Pirfenidone Alleviates Inflammation and Fibrosis of Acute Respiratory Distress Syndrome by Modulating the Transforming Growth Factor-ß/Smad Signaling Pathway.

Acute respiratory distress syndrome (ARDS) occurs as an acute onset condition, and patients present with diffuse alveolar damage, refractory hypoxemia, and non-cardiac pulmonary edema. ARDS progresses through an initial exudative phase, an inflammatory phase, and a final fibrotic phase. Pirfenidone, a powerful anti-fibrotic agent, is known as an agent that inhibits the progression of fibrosis in idiopathic pulmonary fibrosis. In this study, we studied the treatment efficiency of pirfenidone on lipopolysaccharide (LPS) and bleomycin-induced ARDS using rats. The ARDS rat model was created by the intratracheal administration of 3 mg/kg LPS of and 3 mg/kg of bleomycin dissolved in 0.2 mL of normal saline. The pirfenidone treatment group was administered 100 or 200 mg/kg of pirfenidone dissolved in 0.5 mL distilled water orally 10 times every 2 days for 20 days. The administration of LPS and bleomycin intratracheally increased lung injury scores and significantly produced pro-inflammatory cytokines. ARDS induction increased the expressions of transforming growth factor (TGF)-ß1/Smad-2 signaling factors. Additionally, matrix metalloproteinase (MMP)-9/tissue inhibitor of metalloproteinase (TIMP)-1 imbalance occurred, resulting in enhanced fibrosis-related factors. Treatment with pirfenidone strongly suppressed the expressions of TGF-ß1/Smad-2 signaling factors and improved the imbalance of MMP-9/TIMP-1 compared to the untreated group. These effects led to a decrease in fibrosis factors and pro-inflammatory cytokines, promoting the recovery of damaged lung tissue. These results of this study showed that pirfenidone administration suppressed inflammation and fibrosis in the ARDS animal model. Therefore, pirfenidone can be considered a new early treatment for ARDS.

Clinical significance of normalized airflow obstruction in patients with chronic obstructive pulmonary disease.

BACKGROUND: There is ongoing debate regarding the diagnostic criteria for chronic obstructive pulmonary disease (COPD); recent studies have focused on the early COPD detection and management. Here, we compared clinical features and prognosis in patients with FEV1/FVC<0.70 at baseline, according to normalized airflow obstruction status during follow-up. METHODS: We used the Korea COPD Subgroup Study (KOCOSS) cohort database, a prospective nationwide observational COPD study. Normalized obstruction (NO) was defined as FEV1/FVC ≥0.7 in the 2-year follow-up period, whereas fixed obstruction (FO) was defined as FEV1/FVC <0.7. Demographic and clinical data, 1-year exacerbation risk and difference in FEV1 decline over 2 years were compared between NO and FO groups. RESULTS: Among the 670 COPD patients with post-bronchodilator FEV1/FVC <0.7 in this study, 95 (14.2%) displayed NO. Compared with the FO group, the NO group had higher FEV1, and DLCO, body mass index, as well as lower Saint George Respiratory Questionnaire, Beck Depression Index, and Beck Anxiety Index. Blood eosinophil count, IgE level, and FeNO did not significantly differ between two groups. There was no significant difference in exacerbation frequency between the two groups, but the NO group had a significant increase in FEV1 compared with the FO group during follow-up. CONCLUSION: Transient airflow obstruction in the NO group may represent a clinical manifestation of early COPD; close monitoring is needed for such patients.

Evaluating the feasibility of air environment management system for VOCs through 'VOCs specification' of petroleum refining industry.

The chemical industry releases various types of volatile organic compounds (VOCs) into the atmosphere, and the concentration of VOCs emitted from chimneys is regulated worldwide. However, some VOCs such as benzene are highly carcinogenic, while others such as ethylene and propylene may cause secondary air pollution, owing to their high ozone-generating ability. Accordingly, the US EPA(United State, Environment Protect Agency) introduced a fenceline monitoring system that regulates the concentration of VOCs at the boundary of a facility, away from the chimney source. This system was first introduced in the petroleum refining industry, which simultaneously emits benzene, affecting the local community because of its high carcinogenicity, and ethylene, propylene, xylene, and toluene, which have a high photochemical ozone creation potential (POCP). These emissions contribute to air pollution. In Korea, the concentration at the chimney is regulated; however, the concentration at the plant boundary is not considered. In accordance with the EPA regulations, Korea's petroleum refining industries were identified and the limitations of the Clean Air Conservation Act were studied. The average concentration of benzene at the research facility examined in this study was 8.53 µg/m3, which complied with the benzene action level of 9 µg/m3. However, this value was exceeded at some points along the fenceline, in proximity to the benzene-toluene-xylene (BTX) manufacturing process. The composition ratios of toluene and xylene were 27% and 16%, respectively, which were higher than those of ethylene or propylene. These results suggest that reduction measures in the BTX manufacturing process are necessary. This study shows that legal regulations should enforce reduction measures through continuous monitoring at the fenceline of petroleum refineries in Korea.Implications: Although volatile organic compounds(VOCs) are essential in various industrial sites, they adversely affect the health of people in the near community. Benzene is highly carcinogenic, so it is dangerous if exposed continuously. In addition, there are various types of VOCs, which combine with atmospheric ozone to generate smog. Globally, VOCs are managed as Total VOCs. However, through this study, VOCs have priority, and in the case of the petroleum refining industry, it is suggested that VOCs should be preemptively measured and analyzed to be regulated. In addition, it is necessary to minimize the impact on the local community by regulating the concentration at the fenceline beyond the chimney measurement.

Different scoring rules for respiratory event-related leg movements: effects on the prevalence of periodic limb movements during sleep and their association with depressive symptoms in patients with obstructive sleep apnea.

BACKGROUND: We compared the prevalence of periodic leg movements during sleep (PLMS) according to two different scoring rules of the American Academy of Sleep Medicine (AASM) 2012 and World Association of Sleep Medicine (WASM) 2016 and determined their association with depressed mood in patients with obstructive sleep apnea (OSA). METHODS: PLMS, defined as a periodic leg movements index of >15, were diagnosed on a diagnostic and continuous positive airway pressure (CPAP) titration polysomnography using the AASM 2012 and WASM 2016 rules. The Beck Depression Inventory (BDI) and Epworth Sleepiness Scale (ESS) were used, and multiple regression analyses were performed. RESULTS: Among 160 OSA patients, the proportion with PLMS scored by the WASM 2016 criteria was significantly higher than that scored by the AASM 2012 criteria in a diagnostic study (20.6% vs. 16.3%, respectively; P = 0.016) but not in CPAP titration study and only in patients with severe OSA. In adjusted models, PLMS were positively associated with BDI scores and a BDI of ≥10 on both diagnostic and CPAP titration studies when scored by the WASM 2016. By contrast, when scored by the AASM 2012, PLMS were associated with BDI scores (but not BDI of ≥10) only in a CPAP titration study. CONCLUSIONS: There are significant differences in the prevalence of PLMS and their association with depressed mood depending on the scoring rules in patients with OSA. The current AASM scoring criteria underestimate the prevalence of PLMS, and PLMS are more likely associated with depressed mood according to the WASM scoring criteria.

Polydeoxyribonucleotide Attenuates Airway Inflammation Through A2AR Signaling Pathway in PM10-Exposed Mice.

PURPOSE: Inhalation of air containing high amounts of particular matter (PM) causes various respiratory disorders including asthma, chronic obstructive pulmonary disease, and lung cancer. The changes of expression of inflammatory factors by polydeoxyribonucleotide (PDRN) administration in the PM10-exposed trachea inflammation model were evaluated. METHODS: PM10 was administered to mouse trachea to induce acute inflammatory damage, and changes in inflammatory factors were observed after administration of PDRN and 3,7-dimethyl-1-propargylxanthine (DMPX) for 3 days daily. Expression of inflammatory cytokines, adenosine A2A receptor (A2AR), protein kinase A (PKA), 3΄,5΄-cyclic adenosine monophosphate responsive element binding protein (CREB) were detected by enzyme-linked immunosorbent assay, immunofluorescence, and western blot assay. RESULTS: PM-exposed trachea showed increased tumor necrosis factor (TNF)-α and interleukin (IL)-1ß expression, and expression of TNF-α and IL-1ß was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased nuclear factor (NF)-κB phosphorylation, and phosphorylation of nuclear factor-kappa B was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased expression of A2AR, but PDRN treatment more enhanced A2AR expression in PM-exposed mice. PKA phosphorylation was not changed and CREP phosphorylation was decreased, however PDRN treatment increased phosphorylation of PKA and CREB in PM-exposed mice. DMPX treatment blocked all the effects of PDRN on PM-exposed mice, demonstrating that the action of PDRN occurs via A2AR. CONCLUSION: PDRN treatment attenuated inflammation in the trachea of the PM10-exposed mice. This improving effect of PDRN can be ascribed to the activation of A2AR through the cAMP-PKA pathway.

Polydeoxyribonucleotide Attenuates Airway Inflammation Through A2AR Signaling Pathway in PM10-Exposed Mice / 대한배뇨장애요실금학회지

Purpose@#Inhalation of air containing high amounts of particular matter (PM) causes various respiratory disorders including asthma, chronic obstructive pulmonary disease, and lung cancer. The changes of expression of inflammatory factors by polydeoxyribonucleotide (PDRN) administration in the PM10-exposed trachea inflammation model were evaluated. @*Methods@#PM10 was administered to mouse trachea to induce acute inflammatory damage, and changes in inflammatory factors were observed after administration of PDRN and 3,7-dimethyl-1-propargylxanthine (DMPX) for 3 days daily. Expression of inflammatory cytokines, adenosine A2A receptor (A2AR), protein kinase A (PKA), 3΄,5΄-cyclic adenosine monophosphate responsive element binding protein (CREB) were detected by enzyme‐linked immunosorbent assay, immunofluorescence, and western blot assay. @*Results@#PM-exposed trachea showed increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression, and expression of TNF-α and IL-1β was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased nuclear factor (NF)-κB phosphorylation, and phosphorylation of nuclear factor-kappa B was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased expression of A2AR, but PDRN treatment more enhanced A2AR expression in PM-exposed mice. PKA phosphorylation was not changed and CREP phosphorylation was decreased, however PDRN treatment increased phosphorylation of PKA and CREB in PM-exposed mice. DMPX treatment blocked all the effects of PDRN on PM-exposed mice, demonstrating that the action of PDRN occurs via A2AR. @*Conclusions@#PDRN treatment attenuated inflammation in the trachea of the PM10-exposed mice. This improving effect of PDRN can be ascribed to the activation of A2AR through the cAMP-PKA pathway.

Polydeoxyribonucleotide Attenuates Airway Inflammation Through A2AR Signaling Pathway in PM10-Exposed Mice / 대한배뇨장애요실금학회지

Purpose@#Inhalation of air containing high amounts of particular matter (PM) causes various respiratory disorders including asthma, chronic obstructive pulmonary disease, and lung cancer. The changes of expression of inflammatory factors by polydeoxyribonucleotide (PDRN) administration in the PM10-exposed trachea inflammation model were evaluated. @*Methods@#PM10 was administered to mouse trachea to induce acute inflammatory damage, and changes in inflammatory factors were observed after administration of PDRN and 3,7-dimethyl-1-propargylxanthine (DMPX) for 3 days daily. Expression of inflammatory cytokines, adenosine A2A receptor (A2AR), protein kinase A (PKA), 3΄,5΄-cyclic adenosine monophosphate responsive element binding protein (CREB) were detected by enzyme‐linked immunosorbent assay, immunofluorescence, and western blot assay. @*Results@#PM-exposed trachea showed increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression, and expression of TNF-α and IL-1β was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased nuclear factor (NF)-κB phosphorylation, and phosphorylation of nuclear factor-kappa B was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased expression of A2AR, but PDRN treatment more enhanced A2AR expression in PM-exposed mice. PKA phosphorylation was not changed and CREP phosphorylation was decreased, however PDRN treatment increased phosphorylation of PKA and CREB in PM-exposed mice. DMPX treatment blocked all the effects of PDRN on PM-exposed mice, demonstrating that the action of PDRN occurs via A2AR. @*Conclusions@#PDRN treatment attenuated inflammation in the trachea of the PM10-exposed mice. This improving effect of PDRN can be ascribed to the activation of A2AR through the cAMP-PKA pathway.

Attenuation effect of polydeoxyribonucleotide on inflammatory cytokines and apoptotic factors induced by particulate matter (PM10) damage in human bronchial cells.

Particulate matter (PM) of 10-µm-sized fine dust in the air penetrates the respiratory tract and contributes to the increasing incidence of various lung diseases, but its definite mechanism is not known. Recently, polydeoxyribonucleotide (PDRN) has been shown to have anti-inflammatory and regenerative effects in various tissues. However, the bronchial-related mechanism is not well-understood. Hence, this experiment is intended to demonstrate the beneficial effect of PDRN administration on PM10-induced injury in human bronchial-derived NCI-H358 cells. To confirm the protective effect of PDRN, PM10 was applied after PDRN pretreatment to confirm changes in NCI-H358 cells. Experiments were conducted to measure cell survival, cytotoxicity, inflammation, and apoptotic factor changes. WST-8 assay was used to confirm cell viability, and lactate dehydrogenase assay was used to obtain cytotoxicity. In addition, changes in inflammatory cytokines and apoptotic factors were confirmed by enzyme-linked immunosorbent assay and Western blot. Decreased cell viability and increased cytotoxicity, inflammatory cytokines, and apoptotic factors were observed after exposure to PM10. However, pretreatment with PDRN enhanced cell viability and reduced cytotoxicity. In addition, the expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1ß, and cell death factors such as Apaf-1, cyt c, caspase-3, caspase-9, Bid, and Bax/Bcl-2 ratio were decreased by PDRN administration in PM10-exposed NCI-H358 cells. PDRN, an A2AR agonist, affects cAMP activation and regulation of phosphorylation of PKA and CREB. In addition, treatment with A2AR antagonist 3,7-dimethyl-1-propargylxanthine significantly blocked PDRN's effect. These anti-cytotoxicity, anti-inflammation, and anti-apoptosis effects of PDRN can be attributed to the adenosine A2AR enhancing effect on PM10-exposed bronchial cells.

Combination Therapy With Polydeoxyribonucleotide and Pirfenidone Alleviates Symptoms of Acute Respiratory Distress Syndrome in Human Lung Epithelial A549 Cells.

PURPOSE: Acute respiratory distress syndrome (ARDS) is characterized by its acute onset of symptoms such as bilateral pulmonary infiltrates, severe hypoxemia, and pulmonary edema. Many patients with ARDS survive in the acute phase, but then die from significant lung fibrosis. METHODS: The effect of combination therapy with polydeoxyribonucleotide (PDRN) and pirfenidone on ARDS was investigated using human lung epithelial A549 cells. ARDS environment was induced by treatment with lipopolysaccharide and transforming growth factor (TGF)-ß. Enzyme-linked immunoassay for connective tissue growth factor (CTGF) and hydroxyproline were conducted. Western blot for collagen type I, fibroblast growth factor (FGF), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was performed. RESULTS: In this study, 8-µg/mL PDRN enhanced cell viability. Combination therapy with PDRN and pirfenidone and pirfenidone monotherapy suppressed expressions of CTGF and hydroxyproline and inhibited expressions of collagen type I and FGF. Combination therapy with PDRN and pirfenidone and PDRN monotherapy suppressed expression of TNF-α and IL-1ß. CONCLUSION: The combination therapy with PDRN and pirfenidone exerted stronger therapeutic effect against lipopolysaccharide and TGF-ß-induced ARDS environment compared to the PDRN monotherapy or pirfenidone monotherapy. The excellent therapeutic effect of combination therapy with PDRN and pirfenidone on ARDS was shown by promoting the rapid anti-inflammatory effect and inhibiting the fibrotic processes.

Preoperative plateletcrit is a Prognostic Biomarker for Survival in Patients with Non-Small Cell Lung Cancer.

Objectives: Several factors associated with the prognosis of patients with NSCLC have been reported in the literature; however, most of these factors cannot be examined preoperatively. In this study, the clinical utility of platelet parameters in patients with NSCLC who underwent curative resection was evaluated. Materials and Methods: A retrospective study on patients with NSCLC who underwent curative resection from July 2006 to September 2016 was conducted. The Cox proportional hazard regression model was applied to evaluate the variables that demonstrated effects on disease-free and overall survival (DFS and OS). Results: A total of 116 patients with NSCLC were analyzed. There were 15 patients with plateletcrit greater than 0.2755%, and 101 patients whose plateletcrit was 0.2755% or lower. Multivariate analysis identified plateletcrit higher than 0.2755% (hazard ratio [HR] = 4.18, 95% confidence interval [CI] = 1.54-11.34, P =0.004), patient age of 65 years or more (HR = 4.02, 95% CI = 1.67-9.66, P = 0.001), and stage II or IIIA disease (HR = 2.95, 95% CI = 1.26-6.87, P = 0.012) as independent factors for OS that predicted a poor prognosis. Multivariate analysis identified plateletcrit higher than 0.2755% (HR = 4.07, 95% CI = 1.52-10.94, P = 0.005), stage II or IIIA disease (HR = 5.38, 95% CI = 2.71-10.66, P < 0.001) and non-adenocarcinoma (HR = 1.92, 95% CI = 1.02-3.59, P = 0.040) as independent prognostic factors for DFS that predicted a poor prognosis. Conclusion: Our results suggest a potential role of preoperative plateletcrit as an independent prognostic marker for patients with resectable NSCLC.

Polydeoxyribonucleotide ameliorates lipopolysaccharide-induced acute lung injury via modulation of the MAPK/NF-κB signaling pathway in rats.

Acute lung injury (ALI) is characterized by disruption of the alveolar-capillary membrane resulting in pulmonary edema and accumulation of associated proteinaceous alveolar exudate. Initiation of ALI upregulates tumor necrosis factor-α (TNF-α), which activates nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) that induce various pro-inflammatory mediators. Polydexyribonucleotide (PDRN) is an adenosine A2A receptor agonist that exerts anti-inflammatory effects by suppressing the production of pro-inflammatory cytokines and apoptosis. We investigated the therapeutic efficiency of PDRN on ALI induced by lipopolysaccharide (LPS) in rats. ALI was induced by intratracheal instillation of LPS (5 mg/kg) in 200 µL saline. The PDRN treatment group received a single intraperitoneal injection of 500 µL saline including PDRN (8 mg/kg) 1 h after ALI induction. To confirm the involvement of the adenosine A2A receptor in PDRN, 8 mg/kg 7-dimethyl-1-propargylxanthine (DMPX) was applied with PDRN treatment. Rats were then sacrificed 12 h after PDRN and DMPX treatments. Intratracheal administration of LPS caused lung tissue damage and significantly increased the lung injury scores and levels of pro-inflammatory cytokines, and apoptotic factors. In addition, MAPK/NF-κB signaling factors were increased by ALI initiation. PDRN treatment potently suppressed expressions of MAPK/NF-κB signaling factors compared to the PDRN + DMPX co-treated group. These alterations led to a reduction of pro-inflammatory cytokines, apoptotic factors, and NF-κB and MAPK signaling, which promoted the recovery of damaged lung tissue. PDRN therapy demonstrated therapeutic effects for LPS-induced ALI compared to the non-treated and DMPX-treated groups. Therefore, PDRN may be used as a therapy for initial treatment of ALI.

Epidemiology of Antiphospholipid Syndrome in Korea: a Nationwide Population-based Study.

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and venous thrombosis or pregnancy morbidity in patients with persistent antiphospholipid antibodies. However, nationwide population-based epidemiology studies regarding APS are still unavailable. METHODS: We analyzed claims data extracted from the Korean Health Insurance and Review Agency (HIRA) covering more than 52 million Koreans, between January 1, 2008, and December 31, 2017. Patients diagnosed with APS, as determined by the Korean Classification of Disease, 7th edition (D68.6), and a rare intractable disease program (V253), were identified in HIRA. RESULTS: A total of 3,088 newly diagnosed incident cases of 1,215 men and 1,873 women were identified during 2009-2016. The mean age was 44.6 ± 16.6 (men, 47.4 ± 16.3; women, 42.8 ± 16.6) years. The incidence was 0.75 per 105 person-year (95% confidence interval, 0.73-0.78). The prevalence in 2016 was 6.19 per 105 people. For incident cases, women showed incidence peak at ages of 30-39 years and 70-79 years, whereas for men, it was highest at ages of 70-79 years only. Of all patients, 1,766 (57%, 810 men and 956 women) had primary APS, 1,322 (43%, 405 men and 917 women) had secondary APS, and 845 (27%, 216 men and 629 women) were associated with systemic lupus erythematosus (SLE). CONCLUSION: The incidence of APS differs according to age groups and gender. The incidence of primary APS was higher than that of secondary APS in both gender. Furthermore, as already reported, secondary APS is highly associated with SLE; however, we observed that rheumatoid arthritis is also highly related.

Epidemiology of Antiphospholipid Syndrome in Korea: a Nationwide Population-based Study

Epidemiology of Antiphospholipid Syndrome in Korea: a Nationwide Population-based Study

BACKGROUND@#Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and venous thrombosis or pregnancy morbidity in patients with persistent antiphospholipid antibodies. However, nationwide population-based epidemiology studies regarding APS are still unavailable.@*METHODS@#We analyzed claims data extracted from the Korean Health Insurance and Review Agency (HIRA) covering more than 52 million Koreans, between January 1, 2008, and December 31, 2017. Patients diagnosed with APS, as determined by the Korean Classification of Disease, 7th edition (D68.6), and a rare intractable disease program (V253), were identified in HIRA.@*RESULTS@#A total of 3,088 newly diagnosed incident cases of 1,215 men and 1,873 women were identified during 2009–2016. The mean age was 44.6 ± 16.6 (men, 47.4 ± 16.3; women, 42.8 ± 16.6) years. The incidence was 0.75 per 105 person-year (95% confidence interval, 0.73–0.78). The prevalence in 2016 was 6.19 per 105 people. For incident cases, women showed incidence peak at ages of 30–39 years and 70–79 years, whereas for men, it was highest at ages of 70–79 years only. Of all patients, 1,766 (57%, 810 men and 956 women) had primary APS, 1,322 (43%, 405 men and 917 women) had secondary APS, and 845 (27%, 216 men and 629 women) were associated with systemic lupus erythematosus (SLE).@*CONCLUSION@#The incidence of APS differs according to age groups and gender. The incidence of primary APS was higher than that of secondary APS in both gender. Furthermore, as already reported, secondary APS is highly associated with SLE; however, we observed that rheumatoid arthritis is also highly related.

Combination Therapy With Polydeoxyribonucleotide and Pirfenidone Alleviates Symptoms of Acute Respiratory Distress Syndrome in Human Lung Epithelial A549 Cells / 대한배뇨장애요실금학회지

Purpose@#Acute respiratory distress syndrome (ARDS) is characterized by its acute onset of symptoms such as bilateral pulmonary infiltrates, severe hypoxemia, and pulmonary edema. Many patients with ARDS survive in the acute phase, but then die from significant lung fibrosis. @*Methods@#The effect of combination therapy with polydeoxyribonucleotide (PDRN) and pirfenidone on ARDS was investigated using human lung epithelial A549 cells. ARDS environment was induced by treatment with lipopolysaccharide and transforming growth factor (TGF)-β. Enzyme-linked immunoassay for connective tissue growth factor (CTGF) and hydroxyproline were conducted. Western blot for collagen type I, fibroblast growth factor (FGF), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was performed. @*Results@#In this study, 8-μg/mL PDRN enhanced cell viability. Combination therapy with PDRN and pirfenidone and pirfenidone monotherapy suppressed expressions of CTGF and hydroxyproline and inhibited expressions of collagen type I and FGF. Combination therapy with PDRN and pirfenidone and PDRN monotherapy suppressed expression of TNF-α and IL-1β. @*Conclusions@#The combination therapy with PDRN and pirfenidone exerted stronger therapeutic effect against lipopolysaccharide and TGF-β-induced ARDS environment compared to the PDRN monotherapy or pirfenidone monotherapy. The excellent therapeutic effect of combination therapy with PDRN and pirfenidone on ARDS was shown by promoting the rapid anti-inflammatory effect and inhibiting the fibrotic processes.

Epidemiology of Antiphospholipid Syndrome in Korea: a Nationwide Population-based Study

BACKGROUND@#Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and venous thrombosis or pregnancy morbidity in patients with persistent antiphospholipid antibodies. However, nationwide population-based epidemiology studies regarding APS are still unavailable.@*METHODS@#We analyzed claims data extracted from the Korean Health Insurance and Review Agency (HIRA) covering more than 52 million Koreans, between January 1, 2008, and December 31, 2017. Patients diagnosed with APS, as determined by the Korean Classification of Disease, 7th edition (D68.6), and a rare intractable disease program (V253), were identified in HIRA.@*RESULTS@#A total of 3,088 newly diagnosed incident cases of 1,215 men and 1,873 women were identified during 2009–2016. The mean age was 44.6 ± 16.6 (men, 47.4 ± 16.3; women, 42.8 ± 16.6) years. The incidence was 0.75 per 105 person-year (95% confidence interval, 0.73–0.78). The prevalence in 2016 was 6.19 per 105 people. For incident cases, women showed incidence peak at ages of 30–39 years and 70–79 years, whereas for men, it was highest at ages of 70–79 years only. Of all patients, 1,766 (57%, 810 men and 956 women) had primary APS, 1,322 (43%, 405 men and 917 women) had secondary APS, and 845 (27%, 216 men and 629 women) were associated with systemic lupus erythematosus (SLE).@*CONCLUSION@#The incidence of APS differs according to age groups and gender. The incidence of primary APS was higher than that of secondary APS in both gender. Furthermore, as already reported, secondary APS is highly associated with SLE; however, we observed that rheumatoid arthritis is also highly related.

Effects of early detection of peritoneal catheter migration on clinical outcomes: 15-years experiences from a single centre.

AIM: Catheter migration is an important cause of catheter malfunction in peritoneal dialysis (PD). The purpose of this study was to investigate the effect of early detection of catheter migration on clinical outcomes. METHODS: A retrospective review of 135 consecutive patients initiating PD immediately following catheter insertion from 2002 to 2017 was undertaken. In order to detect catheter migration without malfunction early, serial abdominal-pelvic radiographic examinations were performed according to a predefined protocol. Conservative management with rigorous catharsis was undertaken to correct catheter migration. A Kaplan-Meier method was used to calculate survival rate. RESULTS: Mean follow-up period was 42.8 ± 34.9 months. Catheter migration occurred in 62.4%. Among them, 85.9% occurred within the first 2 weeks after catheter insertion. There were no significant associations between catheter migration and variables such as gender, obesity, DM and type of catheter. Success rate of conservative management with rigorous catharsis was 91.1%. Catheter survival at 1 and 5 years were 91.5% and 64.6% in the migration group and 81.2% and 69.9% in the non-migration group, respectively (Log-rank test, P = 0.915). Patient survival at 1 and 5 years were 96.8% and 85.8% in the migration group and 91.9% and 82.3% in the non-migration group, respectively (P = 0.792). CONCLUSION: Early detection of PD catheter migration allowed the migrated tip to be easily corrected with conservative management. Once the migrated catheter tip was restored, catheter migration itself did not affect catheter survival. These findings suggest that early detection and correction of catheter migration is important for improving clinical outcomes.

Polydeoxyribonucleotide Ameliorates Lipopolysaccharide-Induced Lung Injury by Inhibiting Apoptotic Cell Death in Rats.

Lung injury is characterized by diffuse lung inflammation, alveolar-capillary destruction, and alveolar flooding, resulting in respiratory failure. Polydexyribonucleotide (PDRN) has an anti-inflammatory effect, decreasing inflammatory cytokines, and suppressing apoptosis. Thus, we investigated its efficacy in the treatment of lung injury, which was induced in rats using lipopolysaccharide (LPS). Rats were randomly divided into three groups according to sacrifice time, and each group split into control, lung injury-induced, and lung injury-induced + PDRN-treated groups. Rats were sacrificed 24 h and 72 h after PDRN administration, according to each group. Lung injury was induced by intratracheal instillation of LPS (5 mg/kg) in 0.2 mL saline. Rats in PDRN-treated groups received a single intraperitoneal injection of 0.3 mL distilled water including PDRN (8 mg/kg), 1 h after lung injury induction. Percentages of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive, cleaved caspase-3-, -8-, and -9-positive cells, the ratio of Bcl-2-associated X protein (Bax) to B-cell lymphoma 2 (Bcl-2), and expressions of inflammatory cytokines (tumor necrosis factor-α, interleukin-6) were decreased by PDRN treatment in the LPS-induced lung injury rats. Therefore, treatment with PDRN reduced lung injury score. This anti-apoptotic effect of PDRN can be ascribed to the enhancing effect of PDRN on adenosine A2A receptor expression. Based on these results, PDRN might be considered as a new therapeutic agent for the treatment of lung injury.

A randomized crossover study of single biweekly administration of epoetin-α compared with darbepoetin-α in chronic kidney disease patients not receiving dialysis.

BACKGROUND: Recent evidence demonstrates that high doses of epoetin-alpha (EPO-α) can be administrated at extended intervals, despite its relatively short serum half-life. However, no prospective randomized trials on the effects of extended dosing intervals of EPO-α compared with darbepoetin-alpha (DA-α) have been performed. This study was designed to investigate whether a single biweekly (Q2W) administration of a high dose of EPO-α is as effective as DA-α for anemia in chronic kidney disease (CKD) patients not receiving dialysis. METHODS: Sixty non-dialysis CKD patients were equally randomized to either Q2W subcutaneous EPO-α (10,000 unit) or DA-α (50 µg) therapy groups for the first 6 weeks. After a 6-week washout period, the participants of the EPO-α and DA-α treatment groups switched to the alternate regimen for 6 weeks. The mean hemoglobin (Hb) levels after erythropoiesis stimulating agent (ESA) therapy and percentage change in Hb levels from baseline to the end of the study were analyzed. RESULTS: The mean Hb levels of postESA therapy increased significantly compared with those of preESA therapy in both ESA regimens. The percentage increase in Hb levels and erythropoietin resistance index did not show a significant difference between the different ESA regimens. No difference was observed between the regimens regarding mean Hb levels after ESA therapy. Additionally, there were no serious adverse effects leading to withdrawal from treatment. CONCLUSION: Biweekly high doses of EPO-α therapy may be equally as effective as Q2W DA-α therapy in maintaining target Hb levels in non-dialysis CKD patients.

Gastric tuberculosis presenting with a huge abdominal mass.

Tuberculosis of the stomach is extremely rare. We report the case of a 38-year-old woman who presented with epigastric discomfort and a palpable mass that persisted for a period of one month. We also report our findings from the abdominal computed tomographic, upper endoscopic and endoscopic ultrasonographic examinations of the patient. Abdominal computed tomography (CT) showed the presence of a large mass with an irregularly contoured low attenuation lesion. Upper endoscopy and endoscopic ultrasonography revealed a protruding ulcerative mass with an ill-defined heteroechoic subepithelial lesion originating from the gastric submucosal layer. This was previously misdiagnosed as a gastrointestinal stromal tumour. Endoscopic biopsy specimen was positive on acid-fast bacillus staining, and polymerase chain reaction for Mycobacterium tuberculosis was also positive. Abdominal CT and endoscopy at the patient's three-month follow-up showed near complete resolution of the lesion.