FcRn-Targeted Mucosal Vaccination against Influenza Virus Infection.

The respiratory tract is constantly exposed to various airborne pathogens. Most vaccines against respiratory infections are designed for the parenteral routes of administration; consequently, they provide relatively minimal protection in the respiratory tract. A vaccination strategy that aims to induce the protective mucosal immune responses in the airway is urgently needed. The FcRn mediates IgG Ab transport across the epithelial cells lining the respiratory tract. By mimicking this natural IgG transfer, we tested whether FcRn delivers vaccine Ags to induce a protective immunity to respiratory infections. In this study, we designed a monomeric IgG Fc fused to influenza virus hemagglutinin (HA) Ag with a trimerization domain. The soluble trimeric HA-Fc were characterized by their binding with conformation-dependent HA Abs or FcRn. In wild-type, but not FcRn knockout, mice, intranasal immunization with HA-Fc plus CpG adjuvant conferred significant protection against lethal intranasal challenge with influenza A/PR/8/34 virus. Further, mice immunized with a mutant HA-Fc lacking FcRn binding sites or HA alone succumbed to lethal infection. Protection was attributed to high levels of neutralizing Abs, robust and long-lasting B and T cell responses, the presence of lung-resident memory T cells and bone marrow plasma cells, and a remarkable reduction of virus-induced lung inflammation. Our results demonstrate for the first time, to our knowledge, that FcRn can effectively deliver a trimeric viral vaccine Ag in the respiratory tract and elicit potent protection against respiratory infection. This study further supports a view that FcRn-mediated mucosal immunization is a platform for vaccine delivery against common respiratory pathogens.

Anti-reflux Surgery Versus Proton Pump Inhibitors for Severe Gastroesophageal Reflux Disease: A Cost-Effectiveness Study in Korea

Background/Aims@#The economic burden for gastroesophageal reflux disease (GERD) has recently increased in Asian countries. This study investigates the cost-effectiveness between anti-reflux surgery and medication, with proton pump inhibitors (PPIs) for GERD in Korea. @*Methods@#We used a decision tree and Markov model to obtain the costs and quality-adjusted life years (QALYs) of the surgical and medical strategies. Our target cohort was the severe GERD patients aged 50 years old who required a continuous double dose of PPIs. The time horizon was 10 years and all estimates were discounted at 5% per year. The incremental cost-effectiveness ratio of the anti-reflux surgery compared with medication with PPIs was calculated. Sensitivity analyses were performed on all relevant variables. @*Results@#The cost-utility analysis indicated anti-reflux surgery was more cost-effective than medication among severe GERD patients over a 10- year period. The model predicted that the surgical strategy had a cost savings of $551 and the QALYs had a gain of 1.18 as compared with the medical strategy. The break-even point in costs of the anti-reflux surgery over the medication was estimated to be 9 years. Sensitivity analyses using the varying parameter assumptions demonstrated the robustness of the study results. @*Conclusions@#This study showed anti-reflux surgery was less expensive and more effective therapy over the PPI medication after 9 years of follow-up. This suggests the surgical strategy is a cost-effective alternative to PPI medication among patients who need long-term management for GERD in Korea.

Treatment Pattern and Economic Burden of Refractory Gastroesophageal Reflux Disease Patients in Korea

Background/Aims@#The prevalence of gastroesophageal reflux disease (GERD) has increased in Korea, and the economic burden of this chronic disease is substantial. We aim to investigate the treatment pattern and economic burden in Korea of refractory GERD requiring long-term use of proton pump inhibitors (PPIs). @*Methods@#We conducted a cross-sectional analysis of nationally representative sample data obtained from 2012 to 2016 and provided by the Health Insurance Review and Assessment Service. The participants were 86 936 in the medication group and 40 in the surgery group. Age- and sex-standardized prevalence of refractory GERD requiring PPIs medication for more than 12 weeks were analyzed. Generalized linear models were used to estimate cost ratios for comparing the medical costs of the surgery and medication groups after adjustment for demographics and comorbidity. @*Results@#The prevalence of refractory GERD increased from 1.2% in 2012 to 1.9% in 2016, and the estimated total number of GERD patients increased from 402 000 to 736 000 during this time period. The medical expenditures of the surgery group within 90 days of antireflux surgery (ARS) were 16.9-fold higher compared to those of the medication group; the significant difference in medical costs between the 2 groups disappeared after 90 days post-surgery. @*Conclusions@#The prevalence of refractory GERD requiring long-term use of PPIs has been trending upwards recently. Nevertheless, ARS is very rarely performed. Considering the increasing medical costs of long-term PPI use, further cost-effectiveness analysis is needed to compare ARS and PPI therapy for the treatment of GERD in Korea.

The characteristics of antireflux surgery compared to proton pump inhibitor treatment in Korea: a nationwide study using claim data from 2007 to 2016

Purpose@#Laparoscopic antireflux surgery is not widely used in Korea, but published data suggest that its results are comparable to those of Western countries. The purpose of this study was to compare the clinical characteristics, medical utilization, and medical costs of antireflux surgery and proton pump inhibitor (PPI) treatments. @*Methods@#We used Korean patients who underwent fundoplication (n = 342, surgery group) and a 25% random sample of all patients diagnosed with gastroesophageal reflux disease (GERD) who were prescribed PPIs for more than 12 weeks (n = 130,987, medication group) between 2007 to 2016. We compared medical costs and utilization between the 2 groups. @*Results@#The average cost of fundoplication was $4,631. The costs of GERD treatment in the first year after surgery and during the follow-up period were $78.1 and $50.1 per month, respectively. In the surgery group, the average monthly medical expenses decreased as the year progressed, but the average monthly medical expenses ($137.5 per month) did not decrease in the medication group. After stratifying by age group, the medical costs of the surgery group were lower than those of the medication group for all ages except for patients between the ages of 70 and 79. The cost difference between the 2 groups was prominent between the ages of 20 and 49. @*Conclusion@#This study showed that a significant decrease in cost was observed 1 year after surgery, and it was more apparent in younger patients. Further research is needed to determine the appropriateness of antireflux surgery for each group of patients.

The characteristics of antireflux surgery compared to proton pump inhibitor treatment in Korea: a nationwide study using claim data from 2007 to 2016

Purpose@#Laparoscopic antireflux surgery is not widely used in Korea, but published data suggest that its results are comparable to those of Western countries. The purpose of this study was to compare the clinical characteristics, medical utilization, and medical costs of antireflux surgery and proton pump inhibitor (PPI) treatments. @*Methods@#We used Korean patients who underwent fundoplication (n = 342, surgery group) and a 25% random sample of all patients diagnosed with gastroesophageal reflux disease (GERD) who were prescribed PPIs for more than 12 weeks (n = 130,987, medication group) between 2007 to 2016. We compared medical costs and utilization between the 2 groups. @*Results@#The average cost of fundoplication was $4,631. The costs of GERD treatment in the first year after surgery and during the follow-up period were $78.1 and $50.1 per month, respectively. In the surgery group, the average monthly medical expenses decreased as the year progressed, but the average monthly medical expenses ($137.5 per month) did not decrease in the medication group. After stratifying by age group, the medical costs of the surgery group were lower than those of the medication group for all ages except for patients between the ages of 70 and 79. The cost difference between the 2 groups was prominent between the ages of 20 and 49. @*Conclusion@#This study showed that a significant decrease in cost was observed 1 year after surgery, and it was more apparent in younger patients. Further research is needed to determine the appropriateness of antireflux surgery for each group of patients.

Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor.

Human cytomegalovirus (HCMV) can persistently infect humans, but how HCMV avoids humoral immunity is not clear. The neonatal Fc receptor (FcRn) controls IgG transport from the mother to the fetus and prolongs IgG half-life. Here we show that US11 inhibits the assembly of FcRn with ß2m and retains FcRn in the endoplasmic reticulum (ER), consequently blocking FcRn trafficking to the endosome. Furthermore, US11 recruits the ubiquitin enzymes Derlin-1, TMEM129 and UbE2J2 to engage FcRn, consequently initiating the dislocation of FcRn from the ER to the cytosol and facilitating its degradation. Importantly, US11 inhibits IgG-FcRn binding, resulting in a reduction of IgG transcytosis across intestinal or placental epithelial cells and IgG degradation in endothelial cells. Hence, these results identify the mechanism by which HCMV infection exploits an ER-associated degradation pathway through US11 to disable FcRn functions. These results have implications for vaccine development and immune surveillance.

In vitro and in vivo characterization of a West Nile virus MAD78 infectious clone.

The viral determinants governing the varied neuropathogenicity of different West Nile virus (WNV) strains are poorly understood. Here, we generated an infectious clone (WNV-MAD(IC)) of the non-pathogenic strain WNV-MAD78 and compared its replication to that of parental WNV-MAD78 and a WNV-MAD78 infectious clone (WNV-MAD(TX-UTRs)) containing the 5' and 3' untranslated regions (UTRs) of the pathogenic strain WNV-TX. All three viruses replicated at similar rates and caused similar lethality in mice. Thus, the infectious clone is indistinguishable from parental virus in replication and neurovirulence, and the UTRs alone do not account for the increased virulence of WNV-TX compared to WNV-MAD78.

Health Conditions Sensitive to Retirement and Job Loss Among Korean Middle-aged and Older Adults / 예방의학회지

OBJECTIVES: This study was conducted to examine the association between health condition and leaving the labor market among middle-aged and older adults in South Korea. METHODS: Data was obtained from individuals aged 45 years and older participating in the 2006 and 2008 Korean Longitudinal Study of Ageing. We used various health measures including chronic diseases, comorbidities, traffic accident injuries, disabilit of instrumental activities of daily living, depressive symptoms, and self-rated health. The odds ratios of job loss, and retirement, versus employment were calculated using multinomial logistic regression by each health measure. RESULTS: In our cross-sectional and longitudinal analysis, health problems related to physical disabilities had the greatest effect on leaving the worksite. A shift in health condition from good to poor in a short period was a predictor of increased risk of unemployment but a persistent pattern of health problems was not associated with unemployment. Women with health problems showed a high probability of retirement, whereas among men, health problems instantly the possibility of both job loss and retirement. CONCLUSIONS: Health problems of middle aged and older workers were crucial risk factors for retirement and involuntarily job loss. Especially functional defect and recent health problems strongly and instanty affected employment status.

Social Support, Social Network, and Frailty in Korean Elderly

BACKGROUND: The concept of frailty has been extended to include social factors such as poverty and social support networks. The frailty index developed for elderly Canadians was recently examined in terms of the current broader concept of frailty. The present study explored the relationship between social support networks and frailty in Korean elderly individuals aged 65 years or older. METHODS: A total of 1,874 people aged 65 years or older were recruited by judgment sampling of the population of Seocho-gu in Seoul and surveyed in 2011. The Korean Frailty Index, developed by the Korean Geriatric Society, was used as an outcome variable. A proportional odds model was used to evaluate the relationship between social support networks and depressive symptoms. RESULTS: The prevalence of frailty and pre-frailty were 7.7% and 25.5%, respectively. A total of 9.9% of older adults lacked a social network, and 13.6% were deficient in social support. Social support networks were associated with frailty. Adjusting for sociodemographic factors (age, sex, marital status, economic status, and education), lack of a social network and support were associated with increased odds of frailty (social network: odds ratio 2.15, 95% confidence interval 1.58-2.92; social support: odds ratio 2.01, 95% confidence interval 1.54-2.63). CONCLUSION: Consistent with the concept of frailty being broadened to include social factors, frailty among elderly individuals was found to be influenced by social support networks.

Serum HER2 as a Response Indicator to Various Chemotherapeutic Agents in Tissue HER2 Positive Metastatic Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of study was to evaluate the usefulness of serum HER2 as a therapeutic response indicator in patients with HER2 positive metastatic breast cancer (MBC). MATERIALS AND METHODS: The levels of serum HER2 and CA15.3 were assayed in 148 serial serum samples from 50 HER2 positive MBC patients at both the baseline and follow-ups. The changes in the levels of serum HER2 and CA15.3 in relation to the tumor responses to the various chemotherapy regimens were monitored. RESULTS: The levels of serum HER2 and CA15.3 were elevated in 82% and 62% of tissue HER2 positive patients, respectively, prior to therapies, with the changes in both tumor markers showing statistical significance in relation to the tumor responses (p<0.01) in patients with elevated baseline serum markers. CONCLUSION: The level of serum HER2 could be a valuable response indicator, not only for trastuzumab containing therapy, but also for other common MBC chemotherapeutic agents. Also, as it is more frequently elevated, the serum level of HER2 may also be a more useful tumor marker than CA15.3 in HER2 positive MBC.