The study aimed to investigate the role of peripheral NLR family pyrin domain-containing 3 protein (NLRP3) in inflammatory pain development in the orofacial area. Male Sprague–Dawley rats were used in experiments, with orofacial formalin-induced pain behavior and complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia as chronic inflammatory pain models. Administration of 5% formalin produced biphasic nociceptive behavior, and subcutaneous pretreatment with MCC950 (50 and 100 μg/50 μL), an NLRP3 inhibitor, remarkably attenuated nociceptive behavior during the second phase. Subcutaneous CFA injection induced thermal hyperalgesia 1 day after injection, which persisted for 7 days. Five days after CFA injection, subcutaneous treatment with MCC950 (50 and 100 μg/50 μL) significantly attenuated thermal hyperalgesia. Additionally, subcutaneous injection of BMS-986299 (50 and 100 μg/50 μL), an NLRP3 agonist, induced significant nociceptive behavior for 1 hour in naïve rats. Pretreatment with an interleukin-1β (IL-1β) receptor antagonist blocked the nociceptive behavior produced by subcutaneous injection of BMS-986299 (100 μg/50 μL);however, treatment with a hypoxia-inducible factor 1α inhibitor did not. These findings suggest the involvement of the peripheral NLRP3 and IL-1β pathway in chronic inflammatory pain development in the orofacial area, highlighting the potential of blocking this pathway as a strategy for developing future inflammatory pain treatment drugs.

Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Background/Aims: We evaluated the role of next-generation sequencing (NGS)-based disease monitoring for elderly patients diagnosed with acute myeloid leukemia (AML) who received decitabine therapy. Methods: A total of 123 patients aged > 65 years with AML who received decitabine were eligible. We analyzed the dynamics of variant allele frequency (VAF) in 49 available follow-up samples after the fourth cycle of decitabine. The 58.6% VAF clearance (Δ, [VAF at diagnosis − VAF at follow-up] × 100 / VAF at diagnosis) was the optimal cut-off for predicting overall survival (OS). Results: The overall response rate was 34.1% (eight patients with complete remission [CR], six of CR with incomplete hematologic recovery, 22 with partial responses, and six with morphologic leukemia-free status). Responders (n = 42) had significantly better OS compared with non-responders (n = 42) (median, 15.3 months vs. 6.5 months; p < 0.001). Of the 49 patients available for follow-up targeted NGS analysis, 44 had trackable gene mutations. The median OS of patients with ΔVAF ≥ 58.6% (n=24) was significantly better than that of patients with ΔVAF < 58.6% (n = 19) (20.5 months vs. 9.8 months, p = 0.010). Moreover, responders with ΔVAF ≥ 58.6% (n = 20) had a significantly longer median OS compared with responders with VAF < 58.6% (n = 11) (22.5 months vs. 9.8 months, p = 0.004). Conclusions This study suggested that combining ΔVAF ≥ 58.6%, a molecular response, with morphologic and hematologic responses can more accurately predict OS in elderly AML patients after decitabine therapy.

Background: In diffuse large B-cell lymphoma (DLBCL), bone marrow involvement (BMI) has an important clinical implication as a component of staging and International Prognostic Index. This study aimed to determine whether molecular analysis of immunoglobulin heavy chain (IgH) genes and positron emission tomography-computed tomography (PET/CT) could overcome the limitation of defining morphologic BMI by trephination biopsy and could increase the diagnostic accuracy or prognostic prediction. Methods: A total of 94 de novo patients with DLBCL underwent PET/CT, polymerase chain reaction (PCR) test for detection of IgH gene rearrangement, and unilateral bone marrow (BM) trephination at diagnosis. Results: A total of 9 patients (9.6%) were confirmed to present morphologic BMI (mBMI) based on trephination biopsy. On the other hand, 21 patients (22.3%) were confirmed to have IgH clonality (IgH BMI), while 16 (17.0%) were classified with BMI based on the assessment of PET/CT (PET BMI). Each IgH rearrangement PCR and PET/CT showed the high negative predictive value of detecting the BMI. However, the combined assessment of IgH rearrangement and PET/CT could increase the diagnostic accuracy and specificity with 87.2% and 97.0%, respectively. The survival outcome of patients with double positive PET BMI and IgH BMI was significantly worse than that with either single positive PET BMI or IgH BMI, and even less than patients with neither PET BMI nor IgH BMI (3-year PFS: 50.0% vs. 75.4% vs. 97.9%, P = 0.007, 3-year OS: 50.0% vs. 75.6% vs. 80.1%, P = 0.035, respectively). Conclusion This study suggests that the combined evaluation of PET/CT and IgH rearrangement could give additional information for predicting therapeutic outcomes in patients with negative morphologic BMI as an important part of the prognosis.

Purpose: Forced expiratory flow between 25% and 75% (FEF 25%-75%) is known to sensitively reflect bronchial obstruction. Methacholine challenge test (MCT) has shown varying reduction levels of forced vital capacity (FVC) with the reduction in forced expiratory volume in 1 second (FEV1) in asthma. The aim of this study was to evaluate the clinical implication of provocative concentration causing a 20% fall in FEF 25%-75%(PC 20-FEF 25%-75%) and the percentage fall in FVC at the PC 20 dose of methacholine (△FVC). Methods: A total of 194 children who visited the hospital due to respiratory symptoms and underwent MCT were analyzed retrospectively. The patients were divided into 3 groups. Group I had both PC 20-FEV1 and PC 20-FEF 25%-75% above 16 mg/mL; group II had a PC 20-FEF 25%-75% that fell below 16 mg/mL but PC 20-FEV1 was 16 mg/mL or above; group III had a PC 20-FEV1and a PC 20-FEF 25%-75% that both fell below 16 mg/mL. Results: In group II, PC 20-FEV1 was lower (P = 0.026) and the rate of change in FEV1 and FEF 25%-75% from baseline to 16 mg/mL of methacholine concentration was greater than in group I (both P< 0.001). Levels of PC 20-FEF 25%-75% were higher in group II compared to group III (P < 0.001). △FVC showed a correlation with PC 20-FEV1 (P < 0.001) only in the whole group. Conclusion In asthmatic children, PC 20-FEF 25%-75% may be associated with bronchial hyperresponsiveness. △FVC was not associated with other parameters in either group. For subjects with a positive finding of PC 20-FEF 25%-75% and a negative finding of MCT, the progression to asthma can be suspected.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Objective: The emergency medical service (EMS) is expected to improve the prognosis of patients suffering from acutemyocardial infarction (AMI). We investigated the impact of utilizing EMS on the clinical outcomes of AMI patients. Methods: From November 2011 to November 2015, a total of 13,102 patients in the Korea Acute Myocardial InfarctionRegistry-National Institute of Health (KAMIR-NIH) registry were enrolled. Patients were divided into two groups: the EMSgroup, first medical contact (FMC) with 119; the non-EMS group, the FMC at local hospitals that were not available forpercutaneous coronary intervention. The authors analyzed the mortality and major adverse cardiac and cerebrovascularevents during one-year of clinical follow-up. Results: A total of 8,863 patients were finally analyzed for this study, and a total of 1,999 patients (22.6%) utilized theEMS as FMC. The patients utilizing EMS were more frequently diagnosed with ST-segment elevation AMI. At presentation,the EMS group had a higher incidence of Killip class IV, and they had a shorter symptom-to-door time than non-EMS group. The patients utilizing EMS had higher incidence of peri-procedural complications and in-hospital mortality.The multivariate logistic regression analysis with backward elimination revealed that utilizing EMS is an independent factorfor predicting lower one-year mortality. Conclusion This study has demonstrated that the high-risk AMI patients can utilize the EMS in Korea. The EMS grouphas more favorable clinical outcome during one-year follow-up after discharge than the non-EMS group, whereas it had ahigher rate of death during hospitalization compared with that of the non-EMS group.

Background/Aims: Many patients with acute myocardial infarction (AMI) suffer from heart failure due to progressive ischemic left ventricular (LV) remodeling. This study investigated the predictors of ischemic cardiomyopathy (ICMP) in patients with AMI who underwent successful percutaneous intervention. Methods: A total of 547 patients with AMI were divided into two groups: ICMP (n = 66, 67.1 ± 11.9 years, 78.8% males) and non-ICMP (n = 481, 62.5 ± 12.2 years, 70.1% males). Results: On echocardiography, the LVEF was significantly decreased (41.7 ± 10.5 vs. 55.4 ± 10.3%, p < 0.001) but the LV end-diastolic (54.1 ± 7.2 vs. 49.3 ± 5.3 mm, p < 0.001) and systolic (42.1 ± 8.0 vs. 33.5 ± 6.0 mm, p < 0.001) dimensions significantly increased in the ICMP group compared with the non-ICMP group. According to multivariate logistic regression analysis, LVEF < 50% (odds ratio [OR] 8.722, 95% confidence interval [CI] 2.986–25.478, p < 0.001), LV end-diastolic dimension > 55 mm (OR 4.511, 95% CI 1.561–13.038, p = 0.005), and ratio of early mitral inflow velocity to mitral annular early diastolic velocity (E/e’) ≥ 15 (OR 3.270, 95% CI 1.168–9.155, p = 0.024) were independent predictors of ICMP development. Conclusions The present study demonstrates that a larger LV size, lower LV function, and increased E/e’ (≥ 15) were independent predictors of ICMP. Therefore, the development of ICMP should be carefully monitored in AMI patients with these features.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

The present study investigated the participation of D-serine and NR2 in antinociception produced by blockade of central erythropoietin-producing hepatocellular carcinoma (Eph) A4 (EphA4) signaling in rats with trigeminal neuropathic pain. Trigeminal neuropathic pain was modeled in male Sprague-Dawley rats using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia, and a miniature dental implant was placed to induce injury to the inferior alveolar nerve. Our current findings showed that nerve injury induced by malpositioned dental implants significantly produced mechanical allodynia; additionally, the inferior alveolar nerve injury increased the expression of D-serine and NR2 subunits in the ipsilateral medullary dorsal horn (trigeminal subnucleus caudalis). Intracisternal administration of EphA4-Fc, an EphA4 inhibitor, inhibited nerve injury-induced mechanical allodynia and upregulated the expression of D-serine and NR2 subunits. Moreover, intracisternal administration of D-amino acids oxidase, a D-serine inhibitor, inhibited trigeminal mechanical allodynia. These results show that D-serine and NR2 subunit pathways participate in central EphA4 signaling after an inferior alveolar nerve injury.Therefore, blockade of D-serine and NR2 subunit pathways in central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.