BACKGROUND: Epstein-Barr (EB) virus infection stimulates the production of vascular endothelial growth factor (VEGF), which contributes to the progression of angiogenesis. Angiogenesis plays an important role in the development of atherosclerosis. Since serum anti-early antigen EB virus IgG (EBV EA-IgG) titer is a sign of active EB virus infection, EBV EA-IgG titer could be associated with atherosclerosis. The number of minor (T) alleles in VEGF polymorphism rs3025039 has been reported to be inversely associated with serum VEGF concentration, suggesting that rs3025039 might have a strong influence on the association between EBV EA-IgG titer and atherosclerosis. By focusing on the role of VEGF in the development of atherosclerosis, this study aimed to investigate the association between active EB virus infection and atherosclerosis. METHODS: A cross-sectional study of 2,661 older Japanese individuals aged 60-89 years who participated in annual health check-ups during 2017-2019 was conducted. Logistic regression was used to evaluate the association between EBV EA-IgG titer and atherosclerosis in relation to rs3025039 genotype. The influence of rs3025039 (T) allele carrier status on the association between EBV EA-IgG titer and atherosclerosis was also evaluated by using logistic regression. RESULTS: Among rs3025039 CC-homozygotes, with the lowest EBV EA-IgG titer tertile as the reference, the multivariable odds ratio (95% confidence interval) was 1.11 (0.82, 1.50) for the medium tertile and 1.07 (0.78, 1.47) for the high tertile. Among rs3025039 (T) allele carriers, the corresponding values were 1.44 (0.88, 2.36) and 1.88 (1.15, 3.05), respectively. There was a significant interaction between rs3025039 (T) allele carrier status and the association between EBV EA-IgG titer and atherosclerosis (adjusted p = 0.0497). CONCLUSION EBV EA-IgG titer was significantly positively associated with atherosclerosis only among participants who are genetically less likely to have progressive angiogenesis. An angiogenesis-related genetic factor was revealed as a determinant of the association between EBV EA-IgG titer and atherosclerosis. These findings introduce a novel concept that could explain the association between viral infection and atherosclerosis.
Humans ; Aged ; Male ; Middle Aged ; Female ; Japan/epidemiology* ; Atherosclerosis/virology* ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/genetics* ; Epstein-Barr Virus Infections/virology* ; Polymorphism, Single Nucleotide ; Cross-Sectional Studies ; Herpesvirus 4, Human ; Antigens, Viral/immunology* ; Antibodies, Viral/blood* ; Immunoglobulin G/blood* ; Genotype ; East Asian People

BACKGROUND: Subclinical hypothyroidism (SCH) has been reported to be associated with lower endothelial progenitor (CD34-positive) cell count, whereas an inverse association between circulating CD34-positive cell count and height loss is documented. Reports indicate height loss to be associated with all-cause mortality, and a higher CD34-positive cell count has been shown to predict longer life. Therefore, evaluating the association between SCH and height loss provides mechanistic insights underlying the association between height loss and mortality risk. METHODS: A prospective study involving 1,599 participants with normal free triiodothyronine (T3) and free thyroxine (T4) levels was conducted to determine the association between SCH and height loss.Since the free T4 level influences the supply of active thyroid hormone (free T3), the analysis was stratified by the median free T4 level. Height loss was defined as the highest quintile of annual height decrease. RESULTS: SCH was positively associated with height loss in participants with low-normal free T4 levels (below the median), but not in those with high-normal free T4 levels (at or above the median). After adjusting for sex, age, free T3 level, atherosclerosis, and known cardiovascular risk factors, the adjusted odds ratios (95% confidence interval) for height loss were 1.88 (1.02, 3.47) and 1.92 (1.02, 3.62) in the low-normal free T4 group. The corresponding values in the high-normal free T4 group were 0.37 (0.08, 1.69) and 0.43 (0.09, 1.97). CONCLUSION SCH could influence height loss, and free T4 might influence the association between SCH and height loss in euthyroid individuals. These results clarify the mechanisms underlying the association between height loss and mortality risk.
Humans ; Hypothyroidism/epidemiology* ; Thyroxine/blood* ; Male ; Female ; Prospective Studies ; Middle Aged ; Body Height ; Adult ; Aged ; Risk Factors

Objective: In recent years, an association between serum soluble immune checkpoint molecules (sICMs) and malignant tumors has been reported, which may become important biomarkers in the future. Although several reports have suggested a correlation between sICMs and prognosis, their origin is unclear. In this study, changes in serum soluble PD-L1 (sPD-L1) during the perioperative period and its origin were analyzed in patients with lung cancer.Patients and Methods: Patients with lung tumors (n=39) were included. Samples for sPD-L1 measurements were collected at five time points before and after surgery, and their changes over time were analyzed. ELISA was used to measure sPD-L1 levels.Results: Thirty-nine patients with lung tumors (31, males; 8, females; age, 74 (years) ± 7.7 (range: 51–89) years; malignancy/benign, 33/6) were enrolled. Eight cases of driver gene mutation-positive tumors were included. Twenty-eight (72%) patients were smokers, and their performance status was 0-1 in all 39 patients. PD-L1 TPS was ≥50%/1–49%/<1% in 8/10/14 patients. Stage I/II/III/IV/postoperative recurrence of lung cancer was observed in 21/0/6/5/1 patients, respectively. There were no significant correlations between sPD-L1 levels and clinicopathological features and no correlation with PD-L1 TPS. Comparing localized lesions (stages I–III) with advanced lesions (stage IV and postoperative recurrence), the distribution of sPD-L1 was slightly higher in advanced lesions, although the difference was not significant. No obvious changes in sPD-L1 expression were observed before and after surgery.Conclusion: sPD-L1 levels tended to be high in stage III and above lung cancer. There was no change in sPD-L1 levels before and after surgery. sPD-L1 levels did not correlate with the PD-L1 TPS.

Background/Aims: Detailed evaluations of overlapping constipation and gastroesophageal reflux disease (GERD) have not been conducted in Japan. The REACTION-J2 study examined the overlap of these diseases in Japan. Methods: This internet-based survey recruited participants from general public survey panels. Questions included demographic and medical data and assessments based on validated measures for constipation and GERD. Associations between background factors affecting constipation/GERD overlap, disease measures, and treatment were also evaluated. Results: Among 10 000 survey responses received, functional constipation (Rome IV diagnostic criteria) was reported by 439 participants; chronic constipation (Japanese guidelines) by 3804 participants; and subjective constipation symptoms by 2563 participants. The number of participants with constipation/GERD overlap ranged from 73 to 1533 depending on the criteria used. Regardless of the definition used, all GERD groups had significantly higher odds of being constipated than non-GERD participants: the OR (95% CI) for all 9 combinations of definitions ranged between 1.56 (1.21, 2.01) and 2.67 (2.44, 2.92) (all P ≤ 0.001). Straining, hard stools, and sensations of incomplete evacuation and anorectal obstruction/blockage, according to chronic constipation criteria, were common.Participants with constipation/GERD overlap had poorer quality of life (P < 0.001) and worse GERD symptom scores (P < 0.001). The frequency of abnormal stools was highest (P < 0.001) in the constipation/GERD overlap group. In the overlap group, 52.4% and 26.0% used gastric and constipation medication, respectively. Conclusion Individuals with constipation/GERD overlap tend to have worsened symptoms and quality of life.

Background/Aims: Chronic constipation and lifestyle factors can affect sleep quality. We evaluated the relationship between chronic constipation and sleep in the Japanese population. Methods: This cross-sectional internet-based survey included 3000 subjects with constipation, classified according to sleep status (good/poor).Primary endpoints were Bristol stool form scale (BSFS) score and correlations between sleep disorder criteria of the Pittsburgh Sleep Quality Index (PSQI) and sleep status (good/poor sleep). Secondary endpoints included correlations between quality of life (QOL) and mood, medical, lifestyle, and sleep factors. Results: The proportion of participants with BSFS category 4 (normal stool) was significantly higher in the good sleep group (P < 0.001). Sleep disturbance (P < 0.05), sleep quality, and duration, use of hypnotic medication, and daytime dysfunction of PSQI (all P < 0.001) significantly correlated with poor sleep. In the poor sleep group, QOL was significantly worse and anxiety and depression levels were significantly higher (allP < 0.001) compared with the good sleep group. Anemia and smoking (both P < 0.05), recent body weight increases, and poor eating habits (all P < 0.001) were significantly higher in the poor sleep group. Male sex, onset associated with change in frequency of stools, sensation of incomplete evacuation for at least 25% of defecations, and manual maneuvers to facilitate at least 25% of defecations correlated with poor sleep. Conclusions Subjects with constipation and poor sleep experienced severe symptoms and had poor QOL. These data support the need for a multifocal treatment approach, including lifestyle advice and pharmacotherapy.

Background/Aims: Chronic constipation and lifestyle factors can affect sleep quality. We evaluated the relationship between chronic constipation and sleep in the Japanese population. Methods: This cross-sectional internet-based survey included 3000 subjects with constipation, classified according to sleep status (good/poor).Primary endpoints were Bristol stool form scale (BSFS) score and correlations between sleep disorder criteria of the Pittsburgh Sleep Quality Index (PSQI) and sleep status (good/poor sleep). Secondary endpoints included correlations between quality of life (QOL) and mood, medical, lifestyle, and sleep factors. Results: The proportion of participants with BSFS category 4 (normal stool) was significantly higher in the good sleep group (P < 0.001). Sleep disturbance (P < 0.05), sleep quality, and duration, use of hypnotic medication, and daytime dysfunction of PSQI (all P < 0.001) significantly correlated with poor sleep. In the poor sleep group, QOL was significantly worse and anxiety and depression levels were significantly higher (allP < 0.001) compared with the good sleep group. Anemia and smoking (both P < 0.05), recent body weight increases, and poor eating habits (all P < 0.001) were significantly higher in the poor sleep group. Male sex, onset associated with change in frequency of stools, sensation of incomplete evacuation for at least 25% of defecations, and manual maneuvers to facilitate at least 25% of defecations correlated with poor sleep. Conclusions Subjects with constipation and poor sleep experienced severe symptoms and had poor QOL. These data support the need for a multifocal treatment approach, including lifestyle advice and pharmacotherapy.

Background/Aims: We retrospectively analyzed Crohn’s disease (CD) patients with small intestinal strictures who underwent single-balloon enteroscopy (SBE) to ascertain whether prototype SBEs with a passive bending mechanism and high force transmission insertion tube had better insertability in the small intestine than a conventional SBE. Methods: Among 253 CD patients who underwent SBE, we identified 94 CD patients who had undergone attempted endoscopic balloon dilatation (EBD) for small intestinal stenosis for inclusion in this study. We analyzed whether the type of scope used for their initial procedure affected the cumulative surgery-free rate. For the insertability analysis, patients who underwent SBE at least twice were divided into 3 groups according to the type of scope used: conventional SBE only, prototype SBE only, and both conventional and prototype SBEs. For each group, depth of insertion, procedure time, and number of EBDs were compared in the same patient at different time points. Results: The success rate of EBD was 88.3%. The 5- and 10-year cumulative surgery-free rate was 75.7% and 72.8%, respectively. Cox regression analysis indicated that the factors contributing to surgery were long stricture (≥2 cm), EBD failure, and elevated Crohn’s Disease Activity Index, but not the type of scope used for EBD. The prototype SBEs significantly improved the depth of insertion (P=0.03, Wilcoxon’s signed-rank test). Conclusions In CD patients with small intestinal stenosis, the prototype SBEs with a passive bending mechanism and high force transmission insertion tube did not improve long-term EBD outcome but did improve deep insertability. (Clinical Trial Registration No. UMIN000037102)

No abstract available.
Infectious Mononucleosis* ; Splenic Infarction*

A 78-year-old man was diagnosed with adult T-cell leukemia/lymphoma (ATL) and was started on standard chemotherapy 1 year earlier. However, treatment was discontinued because of adverse drug reactions and worsening delirium. Thereafter, he remained stable and was followed up while receiving etoposide. He then visited our hospital because of acute abdominal pain and underwent surgery with a diagnosis of gastrointestinal perforation. Intraoperative observation showed a reddened, concentric wall thickening measuring 4 cm and a perforation site in the ileum, and thus partial resection of the small bowel was performed. The histological diagnosis was small bowel perforation due to tumor cell invasion. Two months postoperatively, he started a less intensive chemotherapy regimen along with palliative care, and died due to the primary disease approximately 5 months postoperatively. ATL involves systemic organs because of its high organ-affinity. Once it involves the gastrointestinal tract, various gastrointestinal symptoms can occur. Patients with ATL are at risk of developing gastrointestinal perforation at any time during the clinical course. Therefore, clinicians should be aware that once gastrointestinal perforation develops, the prognosis becomes extremely poor. Assessment of the disease state, early detection of gastrointestinal lesions, and prevention of opportunistic infections appear to be important in the management of patients with ATL.

BACKGROUND: Sedentary behaviors have recently become an important public health issue. We aimed to investigate the relationship between screen time and nutrient intake in children and adolescents. METHODS: The present study was conducted in 2013. Data were collected from children and adolescents aged between 6 and 15 years old in Shika town. Questionnaires were distributed to 1459 subjects, 1414 of whom participated in the study (96.9%). Sedentary behaviors were assessed based on participants' screen behaviors (television (TV) viewing, personal computer (PC) use, and mobile phone (MP) use). The main outcomes were the intake of nutrients from a validated food frequency questionnaire. Analysis of covariance (ANCOVA) was used to examine the significance of differences in nutrient intake estimates. Multivariate linear regression analyses, adjusting for age, BMI, and physical activity, were used to provide parameter estimates (β) and 95% CI for the relationship between screen time and nutrient intake. RESULTS: In boys, longer TV viewing times correlated or tended to correlate with a lower intake of protein, potassium, calcium, iron, vitamin K, vitamin B-2, and total dietary fiber. In girls, longer TV viewing times correlated with a lower intake of protein, sodium, calcium, vitamin D, and vitamin B-2. Longer TV viewing times correlated with a higher intake of n-6 fatty acids in girls. PC use was related or tended to be related to a lower intake of potassium, iron, vitamin K, and folic acid in boys, but not in girls. A relationship was observed between MP use and a lower intake of vitamin K in boys, and MP use and a higher intake of vitamin D in girls. CONCLUSIONS The present results revealed that longer TV viewing times are associated with less protein, minerals, vitamins, and total dietary fiber intake in children and adolescents. It was also revealed that boys with PC use have less minerals and vitamins. These results support the need to design intervention programs that focus on decreasing TV viewing time in both sexes and PC use in boys while encouraging adherence to dietary guidelines among children and adolescents.
Adolescent ; Body Mass Index ; Child ; Cross-Sectional Studies ; Diet ; Energy Intake ; Exercise ; Female ; Humans ; Japan ; Male ; Screen Time ; Sedentary Behavior ; Sex Factors ; Socioeconomic Factors