Background: Patients with chronic obstructive pulmonary disease (COPD) expressing eosinophilia experience slightly fewer episodes of community-acquired pneumonia (CAP), than those without eosinophilia. However, the severity and burden of hospitalized pneumonia patients with COPD involving eosinophilia have not been assessed. Methods: We evaluated the differences in clinical characteristics between patients with CAP and COPD with or without eosinophilia by a post hoc analysis of a prospective, multi-center, cohort study data. Results: Of 349 CAP patients with COPD, 45 (12.9%) had eosinophilia (blood eosinophil ≥300 cells/μL). Patients with eosinophilia had a lower sputum culture percentile (8.1% vs. 23.4%, p<0.05), a lower percentile of neutrophils (70.3% vs. 80.2%, p<0.05), reduced C-reactive protein levels (30.6 mg/L vs. 86.6 mg/L, p<0.05), and a lower pneumonia severity index score (82.5 vs. 90.0, p<0.05), than those without eosinophilia. The duration of antibiotic treatment (8.0 days vs. 10.0 days, p<0.05) and hospitalization (7.0 days vs. 9.0 days, p<0.05) were shorter in eosinophilic patients. The cost of medical care per day (256.4 US$ vs. 291.0 US$, p<0.05), cost for the medication (276.4 US$ vs. 349.9 US$, p<0.05), and cost for examination (685.5 US$ vs. 958.1 US$, p<0.05) were lower in patients with eosinophilia than those without eosinophilia. Conclusion Eosinophilia serves as a favorable marker for the severity of pneumonia, health-care consumption, and cost of medical care in patients with CAP and COPD.

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) update 2023 proposed new definitions of chronic obstructive pulmonary disease (COPD) and COPD exacerbation. However, an agreement on the definitions has not been made, either internationally or domestically. This study aimed to reach an agreement between experts on the new definitions of COPD and COPD exacerbation in South Korea. Methods: A modified Delphi method was used to make an agreement on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023. We performed two rounds of the survey including 15 Korean experts on COPD, asthma, and tuberculosis. Results: More than two-thirds of the experts agreed on 12 of the 13 statements related to the definitions of COPD and COPD exacerbation in the two rounds of the survey. The experts agreed on the definitions of COPD and COPD exacerbation that should be revised in line with the definitions proposed by the GOLD update 2023. However, the experts showed an uncertain opinion on the statement that the definition of COPD includes patients with persistent airflow obstruction due to bronchiectasis. Conclusion Based on this Delphi survey, experts’ agreement was made on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023.

Background: Respiratory pathogen infections and air pollution are main causes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Air pollution has a direct effect on the airway epithelial barrier and the immune system, which can have an influence on infection. However, studies on the relationship between respiratory infections and air pollutants in severe AECOPD are limited. Thus, the objective of this study was to investigate the correlation between air pollution and respiratory pathogen in severe AECOPD. Methods: This multicenter observational study was conducted by reviewing electronic medical records of patients with AECOPD at 28 hospitals in South Korea. Patients were divided into four groups according to the comprehensive air-quality index (CAI) used in Korea. Identification rates of bacteria and viruses of each group were analyzed. Results: Viral pathogens were identified in 270 (36.7%) of 735 patients. Viral identification rate was different (P = 0.012) according to air pollution. Specifically, the virus detection rate was 55.9% in the group of CAI ‘D’ with the highest air pollution. It was 24.4% in the group of CAI ‘A’ with the lowest air pollution. This pattern was clearly seen for influenza virus A (P = 0.042). When further analysis was performed with particulate matter (PM), the higher/lower the PM level, the higher/lower the virus detection rate. However, no significant difference was found in the analysis related to bacteria. Conclusion Air pollution may make COPD patients more susceptible to respiratory viral infections, especially influenza virus A. Thus, on days with poor air quality, COPD patients need to be more careful about respiratory infections.

Background/Aims: The overall incidence of pneumococcal pneumonia is declining. However, the change in the pathogenic distribution of community-acquired pneumonia (CAP) in chronic obstructive pulmonary disease (COPD) patients and the serotype specificity of Streptococcus pneumoniae have not been evaluated in the post-era of pneumococcal vaccination in Korea. Methods: We conducted a prospective, multi-center, cohort study from seven University-affiliated hospitals. The primary objective was the identification of serotype-specific prevalence of pneumococcal pneumonia in COPD patients hospitalized for CAP. For the purpose, we conducted serotype-specific urine antigen detection (SS-UAD) assays for S. pneumoniae. The secondary objectives were other clinical characteristics of pneumonia including vaccination status. Results: The total number of participants was 349. Most of them were male (95.1%) with old ages (75.55 ± 8.59 y). The positive rate for S. pneumoniae was 9.2% with SS-UAD assay and the common serotypes were 22F, 6A, and 6B. In the sputum, Pseudomonas aeruginosa (5.0%) and Haemophilus influenzae (4.0%) were common pathogens. The vaccination rate was 78.8%, 53.0%, and 25.8% for influenza, pneumococcal polysaccharide vaccine 23 (PPV 23), and pneumococcal protein- conjugated vaccine 13 (PCV 13), respectively. Thirteen patients died during hospitalization (mortality rate; 3.7%). There was no difference in the respective rate of influenza vaccination (79.2% vs. 69.2%, p = 0.288) and PCV 13 vaccination (25.6% vs. 30.8%, p = 0.443) between survivors and the deceased. Conclusions Serotypes 22F, 6A, and 6B, which are covered either by PPV 23 or by PCV 13, are still common pneumococcal serotypes in COPD pneumonia in the post-vaccination era in Korea.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. Methods: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009–2020 were enrolled. Results: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. Conclusion These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Omnichroma (OMN) is a recently introduced structurally colored resin composite that expresses color based on the tooth structure surrounding the cavity. This study aims to investigate the effects of varying the cavity depth on the color blending of OMN.Conventional resin composite (Filtek Z250 in the A2, A3, and A4 shades) and structurally colored resin (Omnichroma) were used. Two types of specimens were prepared using custom silicone molds (diameter: 8 mm, thickness: 2, 3, 4 mm). Single specimens (diameter: 8 mm) comprised only Z250 in the A2, A3, A4 or OMN (n=10 each). Dual specimens comprised an outer ring (diameter : 8 mm) of Z250 in the A2, A3, or A4 and an inner hole (diameter: 4 mm) filled with OMN to different depths (1, 2, 3, or 4 mm, n=10 per shade per thickness). The colors were measuredusing the Commission Internationale d’Eclairage (CIE) L*a*b* system. Color differences (ΔE) according to the cavity depth and translucency parameter were measured.The ΔE values of dual specimens with the A2, A3, and A4 shades of Z250 were 1.66–5.07, 0.50–2.57, and 1.26– 3.48, respectively. At the same specimen thickness, ΔE increased with increasing cavity depth. At the same cavity depth, ΔE increased with decreasing thickness of the bottom of the restoration. The highest translucency parameterwas observed for 2 mm-thick OMN. The color blending of OMN increased with decreasing cavity depth in specimens of the same thickness, and with increasing bottom thickness of the restoration at the same cavity depth.

Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

Objective: To evaluate the efficacy and safety of Daewoong botulinum toxin type A (NABOTA) after its launch in South Korea. Methods: This prospective, multicenter, open-label phase IV clinical trial included 222 patients with stroke. All patients visited the clinic at baseline and at weeks 4, 8, and 12 after injection of upto 360 units of NABOTA into the wrist, elbow, and finger flexor muscles at the first visit. The primary outcome was the change in Modified Ashworth Scale (MAS) score for the wrist flexor muscles between baseline and week 4. The secondary outcomes were the changes in MAS, Disability Assessment Scale (DAS), and Caregiver Burden Scale (CBS) scores between baseline and each visit, and the Global Assessment Scale (GAS) score at week 12. Results: There was a statistically significant decrease in the MAS score for the wrist flexors between baseline and week 4 (-0.97±0.66, p<0.001). Compared with baseline, the MAS, DAS and CBS scores improved significantly during the study period. The GAS was rated as very good or good by 86.8% of physicians and by 60.0% of patients (or caregivers). The incidence of adverse events was 14.4%, which is smaller than that in a previous trial. Conclusion NABOTA showed considerable efficacy and safety in the management of upper limb spasticity in stroke patients.

Background: Gaucher disease (GD) is an autosomal recessive disorder characterized by excessive accumulation of glucosylceramide in multiple organs. This study was performed to determine the detection rate of GD in a selected patient population with unexplained splenomegaly in Korea. Methods: This was a multicenter, observational study conducted at 18 sites in Korea between December 2016 and February 2020. Adult patients with unexplained splenomegaly were enrolled and tested for β-glucosidase enzyme activity on dried blood spots (DBS) and in peripheral blood leukocytes. Mutation analysis was performed if the test was positive or indeterminate for the enzyme assay. The primary endpoint was the percentage of patients with GD in patients with unexplained splenomegaly. Results: A total of 352 patients were enrolled in this study (male patients, 199; mean age, 48.42 yr). Amongst them, 14.77% of patients had concomitant hepatomegaly. The most common sign related to GD was splenomegaly (100%), followed by thrombocytopenia (44.32%) and, anemia (40.91%). The β-glucosidase activity assay on DBS and peripheral leukocytes showed abnormal results in sixteen and six patients, respectively. Eight patients were tested for the mutation, seven of whom were negative and one patient showed a positive mutation analysis result. One female patient who presented with splenomegaly and thrombocytopenia was diagnosed with type 1 GD. The detection rate of GD was 0.2841% (exact 95% CI, 0.0072‒). Conclusion The detection rate of GD in probable high-risk patients in Korea was lower than expected.However, the role of hemato-oncologists is still important in the diagnosis of GD.