Evaluation of cosmetic outcomes in breast reconstruction patients undergoing radiotherapy using an anomaly generative adversarial network model.

Considering the rising prevalence of breast reconstruction followed by radiotherapy (RT), evaluating the cosmetic impact of RT is crucial. Currently, there are limited tools for objectively assessing cosmetic outcomes in patients who have undergone reconstruction. Therefore, we validated the cosmetic outcome using a previously developed anomaly Generative Adversarial Network (GAN)-based model and evaluated its utility. Between January 2016 and December 2020, we collected computed tomography (CT) images from 82 breast cancer patients who underwent immediate reconstruction surgery followed by radiotherapy. Among these patients, 38 received immediate implant insertion, while 44 underwent autologous breast reconstruction. Anomaly scores (AS) were estimated using an anomaly GAN model at pre-RT, 1st follow-up, 1-year (Post-1Y) and 2-year (Post-2Y) after RT. Subsequently, the scores were analyzed in a time-series manner, considering reconstruction types (implant versus autologous), RT techniques, and the incidence of major complications. The median age of the patients was 46 years (range 29-62). The AS between Post-1Y and Post-2Y demonstrated a positive relationship (coefficient 0.515, P < 0.001). The AS was significantly associated with objective cosmetic indices, namely Breast Contour Difference (P = 0.009) and Breast Area Difference (P = 0.004), at both Post-1Y and Post-2Y. Subgroup analysis stratified by type of breast reconstruction revealed significantly higher AS values in patients who underwent prosthetic implant insertion compared to those with autologous reconstruction at all follow-up time points (1st follow-up, P = 0.001; Post-1Y, P < 0.001; and Post-2Y, P < 0.001). A threshold AS of ≥ 1.9 was associated with a 10% predicted risk of developing major complications. The feasibility of an AS generated by a GAN model for predicting both cosmetic outcomes and the likelihood of complications following RT has been successfully validated. Further investigation involving a larger patient cohort is warranted.

Clinical outcomes of radical radiotherapy for pulmonary sarcomatoid carcinoma.

PURPOSE: Pulmonary sarcomatoid carcinoma (PSC) is recognized for its aggressiveness and poor prognosis. The role of radical radiotherapy in PSC remains uncertain due to its scarcity and limited data. In the absence of an effective systemic agent, this study aims to explore the possibility of cure and to investigate potential prognostic factors and treatment outcomes. MATERIALS AND METHODS: From January 2005 to December 2021, 149 PSC patients were identified. Among 62 patients who received radiotherapy for lung lesions, 25 who underwent palliative radiotherapy and 16 who underwent surgery were excluded. RESULTS: The median patient age was 71 years. The majority were male, and 17 patients (81.0%) were diagnosed at an advanced stage. After radical radiotherapy, distant metastasis (47.6%) was the most common site of failure, while the local recurrence rate was quite low (9.5%). Eventually, five patients (26.3%) demonstrated either a partial response or complete remission, including three complete remissions with durable responses. The median progression-free survival (PFS) and overall survival were 4.6 months and 7.9 months, respectively. Univariate and multivariate analyses revealed that a tumor size >5 cm was associated with a worse prognosis (p = 0.045), while a radiation dose >58 GyEQD2 was significantly associated with better PFS (p = 0.038). CONCLUSION: This study demonstrates clinical outcomes after radical radiotherapy in managing PSC, suggesting tumor size and radiation dose could be a predictor of a systemic response. Given the known bad prognosis but complete remission could be achieved in certain subgroups, future research should explore the potential strategies using radical radiotherapy for this challenging patient population.

Treatment patterns and results of salvage treatment for regional recurrences after stereotactic ablative radiotherapy for primary non-small cell lung cancer.

PURPOSE: Stereotactic ablative radiotherapy (SABR) for early-stage lung cancer has shown promising results; however, regional recurrence (RR) development is not uncommon, and salvage treatment strategies have not been established. We aimed to investigate treatment patterns, prognostic factors, and survival outcomes. MATERIALS AND METHODS: A retrospective analysis of 391 patients who underwent SABR for primary lung cancer from 2012 to 2019 was performed. Among these patients, 90 patients showed recurrence, including local recurrence (n = 9), RR (n = 33), distant metastasis (DM) (n = 57), and RR with simultaneous DM (n = 8). The median follow-up duration was 17.3 months. RESULTS: The median age was 75 years, and most patients underwent primary SABR due to poor lung function (69.7%). Various salvage treatments were performed in cases of RR, including chemotherapy (n = 15), radiotherapy (n = 7), concurrent chemoradiotherapy (n = 2), and best supportive care (n = 9). The median overall survival (OS) and post-recurrence OS (PR-OS) were 22.9 and 11.2 months, respectively. In multivariate analysis, age ≤75 years (HR = 0.36, p = 0.040), isolated recurrence (HR = 0.34, p = 0.037), and radiotherapy without chemotherapy (HR = 0.25, p = 0.024) were significant prognostic factors for PR-OS. CONCLUSIONS: Despite various salvage treatments, PR-OS was less than 1 year after RR in our frail patients group who underwent primary SABR. The toxicities of salvage chemotherapy could be quite severe; thus, careful patient selection is required. Further research is needed to validate our findings.

Comparison of the clinical characteristics and mortality of adults infected with human coronaviruses 229E and OC43.

The purpose of the study was to compare clinical characteristics and mortality among adults infected with human coronaviruses (HCoV) 229E and OC43. We conducted a retrospective cohort study of adults (≥ 18 years) admitted to the ward of a university teaching hospital for suspected viral infection from October 2012 to December 2017. Multiplex real-time polymerase chain reaction (PCR) was used to test for respiratory viruses. Multivariate logistic regression was used to compare mortality among patients with HCoV 229E and HCoV OC43 infections. The main outcome was 30-day all-cause mortality. Of 8071 patients tested, 1689 were found to have a respiratory virus infection. Of these patients, 133 had HCoV infection, including 12 mixed infections, 44 HCoV 229E infections, and 77 HCoV OC43 infections. HCoV 229E infections peaked in January and February, while HCoV OC43 infections occurred throughout the year. The 30-day all-cause mortality was 25.0% among patients with HCoV 229E infection, and 9.1% among patients with HCoV OC43 infection (adjusted odds ratio: 3.58, 95% confidence interval: 1.19-10.75). Infections with HCoVs 229E and OC43 appear to have different seasonal patterns, and HCoV 229E might be more virulent than HCoV OC43.

Cesarean delivery may be protective against neoplasms of the uterine cervix in women of childbearing age.

Parity has been reported as a risk factor for cervical cancer. However, no study has investigated the risk of neoplasms of the uterine cervix according to the delivery type. We carried out a retrospective cohort study using nationwide data from the Korean Health Insurance Review and Assessment Database to investigate whether cesarean delivery might be associated with less development of neoplasms of the uterine cervix than a vaginal delivery in women of childbearing age. Women aged 20-44 years, who had undergone vaginal or cesarean deliveries in 2009 were included as subjects. Two individual datasets for carcinoma in situ (CIS) and cancer of the cervix were followed for 8 years until either disease outcomes or 31 December 2016. In total, 260 438 and 132 232 women had undergone vaginal only and cesarean only deliveries, respectively. There were 1505 and 423 new cases of CIS and cervical cancer, respectively, with median follow-up durations of 89.9 and 90.0 months for vaginal delivery and cesarean delivery, respectively. The unadjusted CIS risk ratio for cesarean delivery compared with vaginal delivery was 0.90 [95% confidence interval, (CI), 0.80-1.00]. After adjusting for categorical age, residential area, facility types, and number of visits to obstetrics and gynecology clinics, it was 0.83 (95% CI, 0.75-0.93). The unadjusted and adjusted risk ratios for cervical cancer for cesarean delivery were 0.98 (95% CI, 0.80-1.20) and 0.87 (95% CI, 0.71-1.08), respectively. Cesarean delivery may be more protective against CIS than vaginal delivery in women of childbearing age.

Association between EGFR mutation and ageing, history of pneumonia and gastroesophageal reflux disease among patients with advanced lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is the most frequently encountered oncogenic driver in lung cancer. Risk factors for EGFR mutation may help prevention, surveillance and diagnosis strategies of EGFR-mutated lung cancer. PATIENTS AND METHODS: A nationwide, retrospective, longitudinal, cohort study was performed between January 2002 and December 2015. Patient data were collected from the Korean National Health Insurance Database. The lung cancer group included EGFR tyrosine kinase inhibitor (TKI)-treated patients. Controls were randomly selected from people without a history of lung cancer and determined to be four times the number of patients with EGFR-mutated advanced lung cancer. The risk model of developing EGFR-mutated lung cancer was constructed by multiple logistic regression analysis. RESULTS: Among the 2010 new cases of lung cancer treated in 2010-2015, 214 cases were classified as EGFR-mutated advanced lung cancer. The risk of developing EGFR-mutated advanced lung cancer was higher in patients in their 50s (odds ratio [OR]: 3.42; 95% confidence interval [CI]: 1.68-6.93), 60s (OR: 7.04; 95% CI: 3.35-14.77) and 70s (OR: 10.27; 95% CI: 4.73-22.30) and in those aged >80 years (OR: 5.98; 95% CI: 2.25-15.92) than those in their 40s. The risk of developing EGFR-mutated lung cancer was also higher in hospitalised patients with a history of pneumonia (OR: 5.22; 95% CI: 1.88-14.46) and those with gastroesophageal reflux disease (OR: 2.02; 95% CI: 1.32-3.07). CONCLUSIONS: Patients with EGFR-mutated advanced lung cancer were associated with ageing, history of being hospitalised for pneumonia and gastroesophageal reflux disease.

Lung Cancer development and mortality in interstitial lung disease with and without connective tissue diseases: a five-year Nationwide population-based study.

BACKGROUND: Connective tissue disease associated with interstitial lung disease (CTD-ILD) and interstitial lung disease (ILD) alone have same pathological and imaging backgrounds. However, the differences between lung cancer development and the mortality risk between these two conditions are unclear. Incidence of primary lung cancer and all-cause mortality were studied between interstitial lung disease patients with and without connective tissue disease. METHODS: Data were extracted from the Korean National Health Insurance Research Database in 2009. A total of 12,787 cases of ILD without idiopathic pulmonary fibrosis and 2491 cases of CTD-ILD were diagnosed in 2009. The cohort was followed up until June 30, 2014. Incident lung cancers and all-cause mortality were ascertained. RESULTS: The overall incidence of lung cancer was 165.7 and 161.8 per 10,000 person-years in the CTD-ILD and ILD-only, respectively (rate ratio, 1.08; 95% confidence interval, 0.89-1.30). CTD-ILD patients in the 40-49 and 50-59 years old age groups had lung cancer incidence rates of 92.5 and 139.2, which were 2.0 and 1.7 times higher than those in the ILD-only, respectively. All-cause mortality was significantly higher in the CTD-ILD group compared to ILD-only group in patients aged 50-79 years. All-cause mortality of women in the 50-59, 60-69 and 70-79 age groups was 2.0, 1.8, and 1.4 times higher in the CTD-ILD group than in the ILD-only group, respectively. CONCLUSIONS: CTD-ILD patients aged < 60 years had a higher lung cancer incidence than ILD-only patients in the same age group. Furthermore, CTD-ILD patients aged 50-79 years had higher all-cause mortality than ILD-only patients in the same age group.

Incidence and Risk Factors of Recurrent Venous Thromboembolism after Pulmonary Embolism.

BACKGROUND: Information about the epidemiology of venous thromboembolism (VTE) recurrence in Korea is lacking. The purpose of this study was to investigate VTE cumulative recurrence rates and identify risk factors for VTE recurrence among Korean adults. METHODS: A retrospective cohort study was conducted on adult patients (≥18 years) admitted to a university teaching hospital for pulmonary embolism (PE) from 2005 to 2013. The main outcome of interest was a recurrence of VTE. We used Cox proportional hazard regression analyses to calculate the relative risk of VTE recurrence. RESULTS: Five-year cumulative incidence of recurrent VTE events was 21.5% (95% confidence interval [CI], 17.7-25.4) in all cases of PE; 17% after provoked and 27% after unprovoked PE. Multivariate analysis showed that body mass index (BMI) of ≥25 (hazard ratio [HR], 2.02; 95% CI, 1.17-3.46; p=0.01) and longer anticoagulation therapy duration (HR, 0.90; 95% CI, 0.84-0.96; p<0.01) were independently associated with risk of VTE recurrence. Risk factors not found to be statistically significant at the <0.05 level included history of VTE (HR, 1.81; 95% CI, 0.84-3.88; p=0.12), unprovoked PE (HR, 1.70; 95% CI, 0.89-3.25; p=0.10), symptomatic deep vein thrombosis (HR, 1.62; 95% CI, 0.89-2.94; p=0.10), and female sex (HR, 1.42; 95% CI, 0.78-2.55; p=0.24). We found that age, history of cancer, and other co-morbidities did not significantly affect the risk of VTE recurrence. CONCLUSION: Recurrence of VTE after PE is high. Patients with BMI ≥25 or reduced anticoagulation therapy duration have a higher risk of recurrent VTE.

Cancer Survivors and Returning to Work Perspectives from Occupational Health Physicians in Korea.

BACKGROUND: This study was conducted from an occupational health perspective to document cancer survivors' ability to return to work, the role of clinical care, and the current status of effective return-to-work. METHODS: This cross-sectional study was conducted to evaluate the experiences and opinions of occupational health physicians (OHPs) regarding cancer survivors' return-to-work. A self-reported survey was conducted from December 30, 2015, to January 30, 2016, targeting 337 OHPs. Questions included: 1) treatment experiences of survivors in the words of OHPs, 2) current status of the assessments of fitness for work of cancer survivors, 3) experiences associated with workplace and treatment, and 4) problems of returning to work and overcoming system. RESULTS: Only 25% of the respondents said that they had experience treating cancer survivors, and the average number of patients was 12.6 per annum, which indicated that few cancer survivors were treated. Eleven cases included conducting assessment of fitness for work. There were 17 respondents who did not treat cancer survivors. Both those who had and did not have experience in treating survivors showed higher musculoskeletal system disorders (53.8 vs. 63.5) than cancer (15.5 vs. 11.2) in terms of frequency of the diseases in the assessment of fitness for work. Most respondents said that OHPs evaluate the current role appropriately and preferred OHPs in the future. They responded that OHPs found it difficult to treat cancer survivors, and it was psychologically tough to communicate with them (61.4%). Regarding the association of patient rehabilitation with workplaces, 48.9% said that workplaces provide inadequate support. CONCLUSION: As a preliminary study, we found that OHPs were found to have little experience in treating cancer survivors and undergo difficulties owing to poor collaboration with workplaces and communication with patients. This study will provide basic data for future studies to promote cancer survivors' return to workplaces.

Pneumonia severity index in viral community acquired pneumonia in adults.

Pneumonia severity index (PSI) is an important scoring system that can assess the severity of community acquired pneumonia and determine admission status. However, there is a lack of research on whether this scoring system can be applied to viral community acquired pneumonia. The purpose of this study was to evaluate the usefulness of PSI in viral community acquired pneumonia. This retrospective cohort study included 1,434 adult patients (aged ≥18 years) who were admitted to the emergency department of a university hospital during 2013-2015 because of community-acquired pneumonia. Viral infections were diagnosed by multiplex PCR. Patients diagnosed with non-viral community-acquired pneumonia were included in the control group (N = 1,173). The main outcome was 30-day all-cause mortality. multivariate Cox regression analyses were performed to calculate the risk of death. Respiratory viruses were detected in 261 (18.2%) patients with community-acquired pneumonia. Two types of respiratory viruses were detected in 7 cases. Of the 254 cases detected with only one virus, 62 were influenza A, 18 were influenza B, 65 were rhinovirus, 35 were respiratory syncytial virus, 25 were metapneumovirus, 20 were parainfluenza, 17 were coronavirus, 7 were bocavirus, and 5 were adenovirus. Mortality was not significantly different between patients with respiratory virus and those without respiratory virus; the 30-day all-cause mortality rates were 20.3% and 22.4%, respectively (P = 0.45). Mortality rate increased with an increasing PSI score with or without respiratory viral infection. Pulmonary severity index was significantly associated with mortality adjusted for respiratory virus detection (hazard ratio = 1.024, 95% confidence interval = 1.020-1.028). Pneumonia severity index score is an important factor for assessing the prognosis of patients with community-acquired pneumonia, regardless of respiratory virus detection.

Higher Age Puts Lung Cancer Patients at Risk for Not Receiving Anti-cancer Treatment.

PURPOSE: We aimed to determine the demographic and epidemiologic variables that are associated with no treatment in lung cancer patients. MATERIALS AND METHODS: Patient data were collected from the Korean National Health Insurance Database. The lung cancer group included patients with an initial diagnosis of lung cancer between January 2009 and December 2014. Treated cases were defined as those that underwent surgery, radiation, or chemotherapy until death, after the diagnosis of lung cancer. Risk of no treatment was calculated by multiple logistic regression analysis. RESULTS: Among the 2148 new cases of lung cancer from 2009 to 2104, 612 (28.4%) were not treated. Risk of no treatment was higher in the following patients: patients in their 60s (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.75 to 1.84), 70s (OR, 3.64; 95% CI, 2.41 to 5.50), and >80 years old (OR, 16.55; 95% CI, 10.53 to 25.03) than those in their 50s; patients with previous myocardial infarction (OR, 2.07; 95% CI, 1.01 to 4.25) or chronic kidney disease (OR, 2.88; 95% CI, 1.57 to 5.30); and patients diagnosed at a non-referral hospital (OR, 1.40; 95% CI, 1.01 to 1.92) or primary care provider (OR, 1.81; 95% CI, 1.43 to 2.29) compared with referral hospital. Low-income patients receiving Medicaid were 1.75 times (95% CI, 1.14 to 2.68) more likely to forgo treatment than high-income patients (upper 20%). Risk was not associated with sex or the year in which the lung cancer was diagnosed. CONCLUSION: Age predominantly determines whether patients with lung cancer undergo anti-cancer treatment.

Risk factors for interstitial lung disease: a 9-year Nationwide population-based study.

BACKGROUND: Understanding the risk factors that are associated with the development of interstitial lung disease might have an important role in understanding the pathogenetic mechanism of interstitial lung disease as well as prevention. We aimed to determine independent risk factors of interstitial lung disease development. METHODS: This was a retrospective cohort study with nationwide population-based 9-year longitudinal data. We selected subjects who were aged > 40 years at cohort entry and with a self-reported history of cigarette smoking. Cases were selected based on International Classification of Diseases codes. A cohort of 312,519 subjects were followed until December 2013. We used Cox regression analysis to calculate the hazard ratios (HRs) for interstitial lung disease development. RESULTS: Interstitial lung disease developed in 1972 of the 312,519 subjects during the 9-year period. Smoking (HR: 1.2; 95% confidence interval [CI]: 1.1-1.4), hepatitis C (HR: 1.6; 95% CI: 1.1-2.3), history of tuberculosis (HR: 1.5; 95% CI: 1.1-1.9), history of pneumonia (HR: 1.6; 95% CI: 1.3-2.0), and chronic obstructive pulmonary disease (HR: 1.8; 95% CI: 1.6-2.1), men (HR: 1.9; 95% CI: 1.7-2.1) were significantly associated with the development of interstitial lung disease. The risk of interstitial lung disease development increases with age, and the risk was 6.9 times higher (95% CI: 5.9-8.0) in those aged over 70 than in their forties. CONCLUSIONS: Smoking, hepatitis C, history of tuberculosis, history of pneumonia, chronic obstructive pulmonary disease, male sex, and older age were significantly associated with interstitial lung disease development.

Prevalence of lung cancer in patients with interstitial lung disease is higher than in those with chronic obstructive pulmonary disease.

We aimed to explore lung cancer prevalence in interstitial lung disease (ILD) patients with or without connective tissue disorder (CTD) and idiopathic pulmonary fibrosis (IPF) in comparison with chronic obstructive pulmonary disorder (COPD).We evaluated lung cancer prevalence associated with ILD and IPF using Korean Health Insurance Review and Assessment Service (HIRA) data from January to December 2011. This database (HIRA-NPS-2011-0001) was sampled using random sampling of outpatients; 1,375,842 sample cases were collected, and 670,258 (age ≥ 40 ys) were evaluated. Patients with ILDs, IPF, CTD, or COPD were identified using the International Classification of Disease-10 diagnostic codes.Lung cancer prevalence rates per 100,000 persons for the sample population and those with ILD, IPF, CTD-ILD, and COPD were 420, 7334, 7404, 7272, and 4721, respectively. Lung cancer prevalence was significantly higher in those with ILD than in those with COPD (P < .01).More attention should be paid to lung cancer development in those with ILD as well as COPD.

Interstitial Lung Disease and Lung Cancer Development: A 5-Year Nationwide Population-Based Study.

PURPOSE: In this nationwide 5-year longitudinal population-based study, we aimed at investigating the incidence of lung cancer among patients with interstitial lung disease. MATERIALS AND METHODS: Data was collected from the Korean National Health Insurance Research Database from 49,773,195 Korean residents in 2009. Thirteen thousand six hundred and sixty-six patients with interstitial lung disease diagnosed January-December 2009. The end of follow-up was June 30, 2014. Up to four matching chronic obstructive pulmonary disease controls were selected to compare the lung cancer high-risk group based on age, sex, diagnosis date (within 30 days), and hospital size. The number of patients with newly developed lung cancer was determined. RESULTS: The incidences of lung cancer were 126.98, 156.62, and 370.38 cases per 10,000 person-years (2,732, 809, and 967 cases of cancer, respectively) in the chronic obstructive pulmonary disease, interstitial lung disease, and chronic obstructive pulmonary disease with interstitial lung disease groups, respectively. Of the 879 patients with idiopathic pulmonary fibrosis, 112 developed lung cancer (incidence, 381.00 cases per 10,000 person-years). CONCLUSION: Incidence of lung cancer among patients with interstitial lung disease was high. Interstitial lung diseases have a high potential for developing into lung cancer, even when concurrent with chronic obstructive pulmonary disease.

Risk of mortality associated with respiratory syncytial virus and influenza infection in adults.

BACKGROUND: Respiratory syncytial virus (RSV) infection constitutes a substantial disease burden in the general population. However, the risk of death for RSV infection has been rarely evaluated with confounders or comorbidities adjusted. We aimed to evaluate whether RSV infection is associated with higher mortality than seasonal influenza after adjusting for confounders and comorbidities and the effect of oseltamivir on the mortality in patients with influenza infection. METHODS: A retrospective cohort study was conducted on adult (≥18 years) patients admitted to the emergency department and ward of a university teaching hospital for suspected viral infection during 2013-2015 (N = 3743). RSV infection was diagnosed by multiplex PCR (N = 87). Adults hospitalized for seasonal influenza during the study period were enrolled as a comparison group (n = 312). The main outcome was 20-day all-cause mortality.We used Cox proportional hazard regression analyses to calculate the relative risk of death. RESULTS: Adult patients were less likely to be diagnosed with RSV than with influenza (2.3 vs 8.3%, respectively), were older and more likely to be diagnosed with pneumonia, chronic obstructive pulmonary disease, hypoxemia, and bacterial co-infection. In patients with RSV infection, the 20-day all-cause mortality was higher than that for influenza, (18.4 vs 6.7%, respectively). RSV infection showed significantly higher risk of death compared to the seasonal influenza group, with hazard ratio, 2.32 (95% CI, 1.17-4.58). Oseltamivir had no significant effect on mortality in patients with influenza. CONCLUSIONS: RSV infection was significantly associated with a higher risk of death than seasonal influenza, adjusted for potential confounders and comorbidities.

Survival and prognostic factors in patients with connective tissue disease-associated pulmonary hypertension diagnosed by echocardiography: results from a Korean nationwide registry.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). The survival rates and mortality-predictive factors of a nationwide registry of Korean patients with CTD-PH measured by echocardiography were determined. METHODS: Patients with CTD-PH were enrolled between April 2008 and December 2012. Hemodynamic parameters and clinical data (WHO-functional class [FC], organ involvement, laboratory tests and treatment agents) were recorded. Survival rates were calculated by using the Kaplan-Meier method. Mortality-associated factors were examined by Cox proportional hazards regression analysis. RESULTS: In total, 174 incident PH cases (61 with systemic lupus erythematosus, 50 with systemic sclerosis, 10 with mixed CTD, 22 with rheumatoid arthritis (RA) and 31 with other CTDs) were diagnosed by Doppler echocardiography. Of these, 25 (14%) died during the 3.8 ± 2.7 year follow-up period after PH diagnosis. The 1- and 3-year survival rates were 90.7% and 87.3%, respectively. Compared to the other CTD-PHs, RA-PH had the lowest survival rates (56% 3 year survival; P = 0.022). Multiple regression analysis revealed that low diffusion capacity of carbon monoxide (DLCO), pleural effusion and diabetes mellitus were poor prognostic factors (P = 0.008, 0.04 and 0.009, respectively). Anti-UI-RNP (ribonucleoprotein) antibody positivity was protective (P = 0.022). In patients with WHO-FC III/IV, patients who received vasodilators had lower mortality than those who did not (P = 0.038). CONCLUSIONS: In Korean patients with CTD-PH, the 3-year survival rate was 87%. Low diffusion capacity of carbon monoxide (DLCO), pleural effusion and diabetes mellitus were independent poor prognostic factors. Anti-UI-RNP antibody was protective. Prompt PAH-specific vasodilator therapy may improve the survival of patients with severe CTD-PH.

Efficacy of concurrent administration of cilostazol and methotrexate in rheumatoid arthritis: pharmacologic and clinical significance.

AIMS: This study aimed to assess the beneficial effects of the concurrent administration of cilostazol and methotrexate (MTX) on the synovial fibroblasts obtained from patients with rheumatoid arthritis (RA), and in a mouse model of collagen-induced arthritis (CIA). MAIN METHODS: Production of TNF-α, IL-1ß, IL-6 and MCP-1 on synovial fibroblasts from RA patients was determined by RT-PCR. Cell proliferation, viability and apoptosis were measured. Anti-arthritic effects were evaluated in CIA mice. KEY FINDING: Concurrent use of cilostazol and MTX effectively suppressed proliferation and cell viability associated with enhanced apoptosis of synovial fibroblasts and significantly suppressed cytokine production, including TNF-α, IL-1ß, IL-6, and MCP-1 in an additive manner. In line with these findings, LPS-induced increased expression of NURR1 mRNA and protein were suppressed by cilostazol and MTX in accordance with suppression of NF-κB p65 activity. These suppressed effects were reversed by KT5720 (cAMP-protein kinase inhibitor) and ZM 241385 (A(2A) receptor antagonist), respectively. In CIA mice, treatment with cilostazol, MTX and their combination significantly decreased clinical signs with improvement of histopathological status in the paw of mice, accompanied by reduced serum cytokine levels. Likewise, following concurrent administration, CD68 (+)-cell recruitment, proteoglycan depletion and osteoclast formation were significantly suppressed in association with repressed RANKL expression in the joints of CIA mice. SIGNIFICANCE: In conclusion, a combination of cilostazol and MTX may provide an effective therapeutic strategy for the suppression of inflammation and the prevention of joint damage in RA via activation of the cAMP-dependent protein kinase in the synovial fibroblasts.

RANKL stimulates proliferation, adhesion and IL-7 expression of thymic epithelial cells.

In many clinical situations which cause thymic involution and thereby result in immune deficiency, T cells are the most often affected, leading to a prolonged deficiency of T cells. Since only the thymic-dependent T cell production pathway secures stable regeneration of fully mature T cells, seeking strategies to enhance thymic regeneration should be a key step in developing therapeutic methods for the treatment of these significant clinical problems. This study clearly shows that receptor activator of NF-kappaB ligand (RANKL) stimulates mouse thymic epithelial cell activities including cell proliferation, thymocyte adhesion to thymic epithelial cells, and the expression of cell death regulatory genes favoring cell survival, cell adhesion molecules such as ICAM-1 and VCAM-1, and thymopoietic factors including IL-7. Importantly, RANKL exhibited a significant capability to facilitate thymic regeneration in mice. In addition, this study demonstrates that RANKL acts directly on the thymus to activate thymus regeneration regardless of its potential influences on thymic regeneration through an indirect or systemic effect. In light of this, the present study provides a greater insight into the development of novel therapeutic strategies for effective thymus repopulation using RANKL in the design of therapies for many clinical conditions in which immune reconstitution is required.

National cancer incidence for the year 2002 in Korea.

PURPOSE: Since the revised Cancer Act of October 2006, cancer registration was reactivated, based on the Statistics Law. MATERIALS AND METHODS: The incidence of cancer during 2002 was calculated on the basis of the information available from the National Cancer Incidence Database. Crude and age-standardized rates were calculated by gender for 18 age groups (0 approximately 4, 5 approximately 9, 10 approximately 14, every five years, 85 years and over). RESULTS: The overall crude incidence rates (CRs) were 269.2 and 212.8 per 100,000 for males and females, and the overall age-standardized incidence rates (ASRs) were 287.8 and 172.9 per 100,000, respectively. Among males, the five leading primary cancer sites were stomach (CR 62.4, ASR 65.7), lung (CR 45.4, ASR 51.0), liver (CR 43.2, ASR 43.7), colon and rectum (CR 30.7, ASR 32.7), and prostate (CR 8.0, ASR 9.6). Among females, the most common cancer sites were breast (CR 33.1, ASR 26.9), followed by stomach (CR 32.8, ASR 26.0), colon and rectum (CR 23.1, ASR 18.5), thyroid (CR 19.1, ASR 15.7), and uterine cervix (CR 18.2, ASR 14.7). In the 0~14 age group, leukemia was the most common cancer for both genders. For males, stomach cancer was the most common cancer in the 15 approximately 64 age-group, but lung cancer was more frequent in men 65 or older. For females, thyroid cancer among the 15 approximately 34 age-group, breast cancer among 35 approximately 64 age-group and stomach cancer in women 65 years or older were the most common forms of cancer for each age group. The quality indices for the percentage of deaths, by death certificate only, were 4.7% for males and 4.5% for females. CONCLUSIONS: Since the National Cancer Incidence Database was started, the annual percent change of cancer cases increased by 4.8% (4.1% for males, 5.7% for females) during 1999 approximately 2002. This value reflects the increase in prostate cancer for males and breast and thyroid cancer in females during 2002. The timely reporting of improved quality of cancer registration is needed for evidence-based decisions regarding cancer control in Korea.

Effect of topical dexamethasone versus rimexolone on middle ear inflammation in experimental otitis media with effusion.

CONCLUSION: The lipopolysaccharide (LPS)-induced chinchilla otitis media (OM) model was proven useful in screening anti-inflammatory agents for topical use. Both 1% rimexolone and 1% dexamethasone are effective in reducing the volume of middle ear effusion and mucosal thickness compared with control groups. Topical corticosteroid therapy was efficacious in reducing middle ear mucosal inflammation. OBJECTIVE: OM is one of the most common diseases in the pediatric population. Our previous studies have shown that treatment with systemic antibiotics and corticosteroids was more efficacious than antibiotics alone. The purpose of this study was to determine the effectiveness of topically applied corticosteroids on the outcome of OM. The long-term goal of this study was to develop a better method of OM treatment by demonstrating effectiveness of topically applied anti-inflammatory agents, such as corticosteroids, avoiding systemic side effects. MATERIALS AND METHODS: Three experimental groups were studied in chinchillas. OM with effusion was induced in all groups by injecting LPS. Group 1 consisted of controls in three subgroups as follows. Control-LPS alone, vehicle of dexamethasone (control-dexa), vehicle of rimexolone (control-rimex). Group 2 was treated with dexamethasone and included subgroups of separate concentrations of dexamethasone: 0.1% and 1% suspensions. Group 3 was treated with rimexolone and included subgroups of separate concentrations of rimexolone: 0.1% and 1% suspensions. A total of 58 animals were used: 18 for controls and 40 for experimental groups. All test substances (saline, control-dexa, control-rimex, dexamethasone and rimexolone, 200 microl) were injected at -2, 48 and 60 h; LPS was injected at 0 h. Animals were monitored by daily otomicroscopy. After 4 days, samples of middle ear effusion (MEE) were collected for analysis and temporal bones were harvested for histopathological studies. RESULTS: At the end of 4 days, only in five ears (3/20 with 1% dexamethasone, 1/20 with 1% rimexolone, and 1/20 with 0.1% rimexolone) had the fluid diminished to the point of being unobservable. The volume of MEE, thickness of mucoperiosteum, and the degree of inflammation of middle ear mucosa with 1% dexamethasone and 1% rimexolone was significantly less compared with other groups.