Immunogenicity and safety of influenza vaccine in patients with lung cancer receiving immune checkpoint inhibitors: A single-center prospective cohort study.

INTRODUCTION: Patients with lung cancer have a high risk of influenza complications. International guidelines recommend annual influenza vaccination for patients with cancer. Immune checkpoint inhibitors (ICIs) are progressively used to treat lung cancer. Data regarding immunogenicity and safety of influenza vaccine are limited in patients with lung cancer receiving ICIs; therefore, we conducted this single-center, prospective observational study in the Japanese population. METHODS: Patients with lung cancer receiving ICIs and influenza immunization were enrolled. Blood samples were collected from patients for serum antibody titer measurement pre- and 4 ± 1 weeks post-vaccination. The primary endpoint was seroprotection rate (sP) at 4 ± 1 weeks post-vaccination. The secondary endpoints were geometric mean titer (GMT), mean fold rise, seroresponse rate (sR), seroconversion rate (sC), and immune-related adverse events (irAEs), defined as adverse effects caused by ICI administration, 6 months post-vaccination. RESULTS: Influenza vaccination in the 23 patients included in the immunogenicity analyses significantly increased GMT for all strains, and sP, sR, and sC were 52%-91%, 26%-39%, and 26%-35%, respectively. In the 24 patients included in the safety analyses, 7 (29%) and 5 (21%) patients exhibited systemic and local reactions, respectively. Only one patient (4%) (hypothyroidism, grade 2) showed post-vaccination irAEs. CONCLUSIONS: Overall, influenza vaccination in patients with lung cancer receiving ICIs showed acceptable immunogenicity and safety, thus supporting annual influenza vaccination in this population.

A Nationwide Epidemiological Survey of Adolescent Patients With Diverse Symptoms Similar to Those Following Human Papillomavirus Vaccination: Background Prevalence and Incidence for Considering Vaccine Safety in Japan.

BACKGROUND: Since June 2013, Japan has suspended proactive recommendation of human papillomavirus (HPV) vaccination due to self-reported diverse symptoms, including pain and motor dysfunction, as possible serious adverse events following immunization. Although these symptoms may be seen in adolescents without HPV vaccination, their frequency, taking into account disease severity, has not been examined. METHODS: A two-stage, descriptive, nationwide epidemiological survey was conducted in 2016, with a 6-month target period from July 1 to December 31, 2015, to estimate the prevalence and incidence of diverse symptoms among Japanese adolescents without HPV vaccination. Participants were 11,037 medical departments in hospitals selected nationwide by stratified random sampling. Eligible patients had to satisfy four criteria: (1) aged 12-18 years upon visiting hospital; (2) having at least one of four symptoms/disorders (pain or sensory dysfunction, motor dysfunction, autonomic dysfunction, or cognitive impairment); (3) symptoms/disorders persisting for at least 3 months; and (4) both criteria (2) and (3) influence attendance at school or work. We then extracted data of patients with diverse symptoms similar to those after HPV vaccination while considering opinions of doctors in charge. RESULTS: Estimated 6-month period prevalence of diverse symptoms among girls aged 12-18 years without HPV vaccination was 20.2 per 100,000. Annual incidence was estimated to be 7.3 per 100,000. CONCLUSION: Adolescent Japanese girls without HPV vaccination also visited hospitals with diverse symptoms similar to those following HPV vaccination. Our findings predict the medical demands for coincident diverse symptoms, which are temporally associated with but not caused by HPV vaccination of Japanese adolescents.

Geographic distribution of the incidence of osteonecrosis of the femoral head in Japan and its relation to smoking prevalence.

OBJECTIVES: Alcohol intake and smoking are modifiable lifestyle-related risk factors for osteonecrosis of the femoral head (ONFH). We investigated geographic differences in ONFH incidence in Japan and the correlation with alcohol intake and smoking to develop prevention strategies for ONFH in Japan. METHODS: This ecological study was conducted in Japan primarily using the following data sources: nationwide epidemiological survey and national survey. We estimated the annual ONFH incidence and the prevalence of alcohol drinking and smoking in each prefecture. Prefectural incidence and prevalence were calculated by sex and age-standardization. RESULTS: The mean annual ONFH incidence per 100,000 population was 3.08 in men and 1.63 in women, respectively. There was no significant correlation between ONFH incidence and the prevalence of any levels of alcohol intake, while smoking ≥20 cigarettes/day showed a significant and moderate correlation in men (r = 0.47, p = .01). This correlation remained significant after adjustment for the prevalence of any levels of alcohol intake (standardized partial regression coefficient = 0.47-0.49, p = .009-.01). CONCLUSION: ONFH incidence is geographically variable in Japan, and this may be partly explained by the distribution of smoking prevalence. Smoking cessation may contribute to an effective decline in the overall ONFH incidence in Japan.

Epidemiological study of osteonecrosis of the femoral head using the national registry of designated intractable diseases in Japan.

OBJECTIVES: We aimed to investigate the epidemiological characteristics of osteonecrosis of the femoral head (ONFH) using the designated intractable diseases (DID) database in Japan. METHODS: Data on patients who had received public subsidies for medical costs due to ONFH from 2012 to 2013 were extracted from the DID database. The incidence and prevalence of ONFH, distribution of gender, age, and the prevalence of associated risk factors were assessed. These epidemiological characteristics were compared with those of another nationwide ONFH survey conducted during a similar period. RESULTS: Data on 3264 newly diagnosed patients (incident cases) and 20,042 patients registered until 2013 (prevalent cases) were evaluated. The corrected annual incidence and prevalence of ONFH per 100,000 were 3.0 and 18.2-19.2, respectively. The ratio of males to females was 1.4 in 2012 and 1.2 in 2013, respectively. Peak distribution was observed at ages 40s and 60s in males and females, respectively. The prevalence of the risk factors were steroid-associated: 39%, alcohol-associated: 30%, both: 4%, and none: 27%. CONCLUSIONS: The DID database data showed a similar distribution of gender and age to that in other nationwide surveys but lower incidence and prevalence of ONFH. Sampling bias may affect the epidemiological characteristics of ONFH.

Estimated Prevalence of Cronkhite-Canada Syndrome, Chronic Enteropathy Associated With SLCO2A1 Gene, and Intestinal Behçet's Disease in Japan in 2017: A Nationwide Survey.

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.

Lifestyles Associated with Prognosis After Eradication of Hepatitis C Virus: A Prospective Cohort Study in Japan.

BACKGROUND: Hepatocellular carcinoma develops in some patients with hepatitis C virus (HCV), even after achieving sustained virological response (SVR). AIMS: We examined factors associated with liver disease progression in a prospective cohort study of SVR patients. METHODS: Participants were patients who had visited a hospital for clinical follow-up of chronic HCV infection in 2005 and had reached SVR as a result of subsequent antiviral treatment. Baseline information including lifestyle and dietary habits before SVR was collected in 2005 using self-administered questionnaires, and clinical information before SVR was collected from medical records in 2005. Study outcome was liver disease progression such as liver cirrhosis, hepatocellular carcinoma, and/or liver disease-related death after SVR. Proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals for each variable. RESULTS: Of 180 SVR patients, 27 patients (15%) showed liver disease progression after SVR: 26 (14%) were diagnosed with liver cirrhosis, two (1%) with hepatocellular carcinoma, and/or one (0.6%) with liver-disease-related death. Besides older age at SVR (HR = 11.9, P < 0.01) and aspartate aminotransferase-to-platelet ratio index score ≥ 1.0 before SVR (HR = 2.63, P = 0.03), alcohol drinkers before SVR (HR = 2.82, P = 0.06) were suggested to be associated with liver disease progression after SVR, whereas higher consumption of vitamin B12 before SVR showed a decreased HR for liver disease progression (HR = 0.41, P = 0.09). CONCLUSIONS: Alcohol drinking might be associated with liver disease progression, whereas vitamin B12 intake might have protective effects against liver disease progression after eradication of HCV. Further studies are needed to confirm these findings.

Japanese Orthopaedic Association 2019 Guidelines for osteonecrosis of the femoral head.

PURPOSE: The Clinical Practice Guidelines for Osteonecrosis of the Femoral Head (ONFH) 2019 Edition, written by the working group for ONFH guidelines of the Japanese Investigation Committee (JIC) for ONFH under the auspices of the Japanese Ministry of Health, Labour, and Welfare and endorsed by the Japanese Orthopaedic Association, were published in Japanese in October 2019. The objective of this guideline is to provide a support tool for decision-making between doctors and patients. METHODS: Procedures for developing this guideline were based on the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014, which proposed an appropriate method for preparing clinical guidelines in Japan. RESULTS: This clinical practice guideline consists of 7 chapters: epidemiology; pathology; diagnosis; conservative therapy; surgical treatment: bone transplantation/cell therapy; surgical treatment: osteotomy; and surgical treatment: hip replacement. Twelve background questions and 13 clinical questions were determined to define the basic features of the disease and to be addressed when deciding treatment in daily practice, respectively. CONCLUSIONS: The clinical practice guidelines for the ONFH 2019 edition will be useful for physicians, investigators, and medical staff in clinical practice, as well as for patients, during the decision-making process when defining how to treat ONFH.

Cluster of Severe Acute Respiratory Syndrome Coronavirus 2 Infections Linked to Music Clubs in Osaka, Japan.

BACKGROUND: It is important to understand the mode of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for disease control. We aimed to clarify how soon SARS-CoV-2 transmission can occur after infection by asymptomatically infected individuals. METHODS: We analyzed the publicly available epidemiological information for a cluster of 108 cases of coronavirus disease 2019 (COVID-19) cases in Osaka, Japan. RESULTS: Among cases, 51 cases attended a live music club only once and were considered to have a single visit. Ten remained asymptomatic at the time of COVID-19 diagnosis by reverse-transcription polymerase chain reaction, which was on average 20 days after exposure. Three routes of secondary transmission were identified, with 2-4 days from infection to transmission. All index cases for secondary transmission were asymptomatic at the time of contact with other people. Based on the date of symptom onset in the remaining 41 cases, the period from exposure to illness ranged from 2 to 17 days. CONCLUSIONS: Seemingly healthy people could spread SARS-CoV-2 during intense activities in enclosed environments without sufficient ventilation. Asymptomatically infected persons can transmit the virus as soon as 2 days after infection. Continuous efforts to avoid crowding and to maintain personal hygiene are needed for effective control of COVID-19.

Surgery trends for osteonecrosis of the femoral head: a fifteen-year multi-centre study in Japan.

PURPOSE: The most appropriate procedure and at what type and stage of osteonecrosis of the femoral head (ONFH) these procedures had been argued. We attempted to clarify the trend in surgical operations with respect to the age of patients, type classification, and stage of ONFH over a period of 15 years by using the multi-center sentinel monitoring system in Japan. METHODS: We evaluated the hips of 3844 patients using this system in three phases of every five  years from 2003 to 2017. We classified the surgical procedures as osteotomy (OT), hemiarthroplasty (Hemi), and total hip arthroplasty (THA). We assessed the trend in age, type classification, and stage of ONFH over three time periods; "early," and the "late." We calculated the proportion of surgeries for ONFH in each period. We used the Cochran-Armitage test to evaluate trends in proportion of two levels of characteristics across three time periods. RESULTS: The proportion of younger patients significantly decreased. The proportion of OT and Hemi decreased over time, while the proportion of THA increased. The proportion of patients with types C1 and C2 who underwent OT and Hemi decreased over time. In contrast, that of THA increased. The proportion of patients who underwent OT and Hemi significantly decreased; the proportion of patients who underwent THA significantly increased over time at all stages. CONCLUSIONS: In Japan, the younger patients underwent surgery for ONFH decreased. The patients who underwent OT and Hemi for ONFH decreased, while that of THA increased over time.

Nationwide epidemiologic study of norovirus-related hospitalization among Japanese older adults.

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.

Japanese periodical nationwide epidemiologic survey of aberrant portal hemodynamics.

AIM: Idiopathic portal hypertension (IPH), extrahepatic portal obstruction (EHO), and Budd-Chiari syndrome (BCS) are characterized by aberrant portal hemodynamics of unknown etiology. The aim of this study was to explore trends in the descriptive epidemiology of these diseases through periodical nationwide surveys. METHODS: Nationwide epidemiologic surveys were undertaken in 1999, 2005, and 2015 using the same protocol. The survey targets were selected from all departments of gastrointestinal medicine, surgery, pediatrics, and pediatric surgery in Japan by stratified random sampling according to the number of beds. We asked each department to complete a mail-back questionnaire on the annual numbers of patients with IPH, EHO, and BCS during the preceding year. RESULTS: The estimated number of BCS patients increased from 280 (95% confidence interval, 200-360) in 1999 survey to 410 (300-530) in 2015 survey, whereas the number of IPH and EHO patients has remained largely unchanged during the 15 years (IPH was approximately 1000; EHO was approximately 770 in 2015 survey). The mean age at symptom onset was approximately 45 years for IPH, 30 years for EHO, and 40 years for BCS over the past 15 years. Those who described disease aggravation from the time of diagnosis accounted for approximately 10% of IPH, 15% of EHO, and 20% of BCS patients in each of the three surveys. CONCLUSIONS: In Japan, the prevalence of BCS is increasing, while those of IPH and EHO appear to be stable. Clinical characteristics, including prognoses, have remained largely unchanged in the past 15 years.

Association between dietary iron and zinc intake and development of ulcerative colitis: A case-control study in Japan.

BACKGROUND AND AIM: The prevalence of ulcerative colitis (UC) has been increasing in Japan. Trace elements, such as iron, zinc, magnesium, and copper, can cause digestive symptoms where there is a deficiency or excess. We focused on the dietary intake of trace elements and their associations with UC development. METHODS: A multicenter, hospital-based case-control study was conducted in Japan. Cases were 127 newly diagnosed UC patients, and 171 age-matched and sex-matched hospital controls were recruited. We considered that UC patients had potentially changed their dietary habits due to disease symptoms. The dietary habits were investigated using a self-administered diet history questionnaire to analyze the dietary intakes and frequencies at two points, the previous 1 month and 1 year before. RESULTS: In the assessment of dietary habits 1 year before, the highest intake of iron showed an increased odds ratio (OR) for UC on multivariate analysis (OR = 4.05, 95% confidence interval, 1.46-11.2, P < 0.01). The highest intake of zinc 1 year before showed a decreased OR for UC (OR = 0.39, 95% confidence interval, 0.18-0.85, P = 0.01). Intakes of magnesium and copper had no significant association with UC. Because most UC cases had experienced the first symptom of UC within the previous 11 months, these intakes at 1 year before represented an association with pre-illness dietary habits. CONCLUSION: A high intake of iron has some effect on the development of UC. In contrast, a high intake of zinc has a protective effect on the development of UC.

Nationwide Survey of Pediatric Inpatients With Hand, Foot, and Mouth Disease, Herpangina, and Associated Complications During an Epidemic Period in Japan: Estimated Number of Hospitalized Patients and Factors Associated With Severe Cases.

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 <15 years was about 2,900 (estimated cumulative incidence of hospitalized cases: 17.0 per 100,000 population). Severe cases were significantly associated with younger age. Compared to patients ≥5 years of age, the odds ratios (ORs) for <1 year of age and 1 to <3 years of age were 5.74 (95% confidence interval [CI], 2.14-15.4) and 2.94 (95% CI, 1.02-8.51), respectively. Elevated ORs for hyperglycemia (plasma glucose level of ≥8.3 mmol/L) on admission (OR 3.60; 95% CI, 0.94-13.8) were also observed. CONCLUSIONS: Disease burden of pediatric inpatients with HFMD, HA, and associated complications in Japan was described for the first time. During an EV71 epidemic, younger age and, suggestively, hyperglycemia may have been critical factors requiring more careful treatment.

Lower dietary variety is a relevant factor for malnutrition in older Japanese home-care recipients: a cross-sectional study.

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.

Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 1: Glucocorticoid-Associated Osteonecrosis.

BACKGROUND: Glucocorticoid usage, a leading cause of osteonecrosis of the femoral head (ONFH), and its prevalence was reported in 25%-50% of non-traumatic ONFH patients. Nevertheless, there have been no unified criteria to classify glucocorticoid-associated ONFH (GA-ONFH). In 2015, the Association Research Circulation Osseous addressed the issue of developing a classification scheme. METHODS: In June 2017, a task force was set up to conduct a Delphi survey concerning ONFH. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey consists of questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, the panel reached a consensus on the classification criteria. The response rates were 100% (Round 1), 96% (Round 2), and 100% (Round 3), respectively. RESULTS: The consensus on the classification criteria of GA-ONFH included the following: (1) patients should have a history of glucocorticoid use >2 g of prednisolone or its equivalent within a 3-month period; (2) osteonecrosis should be diagnosed within 2 years after glucocorticoid usage, and (3) patients should not have other risk factor(s) besides glucocorticoids. CONCLUSION: Association Research Circulation Osseous established classification criteria to standardize clinical studies concerning GA-ONFH.

Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 2: Alcohol-Associated Osteonecrosis.

BACKGROUND: Although alcohol is a leading risk factor for osteonecrosis of the femoral head (ONFH) and its prevalence reportedly ranges from 20% to 45%, there are no unified classification criteria for this subpopulation. In 2015, Association Research Circulation Osseous decided to develop classification criteria for alcohol-associated ONFH. METHODS: In June of 2017, Association Research Circulation Osseous formed a task force to conduct a Delphi survey. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey included questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, consensus was reached on the classification criteria. The response rates for the 3 Delphi rounds were 100% (round 1), 96% (round 2), and 100% (round 3). RESULTS: The consensus on the classification criteria of alcohol-associated ONFH included the following: (1) patients should have a history of alcohol intake >400 mL/wk (320 g/wk, any type of alcoholic beverage) of pure ethanol for more than 6 months; (2) ONFH should be diagnosed within 1 year after alcohol intake of this dose; and (3) patients should not have other risk factor(s). CONCLUSION: ARCO-established classification criteria to standardize clinical studies concerning AA-ONFH.

Protective Effect of Maternal Influenza Vaccination on Influenza in Their Infants: A Prospective Cohort Study.

Background: Infants <6 months of age are too young to receive influenza vaccine, despite being at high risk for severe influenza-related complications. Methods: To examine the effectiveness of maternal influenza vaccination in preventing influenza in their infants, we conducted a prospective cohort study of 3441 infants born at participating hospitals before the 2013-2014 influenza season. At the time of recruitment, their mothers completed a questionnaire about influenza vaccination status for the 2013-2014 season. A follow-up survey was conducted after the end of the 2013-2014 season to collect information regarding influenza diagnosis and hospitalization among infants. Results: During the 2013-2014 influenza season, 71 infants (2%) had influenza diagnosed, and 13 infants (0.4%) were hospitalized with influenza. Maternal influenza vaccination (especially prenatal vaccination) decreased the odds of influenza among infants. The effectiveness of prenatal vaccination was 61% (95% confidence interval, 16%-81%), whereas that of postpartum vaccination was 53% (-28%-83%). Although maternal influenza vaccination was also associated with a decreased odds of influenza-related hospitalization among infants, vaccine effectiveness (73%) did not reach statistical significance, owing to the limited number of infants hospitalized because of influenza. Conclusions: The present findings indicated that pregnant women and postpartum women should receive influenza vaccination to protect their infants.

Nationwide multicenter follow-up cohort study of hip arthroplasties performed for osteonecrosis of the femoral head.

PURPOSE: To identify modifiable factors related to post-operative dislocation and reoperation in patients with osteonecrosis of the femoral head (ONFH) in a large cohort. METHODS: We studied 4995 hip arthroplasties: total hip arthroplasty (THA) was performed in 79% of patients; bipolar hemiarthroplasty (BP), 17%; total resurfacing arthroplasty (tRS), 3%; and hemi-resurfacing arthroplasty (hRS), 1%. A new type of BP (accounting for 49% of BPs) comprised a femoral component with a polished or smooth, small-diameter (approximately 10 mm) neck with a round or oval axial cut surface and no sharp corners. RESULTS: The infection rate was relatively low (0.56%) even though 58% of cases of ONFH were associated with systemic steroid use, a known risk factor for infection. Post-operative dislocation occurred in 4.3% of cases, with re-operation needed in 3.9%. The dislocation rate was related to surgery type: 5.2% in THA, 0.9% in BP, and 0% in tRS and hRS. Among total arthroplasties with six month or longer follow-up (3670 THAs and 159 tRSs), the risk factors for post-operative dislocation were younger (≤ 40 years) or older (≥ 62 years) age, higher body weight, posterolateral approach, and smaller prosthetic head diameter. Regarding the need for re-operation, higher body weight and surgery type were identified as risk factors. CONCLUSIONS: The relatively high dislocation rate of 5.2% in THA is a cause for concern. The identified risk factors for dislocation should be considered when selecting THA for treatment. Prosthesis survivorship in hRSs was inferior to that in BPs or THAs. Body weight also affected the survivorship of hip arthroplasties.

Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer.

BACKGROUND: The recently developed reagent, eribulin mesylate (eribulin), is a microtubule dynamics inhibitor with a mechanism of action that differs from those of taxanes and vinca alkaloids. This drug is considered to be a promising chemotherapeutic agent for the treatment of locally advanced or metastatic breast cancer (MBC). In this study, we investigated if variables such as tumor expression of ß-tubulin class III, glutathione S-transferase pi (GSTP) 1 or transducin-like enhancer of split (TLE) 3 might act as predictive factors on the therapeutic effect of eribulin chemotherapy. METHODS: The subjects included 52 patients with MBC who underwent chemotherapy with eribulin. The expression levels of Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor (HER) 2, Ki67, ß-tubulin class III, GSTP-1 and TLE-3 were evaluated using immunostaining employing needle biopsy specimens. RESULTS: Patients with TLE3-negative tumors displayed significantly poorer outcomes regarding progression-free survival than patients with TLE3-positive tumors when prognosis within the group of patients with triple-negative breast cancer (TNBC) lesions was analyzed (p = 0.011, log-rank). In contrast, no such difference in prognosis was found in a comparison of TLE-3 positive/negative patients in the group of all patients (p = 0.433, log-rank) or of patients with non-TNBC lesions (p = 0.659, log-rank). Based on a univariate analysis of 22 TNBC cases, a better progression-free survival correlated significantly with a positive TLE3 expression in the tumor (p = 0.025). A multivariate logistic regression analysis including 22 patients with TNBC also showed that a positive TLE3 expression significantly correlated with a better progression-free survival (p = 0.037). CONCLUSIONS: Our findings suggest that TLE3 is a useful marker for predicting the therapeutic effect of eribulin chemotherapy for TNBC.

Immunogenicity and Efficacy of A/H1N1pdm Vaccine Among Subjects With Severe Motor and Intellectual Disability in the 2010/11 Influenza Season.

BACKGROUND: While the immunogenicity and effectiveness of seasonal influenza vaccines among subjects with severe motor and intellectual disability (SMID) are known to be diminished, the efficacy of the A/H1N1pdm vaccine has not been evaluated. METHODS: We prospectively evaluated 103 subjects with SMID (mean age, 41.7 years) who received trivalent inactivated influenza vaccine during the 2010/11 influenza season. The hemagglutination inhibition (HI) antibody titer was measured in serum samples collected pre-vaccination (S0), post-vaccination (S1), and end-of-season (S2) to evaluate subjects' immunogenicity capacity. Vaccine efficacy was assessed based on antibody efficacy and achievement proportion. RESULTS: The proportions of seroprotection and seroconversion, and the geometric mean titer (GMT) ratio (GMT at S1/GMT at S0) for A/H1N1pdm were 46.0%, 16.0%, and 1.8, respectively-values which did not meet the European Medicines Evaluation Agency criteria. The achievement proportion was 26%. During follow-up, 11 of 43 subjects with acute respiratory illness were diagnosed with type A influenza according to a rapid influenza diagnostic test (RIDT), and A/H1N1pdm strains were isolated from the throat swabs of 5 of those 11 subjects. When either or both RIDT-diagnosed influenza or serologically diagnosed influenza (HI titer at S2/HI titer at S1 ≥2) were defined as probable influenza, subjects with A/H1N1pdm seroprotection were found to have a lower incidence of probable influenza (odds ratio, 0.31; antibody efficacy, 69%; vaccine efficacy, 18%). CONCLUSIONS: In the present seasonal assessment, antibody efficacy was moderate against A/H1N1pdm among SMID subjects, but vaccine efficacy was low due to the reduced immunogenicity of SMID subjects.