Background: Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors are effective treatments for non-small cell lung cancer (NSCLC), but their use can lead to severe pneumonitis. This study aims to evaluate the utility of Krebs von den Lungen-6 (KL-6) for predicting and diagnosing PD-1/PD-L1 inhibitor-related pneumonitis in NSCLC patients. Methods: We conducted a prospective observational study at a university-affiliated tertiary hospital in Korea from February 2022 to June 2023. Baseline KL-6 levels were measured immediately before initiating PD-1/PD-L1 inhibitor therapy. In patients who developed pneumonitis, KL-6 levels were monitored every 1–2 weeks from the onset of pneumonitis. For patients without pneumonitis, KL-6 levels were measured every 6 weeks. We compared clinical characteristics and serial KL-6 levels between the pneumonitis and non-pneumonitis groups. Results: Eighteen patients were enrolled, with 11 developing pneumonitis. Baseline KL-6 levels did not significantly differ between the two groups (261 U/mL in the pneumonitis group vs. 373 U/mL in the non-pneumonitis group, p=0.375). In the pneumonitis group, KL-6 levels generally showed an upward trend, with a median of 412 U/mL at pneumonitis onset. Conversely, KL-6 levels in the non-pneumonitis group showed no clear overall change. Conclusion In this pilot study, baseline KL-6 was not clearly linked to PD-1/PD-L1 inhibitor-related pneumonitis in NSCLC patients. However, increases in KL-6 levels post-baseline were more frequently observed in patients who developed pneumonitis, including cases of all-cause pneumonitis.

Objective: This study compared clinical and cosmetic outcomes of cranioplasty using customized three-dimensional (3-D) printed implants versus autologous bone in patients with aneurysmal subarachnoid hemorrhage (aSAH) after decompressive craniectomy (DC). Methods: We retrospectively reviewed 50 patients who underwent cranioplasty after DC for aSAH between July 2018 and December 2023. Patients were divided into the three-dimensional cranioplasty(3-DC, n=26) and autologous bone cranioplasty (AC, n=24) groups. Demographics, aneurysm characteristics, surgical parameters, morphometric analysis of defect coverage, complications, and functional outcomes assessed by the modified Rankin Scale (mRS) were compared. Results: A total of 54 hemispheres underwent cranioplasty. Compared with AC, the 3-DC group had larger defects but achieved higher coverage (96.7% vs. 93.4%, p=0.044) and smaller residual defects (338.7±274.2 mm² vs. 528.5±331.3 mm², p=0.049). Complication rates were lower in 3-DC (9 cases) than AC (15 cases, p=0.0994). Wound dehiscence and fluid collection were more frequent with 3-DC, while bone flap resorption and epidural abscess occurred only with AC. Revision surgery was required in six patients, five initially treated with autologous bone. Neurological outcomes (mRS) were maintained or improved in both groups. Conclusions In aSAH patients undergoing cranioplasty after DC, customized 3-D printed implants achieved significantly better anatomical restoration and showed a numerical trend toward fewer complications compared with autologous bone. While AC remains feasible, its risks of resorption and infection often necessitate revision. 3-D printed implants may be considered a reasonable alternative, particularly in aSAH patients at higher risk of complications.

Background/Aims: The prognosis of patients with idiopathic pulmonary fibrosis (IPF) and respiratory failure requiring mechanical ventilation is poor. Therefore, mechanical ventilation is not recommended. Recently, outcomes of mechanical ventilation, including those for patients with IPF, have improved. The aim of this study was to investigate changes in the use of mechanical ventilation in patients with IPF and their outcomes over time. Methods: This retrospective, observational cohort study used data from the National Health Insurance Service database. Patients diagnosed with IPF between January 2011 and December 2019 who were placed on mechanical ventilation were included. We analyzed changes in the use of mechanical ventilation in patients with IPF and their mortality using the Cochran- Armitage trend test. Results: Between 2011 and 2019, 1,227 patients with IPF were placed on mechanical ventilation. The annual number of patients with IPF with and without mechanical ventilation increased over time. However, the ratio was relatively stable at approximately 3.5%. The overall hospital mortality rate was 69.4%. There was no improvement in annual hospital mortality rate. The overall 30-day mortality rate was 68.7%, which did not change significantly. The overall 90-day mortality rate was 85.3%. The annual 90-day mortality rate was decreased from 90.9% in 2011 to 83.1% in 2019 (p = 0.028). Conclusions Despite improvements in intensive care and ventilator management, the prognosis of patients with IPF receiving mechanical ventilation has not improved significantly.

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.

Lung cancer is a dismal disease as a leading cause of overall cancer death, but the development of immune checkpoint inhibitors (ICIs) in driver gene mutation negative metastatic non-small cell lung cancer (NSCLC) is changing the paradigm of lung cancer treatment. Recently, ICIs are expanding their treatment area to early-stage NSCLC and ICIs have also changed their treatment strategies of such patients. And it is important to appropriately select patients with resectable early-stage lung cancer through a multidisciplinary team approach and decrease the tumor relapse rate in the ICIs era. In this review article, we discuss the recently released neoadjuvant and adjuvant data of ICIs, their treatment rationale, and unmet needs in the treatment of early-stage NSCLC.

Purpose: Histone deacetylase inhibitors (HDACis) are epigenetic regulators and used clinically for hematopoietic malignancies. Recently, HDACis have received attention as a factor that modulates the immune system. In this study, the role of histone deacetylase (HDAC) expression as a predictive marker in lung cancer patients who were treated with immune checkpoint inhibitors (ICIs) and the role of HDACi and ICI combination treatment in the mouse tumor model were analyzed. Materials and Methods: The overall response rate (ORR) and progression-free survival (PFS) were analyzed by the expression of HDAC. In vitro assay, the mRNA and protein expression levels of cytokines and programmed death-ligand 1 (PD-L1) were analyzed after HDACi treatment. In vivo assay, TC-1 tumor-bearing mice were treated with HDACi and mouse programmed cell death 1 (PD-1) inhibitor. Results: The HDAC6 low expression group showed high ORR and prolonged PFS. When the selective HDAC6 inhibitor was administered to the A549 cell line, the levels of interleukin-1β and interleukin-6 decreased and the expression of PD-L1 was reduced. Mice that received both the mouse PD-1 inhibitor and pan-HDACi had a smaller tumor size than that of the mice from the control group. Moreover, mice treated with the mouse PD-1 inhibitor and pan-HDACi generated greater numbers of E7-specific CD8+ T cells. Conclusion HDAC6 expression can predict the prognosis of non–small cell lung cancerpatients who were treated with ICIs. Furthermore, co-treatment with HDACi and PD-1 inhibitor was shown to decrease the tumor growth rate and create a favorable tumor microenvironment for cytotoxic T lymphocytes in the TC-1 mouse model.

Background/Aims: Adjuvant chemotherapy is the standard of care for resected stage II-IIIA non-small cell lung cancer (NCSLC). The efficacy of adjuvant chemotherapy in stage IB (< 4 cm) NSCLC with high-risk factors is controversial. Methods: This retrospective multicenter study included 285 stage IB NSCLC patients with high-risk factors according to the 8th edition tumor, node, metastasis (TNM) classification from four academic hospitals. High-risk factors included visceral pleural invasion, vascular invasion, lymphatic invasion, lung neuroendocrine tumors, and micropapillary histology patterns. Results: Of the 285 patients, 127 (44.6%) were included in the adjuvant chemotherapy group and 158 (55.4%) were included in the non-adjuvant chemotherapy group. The median follow-up was 41.5 months. Patients in the adjuvant chemotherapy group had a significantly reduced recurrence rate and risk of mortality than those in the non-adjuvant chemotherapy group (hazards ratio, 0.408; 95% confidence interval, 0.221 to 0.754; p = 0.004 and hazards ratio, 0.176; 95% confidence interval, 0.057 to 0.546; p = 0.003, respectively). Adjuvant chemotherapy should be particularly considered for the high-risk factors such as visceral pleural involvement or vascular invasion. Based on the subgroup analysis, adjuvant chemotherapy should be considered when visceral pleural involvement is present, even if the tumor size is < 3 cm. Conclusions Adjuvant chemotherapy may be useful for patients with stage IB NSCLC with high-risk factors and is more relevant for patients with visceral pleural involvement or vascular invasion.

Background: Cardiac dysfunction patients have long been considered at high risk of reintubation. However, it is based on past studies in which only conventional oxygen therapy was applied after extubation. We investigated association between cardiac dysfunction and reintubation rate in situation where high-flow nasal cannula (HFNC) was widely used during post-extubation period. Methods: We conducted a retrospective observational cohort study of patients treated with HFNC after planned extubation in medical intensive care unit of single tertiary center. Patients were divided into normal function group (ejection fraction [EF] ≥45%) and cardiac dysfunction group (EF <45%). The primary outcome was reintubation rate within 72 hours following extubation. Results: Of 270 patients, 35 (13%) had cardiac dysfunction. Baseline characteristics were similar in both groups. There were no differences in the changes in vital signs between the two groups during the first 12 hours after extubation except diastolic blood pressure. The reintubation rates were 20% and 17% for cardiac dysfunction group and normal function group, respectively (p=0.637). In a multivariate Cox regression analysis, cardiac dysfunction was not associated with an increased risk of reintubation within 72 hours following extubation (hazard ratio, 1.56; p=0.292). Conclusion Cardiac dysfunction was not associated with increased reintubation rate within 72 hours when HFNC is immediately applied after planned extubation.

The incidence of quadriplegia following drainage of cerebrospinal fluid by lumbar puncture (LP) below a spinal occupying lesion is rare. We report a case of acute quadriplegia following LP for presumed normal pressure hydrocephalus (NPH) in a 66-year-old man. Acute cervical myelopathy with a herniated cervical disc was subsequently found on magnetic resonance imaging (MRI) at the C5–6 level. After posterior decompression and anterior cervical discectomy and fusion at the C5–6 level with a cervical plate, the patient's motor and sensory functions recovered. Clinicians should be aware that symptoms of NPH and cervical myelopathy may overlap, and that serious complications may occur when performing LP below a spinal lesion. As a safety measure, cervical spine MRI should be performed before LP.

Immune checkpoint inhibitors (ICIs) have been changing the paradigm of cancer treatment. However, immune-related adverse effects (irAEs) have also increased with the exponential increase in the use of ICIs. ICIs can break up the immunologic homeostasis and reduce T-cell tolerance. Therefore, inhibition of immune checkpoint can lead to the activation of autoreactive T-cells, resulting in various irAEs similar to autoimmune diseases. Gastrointestinal toxicity, endocrine toxicity, and dermatologic toxicity are common side effects. Neurotoxicity, cardiotoxicity, and pulmonary toxicity are relatively rare but can be fatal. ICI-related gastrointestinal toxicity, dermatologic toxicity, and hypophysitis are more common with anti- CTLA-4 agents. ICI-related pulmonary toxicity, thyroid dysfunction, and myasthenia gravis are more common with PD-1/PD-L1 inhibitors. Treatment with systemic steroids is the principal strategy against irAEs. The use of immune-modulatory agents should be considered in case of no response to the steroid therapy. Treatment under the supervision of multidisciplinary specialists is also essential, because the symptoms and treatments of irAEs could involve many organs. Thus, this review focuses on the mechanism, clinical presentation, incidence, and treatment of various irAEs.
Autoimmune Diseases ; Cardiotoxicity ; Homeostasis ; Incidence ; Myasthenia Gravis ; Organization and Administration ; Specialization ; Steroids ; T-Lymphocytes ; Thyroid Gland