Potential Molecular Markers Related to Lymph Node Metastasis and Stalk Resection Margins in Pedunculated T1 Colorectal Cancers Using Digital Spatial Profiling: A Pilot Study with a Small Case Series.

There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line (HL) and identify potential molecular risk factors for LNM. By leveraging the Cancer Transcriptome Atlas and digital spatial profiling technology, we meticulously analyzed discrete regions, including the head, HL, proximal stalk region (300-1000 µm from HL), and distal stalk region (1500-2000 µm from HL) to identify spatially sequential molecular changes. Our findings showed significant overall gene expression variations among the head, proximal stalk, and distal stalk regions of pedunculated T1 CRCs compared to the control adenoma. Compared to LNM-negative T1 CRCs, LNM-positive T1 CRC showed that the expression of genes involved in immune-related pathways such as B2M, HLA-B, and HLA-E were significantly downregulated in the distal stalk region compared to the proximal stalk region. In summary, our results may tentatively suggest considering endoscopic resection of the stalk with a minimum 2000 µm margin from the HL, taking into account the gene expression alterations related to immune-related pathways. However, we acknowledge the limitations of this pilot study, notably the small case series, which may restrict the depth of interpretation. Further validation is imperative to substantiate these findings.

Dysregulated microRNA Expression Relevant to TERT Promoter Mutations in Tonsil Cancer-A Pilot Study.

Tonsillar squamous cell carcinomas (TSCCs) exhibit high rates of human papillomavirus (HPV) positivity. The expression profiles of microRNA (miRNA), which are small RNA molecules that play pivotal roles in biological processes, in TSCC in relation to the HPV status and cancer-related genetic mutations are not well investigated. Herein, we expanded our previous research, which was focused on established clinicopathological and genetic mutational data, to profile miRNA expression in TSCC, aiming to identify clinically relevant targets for early diagnosis and therapeutic intervention. The miRNA profiles were analyzed using the nCounter Nanostring miRNA Expression assay in 22 surgically resected TSCC tissues and their contralateral normal tonsil tissues. The TERT promoter (TERTp) gene was the only relevant candidate gene associated with differentially expressed miRNAs in TSCC. Hierarchical clustering analysis revealed high expression levels of hsa-miR-1285-5p, hsa-miR-1203, hsa-miR-663a, hsa-miR-1303, hsa-miR-33a-5p, and hsa-miR-3615 coupled with low expression levels of hsa-miR-3182, hsa-miR-219a-2-3p, and hsa-miR-767-3p, which were associated with HPV-positive TSCC (p = 0.009). Functional enrichment analysis revealed that these dysregulated miRNAs tended to be involved in protein binding (molecular function) and cellular components (biological processes). Therefore, hsa-miR-1285-5p and hsa-miR-663a may be associated with HPV-positive TERTp-mutated tumors and may serve as potential treatment targets and biomarkers for early detection.

An elevated likelihood of stroke, ischemic heart disease, or heart failure in individuals with gout: a longitudinal follow-up study utilizing the National Health Information database in Korea.

Objective: Accumulating evidence from other countries indicates potential associations between gout and cardiovascular diseases; however, the associations of gout with cardiovascular diseases, particularly stroke, ischemic heart disease, and heart failure, remain ambiguous in the Korean population. We hypothesized that individuals with gout are at a higher likelihood of stroke, ischemic heart disease, or heart failure. This study expands upon previous research by ensuring a comparable baseline between patient and control groups and analyzing 16 years of data derived from an extensive healthcare database. Methods: We selected 22,480 patients with gout and 22,480 control individuals from the Korean National Health Insurance Service-Health Screening Cohort database (2002-2019), and matched them at a 1:1 ratio according to sex, age, income, and residence. A Cox proportional hazard model with weighted overlap was employed to examine the relationship between gout and the risk of stroke, ischemic heart disease, or heart failure after adjustment for several covariates. Results: The incidences of stroke, ischemic heart disease, or heart failure in participants with gout were slightly higher than those in controls (stroke: 9.84 vs. 8.41 per 1000 person-years; ischemic heart disease: 9.77 vs. 7.15 per 1000 person-years; heart failure: 2.47 vs. 1.46 per 1000 person-years). After adjustment, the gout group had an 11% (95% confidence interval [CI] = 1.04-1.19), 28% (95% CI = 1.19-1.37), or 64% (95% CI = 1.41-1.91) higher likelihood of experiencing stroke, ischemic heart disease, or heart failure, respectively, than the control group. Conclusion: The present findings suggest that individuals with gout in the Korean population, particularly those aged ≥ 60 years, were more likely to have stroke, ischemic heart disease, or heart failure.

Benefits of Music Intervention on Anxiety, Pain, and Physiologic Response in Adults Undergoing Surgery: A Systematic Review and Meta-analysis.

PURPOSE: Evidence on factors influencing the variations of music's effect on anxiety and pain in surgical patients is unclear. We aimed to elucidate the effects of music intervention on anxiety and pain throughstudy characteristics. METHODS: We conducted a search on the PubMed, CINAHL, Embase, Cochrane, and Web of Science databases from March 7 to April 21, 2022, for randomized controlled trials (RCTs) for the effect of music intervention on anxiety, pain, and physiological responses in surgical patients. We included studies published within the last 10 years. We assessed the risk of bias in the study using the Cochrane risk of bias tool for randomized trials and performed meta-analyses using a random-effects model for all outcomes. We used change-from-baseline scores as summary statistics and computed bias-corrected standardized mean differences (Hedges'g) for anxiety and pain outcomes and mean differences (MD) for blood pressure and heart rate. RESULTS: Of the 454 records retrieved, 30 RCTs involving 2280 participants were found to be eligible. Music intervention was found to be superior to standard care in reducing anxiety (Hedges' g = -1.48, 95% confidence interval: -1.97 to -0.98), pain (Hedges's g = -0.67, -1.11 to -0.23), systolic blood pressure (MD = -4.62, -7.38 to -1.86), and heart rate (MD = -3.37, -6.65 to -0.10) in surgical patients. The impact of music on anxiety and pain relief varied significantly depending on the duration of the intervention. The largest effect was observed in interventions lasting between 30 and 60 minutes, with a decrease in anxiety and pain. CONCLUSIONS: Music intervention is an effective way to reduce anxiety, pain, and physiological responses in surgical patients. Future reviews examining the influence of different types of surgery on the effects of music would add to the body of knowledge in this field. This study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) under the number CRD42022340203, with a registration date of July 4, 2022.

Comparison of the Concordance of Allergic Diseases between Monozygotic and Dizygotic Twins: A Cross-Sectional Study Using KoGES HTS Data.

Several epidemiological studies have demonstrated that genetic and environmental factors contribute to the development of allergic diseases. However, there is limited information on these factors in the Korean population. This study investigated the importance of genetic and environmental factors in allergic diseases, such as allergic rhinitis, asthma, allergic conjunctivitis, or atopic dermatitis, by comparing the disease incidence in Korean adult monozygotic and dizygotic twins. This cross-sectional study utilized data from 1296 twin pairs, including 1052 monozygotic and 244 dizygotic twins, aged over 20 years, from the Korean Genome and Epidemiology Study (2005-2014). The study utilized binomial and multinomial logistic regression models to compute odds ratios of disease concordance. The concordance rate (92%) of the presence or absence of atopic dermatitis in monozygotic twins was slightly higher than that in dizygotic twins (90.2%), which only had a borderline significance (p = 0.090). The concordance rates of other allergic diseases within monozygotic twins were lower compared to dizygotic twins (asthma, 94.3% vs. 95.1%; allergic rhinitis, 77.5% vs. 78.7%; allergic conjunctivitis, 90.6% vs. 91.8%), of which the differences were not statistically significant. Monozygotic twins had a higher proportion of cases in which both siblings had allergic diseases than dizygotic twins (asthma, 1.1% vs. 0.0%; allergic rhinitis, 6.7% vs. 3.3%; atopic dermatitis, 2.9% vs. 0.0%; allergic conjunctivitis, 1.5% vs. 0.0%), of which the differences were also not statistically significant. In conclusion, our results appear to indicate the relative importance of environmental factors over genetic factor in the development of allergic diseases in Korean adult monozygotic twins.

Different miRNAs Related to FBXW7 Mutations or High Mitotic Indices Contribute to Rectal Neuroendocrine Tumors: A Pilot Study.

Recent studies suggest that miRNA may be involved in the development of rectal neuroendocrine tumors (NETs). We explored the frequency of clinicopathologically relevant mutations and miRNA expression in rectal NETs to examine molecular profiles related to prognosis and behavior. Twenty-four eligible specimens with endoscopically excised rectal NETs were selected. Next-generation sequencing and an miRNA expression assay were used to evaluate the expression profile relevant to common genetic mutations in rectal NETs. Kyoto Encyclopedia of Genes and Genomes analysis predicted that the possible target signaling pathways were correlated with dysregulated miRNAs. Nineteen rectal NETs harbored more than one mutation in the 24 cancer-related genes. Seven miRNAs (hsa-miR-769-5p, hsa-miR-221-3p, hsa-miR-34a-5p, hsa-miR-181c-5p, hsa-miR-1246, hsa-miR-324-5p, and hsa-miR-361-3p) were significantly down-regulated in tumors harboring the FBWX7 mutation. Unsupervised hierarchical clustering analysis showed that up-regulation of these seven miRNAs may result in high mitotic indices, indicating the role of miRNAs in tumor progression. Among the down-regulated miRNAs, hsa-miR-769-5p was strongly correlated with extracellular matrix-receptor interaction and lysine degradation. Among the clinicopathological factors, up-regulated hsa-miR-3934-5p was linked to an increased mitotic count. No change in miRNA expression was associated with a tumor size >1 cm, lymphovascular invasion, or Ki-67 index. In summary, we identified different miRNA signatures involved in FBXW7 mutations or high mitotic indices in rectal NETs, which may play a critical role in tumor behavior.

Assessment of the Mutation Profile of Tonsillar Squamous Cell Carcinomas Using Targeted Next-Generation Sequencing.

Data regarding driver mutation profiles in tonsillar squamous cell carcinomas (TSCCs) remain scarce, limiting the understanding of its pathogenesis and unexpected behavior in the updated staging system. We investigated the incidence of clinically relevant mutations and their contribution in the prognosis of the condition, and their association with human papillomavirus (HPV) infection and adjuvant therapy. We subjected 43 surgically resected TSCC samples to targeted next-generation sequencing, determined their HPV status using polymerase chain reaction, and performed The Cancer Genomic Atlas and Gene Set Enrichment analyses. Thirty-five TSCC samples (81.4%) showed at least one oncogenic/likely oncogenic mutation among twenty-nine cancer-related genes. The top five mutated genes were TP53 (46.5%), PIK3CA (25.6%), PTEN (18.6%), EGFR (16.3%), and SMAD4 (14.0%). The EGFR pathway was the most frequently affected (51.2%), followed by the p53 (48.8%), PI3K (39.5%), and RTK (34.9%) pathways. The gene set enrichment analysis confirmed that the genes involved in signal transduction, such as growth factor receptors and second messengers, EGFR tyrosine kinase inhibitors, and PI3K signaling pathways, were mostly related with TSCCs. TP53 mutation was an independent prognostic factor predicting worse overall survival in the adjuvant therapy group. RTK mutations were related to survival in all patients and in the HPV-positive group, but multivariate analyses showed no significance. In conclusion, oncogenic/likely oncogenic mutations were relatively high in TSCCs, and TP53 and RTK mutations may be candidate predictors for poor prognosis in the adjuvant therapy and HPV-positive groups, respectively, under the updated staging system.

Comparison of the Concordance of Cardiometabolic Diseases and Physical and Laboratory Examination Findings between Monozygotic and Dizygotic Korean Adult Twins: A Cross-Sectional Study Using KoGES HTS Data.

This study investigated the contribution of genetic and environmental factors to cardiometabolic diseases (CMDs) by comparing disease concordance in monozygotic and dizygotic twins. This cross-sectional study analyzed 1294 (1040 monozygotic and 254 dizygotic) twin pairs (>20 years) based on the Korean Genome and Epidemiology Study data (2005−2014). The odds ratios of disease concordance were calculated using binomial and multinomial logistic regression models. The occurrence of CMDs (hypertension, hyperlipidemia, type 2 diabetes, cerebral stroke, transient ischemic attack, and ischemic heart disease) and related physical and laboratory levels did not differ between the monozygotic and dizygotic twin groups. The odds for concordance of the presence/absence of CMDs and the likelihood of incident CMD within monozygotic twins were comparable to that of dizygotic twins. The absolute differences in hemoglobin A1c, insulin, low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, and systolic blood pressure were lower in monozygotic twins than in dizygotic twins. Absolute differences in fasting glucose and diastolic blood pressure did not differ between groups. Although baseline levels of several laboratory parameters related to CMD showed a strong likelihood of heritability in monozygotic twins, CMD phenotype appears to be largely affected by environmental factors.

Comparison of Concordance of Peptic Ulcer Disease, Non-Adenomatous Intestinal Polyp, and Gallstone Disease in Korean Monozygotic and Dizygotic Twins: A Cross-Sectional Study.

Epidemiological studies have suggested the role of multiple genetic and environmental factors in the development of non-neoplastic gastrointestinal (GI) diseases; however, little information is available on these factors in the Korean population. Therefore, this cross-sectional study explored the effect of these factors by analyzing the concordance of several benign GI disorders in 525 monozygotic twins compared to that in 122 dizygotic twins aged >20 years from the Healthy Twin Study data of the Korean Genome and Epidemiology Study (2005-2014). Chi-square test, Wilcoxon rank-sum, and binomial and multinomial logistic regression models were used for statistical analysis. There was lack of concordance of gastric/duodenal ulcers and cholelithiasis/cholangitis between monozygotic twins compared to that in dizygotic twins, suggesting that environmental factors may mediate those concordant disease expressions in monozygotic twins. The concordance of intestinal polyps in monozygotic twins was 32% lower than that in dizygotic twins (p = 0.028), indicating that the effect of genetic factors on the risk for intestinal polyp development may be low. In conclusion, the lack or low concordance of several benign GI diseases between monozygotic and dizygotic twin groups suggests the relative importance of environmental factors, indicating that these are preventable diseases.

Comparison of the Coincidence of Osteoporosis, Fracture, Arthritis Histories, and DEXA T-Score between Monozygotic and Dizygotic Twins: A Cross-Sectional Study Using KoGES HTS Data.

We explored the genetic and environmental inter-relationships among osteoporosis, fracture, arthritis, and bone mineral density concordance in monozygotic twins compared to those in dizygotic twins. This cross-sectional research assessed data of 1032 monozygotic and 242 dizygotic twin pairs aged >20 years included in the Healthy Twin Study data of the Korean Genome and Epidemiology Study between 2005 and 2014. Outcomes of interest included illness concordance and absolute differences in dual-energy X-ray absorptiometry (DEXA) T-scores. We found comparable concordances of osteoporosis, fractures, osteoarthritis, and rheumatoid arthritis between monozygotic and dizygotic twins. Medical histories of osteoporosis, fractures caused by accident or falling, osteoarthritis, and rheumatoid arthritis were not distinct between monozygotic and dizygotic twins. Accidental fracture occurrence in both monozygotic twins showed significantly lower odds than that in dizygotic twins. Genetic influence on liability to fracture risk might thus be maintained. DEXA T-scores for bone mineral density indicated more comparable tendencies within monozygotic twin pairs than within dizygotic ones, suggesting the relative importance of genetic contribution to bone mineral density. The relative importance of genetic factors in bone mineral density is sustained between monozygotic twins; overt disease expression of osteoporosis, fractures, or arthritis may be affected by environmental factors.

Changes in the Incidence Rates of Gastrointestinal Diseases Due to the COVID-19 Pandemic in South Korea: A Long-Term Perspective.

We investigated whether the coronavirus disease 2019 (COVID-19) pandemic, in conjunction with public health measures, influenced the incidence of gastrointestinal diseases according to age and sex during the pandemic. Changes in the monthly incidence rates (January 2018 to June 2021) of common gastrointestinal diseases were assessed using data from the Korean National Health Insurance Service by comparing the data of two periods: before COVID-19 (January 2018-February 2020) and during COVID-19 (March 2020-June 2021). The Mann-Whitney U test and Levene's test were used to compare the differences in the incidences before and during the pandemic. In the pandemic period, compared to in the pre-COVID-19 period, the incidence rates of ulcerative colitis, Crohn's disease, cholelithiasis, and esophageal reflux significantly increased, whereas those of infective enteritis and irritable bowel syndrome decreased, regardless of age or sex. There were no significant changes in the incidence rates of pancreatitis, acute appendicitis, liver cirrhosis, and hemorrhoids. No seasonal variations in gastrointestinal disease occurrence were observed. In conclusion, the COVID-19 pandemic may have had unprecedented and long-term impacts on the epidemiology of gastrointestinal disease. These changes may indicate a substantial future burden on healthcare resources during the recovery phase of the pandemic and thereafter.

Potential Cancer Risk in Patients with Rheumatoid Arthritis: A Longitudinal Korean Population-Based Analysis.

The potential link between rheumatoid arthritis (RA) and cancer incidence needs to be validated due to inconsistent results between Asian and Western countries. We explored the long-term association of RA with the overall and organ-specific cancer incidence using nationwide population data. This longitudinal follow-up study (2002-2015) included 3070 patients with RA and 12,280 controls (1:4 propensity score-matched for sex, age, residence, and income) from the Korean National Health Insurance Service-Health Screening Cohort database. A Cox proportional hazard model estimated the hazard ratio for malignancy following adjusting for covariates. Despite the similar overall cancer incidence between RA and control groups, differences in the incidence of organ-specific cancers were noted: the RA group had a 1.63-fold greater likelihood for lung cancer (95% confidence interval 1.11-2.40). In the sex-stratified subgroup analyses, the male RA patients exhibited higher odds of lung and thyroid cancer but a lower probability for colorectal cancer; no such associations were detected in either female patients with RA or age subgroups. In summary, the higher likelihood for lung cancer in Korean RA patients, especially thyroid and lung cancer in male RA patients, seems to be characteristic, which needs to be carefully monitored.

Possible Association between the Use of Proton Pump Inhibitors and H2 Receptor Antagonists, and Esophageal Cancer: A Nested Case-Control Study Using a Korean National Health Screening Cohort.

Although safety concerns regarding proton pump inhibitor (PPI)/H2-receptor antagonists (H2RA) in the incident esophageal cancer have been raised, the Asian-based report is unclear. We investigated the estimated likelihood of incident esophageal cancer­its mortality depending on prior history of PPI/H2RA use­and gastroesophageal reflux disease (GERD) in Koreans. Using the Korean National Health Insurance Service-Health Screening Cohort data (2002−2015), a case−control study was retrospectively conducted, including 811 patients with incident esophageal cancer and 3244 controls matched with sex, age, income, and residence. Propensity score overlap weighting was adjusted to balance the baseline covariates. Overlap propensity score-weighted logistic regression analyses were assessed to determine associations of the prior exposure of PPI/H2RA (current vs. past) and the medication duration (<30-, 30−90-, vs. ≥90-days) with incident esophageal cancer and its mortality among the total participants or those with/without the GERD episodes, after adjusting for multiple covariates including PPI/H2RA. The current exposure to either PPI or H2RA showed higher odds for incident esophageal cancer than the nonuser group ([13.23; 95%CI 10.25−17.06] and [4.34; 95%CI 3.67−5.14], respectively), especially in all adults over the age of 40 years without GERD. Both current and past exposures to PPI showed a decreased probability of mortality compared with those of the nonuser group ([0.62; 95%CI 0.45−0.86] and [0.41; 95%CI 0.25−0.67], respectively). However, current or past exposure to H2RA harbored the mutually different likelihoods for mortality depending on the presence of GERD and old age. This study carefully speculates on the possible link between PPI/H2RA and incident esophageal cancer in the Korean population. Mortality appears to be affected by certain risk factors depending on drug types, exposure history, old age, and the presence of GERD.

Potential Association of Osteoporosis and Not Osteoporotic Fractures in Patients with Gout: A Longitudinal Follow-Up Study.

Health issues associated with gout and increased occurrence of osteoporosis or fractures have been raised; however, the results are elusive. Herein, we explored the possible link between gout and incident osteoporosis/osteoporotic fractures based on long-term follow-up nationwide data. This study enrolled 16,305 patients with gout and 65,220 controls who were matched by propensity score at a 1:4 ratio on the basis of sex, age, income, and residence from the Korean National Health Insurance Service-Health Screening Cohort database (2002−2015). A Cox proportional hazard model was employed to identify the relevance between gout and incident osteoporosis/fractures, following adjustment for various covariates. In the follow-up period, osteoporosis developed in 761 individuals with gout and 2805 controls (incidence rates: 8.0 and 7.3/1000 person-years, respectively), and each osteoporotic fracture in the distal radius (2.8 vs. 2.7/1000 person-years), hip (1.3 vs. 1.3/1000 person-years), and spine (4.5 vs. 4.5/1000 person-years) occurred in gout and control groups, respectively. After adjustment, the gout group presented an 11% higher development of osteoporosis (95% confidence interval = 1.02−1.20) than the controls (p = 0.011). Subgroup analyses maintained the augment of incident osteoporosis in sufferers with gout, particularly in either men or <60 years. However, no such relevance was identified between gout and incident osteoporotic fractures at any site. In conclusion, gout may result in a slightly elevated likelihood of developing osteoporosis, and not osteoporotic fractures, in the Korean population.

The Occurrence of Alzheimer's Disease and Parkinson's Disease in Individuals With Osteoporosis: A Longitudinal Follow-Up Study Using a National Health Screening Database in Korea.

Background: Public health concerns regarding the potential link between osteoporosis and the increased occurrence of Alzheimer's disease (AD) and Parkinson's disease (PD) have been raised, but the results remain inconsistent and require further validation. Here, we investigated the long-term relationship of osteoporosis with the occurrence of AD/PD using data from a large-scale nationwide cohort. Methods: This longitudinal follow-up study included 78,994 patients with osteoporosis and 78,994 controls from the Korean National Health Insurance Service-Health Screening Cohort database (2002-2015) who were matched using propensity score matching at a 1:1 ratio based on age, sex, income, and residential area. A Cox proportional hazard model was used to assess the association between osteoporosis and the occurrence of AD/PD after adjusting for multiple covariates. Results: During the follow-up period, AD occurred in 5,856 patients with osteoporosis and 3,761 controls (incidence rates: 10.4 and 6.8 per 1,000 person-years, respectively), and PD occurred in 1,397 patients and 790 controls (incidence rates: 2.4 and 1.4 per 1,000 person-years, respectively). The incidences of AD and PD were significantly higher in the osteoporosis group than in the matched control group. After adjustment, the osteoporosis group exhibited 1.27-fold and 1.49-fold higher occurrences of AD (95% confidence interval (CI) = 1.22-1.32) and PD (95% CI = 1.36-1.63) than the controls, respectively. The results of subgroup analyses supported the increased occurrence of AD and PD in patients with osteoporosis, independent of income, residential area, obesity, smoking, alcohol consumption, hyperlipidemia, hypertension, or blood glucose level. Conclusion: Our results indicate that the presence of osteoporosis may increase the likelihood of developing two common neurodegenerative diseases in adults aged ≥40 years.

Association between Statin Use and Gastric Cancer: A Nested Case-Control Study Using a National Health Screening Cohort in Korea.

Concerns about the hazards of statins on the development and mortality of stomach cancers remain controversial. Here, we investigated the likelihood of incident gastric cancers and related mortality depending on statin exposure, statin type, and the duration of use. This nested case-control-designed study was composed of 8798 patients who were diagnosed with gastric cancer and matched with 35,192 controls at a 1:4 ratio based on propensity scores of age, sex, residential area, and income from the Korean National Health Insurance Service-Health Screening Cohort database (2002-2015). Propensity score overlap weighting was adjusted to balance the baseline covariates. Overlap propensity score-weighted logistic regression analyses were assessed to determine associations of the prior use of statins (any statin, hydrophilic statins vs. lipophilic statins) with incident gastric cancer and its mortality depending on the medication duration (<180 days, 180-545 days, and >545 days) after adjusting for multiple covariates. After adjustment, the use of any statin, hydrophilic statins, or lipophilic statins showed significant associations with lower odds for incident stomach cancer when used for a short-term period (180-545 days) (OR = 0.88, 95% CI = 0.81-0.86, p = 0.002; OR = 0.78, 95% CI = 0.66-0.92, p = 0.004; and OR = 0.91, 95% CI = 0.84-0.99, p = 0.039, respectively) compared to the control group. Hydrophilic statin use for 180-545 days was associated with 53% lower overall mortality (OR = 0.47; 95% CI = 0.29-0.77). In subgroup analyses, beneficial effects on both cancer development and mortality persisted in patients ≥65 years old, patients with normal blood pressure, and patients with high fasting glucose levels. There were no such associations with long-term statin use (>545 days). Thus, the current nationwide cohort study suggests that prior short-term statin use may have anti-gastric cancer benefits in elderly patients with hyperglycemia.

Effects of Lavender on Anxiety, Depression, and Physiological Parameters: Systematic Review and Meta-Analysis.

PURPOSE: The recent evidence suggested substantial anxiolytic efficacy of lavender. The aim of this study was to examine the efficacy of lavender for anxiety, depression, and physiological parameters and to elucidate the differential effects of lavender on anxiety and depression by study characteristics. METHODS: A systematic review and meta-analysis was performed following the PRISMA guidelines. We searched PubMed, Embase, Cochrane Library, Web of Science, and Cumulative Index of Nursing and Allied Health Literature databases for randomized controlled trials investigating the efficacy of lavender on anxiety, depression, or physiological parameters in humans. We assessed the risk of bias within studies with the revised Cochrane risk of bias tool for randomized trials. We used random effect model to estimate the average effect and computed bias-corrected standardized mean difference as effect size metric, Hedges' g for all outcomes. RESULTS: Lavender was superior to placebo or no treatment in reducing anxiety (Hedges' g = -0.72, 95% confidence interval [CI] -0.90 to -0.55, p value <.001), depression (Hedges' g = -0.43, 95% CI, -0.59 to -0.27, p value <.001), and systolic blood pressure (Hedges' g = -0.23, 95% CI, -0.41to -0.05, p value = .01). The moderator analysis by meta-regression indicated that route of administration accounted 6.5% (p value = .187) for the heterogeneity in anxiolytic effects, sessions of treatment accounted 13.2% (p value = .055), and participants' health state accounted 8.9% (p value = .131) for the variance in anxiolytic effects. CONCLUSION: Lavender aromatherapy showed substantial effect in reducing anxiety and depression, and sessions of administration increased the anxiolytic effects. The effects on physiological parameters showed small with inconsistent significances and randomized controlled trials on the effect of lavender on depression were scarce. Future trials on depression and physiological parameters are recommended, and increasing the sessions of administration is recommended.

Negative Prognostic Implication of TERT Promoter Mutations in Human Papillomavirus-Negative Tonsillar Squamous Cell Carcinoma Under the New 8th AJCC Staging System.

Telomerase reverse transcriptase gene promoter (TERTp) mutation is a potential candidate for pathogenesis and therapeutic target of tonsillar squamous cell carcinomas (TSCCs) in association with human papillomavirus (HPV). Their clinical relevance has not been validated under the new 8th American Joint Committee on Cancer (AJCC) staging system. We analyzed real-time peptide nucleic acid-mediated PCR and sequencing methods (TERTp mutation) and real-time PCR-based assay (HPV) in 80 surgically resected TSCCs. The 8th edition staging system improved the stratification of the early and advanced stages and between T or N categories for overall survival over the 7th edition. TERTp mutation was found in 7.5%, and HPV in 80.0% of the patients. The majority (83.3%) of TERTp mutation cases were HPV-positive TSCCs. Applying the 8th edition staging system, TERTp mutation was an independent factor of poor prognosis for disease-free survival (DFS) in TSCC patients, supporting the clinical significance of TERTp mutation in tonsil cancer. TERTp mutations were also negatively correlated with overall survival and DFS in HPV-negative TSCCs. Conclusively, TERTp mutation provides negative prognostic impact on survival of surgically managed tonsil cancers staged with the AJCC 8th edition.

Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC. METHODS: We investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers. RESULTS: PD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002). CONCLUSIONS: PIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.