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Abstract To evaluate the antibody response following the initial four doses of mRNA vaccines (BNT162b2 or mRNA-1273) in SARS-CoV-2-naïve healthy adults and investigate factors influencing antibody titer increases, this prospective cohort study was conducted in Japan from March 2021. The study included participants who received either the 1st and 2nd doses (n = 467), 3rd dose (n = 157), or 4th dose (n = 89). Blood samples were collected before and up to 6 months after each dose, and anti-receptor-binding domain antibody levels were measured. Multivariate analysis (usin multiple linear regression or linear mixed models) revealed several factors significantly associated with higher post-vaccination antibody levels, including mRNA-1273 vaccine (after the 1st and 2nd dose), male gender (after the 3rd and 4th doses), younger age (after the 1st and 2nd dose), non-smoking status (after the 2nd dose), non-use of immunosuppressive agents (after the 1st dose), higher pre-vaccination antibody titers (after the 2nd, 3rd, and 4th doses), and higher post-vaccination fever (after the 2nd and 4th doses). Furthermore, longer intervals since the last dose were significantly associated with higher antibody levels after the 3rd and 4th doses. These findings provide valuable insights for optimizing vaccination strategies.

Background: To evaluate antibody responses against the primary series of vaccination of severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2] vaccines in the staff and residents of Japanese geriatric intermediate care facilities. Methods: All subjects (159 staff and 96 residents) received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Baseline data of subject were collected using a structured form. Serum samples were collected three times: before vaccination, 3 weeks after the first dose, and 4 weeks after the second dose, and anti-receptor binding domain of the spike protein of SARS-CoV-2 [anti-RBD] IgG was measured using two immunoassays. Results: After the second dose, geometric mean titers [GMT] of anti-RBD with both the Abbott and Roche assay were significantly lower in residents than staff (2282 AU/mL vs. 8505 AU/mL, and 258 U/mL vs. 948 U/mL, respectively). Multivariate analysis of characteristics affecting antibody responses (≥1280 AU/mL for Abbott and > 210 U/mL for Roche) showed lower odds ratios [ORs] for older age (adjusted OR per 10 year increase [aOR] = 0.62, 95 % confidence interval [95 %CI]; 0.38–1.02), steroid usage (aOR = 0.09, 95 %CI; 0.01–0.60) and regular nonsteroidal anti-inflammatory drugs [NSAIDs] usage (aOR = 0.16, 95 %CI; 0.03–0.88). Conclusions: Elderly people and steroid and NSAID users had lower antibody responses following the second vaccine dose.

Abstract Background and Aim The number of patients with ulcerative colitis (UC) has been increasing in Japan. To elucidate the risk factors for developing UC in Japan, a hospital‐based case–control study was conducted. This study examined the association between smoking/drinking habits and UC onset in detail. Methods Cases comprised 132 Japanese patients who had been newly diagnosed with UC between 2008 and 2014 at 38 collaborating hospitals in Japan, and controls comprised 167 patients without UC. Detailed data on smoking and drinking habits were collected using a self‐administered questionnaire. Results Ex‐smokers showed an increasing odds ratio (OR) for UC development compared with never smokers (OR 2.42, 95% confidence interval 1.24–4.72). The ORs of ex‐smokers were particularly high among subjects aged less than 40 years, subjects who had smoked more than 10 pack‐years, and subjects who were within 13 years of quitting smoking. Regarding drinking habits, ex‐drinkers also showed a more than twofold higher OR for UC compared to never drinkers. Ex‐drinkers 40 years or older, ex‐drinkers who had consumed more than 364 drink‐years, and subjects who were less than 6 years after quitting drinking showed increased ORs for UC. Conclusion These findings suggest the need for careful attention for UC onset among heavy smokers who quit smoking before 40 years of age and heavy drinkers who quit drinking at ≥40 years of age.

Background: Mumps deafness causes serious problems, and incidence data are needed to identify its disease burden. However, such data are limited, and the reported incidence is highly variable. Nationwide studies in Japan with a large age range are lacking. Methods: This was a retrospective observational investigation of the 2005–2017 mumps burden using employment-based health insurance claims data. Data were analyzed for 5,190,326 people aged 0–64 years to estimate the incidence of mumps deafness. Results: Of 68,112 patients with mumps (36,423 males; 31,689 females), 102 (48 males; 54 females) developed mumps deafness—an incidence of 15.0 per 10,000 patients (1 in 668 patients). Fifty-four (52.9%) patients had mumps deafness in childhood (0–15 years), and 48 (47.1%) had mumps deafness in adolescence and adulthood (16–64 years); most cases occurred in childhood, the peak period for mumps onset. The incidence of mumps deafness per 10,000 patients was 73.6 in adolescence and adulthood, 8.4 times higher than the incidence of 8.8 in childhood (P < 0.001). In childhood, the incidence of mumps deafness was 7.2 times higher among 6–15-year-olds (13.8; 95% CI, 10.2–18.2) than among 0–5-year-olds (1.9; 95% CI, 0.6–4.5), and this difference was statistically significant (P < 0.001). No sex difference was observed. Conclusions: The incidence of mumps deafness per 10,000 patients aged 0–64 years was 15.0 (1 in 668 patients). A secondary risk of deafness following mumps virus infection was identified not only for children, but also for adolescents and adults.

Although nationwide immunization with SARS-CoV-2 mRNA vaccines began in February 2021, the evaluation of vaccine effectiveness (VE) using a test-negative design has not been conducted adequately in Japan. To evaluate the effectiveness of the SARS-CoV-2 mRNA vaccines, we conducted a test-negative case–control study during the periods dominated by the Delta and Omicron variants. In total, 518 and 358 adult participants with COVID-19-like symptoms were tested for the virus from August to October 2021 (Delta variant predominance) and in February 2022 (Omicron variant surge), at the Kawasaki Saiwai Clinic. During Delta variant predominance, the effectiveness of full vaccination was 90.4% (95% confidence interval [CI]: 82.1–94.8) and 97.3% (95% CI: 71.7–99.7) against all COVID-19 and moderate-to-severe disease, respectively. However, partial vaccination failed to show effectiveness against moderate-to-severe COVID-19. The effectiveness of the mRNA vaccines against all COVID-19 infection declined to 16.1% (95% CI: −81.0 to 61.1) in February 2022. Our results indicated that, although mRNA vaccines showed significant preventive effects against all COVID-19 during Delta variant predominance, these preventive effects waned during Omicron variant surge. To the best of our knowledge, this is the first study that evaluated VE in the Japanese population during both periods.

Congenital diaphragmatic hernia (CDH) is a life-threatening condition characterized by the herniation of abdominal organs into the thorax, resulting in hypoplastic lungs and pulmonary hypertension. The impact of the first cry, a crucial event for lung transition during birth, on CDH patients remains unclear. This study investigated the impact of the first cry during birth on CDH patient survival, along with other prognosis factors. A multi-institutional retrospective study assessed CDH patient characteristics and survival rates by analyzing factors including the first cry, disease severity, birth weight, Apgar scores, oxygenation index (OI) and surgical closure. Among the CDH patients in the study, a positive first cry was linked to 100% survival, regardless of disease severity (p < 0.001). Notably, the presence of a positive first cry did not significantly affect survival rates in patients with worse prognostic factors, such as low birth weight (

Background: Mumps vaccination coverage is low in Japan, partly because of its voluntary nature. Although pediatric cases of mumps virus infection are captured by the National Epidemiological Surveillance of Infectious Diseases program under the Infectious Disease Law, there are currently no data regarding the occurrence of mumps and its complications in adults. Methods: We investigated the annual incidence rates of mumps and its complications based on health insurance reimbursement data for 5,209,660 individuals aged 0–64 years for 2005–2017, obtained from JMDC Inc., to estimate the mumps-related disease burden during this period. Results: There were three mumps outbreaks (2006, 2010, and 2016) during 2005–2017. The annual incidence of mumps was highest in individuals aged 0–5 years (808–3,792 per 100,000 persons), followed by those aged 6–15 years (658–2,141 per 100,000 persons). The incidence of mumps was higher in females than in males (male/female ratio, 0.90). Among mumps-related complications, the overall incidence (per 1,000 mumps cases) was highest for orchitis (6.6), followed by meningitis (5.8), deafness (1.3), pancreatitis (0.5), and encephalitis (0.3). No cases of oophoritis were noted. The overall incidence of mumps-related complications was 2.5 times higher in males than in females. Conclusions: This study revealed the disease burden due to mumps and its complications in Japan during 2005–2017. These data suggest the need for mumps-prevention measures in adolescents and adults, as well as in children.

Abstract A large prospective cohort study in the United States examined the association between coffee intake and overall and cause-specific mortality and showed a inverse association between pneumonia and influenza deaths and coffee intake. In Japan, the mortality rate of pneumonia in elderly people is high, and its prevention is an important issue. The present study investigated the association between coffee and green tea intake and pneumonia among the elderly. The design was a hospital-based case control study. The cases were patients over 65 years old newly diagnosed as pneumonia. As a control, patients with the same sex and age (range of 5 years) who visited the same medical institution around the same time (within 2 months after examination of the case) for a disease other than pneumonia were selected. There were two controls per case. Odds ratio (OR) and 95% confidence interval (CI) for pneumonia of coffee and green tea intake during the past month were calculated using a conditional logistic regression model. A total of 199 cases and 374 controls were enrolled. When compared to those who do not drink coffee, the OR for pneumonia of those who drink less than one cup of coffee per day was 0.69 (95% CI 0.39–1.21), OR of those who drink one cup was 0.67 (0.38–1.18), and OR of those who drink two or more cups was 0.50 (0.28–0.88) (Trend p = 0.024). No association was found between pneumonia and green tea consumption. This study suggested a preventive association between coffee intake over 2 cups per day and pneumonia in the elderly.

Background: Cronkhite-Canada syndrome (CCS), chronic enteropathy associated with SLCO2A1 gene (CEAS), and intestinal Behçet’s disease (BD) are classified as intractable intestinal disorders in Japan. However, the national prevalence of these diseases remains unknown. We performed a nationwide survey to estimate the patient numbers and prevalence rates of these diseases throughout Japan in 2017. Methods: We conducted a mail-based survey targeting hospitals across Japan to estimate the annual numbers of patients with CCS, CEAS, and intestinal BD in 2017. Using a stratified random sampling method, we selected 2,979 hospital departments and asked them to report the number of patients who met specific diagnostic criteria. The total number of patients for each disease was estimated by multiplying the reported numbers by the reciprocal of the sampling rate and response rate. The corresponding prevalence rates per 1,000,000 population were calculated based on the mid-year population of Japan in 2017. Results: The overall survey response rate was 68.1% (2,029 departments). The estimated numbers of patients with CCS, CEAS, and intestinal BD were 473 (95% confidence interval [CI], 357–589), 388 (95% CI, 289–486), and 3,139 (95% CI, 2,749–3,529), respectively; the prevalence rates per 1,000,000 population were 3.7 (male: 4.0; female: 3.5), 3.1 (male: 3.0; female: 3.1), and 24.8 (male: 24.5; female: 25.0), respectively. The male-to-female ratios were 1.10, 0.94, and 0.93 for patients with CCS, CEAS, and intestinal BD, respectively. Conclusions: Estimates of the national prevalence of CCS, CEAS, and intestinal BD in Japan were generated and found to be higher than those previously reported.

Abstract Background and Aim The purpose of this study was to identify lifestyle risk factors, such as cigarette smoking and alcohol consumption, in relation to the development of hepatocellular carcinoma (HCC) among chronic hepatitis C patients who have achieved a sustained virologic response (SVR). Methods This cross‐sectional study was conducted between 2014 and 2017 using self‐administered questionnaires and medical information at two tertiary hospitals in Osaka, Japan. Study subjects were chronic hepatitis C patients who had achieved SVR without HCC following antiviral treatment that was completed more than 1 year earlier. A logistic regression model was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the development of post‐SVR HCC for each factor. Results Of 202 participants, 18 patients were diagnosed with post‐SVR HCC. After considering potential confounders, former drinkers at the time of SVR (OR, 9.51; 95% CI, 1.08–83.90) and patients with a history of gastric or duodenal ulcer (OR, 4.14; 95% CI, 1.37–12.46) were significantly associated with HCC. In addition, among patients with severe fibrosis, current smokers at the time of SVR had an increased OR for HCC compared with never smokers, with marginal significance (OR, 5.61; 95% CI, 0.97–32.63). Conclusions In chronic hepatitis C patients with severe fibrosis, continuing smoking after achieving SVR could be a risk factor for post‐SVR HCC. The relationship between gastric or duodenal ulcer history and post‐SVR HCC should be investigated further.

Background: Pregnant women are in the highest priority group for receiving influenza vaccination. However, they may be reluctant to receive the vaccination due to concerns about the influence of vaccination on the fetuses. Methods: This prospective cohort study of 10 330 pregnant women examined the safety of influenza vaccination in terms of adverse birth outcomes. Influenza vaccination during pregnancy was determined from questionnaires before and after the 2013/2014 influenza season. All subjects were followed until the end of their pregnancy. Adverse birth outcomes, including miscarriage, stillbirth, preterm birth, low birth weight, and malformation, were assessed by obstetrician reports. Results: Adverse birth outcomes were reported for 641 (10%) of the 6387 unvaccinated pregnant women and 356 (9%) of the 3943 vaccinated pregnant women. Even after adjusting for potential confounders, vaccination during pregnancy showed no association with the risk of adverse birth outcomes (odds ratio 0.90, 95% confidence interval 0.76–1.07). Vaccination during the first or second trimester displayed no association with adverse birth outcomes, whereas vaccination during the third trimester was associated with a decreased risk of adverse birth outcomes (odds ratio 0.70, 95% confidence interval 0.51–0.98). Conclusions: Influenza vaccination during pregnancy did not increase the risk of adverse birth outcomes, regardless of the trimester in which vaccination was performed, when compared to unvaccinated pregnant women. Keywords: Adverse birth outcomes, Influenza vaccine, Pregnant women, Prospective cohort study, Vaccine safety

Background: In Japan, freeze-dried live attenuated varicella-zoster vaccine BIKEN is available for adults aged ≥50 years to prevent herpes zoster (HZ). A prospective cohort study of 1200 healthy adults and 300 patients with underlying illness confirmed vaccine safety between 2016 and 2017. However, evidence of vaccine effectiveness (VE) is limited. Methods: VE against HZ and postherpetic neuralgia (PHN) was evaluated in the vaccinated cohort of the previous safety study in a follow-up study between 2021 and 2022 and compared with unvaccinated family members. Self-administered questionnaires determined retrospective experiences of HZ and PHN diagnosis. Logistic regression estimated the VE by calculating the outcome odds ratio (OR) in vaccinated vs. unvaccinated groups: VE = (1 − OR) × 100(%). Results: Overall, 1098 vaccinated and 518 unvaccinated subjects were analysed. Between 2016 and 2022, 26 vaccinated (2.4%) and 22 unvaccinated (4.2%) subjects reported HZ diagnosis, and 3 vaccinated (0.3%) and 2 unvaccinated (0.4%) subjects reported PHN. Adjusted VE against a clinical diagnosis was 41% for HZ [−6% to 67%], with marginal significance, and 16% [−408% to 86%] for PHN. Stratification by age, sex, or comorbidities had an adjusted VE against HZ of ~40%, which was similar between strata. Conclusion: Freeze-dried live attenuated varicella-zoster vaccine reduces the risk of HZ regardless of age, sex, or comorbidities.

Background: The government of Japan declared a state of emergency on April 16, 2020, owing to the coronavirus disease 2019 (COVID-19) pandemic. The subsequent lockdown altered lifestyles and worsened mental illnesses. Inflammatory bowel disease (IBD) is an intestinal disorder that is affected by environmental factors. Therefore, we aimed to assess the effects of COVID-19 and the state of emergency on the lifestyle and disease activity of patients with IBD.Methods: We conducted a questionnaire survey on patients with IBD from June 16 to August 21, 2020 during their regular follow-up at our hospital, 2 months after the state of emergency was declared.Results: Overall, 241 patients with ulcerative colitis (UC) and 210 with Crohn's disease (CD) completed the survey, of which 82 (34%) and 97 (46%) patients, respectively, reported disease exacerbation within 2 months after the lockdown. Multivariate logistic regression analysis identified age at enrollment (odds ratio, OR 0.98, 95% CI 0.96–0.99; P < 0.05), sleep hours (OR, 0.74; 95% CI, 0.57–0.97; P < 0.05), and increased stress due to the COVID-19 pandemic (OR, 6.06; 95% CI, 1.79–20.50; P < 0.01) as independent factors associated with UC exacerbation. Patients with exacerbated CD were younger at CD onset and had higher patient-reported outcome 2 scores before the state of emergency than patients with non-exacerbated CD. On multivariate analysis, age (OR, 0.97; 95% CI, 0.95–0.99; P < 0.01) and active disease before the state of emergency (OR, 2.20; 95% CI, 1.23–3.95; P < 0.01) were independently associated with CD exacerbation.Conclusions: Improving sleep quality and preventing psychological stress may be crucial in IBD management during a pandemic, especially in young patients.

At present, there are few reports that have clarified the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia or pneumococcal pneumonia in community-acquired pneumonia (CAP) in older individuals in Japan. We conducted a hospital-based matched case-control study to investigate separately the preventive effects of PPSV23 and trivalent influenza vaccine (TIV) on all-cause CAP and pneumococcal CAP in older individuals in Japan. Cases were individuals aged 65 years or older who were newly diagnosed with CAP from October 2010 to September 2014. Two control patients with a different disease (one respiratory medicine and one non-respiratory medicine) matched for sex, age, date of outpatient visit, and medical institution were selected for each case. Odds ratios (ORs) and 95% confidence intervals (CIs) of PPSV23 and TIV for the occurrence of all-cause CAP and pneumococcal CAP were calculated using conditional and unconditional logistic regression models. The analysis included 161 cases and 308 controls from the 4-year period. The adjusted OR for the occurrence of all-cause CAP was 0.76 (95%CI = 0.44–1.32) with PPSV23 vaccination and 0.79 (95%CI = 0.50–1.25) with TIV vaccination compared with unvaccinated individuals. When the outcome index was restricted to pneumococcal CAP, the adjusted OR significantly decreased to 0.23 (95%CI = 0.08–0.66) with PPSV23 vaccination, but not with TIV vaccination (adjusted OR = 0.65, 95%CI = 0.31–1.36). PPSV23 vaccination is likely effective in reducing incidence of pneumococcal CAP in older individuals, although its preventive effect for all-cause CAP has not been achieved.

Background: Severe pediatric cases of hand, foot, and mouth disease (HFMD), herpangina (HA), and associated complications caused by enterovirus 71 (EV71) infection have brought substantial public health impact in Asia. This study aimed to elucidate the epidemiology of these pediatric cases in Japan. Methods: A nationwide survey was conducted using stratified random sampling of hospital pediatric departments. We estimated the number of inpatients with HFMD, HA, and associated complications between April 1 and September 30, 2010, during which EV71 was circulating predominantly. Factors associated with severe cases with ≥7 days of admission, sequelae, or outcome of death were analyzed using multivariate logistic regression. Results: During the 6-month epidemic period, the number of pediatric inpatients aged

Abstract Background Nutritional status of the older people is affected by various life-style factors. Although dietary habit is one of the life-style factors, it is unknown which of older home-care recipients’ dietary habits are associated with malnutrition. The purpose of this study was to examine the association of dietary variety, as an evaluation index for dietary habits, with malnutrition in Japanese older home-care recipients. Methods This cross-sectional study was conducted in a single city, Hyogo Prefecture, Japan between July and October 2016. Three hundred thirty-three community-dwelling older care recipients (aged 65 years or older who were receiving home-visit nursing care services) were enrolled. Their nutritional status (Mini Nutritional Assessment®-short form: MNA®-SF), dietary variety (Food frequency score [FFS]), socio-demographic characteristics (age, sex, marital status, etc.), health indicators (comorbidity [Charlson Comorbidity Index] and dysphagia status [Dysphagia Severity Scale]) were assessed. The participants were classified into two groups: malnourished (0–7 points) and non-malnourished (8–14 points), according to their MNA®-SF scores. Multivariate logistic regression analysis was used to examine the factors associated with malnutrition. Results A total of 317 participants were analyzed (118 men, 199 women, median age: 84 years). Compared to the fourth (highest) quartile of FFS, odds ratios (OR) (95% confidence intervals [CI]) of the third, second, and first (lowest) quartiles of FFS were 1.08 (0.42–2.80), 1.29 (0.56–2.98), and 2.30 (1.02–5.19), respectively (p for trend = 0.049). Higher Charlson Comorbidity Index score and the presence of dysphagia were also significantly associated with malnutrition (OR: 2.08, 95% CI: 1.08–4.00 and OR: 3.86, 95% CI: 2.08–7.17, respectively). Conclusion Lower dietary variety was significantly associated with malnutrition in Japanese older home-care recipients.

Abstract Background Older adults are vulnerable to hospitalization or death from norovirus infection, but the actual disease burden remains unknown. Therefore, we conducted a nationwide survey to estimate the number of inpatients with norovirus gastroenteritis and associated deaths among Japanese older adults. Methods We performed a nationwide two-step query targeting 4184 hospital departments selected from 17,575 departments using stratified random sampling according to the number of beds. We asked each department to complete a mail-back questionnaire on the annual numbers of inpatients with infectious gastroenteritis and associated deaths between administrative years 2012 and 2014, and the implementation status of norovirus infection testing. In a second query, we investigated the annual number of inpatients with norovirus gastroenteritis and associated deaths in departments that had reported infectious gastroenteritis inpatients in the first query. Clinical information was collected for inpatients with norovirus gastroenteritis in administrative year 2014. Results Norovirus testing for patients hospitalized for acute gastroenteritis was routinely conducted in 16% of the responding departments. Although half the departments responded that some acute gastroenteritis inpatients received such testing but others did not. In this situation, numbers of inpatients with norovirus gastroenteritis in Japan were estimated as 31,800 (95% CI: 25,700-37,900) in administrative year 2012, 21,600 (95% CI: 17,700–25,500) in administrative year 2013, and 15,700 (95% CI: 12,900–18,500) in administrative year 2014. The estimated number of associated deaths was approximately 600 in each administrative year. Factors associated with death included higher age, living in long-term care facilities, underlying illnesses such as chronic respiratory diseases, and complications such as aspiration pneumonia. Conclusions The actual number of norovirus inpatient would be higher than the estimated here due to the low rate of routinely implemented norovirus testing. Considering Japan’s rapidly aging society and the disease burden of norovirus infection among Japanese older adults, it is important to protect this high-risk population from norovirus infection.

Abstract Background In Japan, freeze-dried live attenuated varicella-zoster vaccine is available for adults aged ≥50 years to prevent herpes zoster. However, limited evidence has been accumulated regarding vaccine safety for patients with underlying illnesses, who have been considered as the high-risk group for herpes zoster. Methods A prospective cohort study of 1200 healthy adults and 300 patients with underlying illnesses such as malignancy, diabetes mellitus, autoimmune diseases, and renal diseases was conducted. All subjects were vaccinated and then their adverse events (AEs) were followed for 28 days after vaccination. Key safety measures included any AEs, severe AEs (SAEs), and vaccine-related AEs such as injection-site AEs and systemic AEs. The frequencies and 95% confidence intervals of AEs were calculated. Results During the follow-up period, 2 SAEs (bone fracture and acute cholecystitis) among healthy adults and 1 SAE (disseminated mycobacteriosis) among patients with underlying illnesses were reported, although none of them was diagnosed as vaccine-related. Vaccine-related AEs were reported in 42% of healthy adults and patients with underlying illnesses, and the proportions were similar between the groups. The most frequent AEs were injection-site AEs in both groups (i.e., 41 and 39%), and systemic AEs were observed in 4% of both groups. Only among healthy adults, those with a history of herpes zoster were more likely to report injection-site AEs than those without a history of herpes zoster (53% vs 39%). Conclusions The present study confirmed the safety of freeze-dried, live attenuated varicella-zoster vaccine even in patients with underlying illnesses. A history of herpes zoster might be related to development of injection-site AEs in healthy adults. Trial registration The study was prospectively registered on Japic-Clinical Trials Information as JapicCTI-163415 on October 31, 2016.

ObjectivesPouchitis is a major complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). Although there have been many investigations of the neutrophil-to-lymphocyte ratio (NLR) in various diseases, its role in predicting the development of pouchitis remains unclear. We aimed to evaluate the clinical utility of the NLR for predicting the development of pouchitis after IPAA in UC patients.Materials and methodsUC patients who underwent IPAA at Osaka City University Hospital between May 2006 and March 2019 were included. The incidence of pouchitis was estimated using the Kaplan-Meier method. Potential preoperative, intraoperative, and postoperative predictors for pouchitis, including various demographic and clinical variables, were analyzed. The combined impact of the NLR and other known prognostic factors were investigated using Cox proportional hazard regression with inverse probability of treatment weighting (IPTW).ResultsForty-nine patients with UC who underwent IPAA were included. The median follow-up period was 18.3 months (interquartile range: 10.7-47.2 months). Eighteen patients (36.7%) developed pouchitis. The incidence of pouchitis was 19.2%, 32.6%, and 45.9% at 1, 2, and 5 years, respectively. NLR was significantly associated with the development of pouchitis in the univariate Cox regression analysis (hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.01-1.28; P = 0.03). The NLR cutoff value of 2.15 was predictive of the development of pouchitis according to receiver operating characteristic analysis (specificity: 67.7%, sensitivity: 72.2%). The incidence of pouchitis was significantly lower in the low NLR group than that in the high NLR group (P = 0.01, log-rank test). Cox regression analyses using IPTW also identified NLR as a prognostic factor for the development of pouchitis by statistically adjusting for background factors (HR, 3.60; 95% CI, 1.31-9.89; P = 0.01).ConclusionsNLR may be a novel and useful indicator for predicting the development of pouchitis after IPAA in UC and should be introduced in clinical practice.

It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups. Pneumococcal immunoglobulin G (IgG) titers of serotypes 23F, 3, 4, 6B, 14, and 19A were assessed. The primary endpoint was the serotype 23F response rate (a ≥2-fold increase in IgG concentrations 4–6 weeks after PPSV23 vaccination). With the non-inferiority margin set at 20% fewer patients, the response rate of serotype 23F in the simultaneous group (77.8%) was not inferior to that of the sequential group (77.6%; difference, 0.1%; 90% confidence interval, −10.8% to 11.1%). None of the pneumococcal IgG serotype titers were significantly different between the groups 4–6 weeks after vaccination. Simultaneous administration did not show a significant decrease in seroprotection odds ratios for H1N1, H3N2, or B/Phuket influenza strains other than B/Texas. Additionally, simultaneous administration did not increase adverse reactions. Hence, simultaneous administration of PPSV23 and QIV shows an acceptable immunogenicity that is comparable to sequential administration without an increase in adverse reactions. (This study was registered with ClinicalTrials.gov [NCT02592486]).

Background: Although annual influenza vaccination is an important strategy used to prevent influenza-related morbidity and mortality, some studies have reported the negative influence of prior vaccination on vaccine effectiveness (VE) for current seasons. Currently, the influence of prior vaccination is not conclusive, especially in children. Methods: We evaluated the association between current-season VE and prior season vaccination using a test-negative design in children aged 1–5 years presenting at nine outpatient clinics in Japan during the 2016/17 and 2017/18 influenza seasons. Children with influenza-like illness were enrolled prospectively and tested for influenza using real-time RT-PCR. Their recent vaccination history was categorized into six groups according to current vaccination doses (0/1/2) and prior vaccination status (unvaccinated = 0 doses/vaccinated = 1 dose or 2 doses): (1) 0 doses in the current season and unvaccinated in prior seasons (reference group); (2) 0 doses in the current season and vaccinated in a prior season; (3) 1 dose in the current season and unvaccinated in a prior season; (4) 1 dose in the current season and vaccinated in a prior season; (5) 2 doses in the current season and unvaccinated in a prior season, and (6) 2 doses in the current season and vaccinated in a prior season. Results: A total of 799 cases and 1196 controls were analyzed. The median age of the subjects was 3 years, and the proportion of males was 54%. Overall, the vaccination rates (any vaccination in the current season) in the cases and controls were 36% and 53%, respectively. The VEs of the groups were: (2) 29% (95% confidence interval: −25% to 59%); (3) 53% (6% to 76%); (4) 70% (45% to 83%); (5) 56% (32% to 72%), and (6) 61% (42% to 73%). The one- and two-dose VEs of the current season were significant regardless of prior vaccination status. The results did not differ when stratified by influenza subtype/lineage. Conclusion: Prior vaccination did not attenuate the current-season VE in children aged 1 to 5 years, supporting the annual vaccination strategy.

The vaccine confidence index in Japan is one of the lowest worldwide. This study aimed to examine the proportion of COVID-19 vaccine hesitancy in the Japanese population using a larger sample and more robust statistical methods than previously, and to identify factors associated with vaccine hesitancy. We conducted a nationwide, cross-sectional Internet survey on 8–26 February 2021, and calculated the proportion and odds ratios for vaccine hesitancy. Among 23,142 responses analyzed, the proportion of COVID-19 vaccine hesitancy was 11.3% (10.9–11.7%). The proportion was higher among younger respondents and female respondents, and especially among younger female respondents (15.6%) compared with the lowest proportion among older male respondents (4.8%). The most cited reason for not getting vaccinated was concerns about adverse reactions in more than 70% of the respondents. The proportion of COVID-19 vaccine hesitancy in Japan was comparable to that in previous studies overseas, and the proportion among younger respondents was more than double that among older respondents. Factors associated with the hesitancy were female sex, living alone, low socioeconomic status, and presence of severe psychological distress, especially among older respondents. Thus, adequate measures should be taken to ensure that vaccines are delivered to people with these factors.

Lung cancer is a leading cause of cancer-related death, and patients with lung cancer are a priority group for influenza vaccination. However, few studies have assessed the immunogenicity of the influenza vaccine in these patients. Here, we performed a prospective study to evaluate the immunogenicity of the influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy. Twenty-five patients with lung cancer undergoing anticancer chemotherapy and 26 patients with chronic obstructive pulmonary disease (COPD) as controls were enrolled. A trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012 was administered as a single subcutaneous injection. Serum samples were collected before vaccination, and at 4–6 weeks after vaccination. Levels of serum antibody to hemagglutinin were measured. Among patients with lung cancer, the seroprotection rate (postvaccination titer > 1:40) was 84% for both A(H1N1) and A(H3N2), similar to the levels observed in patients with COPD. However, the seroprotection rate for the B strain was significantly lower in patients with lung cancer than in patients with COPD (64% versus 92%). Even after adjustment for potential confounders, patients with lung cancer had a significantly lower odds ratio for seroprotection against the B strain than patients with COPD. Moreover, in patients with lung cancer, those receiving the platinum doublet treatment tended to exhibit a lower seroprotection rate than those receiving a single agent. Thus, patients with lung cancer undergoing anticancer chemotherapy showed acceptable immune responses to a trivalent influenza vaccine, supporting the recommendation for annual influenza vaccination in these patients.

BackgroundThe number of patients with Crohn's disease (CD) in Japan has recently been increasing. We examined the association between environmental factors and the development of CD in Japanese focusing on passive smoking.MethodsWe conducted a multicenter case-control study and compared the environmental factors of 93 cases who were newly diagnosed with CD to the environmental factors of 132 controls (hospital-, age-, and sex-matched patients with other diseases). The odds ratio (OR) of each factor for the development of CD and the 95% confidence interval (CI) were calculated using a logistic regression model. The association between the details of passive smoking history and the development of CD was examined for those who had an active smoking history "no". Odds ratios of number of passively smoked cigarettes (per day), time of passive smoking (per day) and period of passive smoking (year) were calculated using "passive smoking 'No'" as a reference.ResultsHistory of appendicitis, family history of inflammatory bowel disease, and active smoking history were not significantly associated with the development of CD. Drinking history showed a decreased OR for the development of CD (0.39, 0.19-0.77). "Passive smoking Yes" showed significantly increased OR (2.49, 1.09-5.73). Regarding the association between passive smoking and the development of CD, the OR increased as the number of cigarettes per day, smoking time per day, and smoking duration increased, and there was a dose-response relationship (trend P = 0.024, 0.032, 0.038).ConclusionsThe association between environmental factors and the development of CD among Japanese was examined by case-control study. It was suggested that the passive smoking history may be associated to the development of CD.

Hepatocellular carcinoma (HCC) develops in some patients who achieve sustained virological response (SVR) against hepatitis C virus (HCV) infection via anti-HCV therapy. To examine the pathogenesis of HCC development after HCV eradication, histopathological changes and clinical markers were evaluated in SVR patients.Of 654 SVR patients treated with interferon (IFN)-based therapies, 34 patients who had undergone liver biopsy before initiating IFN therapy and after SVR achievement were enrolled: 11 patients with HCC and 23 patients without HCC (male/female, 9/2 and 8/15, respectively: age, 58 ± 5 and 54 ± 11 years, respectively). We compared the clinical and histopathological factors between the two groups. Immunohistochemistry for Cytoglobin (CYGB) and α smooth muscle actin (α-SMA) was also performed.At baseline, prior to initiating the IFN-based therapy, there were significant differences between the SVR-non-HCC and SVR-HCC groups in the male gender, HBc antibody positivity, prothrombin activity, and histological inflammatory grade. Histopathological evaluation, using the new Inuyama classification system, revealed an improvement in the inflammatory grade, from 2.1 ± 0.6 to 1.0 ± 0.6 (p < 0.0001), whereas the fibrosis stage remained unchanged, from 2.3 ± 0.9 to 2.0 ± 1.2 (p = 0.2749), during the 97 ± 72-month observation period in the SVR-HCC group. Both the grade and stage scores were significantly improved in the SVR-non-HCC group. The area of collagen deposition, evaluated using Sirius red staining, showed a marked decrease, from 18.6 ± 7.6% to 7.7 ± 4.6%, in the SVR-non-HCC group, with no change in the SVR-HCC group. CYGB- and α-SMA-positive hepatic stellate cells (HSCs), indicative of the HSC activated phenotype, remained in the fibrotic tissue of livers among patients in the SVR-HCC group.Stagnation of fibrosis regression is associated with a high risk for HCC after SVR. HSC activation may inhibit improvement in fibrosis after SVR and potentially contribute to hepatocarcinogenesis.

[This corrects the article DOI: 10.1371/journal.pone.0194163.].

Previous studies have suggested that estrogens play a role in the development of ulcerative colitis (UC). Because isoflavones have a similar structure to 17β-estradiol, dietary consumption of isoflavones may have similar influences on the development of UC. We examined the association between pre-illness isoflavone consumption and the risk of UC.We conducted a hospital-based case control study, and compared the dietary habits of 126 newly diagnosed UC cases with those of 170 age- and gender-matched hospital controls. Information on dietary factors was collected using a self-administered diet history questionnaire. To consider potential changes in dietary habits due to disease symptoms, the habits were assessed separately during the previous 1 month and at 1 year before the recruitment.In the assessment of dietary habits during the previous 1 month, the highest tertile of isoflavone consumption revealed an increased odds ratio (OR) for UC (OR = 2.79; 95% confidence interval (CI), 1.39-5.59; Trend P = 0.004). A significant association was also observed for the dietary assessment at 1 year before, when most UC cases had not yet experienced their first disease symptoms (OR = 2.06; 95% CI, 1.05-4.04; Trend P = 0.04). Associations were more pronounced in females (OR in highest tertile of isoflavone consumption at 1 year before = 4.76; 95% CI, 1.30-17.5; Trend P = 0.02) but were obscured in males (corresponding OR = 1.21; 95% CI, 0.49-3.01; Trend P = 0.63).Dietary isoflavone consumption may be associated with an increased risk of UC, particularly in females. Prospective cohort studies are warranted to confirm these findings.

INTRODUCTION: To date, there have been no prospective studies examining the effect of coffee consumption on serum alanine aminotransferase (ALT) level among individuals infected with the hepatitis C virus (HCV). We conducted a hospital-based cohort study among patients with chronic HCV infection to assess an association between baseline coffee consumption and subsequent ALT levels for 12 months. MATERIALS AND METHODS: From 1 August 2005 to 31 July 2006, total 376 HCV-RNA positive patients were recruited. A baseline questionnaire elicited information on the frequency of coffee consumption and other caffeine-containing beverages. ALT level as a study outcome was followed through the patients' medical records during 12 months. The association between baseline beverage consumption and subsequent ALT levels was evaluated separately among patients with baseline ALT levels within normal range (≤45 IU/L) and among those with higher ALT levels (>45 IU/L). RESULTS: Among 229 patients with baseline ALT levels within normal range, 186 (81%) retained normal ALT levels at 12 months after recruitment. Daily drinkers of filtered coffee were three times more likely to preserve a normal ALT level than non-drinkers (OR=2.74; P=0.037). However, decaffeinated coffee drinkers had a somewhat inverse effect for sustained normal ALT levels, with marginal significance (OR=0.26; P=0.076). In addition, among 147 patients with higher baseline ALT levels, 39 patients (27%) had ALT reductions of ≥20 IU/L at 12 months after recruitment. Daily drinkers of filtered coffee had a significantly increased OR for ALT reduction (OR=3.79; P=0.034). However, in decaffeinated coffee drinkers, OR could not be calculated because no patients had ALT reduction. CONCLUSION: Among patients with chronic HCV infection, daily consumption of filtered coffee may have a beneficial effect on the stabilization of ALT levels.