korean adults. This study was retrospectively designed based on the National Health Insurance Service-National Health Screening cohort. Seventy three thousand and fifty-two participants aged between 40 and 79 years old at baseline (2009-2010) were included in the final analyses. The study population was classified into three tertile groups (T 1 , T 2 , and T 3 ) according to the TG/HDL-C ratio by sex. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD were calculated using Cox proportional hazard regression models. The median follow-up duration was 5.9 years. Higher tertile groups of the TG/HDL-C ratio had lower estimated glomerular filtration rates in both sexes. The cumulative incidence of CKD of T 1 , T 2 , and T 3 was 11.89%, 12.90%, and 12.91%, respectively, in men and 10.17%, 10.61%, and 14.87%, respectively, in women (all p values < 0.001). Compared with T 1 of the TG/HDL-C ratio, the HRs (95% CIs) of T 2 and T 3 for CKD were 1.212 (1.118-1.315) and 1.183 (1.087-1.287), respectively, in men and 0.895 (0.806-0.994) and 1.038 (0.937-1.150), respectively, in women after being fully adjusted. Higher TG/HDL-C ratios were positively associated with CKD development in men, while middle levels of TG/HDL ratios reduced the CKD incidence in women., (© 2021 AOCS.)

Background: Multiple drug hypersensitivity syndrome (MDHS) results in treatment delay or failure and often results in severe drug hypersensitivity reactions. There are few reports of MDHS in response to anti-tuberculosis drugs; however, clinical information is scarce. Understanding the frequency and clinical characteristics of simultaneous MDHS against first-line anti-tuberculosis drugs in patients with non-severe drug hypersensitivity reactions is necessary., Methods: We reviewed 27 patients with drug fever or maculopapular exanthem in response to first-line anti-tuberculosis drugs between January 2010 and June 2019. Drug fever or maculopapular exanthem occurred when isoniazid, rifampin, ethambutol, and pyrazinamide were administered simultaneously. Drug provocation tests for the 4 drugs were performed to identify the culprit drugs., Results: All patients showed positive reactions to 1 or more drugs. MDHS was diagnosed in 13 (48%) patients, of whom 11 and 2 patients reacted to 2 and 3 drugs, respectively. In comparison to the patients with single-drug hypersensitivity, the patients with MDHS did not exhibit any differences in characteristics. Ethambutol and rifampin were the common drugs that induced a reaction, and the combination of these 2 drugs induced MDHS most frequently. Among the patients with MDHS, there were no differences between the drugs that caused drug fever and maculopapular exanthem. All patients with MDHS were successfully treated with alternative drugs., Conclusions: Simultaneous MDHS may occur frequently in patients with drug fever or maculopapular exanthem caused by first-line anti-tuberculosis drugs, indicating the need to evaluate the allergy responses for all 4 drugs, even in patients without severe drug hypersensitivity. The combination of ethambutol and rifampin was the most common trigger that induced MDHS., Competing Interests: The authors have declared that they have no conflicts of interest in this work., (© 2021 The Authors.)

The importance of developing more potent antimicrobials and robust infection prevention practices has been highlighted recently with the increase in reports of emerging bacterial resistance mechanisms and the development of antibiotic-resistant microbes. In this study, a quaternary ammonium chitosan derivative, N,N,N-trimethyl chitosan chloride (TMC) with inherent bactericidal property was synthesized and complexed with povidone‑iodine (PVP-I) to create a potentially more potent antiseptic solution that could also significantly enhance the wound healing process. TMC, a positively charged, water-soluble derivative of chitosan, formed stable solutions with PVP-I at 5% w/v TMC concentration (TMC5/PVP-I). TMC5/PVP-I was significantly effective against multidrug-resistant bacteria S. aureus compared with PVP-I alone. TMC/PVP-I solutions also showed fungicidal property against C. albicans, with no cytotoxic effects when tested against human fibroblast cells cultured in vitro. Wound healing assessment in vivo revealed early collagen formation and re-epithelialization for TMC5/PVP-I treated wounds in rats relative to control and PVP-I only. Formulation of TMC/PVP-I solutions presented in the study can be easily adapted in the existing production of commercial PVP-I creating a new product with more potent bactericidal and enhanced wound healing properties for optimal wound care., (Copyright © 2021. Published by Elsevier B.V.)

We aimed to investigate if a home meal replacement (HMR), designed with a low ω-6/ω-3 fatty acid ratio, improves cardiometabolic parameters, including metabolic syndrome (MetS) in obese individuals. We conducted a monocentric, controlled, randomized crossover trial. The HMR contains higher protein and fat content, lower carbohydrate content, and a lower ω6FA/ω3FA ratio than the regular diet. Sixty-four participants were randomized into two groups and switched to the other group following a 4-week intervention. While subjects in the HMR group were provided three HMRs daily, those in the control group were requested to maintain their regular dietary pattern. We conducted paired t-tests, repeated measures analysis of variance, and McNemar tests before and after the intervention. Body mass index (BMI) and weight were lower in the HMR group after adjusting for age, sex, and total energy intake and significantly changed in the between-group differences. The waist circumference, systolic blood pressure, triglycerides, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were reduced in the HMR group (all p < 0.05). The percentage of subjects with MetS significantly decreased from 39.1% at baseline to 28.1% post-intervention ( p = 0.035). Using the HMR for 4 weeks reduced the BMI, weight, and MetS prevalence in individuals with obesity. This trial was registered at clinicaltrials.gov (NCT04552574).

Extrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate Cox-regression analysis was performed to identify the variables associated with EHR. EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, pathologic modified Union for International Cancer Control stage (III, IVa), surgical margin involvement, tumor necrosis, sum of tumor size > 7 cm, and macrovascular invasion were predictive factors of EHR. Four risk levels and their respective EHR rates were defined as follows: very low risk, 1-/5-year, 3.1%/11.6%; low risk, 1-/5-year, 12.0%/27.7%; intermediate risk, 1-/5-year, 36.3%/60.9%; and high risk, 1-year, 100.0%. Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.

Introduction: Iron deficiency anemia (IDA) is common among obstetric and gynecologic patients. This systematic review aimed to assess the comparative efficacy and safety of commonly used intravenous (IV) iron formulations, ferric carboxymaltose (FCM), and iron sucrose (IS) in the treatment of IDA in obstetric and gynecologic patients., Methods: We systematically searched PubMed, EMBASE, Cochrane CENTRAL, and Google Scholar for eligible randomized controlled trials (RCTs) comparing IV iron replacement using FCM and IS up to October 2019. The primary outcome was to compare the efficacy of FCM and IS, assessed by measuring serum hemoglobin (Hb) and ferritin levels before and after iron replacement. The secondary outcome was to compare the safety of FCM and IS, assessed by the incidence of adverse events during iron replacement. The meta-analysis was performed using RevMan 5.3., Results: We identified 9 RCTs with 910 patients (FCM group, n = 456; IS group, n = 454). Before iron replacement, FCM and IS group patients had similar baseline Hb (mean difference [MD], 0.04 g/dL; 95% confidence interval [CI], -0.07 to 015; I2 = 0%; P = 0.48) and ferritin levels (MD, -0.42 ng/mL; 95% CI, -1.61 to 0.78; I2 = 45%; P = 0.49). Following iron replacement, patients who received FCM had higher Hb (MD, 0.67; 95% CI, 0.25-1.08; I2 = 92%; P = 0.002) and ferritin levels (MD, 24.41; 95% CI, 12.06-36.76; I2 = 75%; P = 0.0001) than patients who received IS. FCM group showed a lower incidence of adverse events following iron replacement than IS group (risk ratio, 0.53; 95% CI, 0.35-0.80; I2 = 0%; P = 0.003). Serious adverse events were not reported in any group., Conclusion: FCM group showed better efficacy in increasing Hb and ferritin levels and a favorable safety profile with fewer adverse events compared with IS group for IDA treatment among obstetric and gynecologic patients. However, this meta-analysis was limited by the small number of RCTs and high heterogeneity., Trial Registration: The review was prospectively registered with the International Prospective Registry of Systematic Reviews (https://www.crd.york.ac.uk/prospero/, registration number CRD42019148905)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Interscalene block is the most commonly used nerve block for shoulder surgery, and superior trunk block has been investigated as a phrenic-sparing alternative. This randomized controlled trial compared ultrasound-guided interscalene block and superior trunk block as anesthesia for arthroscopic shoulder surgery., Objectives: Our aims were to determine the superiority of anesthesia quality and compare the risk of hemidiaphragmatic paralysis between these 2 blocks., Study Design: A randomized, controlled trial., Setting: Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital., Methods: Forty-eight patients undergoing elective arthroscopic shoulder surgery under an ultrasound guided brachial plexus block were randomized to receive either an interscalene block (ISB group, n = 24) or a superior trunk block (STB group, n = 24) for surgery. Ten milliliters of 2% lidocaine and 10 mL of 0.75% ropivacaine were used as local anesthesia in both brachial plexus block groups (total 20 mL). In the ISB group, the local anesthesia was injected between the C5-C6 root and at the upper part of C5 with equally divided doses. In the STB group, the local anesthesia was injected into the anterior and posterior parts of the superior trunk with equally divided doses. Sensory blockade of each trocar's insulting site (supraclavicular, axillary, and suprascapular nerve areas) and motor blockade of the axillary nerve (shoulder abduction) and the suprascapular nerve (shoulder external rotation) were assessed by a blinded observer at 5-minute intervals for 30 minutes after the block. Anesthesia quality was assessed using 3 grades (excellent/insufficient/failure). The blinded investigator also assessed the grade of hemidiaphragmatic paralysis (normal/partial/complete) by comparing pre- and postoperative chest radiographs. Primary outcome variables were anesthesia grade and rate of hemidiaphragmatic paralysis. Secondary outcome variables were performance time and anesthesia onset time., Results: The anesthetic grade was significantly different between the 2 groups (22/2/0 in the ISB group vs. 16/3/5 in the STB group, P = 0.046). Both groups displayed equivalent incidence of hemidiaphragmatic paralysis (12/6/6 in the ISB group vs. 7/14/3 in the STB group, P = 0.063). No intergroup differences were found in terms of performance time and anesthesia onset time., Limitations: Our sensory and motor function test was not applied to the subscapular nerve, which serves internal rotation of the humeral head so may be difficult to evaluate in patients with rotator cuff tears. We assessed the diaphragmatic movement by chest radiographs instead of by ultrasound., Conclusions: The superior trunk block provided lower quality of surgical anesthesia than the interscalene block and did not effectively decrease the risk of hemidiaphragmatic paralysis during arthroscopic shoulder surgery for rotator cuff syndrome.

Many people spend most of their time indoors, thereby exposing themselves to indoor environmental microbial communities that might interact with the human microbiota. These potential interactions have only been considered for personal identification; however, accumulating evidence indicates that these microbial interactions are potentially implicated with the identification of human interactions and location-specific factors including time and seasonal variations in the microbial community. To augment the potential of metagenomics-based forensic tools, we compared the composition of microbial communities in blood spot surfaces from healthy adults placed in different environments, such as in the bathroom of a female single-person household and on a laboratory, which were sampled across seasons and time points. The laboratory samples showed more changes in the bacterial community over time owing to the higher number of individuals using the laboratory, whereas the microbial communities in the bathroom samples remained relatively stable over time. Moreover, the two locations could be distinguished according to their specific bacterial community compositions. Variations were also observed related to changes in temperature and humidity, allowing for prediction of season-based microbial community. These findings offer a new perspective regarding the use of microbial community analysis in forensic science., (© The Author(s) 2021. Published by Oxford University Press on behalf of FEMS.)

Background: The 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of tobacco-specific lung carcinogen that can be found in both smokers and non-smokers. Particularly, NNAL levels of children with a history of exposure to second-hand smoke (SHS) are higher than those of adults. Thus, we aimed to investigate the association between SHS exposure and urine NNAL levels in Korean adolescents., Methods: This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey VII. Overall, 648 never-smoking adolescents (425 boys and 223 girls) aged 12 to 18 were included in this study. Logistic regression analyses identified the relationship between SHS exposure and elevated urine NNAL levels., Results: The mean urine NNAL levels of the no exposure and exposure group in boys were 1.39 and 2.26 ng/mL, respectively, whereas they were 1.01 and 2.45 ng/mL in girls, respectively ( P < 0.001). Among the adolescents exposed to SHS, the confounder-adjusted odds ratio (95% confidence intervals) for elevated urine NNAL levels according to exposure area as overall, home, and public area were 2.68 (1.58-4.53), 31.02 (9.46-101.74), and 1.89 (1.12-3.17) in boys; and 6.50 (3.22-13.11), 20.09 (7.08-57.04), and 3.94 (1.98-7.77) in girls, respectively., Conclusion: SHS exposure was significantly associated with elevated urine NNAL levels in Korean adolescents, particularly in female adolescents and in those with home exposure. These findings remind us of the need to protect adolescents from SHS., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Abstract: Malignant neoplasms are the leading cause of death in Korea. We aimed to examine if metformin use in cancer survivors reduces all-cause mortality. This study was retrospectively designed based on data from the Korean National Health Insurance Service-National Health Screening Cohort (HEALS) between 2002 and 2015. The Kaplan-Meier estimator and log-rank test was performed to estimate the survival function according to metformin usage (3721 metformin non-users with diabetes, 5580 metformin users with diabetes, and 24,483 non-diabetic individuals). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated using Cox proportional hazards regression models.The median follow-up duration was 4.2 years. The HRs (95% CIs) for all-cause mortality of metformin users and the non-diabetic group were 0.762 (0.683-0.850) and 1.055 (0.966-1.152) in men and 0.805 (0.649-0.999), and 1.049 (0.873-1.260) in women, respectively, compared with metformin non-users among diabetic cancer survivors, in a fully adjusted model. After stratifying metformin users into pre- and post-diagnosis of cancers, adjusted HRs (95% CIs) of pre- and post-diagnosis metformin users for all-cause mortality were 0.948 (0.839-1.071) and 0.530 (0.452-0.621) in men and 1.163 (0.921-1.469) and 0.439 (0.323-0.596) in women, respectively.Metformin use in cancer survivors with diabetes reduced overall mortality rates. In particular, metformin use after cancer diagnosis, not before cancer diagnosis, was inversely associated with overall mortality.Active treatment with metformin for diabetic cancer survivors after cancer diagnosis can improve their survival rates., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study aimed to investigate the association between metformin usage and the risk of colorectal cancer (CRC) using data from the Korean National Health Insurance Service-National Health Screening Cohort database., Methods: Data from the NHIS-HEALS cohort between 2002 and 2015 were longitudinally analyzed. Subjects were divided into three groups: metformin non-users with diabetes mellitus (DM), metformin users with DM, and no DM group. CRC was defined using the ICD-10 code (C18.0-C20.0) at the time of admission. Cox proportional hazard regression models were adopted after stepwise adjustment for confounders to investigate the association between metformin usage and colorectal cancer risk., Results: During the follow-up period, of the total 323,430 participants, 2341 (1.33%) of the 175,495 males and 1204 (0.81%) of the 147,935 females were newly diagnosed with CRC. The estimated cumulative incidence of CRC was significantly different among the three groups based on Kaplan-Meier's survival curve (p values < 0.05 in both sexes). Compared with metformin non-users, hazard ratios (95% CIs) of metformin users and the no DM group were 0.66 (0.51-0.85) and 0.72 (0.61-0.85) in males and 0.59 (0.37-0.92) and 0.93 (0.66-1.29) in females, respectively, after being fully adjusted., Conclusions: Metformin users with diabetes appear to have a significantly lower risk of CRC compared with metformin non-users.

(1) Background: Subclinical inflammation as a risk factor of cardiovascular diseases was clinically measured using C-reactive protein (CRP) level. (2) Methods: This study was cross-sectionally designed based the 2015-2018 Korean National Health and Nutrition Examination Survey (KNHANES). The ratio of daily omega-3 fatty acids to energy intake (ω3FA ratio) was classified into four quartile groups (Q1, <0.3%; Q2, 0.3%-<0.6%; Q3, 0.6%-<1.0%; and Q4, ≥1.0% in both sexes). Logistic regression analysis was conducted to investigate the association between the ω3FA ratio and subclinical inflammation defined as CRP levels ≥3 mg/dL. (3) Results: The ω3FA ratio in subjects without and with subclinical inflammation was 0.8% and 0.7% in men ( p -value = 0.001), and 0.8% and 0.8% in women ( p -value = 0.491), respectively. The prevalence of subclinical inflammation in males decreased with increasing quartile of ω3FA ratio (12.9%, 9.6%, 7.4%, and 7.7%, p -value = 0.033), while female prevalence was not significant among quartile groups. Compared to Q1, odds ratios (95% confidence intervals) for subclinical inflammation of Q2, Q3, and Q4 were 0.740 (0.465-1.177), 0.564 (0.341-0.930), and 0.549 (0.317-0.953) in males, and 1.066 (0.653-1.741), 1.105 (0.600-1.718), and 0.934 (0.556-1.571) in females after full adjustment. (4) Conclusion: The ω3FA ratio is associated with subclinical inflammation in men.

Introduction: Dyslipidemia is a known risk factor for chronic kidney disease (CKD). The effects of statins on CKD have already been studied in patients with CKD; however, data on the general population are limited. This study aimed to determine the relationship between statin use and the incidence of CKD in patients with hypercholesterolemia having normal renal function., Methods: A total of 7,856 participants aged 40-79 years at baseline (2009-2010) were included in the final analyses. The participants were divided into statin users (n = 4,168) and statin nonusers (n = 3,668), according to the statin usage. The Cox proportional hazard regression model was used to evaluate the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CKD., Results: The median follow-up duration was 5.8 years. A total of 543 cases of CKD (285 cases in males and 258 cases in females) occurred during the study period. The estimated cumulative incidence of CKD was significantly different between male statin nonusers and users (p < 0.001), while it was not statistically significant between female statin nonusers and users (p = 0.126). Compared with statin nonusers, the fully adjusted HRs (95% CIs) for CKD in statin users were 1.014 (0.773-1.330) in males and 1.117 (0.843-1.481) in females., Conclusion: Dyslipidemia is an obvious risk factor for CKD; however, statin use in patients with hypercholesterolemia having normal renal function does not demonstrate a clear relationship with the incidence of CKD., (© 2021 S. Karger AG, Basel.)

Objectives: This study aimed to examine the association between statin exposure and dementia risk in individuals with hypercholesterolaemia using data from the NHIS-HEALS database between 2002 and 2015., Methods: Subjects were classified into statin exposure and statin nonexposure groups according to medication possession ratio. Dementia was defined as those with primary diagnostic dementia codes such as F00-F03, G30, G31.1, G31.9 or G31.82. Cox proportional hazards regression models were adopted after stepwise adjustment for confounders to investigate the prospective association between statin exposure and dementia risk., Results: During the follow-up period (median follow-up 11.7 years), 711 cases of dementia occurred, accounting for 11.5% of the total study population (statin exposure group, 8.2%; statin nonexposure group, 12.9%). Compared to the statin nonexposure group, fully adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for overall dementia in the statin exposure group were 0.63 (0.43-0.91) and 0.62 (0.50-0.78) in men and women, respectively. Compared to the statin nonexposure group, the HRs (95% CIs) for Alzheimer's disease and related dementia, vascular dementia and other types of dementia in the statin exposure group were 0.54 (0.32-0.91), 2.45 (0.69-8.68) and 0.59 (0.32-1.07), respectively, in men and 0.53 (0.38-0.73), 1.29 (0.42-3.96) and 0.70 (0.51-0.96), respectively, in women., Conclusions: Hypercholesterolaemic individuals exposed to statin had a lower risk of overall dementia and Alzheimer's disease and related dementia in both sexes, and a lower risk of other types of dementia in women, than subjects who were not exposed to statins., (© 2020 The Association for the Publication of the Journal of Internal Medicine.)

Aims: The aim of this study is to investigate the association between metformin usage and dementia in an elderly Korean population., Methods: Participants were divided into five groups: metformin non-users with diabetes mellitus (DM), metformin users with DM (low-, mid-, and high-users), and non-diabetic Individuals. Dementia was defined with primary diagnostic dementia codes according to the 10th edition of the International Classification of Diseases. To compare the incidence rate of dementia among the five groups, Kaplan-Meier estimates and log-rank test were employed. Also, to control the confounding factors, Cox proportional hazards regression models were fitted in a sequential adjustment., Results: The median follow-up was 12.4 years. The overall incidence rate of dementia was 11.3% (8.4% in men and 13.9% in women). Compared with metformin non-users, hazard ratios (95% confidence intervals) of low-, mid-, and high-users and non-diabetic individuals for dementia were 0.97 (0.73-1.28), 0.77 (0.58-1.01), 0.48 (0.35-0.67), and 0.98 (0.84-1.15), respectively, in men, respectively, and 0.90 (0.65-0.98), 0.61 (0.50-0.76), 0.46 (0.36-0.58), and 0.92 (0.81-1.04), respectively, in women, after full adjustment of confounding variables., Conclusions: Metformin use in an elderly population with DM reduced dementia risk in a dose-response manner., Competing Interests: Declaration of Competing Interest All authors have nothing to declare: no affiliations with or involvement in any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work; and no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Metformin is the first option in managing type 2 diabetes mellitus (DM) and has pleotropic effects. We studied the incidence of lung cancer in patients who received metformin therapy., Patients and Methods: This study was retrospectively designed and based on the Korean National Health Insurance Service-National Health Screening Cohort to determine whether metformin reduces lung cancer risk in the diabetic population. At baseline, all participants were 40 to 69 years old and were categorized into 3 groups: metformin nonrecipients with DM, metformin recipients with DM, and the nondiabetic group., Results: A total of 336,168 individuals were included in the final analysis (314,291 nondiabetic individuals, 8806 metformin recipients, and 13,071 metformin nonrecipients). The study median follow-up period was 12.86 years. The estimated cumulative lung cancer incidence of metformin nonrecipients, metformin recipients, and the nondiabetic group was 1.80%, 1.97%, and 1.24% in men and 1.87%, 0.61%, and 0.41% in women, respectively (P < .05). Compared to metformin nonrecipients, the hazard ratios (95% confidence intervals) for lung cancer incidence of metformin recipients and the nondiabetic group were 1.287 (0.979-1.691) and 0.835 (0.684-1.019) in men and 0.664 (0.374-1.177) and 0.553 (0.359-0.890) in women, respectively. The hazard ratios (95% confidence intervals) were statistically significant in male ever smokers (0.784 [0.627-0.979]) and female nonsmokers (0.498 [0.320-0.774]) after stratification according to smoking status., Conclusion: Metformin therapy did not reduce lung cancer incidence in the diabetic population. However, individuals without DM were at a lower risk of lung cancer, especially in male ever smokers and female nonsmokers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Synbiotics intake can alter the composition of intestinal microbes beneficially. We aimed to detect the changes in the intestinal microbiomes of 37 healthy elderly Korean women after the intake of a synbiotic drink. This was a longitudinal study controlled with a temporal series, including a control period of 3 weeks before intake, synbiotic intake for 3 weeks, and a washout period of 3 weeks. Fecal microbiota composition was analyzed by sequencing the V3-V4 hypervariable regions of 16S rRNA. Physical fecal activity increased with improvement in fecal shape. Thirty intestinal bacterial taxa were observed to change only after the intake period. In particular, Ellagibacter appeared only after ingestion. In addition, the abundance of Terrisporobacter showed a positive correlation with C-reactive protein, triglyceride. Lachnospiraceae&#95;uc, Eubacterium&#95;g5, and Blautia had a positive correlation with creatinine, whereas PAC001100&#95;g had a negative correlation with creatinine. Short-term (3 weeks) intake of symbiotic organisms changes the composition of the gut microbiota in healthy elderly Korean women.

Klebsiella pneumoniae is an opportunistic pathogenic bacterium that commonly causes pneumonia in elderly people. OmpA, a toxin that is highly expressed in the outer membrane of the bacterium, is one of the primary factors implicated in the pulmonary pathogenesis of K. pneumoniae. To evaluate the associated pyroptosis mechanism of infection, the ompA gene was cloned, and the protein was expressed, extracted, and used to treat human larynx epithelial cells. We observed that OmpA induces reactive oxygen species production and cell-cycle arrest in the G2/M phase in host cells, leading to subsequent apoptosis. Moreover, OmpA was found to induce IL-1β and IL-18 production in host cells, resulting in caspase-1 activation, which simultaneously stimulated pyroptosis, thus leading to the death of the host cells. We next sought to examine differential gene expression via RNA sequencing to better elucidate the mechanisms associated with these cellular changes, and found that genes associated with these pathways were more highly expressed in OmpA-treated cells than in K. pneumoniae-infected cells. Thus, cell-cycle arrest, apoptosis, and pyroptosis may serve as the primary defenses employed by host cells against OmpA. These results provide novel insights into the host defense against K. pneumoniae infection., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest (commercial or otherwise) to declare regarding this study., (Copyright © 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background and Aim: Several studies have reported the preventive effect of metformin on cancer development. This study aimed to investigate the relationship between use of metformin and risk of cancer in Koreans., Methods and Results: This study was designed retrospectively using the National Health Insurance Service-National Health Screening Cohort conducted between 2002 and 2015. 40 to 69-year-old subjects who received a health screening examination from 2002 to 2003 were enrolled. Hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer were estimated in a multivariate Cox proportional regression analysis. A total of 323,430 subjects was enrolled (301,905 individuals without diabetes [No DM], 8643 diabetic patients with metformin treatment [metformin users], and 12,882 diabetic patients without metformin treatment [metformin non-users]). The median follow-up period was 12.7 years. Cumulative incidence of overall cancer was 7.9% (7.7, 10.3, and 11.1% in No DM, metformin users and non-users, respectively). Compared to metformin non-users, the fully adjusted HRs (95% CIs) of metformin users and No DM for overall cancer incidence were 0.73 (0.66-0.81) and 0.75 (0.64-0.88), respectively, in men and 0.83 (0.78-0.89) and 0.81 (0.72-0.92) in women., Conclusions: Diabetic patients receiving metformin treatment, and individuals without diabetes were at lower risk for cancer incidence than diabetic patients without metformin treatment., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aim: We investigated the association between statin use and new-onset diabetes (NODM) in Korean adults with hypercholesterolemia., Methods: This study performed based on data from the National Health Insurance Service-National Health Screening Cohort for the years from 2002 to 2015. Statin users classified as high- or low- users according to medication possession ratio. Statin non-users consisted of hypercholesterolemic participants who never used statin over the entire follow-up period. 21,469 participants (10,880 statin users, 10,589 statin non-users) with a median follow-up period of 12.5 years were included. We estimated the NODM risk based on the survival analyses. In particular, to adjust for confounding effects, we considered Cox proportional hazards regression models over three stages., Results: Compared to non-users, statin users had a significantly higher risk for NODM. The fully adjusted hazard ratios (aHRs) (95% confidential intervals [95% CIs]) of statin users for NODM were 1.43 (1.31-1.57) in men, and 1.86 (1.66-2.10) in women, respectively after adjusted confounding factors including age and lifestyle factors. Compared to high-users, aHRs (95% CIs) of low-users for NODM were 1.16 (1.03-1.30) and 1.28 (1.16-1.43) in men and women, respectively., Conclusions: In hypercholesterolemic patients, statin users have a higher risk of NODM than non-users., (Copyright © 2019 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

For bacteria sampling studies, various collection methods have been used to identify bacteria. To obtain accurate information about bacteria, high quality samples should be obtained. In order to obtain a high quality sample, a stable and large number of DNA copies must be collected. This study compared the efficiency of different methods of bacterial gDNA extraction and bacteria collection according to swabbing solution volumes and types. The efficiency of bacterial genomic DNA extraction was compared using a AccuPrep ® Genomic DNA Extraction kit, a QIAamp ® DNA Mini kit, and a MOBIO ® DNeasy PowerSoil kit. The DNA Mini kit was shown to extract the highest amount of gDNA, and sub-experiments were conducted using this kit. Phosphate-buffered saline and phosphate-buffered saline with 0.1% Tween 20 were used as collection solutions of various volumes (0, 40, 50, 60, 70, 80, 90, 100, 110, and 120 μL) using cotton swabs. Bacteria collection efficiency was highest when 70 μL PBS was used. The target strains collected in this experiment were Staphylococcus aureus and Escherichia coli , and these were quantified using the number of colony-forming units, DNA concentrations, and the number of DNA copies. These results can be used to efficiently bacterial collection for experiments in various fields., Competing Interests: Conflict of interestNo conflict of interest declared., (© Association of Microbiologists of India 2020.)

Though overall death from opioid overdose are increasing in the United States, the death rate in some states and population groups is stabilizing or even decreasing. Several states have enacted a Naloxone Accessibility Laws to increase naloxone availability as an opioid antidote. The extent to which these laws permit layperson distribution and possession varies. The aim of this study is to investigate differences in provisions of Naloxone Accessibility Laws by states mainly in the Northeast and West regions, and the impact of naloxone availability on the rates of drug overdose deaths.This cross-sectional study was based on the National Vital Statistics System multiple cause-of-death mortality files. The average changes in drug overdose death rates between 2013 and 2017 in relevant states of the Northeast and West regions were compared according to availability of naloxone to laypersons.Seven states in the Northeast region and 10 states in the Western region allowed layperson distribution of naloxone. Layperson possession of naloxone was allowed in 3 states each in the Northeast and the Western regions. The average drug overdose death rates increased in many states in the both regions regardless of legalization of layperson naloxone distribution. The average death rates of 3 states that legalized layperson possession in the West region decreased (-0.33 per 100,000 person); however, in states in the West region that did not allow layperson possession and states in the Northeast region regardless of layperson possession increased between 2013 and 2017.The provision to legalize layperson possession of naloxone was associated with decreased average opioid overdose death rates in 3 states of the West region.