We aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). This is a secondary study of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29-0.97). In multivariate analysis, patient age (p=0.014) and gross tumor volume (GTV, p=0.031) were significant factors associated with overall survival, while TLC reduction (p=0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p=0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. Immunohistochemical analysis of programmed death ligand 1 and CD8 expression on T cells was performed on 84 patients. CD8 expression was not significantly associated with the pretreatment lymphocyte count (p=0.673), and PDL1 expression was not significantly associated with OS or PFS. Univariate analysis revealed that high CD8 expression in TILs was associated with favorable OS and was significantly associated with favorable PFS (p=0.032). TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, in the era of immunotherapy, constraining the volume of the radiation dose to the whole heart must be prioritized for the better survival outcomes.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Purpose: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. Methods The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuumassisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years.Discussion: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been acknowledged as an effective mean of preventing infection and hospitalization.However, the emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) has led to substantial increase in infections among children and adolescents. Vaccineinduced immunity and longevity have not been well defined in this population. Therefore, we aimed to analyze humoral and cellular immune responses against ancestral and SARSCoV-2 variants after two shots of the BNT162b2 vaccine in healthy adolescents. Although vaccination induced a robust increase of spike-specific binding Abs and neutralizing Abs against the ancestral and SARS-CoV-2 variants, the neutralizing activity against the Omicron variant was significantly low. On the contrary, vaccine-induced memory CD4+ T cells exhibited substantial responses against both ancestral and Omicron spike proteins.Notably, CD4+ T cell responses against both ancestral and Omicron strains were preserved at 3 months after two shots of the BNT162b2 vaccine without waning. Polyfunctionality of vaccine-induced memory T cells was also preserved in response to Omicron spike protein.The present findings characterize the protective immunity of vaccination for adolescents in the era of continuous emergence of variants/subvariants.

Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period. Methods: This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19–50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects. Results: After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (β, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (β, –0.642; p = 0.009). Conclusion: We observed short-term effects and safety during the tolvaptan titration period. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.

Background: Food allergy (FA) can have a profound effect on quality of life (QoL), stress, and anxiety in the family. We aimed to validate the Korean version of the Food Allergy Quality of Life-Parental Burden (FAQL-PB) and identify factors related to the parental psychosocial burden of caring for children with FAs. Methods: Parents of children aged between 6 months and 17 years with immunoglobulin E (IgE)-mediated FAs from the Pediatric Allergy Department of five university hospitals in Korea were enrolled in the study. Parents were asked to complete the FAQL-PB, Food Allergy Independent Measure-Parent Form (FAIM-PF), Child Health Questionnaire-Parents Form 28 (CHQ-PF28), Beck’s Anxiety Inventory, Connor-Davidson Resilience Scale, and Patient Health Questionnaire-9 for depression. Statistical analyses included internal consistency, test-retest reliability, concurrent validity, discriminative validity, and logistic regression analyses. Results: A total of 190 parents were enrolled. Social activity limitation was the item with the highest FAQL-PB scores. The Cronbach’s α for each item was higher than 0.8. The test-retest reliability was good (intra-class correlation coefficient, 0.716; 95% confidence interval [CI], 0.100–0.935). An increase in the FAQL-PB was significantly associated with an increase in the FAIM-PF (β = 0.765, P < 0.001) (concurrent validity). There was a positive correlation between parental burden, anxiety, and depression, while resilience was inversely correlated with parental burden (all P < 0.001). The total FAQL-PB score in parents of children who had experienced anaphylaxis was significantly higher than that in parents of children who did not experience it (P = 0.008). When adjusting for age, sex, and underlying diseases, anaphylaxis β = 9.32; 95% CI, 2.97 to 15.68), cow’s milk (CM) allergy (β = 8.24; 95% CI, 2.04 to 14.44), soybean allergy (β = 13.91; 95% CI, 1.62 to 26.20), higher anxiety (β = 1.05; 95% CI, 0.07 to 1.41), higher depression (β = 2.15; 95% CI, 1.61 to 2.69), and lower resilience (β = −0.42; 95% CI, −0.61 to −0.2) were significantly associated with greater parental burden in children with IgE-mediated FAs. Conclusion FAQL-PB is a reliable and valid tool for use in Korea. Anaphylaxis, CM or soybean allergies, more anxiety and depression symptoms, and lower resilience are associated with poorer QoL in parents of children with FAs.

Purpose: Mycoplasma pneumoniae pneumonia (MP) is a major cause of community-acquired pneumonia (CAP) in children and is associated with extrapulmonary manifestations (EPM). The incidence and risk factors for EPM in children are unknown. Methods: This was a retrospective study involving 65,243 pediatric patients with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Medical records were reviewed to collect information regarding the clinical characteristics, radiological results, and laboratory findings. Logistic regression with multivariate analysis was performed to evaluate the risk factors associated with EPM in MP. Results: The incidence of EPM was 23.9%, including elevation of liver enzymes (18.1%), mucocutaneous manifestations (4.4%), proteinuria (4.1%), cardiovascular and neurological manifestations (0.4%), hematologic manifestations (0.2%), and arthritis (0.2%). Statistical analysis showed that mucocutaneous manifestations significantly increased with elevated alanine aminotransferase (adjusted odds ratio [aOR], 3.623; 95% confidence interval [CI], 1.933-6.790) and atopic sensitization (aOR, 2.973; 95% CI, 1.615–5.475) and decreased with respiratory virus coinfection (aOR, 0.273; 95% CI, 0.084–0.887). Elevated liver enzymes were significantly associated with elevated lactate dehydrogenase (aOR, 3.055; 95% CI, 2.257–4.137), presence of pleural effusion (aOR, 2.635; 95% CI, 1.767–3.930), and proteinuria with respiratory virus coinfection (aOR, 2.245; 95% CI, 1.113–4.527). Conclusion Approximately 24% of pediatric patients with MP had various EPM. As the risk factors associated with each EPM were different, it is necessary to evaluate the various clinical aspects and findings of MP to predict and prepare for the occurrence of EPM.

Purpose: The patient perception of study medication (PPSM) questionnaire consists of 12 questions designed to quantify patient satisfaction with the efficacy of study treatment by focusing on specific changes that patients experience during the study period. This study aimed to develop a Korean version of the PPSM questionnaire. Methods: The linguistic validation process consisted of obtaining permission for translation, forward translation, reconciliation, backward translation, cognitive debriefing, and proofreading. Two independent bilingual translators translated the original version of the questionnaire, and a panel discussed and combined the 2 versions. Another independent translator performed backward translation of the reconciled version, after which 15 patients underwent the cognitive debriefing. Results: The 12 questions and 4 response scales of the PPSM questionnaire were forward translated into 2 Korean versions. The terms were adjusted to conceptually equivalent expressions in Korean. After backward translation, the panel made minor changes to the forward translations for brevity and better readability. No difficulties were experienced during cognitive debriefing by 15 patients, and all items were reported to be generally easy to understand. Conclusions The Korean version of the PPSM questionnaire has been successfully translated and validated. The questionnaire is appropriate for assessing symptom satisfaction in patients that undergo benign prostatic hyperplasia pharmacotherapy.