Concomitant Use of Sodium-Glucose Cotransporter 2 Inhibitors and Overactive Bladder Drugs and the Risk of Urinary Tract Infection.

Concomitant use of sodium glucose cotransporter-2 inhibitors (SGLT-2i) and overactive bladder (OAB) drugs potentially poses a risk of urinary tract infections (UTIs) due to the urinary retention of highly concentrated glucose in the urine. Thus, this study aimed to investigate the risk of UTIs among patients who initiated SGLT-2i treatment while taking OAB drugs. This population-based cohort study included new-users of SGLT-2i or comparator antidiabetics (dipeptidyl peptidase-4 inhibitor (DPP-4i); glucagon-like peptide-1 receptor agonist (GLP-1RA)) with OAB drugs between 2014 and 2020 using claim data from Korea. Primary outcome was a composite UTI event composite end point comprising pyelonephritis, cystitis, and urethritis, using both inpatient and outpatient diagnoses. Propensity score fine stratification was used to adjust for potential confounding factors. Weighted hazard ratios (HR) were calculated using the Cox proportional hazards model. In the first cohort, 796 and 9,181 new-users of SGLT-2i and DPP-4i with OAB drugs were identified, respectively. This study found a similar risk of UTIs in concomitant users of SGLT-2i and DPP-4i (weighted HR 1.08, 95% confidence interval: 0.88-1.32) with OAB drugs. In the second cohort, 2,387 and 280 new-users of SGLT-2i and GLP-1RA with OAB drugs were identified, respectively. Initiation of SGLT-2i while on OAB treatment was not associated with increased risk of UTI (0.89, 0.50-1.60), compared with initiation of GLP-1RA. These results show that the concomitant use of SGLT-2i with OAB drugs was not associated with an increased risk of UTI compared with the concomitant use of DPP-4i or GLP-1RA with OAB drugs.

Comparative safety analysis of mRNA and adenoviral vector COVID-19 vaccines: a nationwide cohort study using an emulated target trial approach.

OBJECTIVE: This nationwide cohort study compared the incidence of adverse events of special interest (AESIs) between adenoviral vector-based (ChAdOx1) and mRNA-based (BNT162b2 or mRNA-1273) coronavirus disease 2019 (COVID-19) vaccines. METHODS: A targeted trial emulation study was conducted using data from the National Health Insurance Service database. Vaccinees aged 18-85 years who had received at least one dose of ChAdOx1 or an mRNA-based vaccine were identified. The 42-day risks of AESIs were calculated. RESULTS: A total of 1 767 539 ChAdOx1 vaccinees were matched exactly with mRNA vaccinees according to their risk factors. The 42-day risks of adverse events were low (∼0 to 176 events per 100 000 persons in both vaccine groups), and the incidence rates of AESIs were comparable between the two platforms, except for a higher occurrence of acute cardiac injury (incidence rate ratio [IRR], 1.22; 95% CI, 1.10-1.35), myocarditis or pericarditis (IRR, 2.14; 95% CI, 1.14-4.04), and arrhythmia (IRR, 1.46; 95% CI, 1.24-1.71) in mRNA vaccinees. The incidence of Guillain-Barré syndrome (IRR, 0.20; 95% CI, 0.06-0.69), vasovagal syncope (IRR, 0.77; 95% CI, 0.62-0.97), radiculopathy (IRR = 0.59, 95% CI, 0.41-0.84), and aseptic arthritis (IRR, 0.81; 95% CI, 0.70-0.93) was significantly lower in mRNA-based vaccinees compared with ChAdOx1 vaccinees. DISCUSSION: A remarkable platform-dependent difference was observed in the safety profiles of COVID-19 vaccines, particularly for myocarditis or pericarditis and Guillain-Barré syndrome. However, the overall risk of AESIs was low for both vaccine platforms.

Burden of Herpes Zoster in Individuals with Immunocompromised Conditions and Autoimmune Diseases in the Republic of Korea: A Nationwide Population-Based Database Study.

INTRODUCTION: To estimate herpes zoster (HZ) incidence rate (IR) and economic burden in individuals with immunocompromised conditions and autoimmune diseases (IC/AID) in the Republic of Korea (ROK). METHODS: The nationwide Health Insurance Review and Assessment Service database was used to identify HZ cases from 2016 to 2020 in ROK. HZ and non-HZ IC/AID cases were matched 1:3 using age, sex, institution, Charlson comorbidity index, IC/AID, and index date. Annual HZ IRs/1000 persons and 1-year HZ-associated all-cause direct medical costs for IC/AID cases were calculated. RESULTS: Among 65,976 individuals with IC/AID (mean age 57.14 years [standard deviation 14.1]; 64.94% female), annual HZ IR (95% confidence interval) fluctuated from 2016 to 2020, averaging 23.41/1000 persons (22.21-24.62) and was higher in women (26.85 [25.40-28.31]) than men (18.96 [18.03-19.89]). IRs were highest in individuals aged ≥ 50 years, and in those with transplants (including solid organ and hematopoietic stem cell transplants; 37.12 [35.45-38.79]) and hemato-oncology conditions (35.5 [31.6-39.3]). Mean 12-month all-cause direct medical costs were higher in individuals with IC/AID and HZ (4,759,671 Korean Republic won [KRW]; approximately 4046 United States dollar [USD; according to the 2020 conversion rate from UNCTAD; 1 KRW = 0.00085 USD]) than those without HZ (3,786,658 KRW; 3219 USD). CONCLUSION: Individuals with IC/AID have a substantial disease and economic burden from HZ in ROK, highlighting the need for appropriate HZ prevention measures in the IC/AID population.

Herpes Zoster Reactivation After mRNA and Adenovirus-Vectored Coronavirus Disease 2019 Vaccination: Analysis of National Health Insurance Database.

BACKGROUND: Our study aimed to determine the risk of herpes zoster reactivation and coronavirus disease 2019 (COVID-19) vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19]). METHODS: This retrospective study analyzed herpes zoster cases diagnosed between 26 February 2021 and 30 June 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed. RESULTS: In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose adjusted odds ratio [aOR], 1.11; 95% confidence interval [CI], 1.06-1.15; second dose aOR, 1.17; 95% CI, 1.12-1.23). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR], 1.09; 95% CI, 1.02-1.16). BNT162b2 was associated with an increased risk at 18 days postvaccination (aHR, 1.65; 95% CI, 1.35-2.02) and second dose (aHR, 1.10; 95% CI, 1.02-1.19). However, the risk did not increase in both analyses of ChAdOx1 vaccination. CONCLUSIONS: mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required.

Targeted literature review of the burden of extraintestinal pathogenic Escherichia Coli among elderly patients in Asia Pacific regions.

BACKGROUND: Extraintestinal Pathogenic Escherichia coli (ExPEC) is a leading cause of invasive disease, including bacteremia and sepsis. Invasive ExPEC disease (IED) has the potential to complicate the clinical treatment of other conditions and is associated with an increased mortality, hospitalization, and worse outcomes. Older adults and individuals with comorbid conditions are at higher risk of IED. ExPEC is of particular concern in the Asia Pacific region due to aging populations and rising antimicrobial resistance. OBJECTIVES: This study aimed to synthesize most recent data on the epidemiology, clinical and economic burden of IED in the elderly/high risk populations in China, Japan, South Korea, Taiwan, and Australia. METHODS: A targeted literature review was conducted using Embase, Medline, as well as local scientific databases. We included studies published in English and local languages published from January 1, 2010 to October 7, 2020 that were relevant to the research objectives. Studies were narratively synthesized. RESULTS: A total of 1,047 studies were identified and 34 of them were included in this review. ExPEC accounted for 46.0% (1,238/2,692) of bacteria-related invasive diseases in patients aged above 60 years in South Korea, followed by China (44.4% (284/640)), Taiwan (39.0% (1,244/3,194)), and Japan (18.1% (581/3,206)), while Australia reported ExPEC out of all pathogens (54.7% (4,006/7,330)) in general adults. Comorbidities such as diabetes or cancer were common in these patients. Studies reported increases in length-of-stay, and in-hospital 30-day all-cause mortality related to ExPEC associated bacteremia was between 9% to 12%. From a cost perspective, a 3-fold increase in sepsis-associated cost was reported in South Korea between 2005 and 2012. In Australia, antimicrobial resistance contributed to an additional cost of AUD $5.8 million per year (95% uncertainty interval [UI], $2.2-$11.2 million) in the treatment of bloodstream infections (BSIs). CONCLUSION: ExPEC was a major cause of blood stream infection across China, Japan, South Korea, Taiwan, and Australia. Both the clinical and economic burden associated to ExPEC infections as well as the antimicrobial resistance observed in the elderly call for preventive and curative actions in these regions.

Extraintestinal Pathogenic Escherichia coli (ExPEC) is a leading cause of invasive disease, including bacteremia and sepsis.A targeted literature review included the most recent data from 34 published studies on the epidemiology and clinical and economic burden of IED in the elderly/high risk populations in China, Japan, South Korea, Taiwan, and Australia.ExPEC accounted for 46.0% (1,238/2,692) of bacteria-related invasive diseases in patients aged above 60 years in South Korea, followed by China (44.4% (284/640)), Taiwan (39.0% (1,244/3,194)), and Japan (18.1% (581/3,206)), while Australia reported ExPEC out of all pathogens (54.7% (4,006/7,330)) in general adults. Studies reported increases in length-of-stay and in-hospital 30-day all-cause between 9% to 12%. These factors, along with antimicrobial resistance observed in the elderly, call for preventive and curative actions in these regions.Data for costs associated with ExPEC induced BSI or sepsis in this region are limited, but evidence shows increasing expenditures.

Cancer Incidence Among Adults With HIV in a Population-Based Cohort in Korea.

Importance: In combination with a decreased risk of AIDS-defining cancers and improved survival of people infected with HIV, the burden of non-AIDS-defining cancer has increased markedly. Although a substantial number of studies have measured the cancer risk among people with HIV in developed countries, little research has been conducted on the risk of cancer in HIV-infected people in Asia. Objective: To examine the cancer incidence and the estimated risk of cancer among people in Korea infected with HIV compared with the general population. Design, Setting, and Participants: This retrospective cohort study evaluated patients without cancer newly diagnosed with HIV from January 1, 2006, to December 31, 2018, using a nationwide population-based claims database embedded in the National Health Insurance Service database. Data were analyzed between December 6, 2021, and February 28, 2022. Exposures: Infection with HIV. Main Outcomes and Measures: Cancer incidence and standardized incidence rate (SIR) through indirect standardization. Results: A total of 11 552 individuals without cancer (10 444 male [90.4%]; mean [SD] age, 39.9 [11.2] years) diagnosed with HIV were identified. The SIR for all cancers was 1.68 (95% CI, 1.50-1.87) in men and 1.26 (95% CI, 0.89-1.64) in women. In men, the highest SIRs were for Kaposi sarcoma (SIR, 349.10; 95% CI, 196.10-502.20) and anal cancer (SIR, 104.20; 95% CI, 55.56-149.90). The incidence of non-Hodgkin lymphoma (SIR, 15.62; 95% CI, 11.85-19.39), Hodgkin lymphoma (SIR, 16.67; 95% CI, 4.32-29.02), and oropharyngeal cancer (SIR, 2.97; 95% CI, 1.36-4.58) in men infected with HIV was higher than in the general population. In women infected with HIV, an increased incidence of cervical cancer (SIR, 4.98; 95% CI, 1.29-8.66) and non-Hodgkin lymphoma (SIR, 11.78; 95% CI, 2.35-21.21) compared with the general population was observed. The SIR of thyroid cancer in patients with HIV was lower than in the general population in both men (SIR, 0.63; 95% CI, 0.27-0.99) and women (SIR, 0.48; 95% CI, 0.06-0.90). Conclusions and Relevance: In this cohort study, cancer risks, especially AIDS-defining cancer and virus-related cancer, were elevated in people with HIV. Efforts for cancer prevention, screening, and better accessibility to medical care in HIV-infected people are warranted.

Early Safety Monitoring of COVID-19 Vaccines in Healthcare Workers.

Hospital-based surveillance for adverse events was conducted on healthcare workers after they received the first dose of coronavirus disease 2019 (COVID-19) vaccine. Among the two new platform vaccines (messenger RNA- and adenoviral vector-based vaccines), the rates of systemic adverse events were significantly higher among adenovirus-vectored vaccine recipients. Fatigue (87.6% vs. 53.8%), myalgia (80.8% vs. 50.0%), headache (72.0% vs. 28.8%), and fever (≥ 38.0°C, 38.7% vs. 0%) were the most common adverse events among adenovirus-vectored vaccine recipients, but most symptoms resolved within 2 days. Both types of COVID-19 vaccines were generally safe, and serious adverse events rarely occurred.

The Practice Guideline for Vaccinating Korean Patients with Autoimmune Inflammatory Rheumatic Disease.

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and the Korean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measles-mumps-rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

Clinical characteristics and disease burden of respiratory syncytial virus infection among hospitalized adults.

The disease burden of respiratory syncytial virus (RSV) infection in the adult population has not been well characterized compared to children. Investigation of the clinical characteristics and disease burden of adult RSV infection would help to establish public health policy and a future vaccine strategy. We retrospectively collected medical records of hospitalized adult patients who were diagnosed with RSV infection from January 2012 to December 2015 from three tertiary hospitals. Baseline characteristics, clinical outcomes and economic charge during hospitalization were compared by age groups (19-49 years, 50-64 years, and ≥ 65 years) using Chi-square test. The odds of risk factors of RSV pneumonia were calculated using binary logistic regression. A total of 204 patients from three hospitals were enrolled. Patients who older than 65 years were 132 (64.7%). 118 (57.8%) patients had clinically confirmed pneumonia and 22 (10.8%) died in a hospital. The median medical cost of RSV pneumonia was 2,855.26 USD (interquartile range, 1,561.85-5,379.55) per each admission. Solid cancer (adjusted OR, 3.85; 95% CI, 1.65-9.02, p = 0.002) and hematologic malignancy (all patients had pneumonia) were shown to be risk factors for RSV pneumonia. RSV infection in South Korea seemed to have a significant burden among adults as pneumonia, care in the intensive care unit and mortality. Nationwide awareness and further effort to recognize the current burden, prepare specific treatment, and prevent adult RSV infection would be necessary.

Characteristics of residual lymph nodes after six months of antituberculous therapy in HIV-negative individuals with cervical tuberculous lymphadenitis.

BACKGROUND: The therapeutic response of cervical tuberculous lymphadenitis (CTBL) may be delayed or paradoxical, with the frequent development of residual lymph nodes (LNs) during and after antituberculous treatment. We investigated the incidence of residual LNs and the clinical, radiological, microbiological, and pathologic responses of patients with CTBL after 6 months of antituberculous therapy. METHODS: The medical records of HIV-negative adult patients with CTBL diagnosed between July 2009 and December 2017 were analyzed. After 6 months of first-line antituberculous treatment, computed tomography (CT) scans were conducted to evaluate for residual LNs. Fine-needle aspiration biopsy (FNAB) was carried out if a patient presented with residual LNs > 10 mm in diameter with central necrosis, peripheral rim enhancement, or perinodal inflammation on CT scan. RESULTS: Residual LNs were detected in 35 of 157 patients who underwent follow-up CT scans and were more commonly observed in younger patients who completed the treatment (mean years ± standard deviation [SD]: 33 ± 13 vs. 44 ± 16, p < 0.001). The recurrence rate was approximately 5%, which was not significantly different in both groups. Among the 15 patients who underwent FNAB, 3 (30%) presented with granuloma, and 2 of 15 and 10 of 14 patients had positive AFB and TB PCR results, respectively. The TB culture results of 15 patients were negative. CONCLUSIONS: Residual LNs may still be observed after 6 months of antituberculous treatment. Although the radiologic and pathologic findings after treatment are still indicative of TB, not all residual LNs indicate recurrence or treatment failure. A six-month therapy may be sufficient for cervical tuberculous lymphadenitis.

Development of a SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets.

Although the incidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection has increased from its discovery with a mortality rate of 10-20%, no effective vaccines are currently available. Here we describe the development of a SFTSV DNA vaccine, its immunogenicity, and its protective efficacy. Vaccine candidates induce both a neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets. When the vaccine efficacy is investigated in aged-ferrets that recapitulate fatal clinical symptoms, vaccinated ferrets are completely protected from lethal SFTSV challenge without developing any clinical signs. A serum transfer study reveals that anti-envelope antibodies play an important role in protective immunity. Our results suggest that Gn/Gc may be the most effective antigens for inducing protective immunity and non-envelope-specific T cell responses also can contribute to protection against SFTSV infection. This study provides important insights into the development of an effective vaccine, as well as corresponding immune parameters, to control SFTSV infection.

Supine lateral radiographs at 90° of knee flexion have a similar diagnostic accuracy for chronic posterior cruciate ligament injuries as stress radiographs.

PURPOSE: This study aimed to evaluate whether supine lateral radiographs (SLRs) could replace stress radiographs for diagnosing chronic posterior cruciate ligament (PCL) injuries and identifying combined PCL injuries (defined as PCL injury with medial collateral ligament or posterolateral ligament complex injury). METHODS: In this retrospective study, both SLRs at 30° and 90° of knee flexion (30/90 SLRs) and Telos stress radiographs of patients with chronic PCL injuries (n = 38) and only 30/90 SLRs of healthy controls (n = 84) were taken. Injured-to-normal differences on 30/90 SLRs and stress radiographs were assessed. Correlation analysis was performed to evaluate injured-to-normal differences on 30/90 SLRs and stress radiographs in patients with chronic PCL injury. Subgroup analysis was performed to compare injured-to-normal differences on 30/90 SLRs and stress radiographs between the isolated and combined PCL injury groups. Receiver operating characteristic curves based on 30/90 SLRs were calculated to determine the cut-off value for diagnosing chronic PCL injury and identifying combined PCL injury. RESULTS: Injured-to-normal differences on both 30 SLRs (3.1 ± 3.6 vs 1.6 ± 1.2, P = 0.019) and 90 SLRs (7.5 ± 3.5 vs 1.2 ± 1.0, P < 0.001) were significantly greater in patients with chronic PCL injuries than in healthy controls. Further, 90 SLRs had a highly accurate diagnostic value for chronic PCL injuries (area under the curve 0.958). The cut-off value for diagnosing chronic PCL injuries based on 90 SLRs was 3.0 mm (sensitivity, 94.7%; specificity, 92.9%). Injured-to-normal differences on 30/90 SLRs were significantly correlated with those on stress radiographs. The correlation coefficients were 0.397 (P = 0.014) for 30 SLRs and 0.605 (P < 0.001) for 90 SLRs. The cut-off value for diagnosing combined PCL injuries based on 90 SLRs was 9.6 mm (area under the curve 0.72). CONCLUSIONS: The diagnostic accuracy of 90 SLRs for chronic PCL injuries was similar to that of stress radiographs. Therefore, the 90 SLRs are reliable alternative method to assess the posterior knee laxity when the stress radiographs are not available. LEVEL OF EVIDENCE: Level IV, case series.

Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older.

Background: The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods: Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results: After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions: Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination. Clinical Trials Registration: NCT01165177; NCT01165229.

Diagnosis and treatment of spontaneous pneumomediastinum: experience at a single institution for 10 years.

OBJECTIVE: The aim of this study was to identify appropriate method of diagnosis and treatment of spontaneous pneumomediastinum (SPM) based on our experience. METHODS: The medical records of patients who were diagnosed with SPM and treated at our hospital between April 2006 and July 2015 were, retrospectively, analyzed. The data included characteristics of the patients, method of diagnosis, treatment and clinical course. RESULTS: Forty-five patients were diagnosed with SPM and treated at our hospital. The mean age of patients was 18.96 ± 4.65 years and 35 patients were male. The main symptoms expressed by these patients were chest pain, throat pain or discomfort, and dyspnea. Nine patients had a precipitating event leading to SPM. Twelve patients had normal chest X-ray findings but were subsequently diagnosed with SPM on chest computed tomography (CT). Additional procedures including esophagogram (n = 36), bronchoscopy (n = 14) and endoscopy (n = 1) were done but none of patients were found to have organ damage. All patients received oxygen inhalation therapy. Oral intake was restricted in 36 patients and 43 patients received prophylactic antibiotics. The mean time taken for symptomatic improvement was 1.73 ± 0.85 days from diagnosis. The mean hospital stay was 3.93 ± 1.44 days and no patient developed recurrence of SPM during the follow-up period. CONCLUSIONS: In addition to chest X-ray, chest CT is recommended for accurate diagnosis of SPM. However, further invasive investigations, restriction of oral intake and the use of prophylactic antibiotics have minimal role in the diagnosis and treatment of SPM.

Heterodimeric interaction between GKN2 and TFF1 entails synergistic antiproliferative and pro-apoptotic effects on gastric cancer cells.

BACKGROUND: GKN2 and TFF1 form a heterodimer that is only generated in the mucus-secreting cells of the normal stomach. The formation of this heterodimer is frequently disrupted in gastric cancer. However, the precise roles of GKN2 alone and in the heterodimer with TFF1 as well as the contributions of GKN2 and the heterodimer to gastric carcinogenesis are poorly understood. METHODS: Cell viability, proliferation, and apoptosis were analyzed in AGS, MKN1, MKN28, and MKN45 gastric cancer cells transfected with GKN2 and/or TFF1 using MTT, BrdU incorporation, and apoptosis assays, respectively. In addition, cell viability was examined in HFE-145 non-neoplastic gastric epithelial cells after GKN2 and/or TFF1 silencing. Furthermore, the cell cycle and the expression of cell cycle and apoptosis related proteins were assessed. The interaction between GKN2 and TFF1 was confirmed by co-immunoprecipitation. Immunohistochemistry was employed to explore TFF1 expression in 169 gastric cancer tissues. RESULTS: Co-transfection with GKN2 and TFF1 significantly inhibited cell viability and proliferation by inducing G1/S cell cycle arrest and suppressing positive cell cycle regulators. Simultaneous knockdown of GKN2 and TFF1 in HFE-145 cells resulted in markedly increased cell viability. Moreover, the interaction of GKN2 and TFF1 promoted cell death by enhancing caspase-3/7 activity and upregulating pro-apoptotic proteins. At the mRNA level, GKN2 and TFF1 were found to be positively correlated in non-tumor and tumor samples. Immunohistochemistry revealed loss of TFF1 expression in 128 (75.73%) of 169 gastric cancers. There was a borderline-significant association between GKN2 and TFF1 protein expression in gastric cancers (P = 0.0598). CONCLUSION: Collectively, our data demonstrated that the interaction between GKN2 and TFF1 can have synergistic antiproliferative and pro-apoptotic effects on gastric cancer.

Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression.

BACKGROUND: We investigated whether GKN1, a gastric tumor suppressor, contributes to the progression of gastric cancer by regulating RhoA expression. METHODS: We analyzed the expression of GKN1, RhoA, miR-185, and miR-34a in 35 gastric cancer tissues, and compared their expression with T category and TNM stage. Cell migration and invasion, as well as the expression of epithelial-to-mesenchymal transition (EMT)-related proteins, were assessed in GKN1- and RhoA small interfering RNA (siRhoA)-transfected and recombinant-GKN1-treated AGS and MKN1 gastric cancer cells. RESULTS: Expression of RhoA protein and messenger RNA (mRNA) was increased in 15 (42.9 %) and 17 (48.6 %) of 35 gastric cancer tissues respectively, and was associated with higher T category and TNM stage. GKN1 expression was significantly decreased in 27 gastric cancers (77.1 %) with a higher T category, and was inversely correlated with RhoA mRNA expression. In AGS and MKN1 cells, GKN1 expression increased miR-185 and miR-34a expression and reduced RhoA mRNA and protein expression. A positive relationship between GKN1 and miR-34a and miR-185 expression and an inverse relationship between miR-34a and RhoA expression were observed in gastric cancer tissues. Cell migration and invasiveness were markedly decreased in GKN1- and siRhoA-transfected cells. GKN1 expression and silencing of RhoA decreased the expression of the proteins Snail, Slug, and vimentin. Furthermore, miR-185 and miR-34a silencing in MKN1 cells transfected with GKN1 stimulated cell migration and invasion, and increased the expression of EMT-related proteins. CONCLUSION: Our data suggest that GKN1 may inhibit gastric cancer cell migration and invasion by downregulating RhoA expression in a miR-185- and miR-34a-dependent manner.

NKX6.3 Is a Transcription Factor for Wnt/ß-catenin and Rho-GTPase Signaling-Related Genes to Suppress Gastric Cancer Progression.

Despite ongoing research and recent progress, the prognosis for patients with advanced gastric cancer remains poor. Wnt/ß-catenin and Rho-GTPase signaling pathways are known to play essential roles in malignant transformation and progression of various tumors, including gastric cancer. Here, we identify that NKX6 transcription factor, locus 3 (NKX6.3) binds directly to specific promoter regions of Wnt/ß-catenin and Rho-GTPase pathway-related genes, resulting in inhibition of cancer cell migration and invasion. Additionally, we find that the expression level of NKX6.3 is involved in regulation of gastric cancer progression and expression of Wnt/ß-catenin and Rho-GTPase pathway-related genes in clinical samples. These results suggest that NKX6.3 prevents EMT and cell migration, implying that NKX6.3 inactivation might be one of the key mechanisms of gastric cancer cell invasion and metastasis.

The acceptable duration between occupational exposure to hepatitis B virus and hepatitis B immunoglobulin injection: Results from a Korean nationwide, multicenter study.

BACKGROUND: Postexposure prophylaxis for occupational exposure to hepatitis B virus (HBV) plays an important role in the prevention of HBV infections in health care workers (HCWs). We examined data concerning the acceptable duration between occupational exposure and administration of a hepatitis B immunoglobulin (HBIG) injection in an occupational clinical setting. METHODS: A retrospective analysis was conducted with data from 143 cases of HCWs exposed to HBV in 15 secondary and tertiary teaching hospitals between January 2005 and June 2013. Data were taken from the infection control records of each hospital. RESULTS: Active vaccination after HBV exposure was started in 119 cases (83.2%) and postvaccination testing for hepatitis B antibody showed positive seroconversion in 93% of cases. In 98 cases (68.5%), HBIG was administered within 24 hours after HBV exposure; however, 45 HCWs (31.5%) received an HBIG injection more than 24 hours postexposure and 2 among the 45 received an injection after 7 days. Although 31.5% received an HBIG injection more than 24 hours postexposure, no cases of seroconversion to hepatitis b antibody positivity occurred. CONCLUSIONS: For susceptible HCWs, HBIG administered between 24 hours and 7 days postexposure may be as effective as administration within 24 hours in preventing occupational HBV infection.

Gastrokine 1 inhibits gastrin-induced cell proliferation.

BACKGROUND: Gastrokine 1 (GKN1) acts as a gastric tumor suppressor. Here, we investigated whether GKN1 contributes to the maintenance of gastric mucosal homeostasis by regulating gastrin-induced gastric epithelial cell growth. METHODS: We assessed the effects of gastrin and GKN1 on cell proliferation in stable AGS(GKN1) and MKN1(GKN1) gastric cancer cell lines and HFE-145 nonneoplastic epithelial cells. Cell viability and proliferation were analyzed by MTT and BrdU incorporation assays, respectively. Cell cycle and expression of growth factor receptors were examined by flow cytometry and Western blot analyses. RESULTS: Gastrin treatment stimulated a significant time-dependent increase in cell viability and proliferation in AGS(mock) and MKN1(mock), but not in HFE-145, AGS(GKN1), and MKN1(GKN1), cells, which stably expressed GKN1. Additionally, gastrin markedly increased the S-phase cell population, whereas GKN1 significantly inhibited the effect of gastrin by regulating the expression of G1/S cell-cycle regulators. Furthermore, gastrin induced activation of the NF-kB and ß-catenin signaling pathways and increased the expression of CCKBR, EGFR, and c-Met in AGS and MKN1 cells. However, GKN1 completely suppressed these effects of gastrin via downregulation of gastrin/CCKBR/growth factor receptor expression. Moreover, GKN1 reduced gastrin and CCKBR mRNA expression in AGS and MKN1 cells, and there was an inverse correlation between GKN1 and gastrin, as well as between GKN1 and CCKBR mRNA expression in noncancerous gastric mucosae. CONCLUSION: These data suggest that GKN1 may contribute to the maintenance of gastric epithelial homeostasis and inhibit gastric carcinogenesis by downregulating the gastrin-CCKBR signaling pathway.

Influence of the hTERT rs2736100 polymorphism on telomere length in gastric cancer.

AIM: To investigate the functional consequences of rs2736100 polymorphism in telomere length and examine its link to gastric cancer risk. METHODS: Telomere length and human telomerase reverse transcriptase (hTERT) mRNA expression were measured in 35 gastric cancer tissues and 5 cell lines and correlated to rs2736100 polymorphism. The relationship between rs2736100 polymorphism and the risk of gastric cancer were examined in 243 gastric cancer patients and 246 healthy individuals. RESULTS: The rs2736100 A allele carrier is closely associated with reduced hTERT mRNA expression and shortened telomere length in gastric cancer tissue and cell lines. When gastric cancers were stratified by histological subtype, telomere length and hTERT mRNA levels were significantly increased in those with the C/C genotype in intestinal-type gastric cancer, but not in diffuse-type gastric cancer. Interestingly, there was no significant difference in the genotype and allele frequencies of the rs2736100 polymorphism between the patients with gastric cancer and healthy controls. CONCLUSION: The rs2736100 polymorphism of the hTERT gene is involved in the regulation of hTERT expression and telomere length, but not in the risk of gastric cancer.