Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from the bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, a higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to the reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating the acquisition of a rapid supply of ATP for proliferation in AML. Therefore, the targeting of mesothelin presents a potentially promising approach to mitigating the progression of AML through the inhibition of glycolysis and mitochondrial respiration in myeloid cells.

Quantitative Computed Tomography Lung COVID Scores with Laboratory Markers: Utilization to Predict Rapid Progression and Monitor Longitudinal Changes in Patients with Coronavirus 2019 (COVID-19) Pneumonia.

Coronavirus disease 2019 (COVID-19), is an ongoing issue in certain populations, presenting rapidly worsening pneumonia and persistent symptoms. This study aimed to test the predictability of rapid progression using radiographic scores and laboratory markers and present longitudinal changes. This retrospective study included 218 COVID-19 pneumonia patients admitted at the Chungnam National University Hospital. Rapid progression was defined as respiratory failure requiring mechanical ventilation within one week of hospitalization. Quantitative COVID (QCOVID) scores were derived from high-resolution computed tomography (CT) analyses: (1) ground glass opacity (QGGO), (2) mixed diseases (QMD), and (3) consolidation (QCON), and the sum, quantitative total lung diseases (QTLD). Laboratory data, including inflammatory markers, were obtained from electronic medical records. Rapid progression was observed in 9.6% of patients. All QCOVID scores predicted rapid progression, with QMD showing the best predictability (AUC = 0.813). In multivariate analyses, the QMD score and interleukin(IL)-6 level were important predictors for rapid progression (AUC = 0.864). With >2 months follow-up CT, remained lung lesions were observed in 21 subjects, even after several weeks of negative reverse transcription polymerase chain reaction test. AI-driven quantitative CT scores in conjugation with laboratory markers can be useful in predicting the rapid progression and monitoring of COVID-19.

Abdominal aortic calcification in patients newly diagnosed with essential thrombocythemia.

Background: Although atherosclerosis is likely to be involved in the development of arterial thrombotic events in patients with essential thrombocythemia (ET), abdominal aortic calcification (AAC) has rarely been investigated. We evaluated the prevalence and clinical relevance of AAC at the time of ET diagnosis. Methods: This retrospective study included patients newly diagnosed with ET who underwent abdominal computed tomography (CT) at the time of diagnosis between January 2002 and December 2021 at Chungnam National University Hospital, Daejeon, Korea. CT images were reviewed and an aortic calcification score was assigned. Results: Of the 94 patients (median age, 62 yr; range, 18‒90 yr), AAC was detected in 62 (66.0%). AAC was most commonly mild (33.0%), followed by moderate (22.7%) and severe (5.3%). Old age [odds ratio (OR), 34.37; 95% confidence interval (CI), 12.32‒95.91; P＜0.001] was an independent risk factor for AAC. The patients with AAC had a higher WBC count (11.8±4.7 vs. 9.7±2.9×109/L, P=0.017), higher neutrophil-to-lymphocyte ratio (4.3±2.7 vs. 3.1±1.5, P=0.039), and higher JAK2V617F positivity (81.5% vs. 58.8%, P=0.020) compared to those without AAC. AAC was an independent risk factor for arterial thrombotic vascular events that occurred before or at diagnosis of ET (OR, 4.12; 95% CI, 1.11‒15.85; P=0.034). Conclusion: AAC is common in patients with ET and is associated with arterial thrombotic events.

Autoimmune Limbic Encephalitis in Patients with Hematologic Malignancies after Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide.

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with post-transplant cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflammatory biomarkers, and reconstitution of various T cell populations. Of 35 patients, 4 developed LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.

The first case report of Paragonimus westermani infection diagnosed by transbronchial lung cryobiopsy.

We report a case of pulmonary paragonimiasis diagnosed by transbronchial lung cryobiopsy (TBLC). TBLC is likely to be a superior method to transbronchial forceps biopsy because TBLC can get larger specimens, resulting in a higher chance of containing the eggs. A male patient aged 57 years presented with hemoptysis and dyspnea on exertion. His initial chest computed tomography scans showed a cavitary nodule with a peripheral ground-glass appearance, leading to a prescription of an oral antibiotic, with an initial assumption of pneumonia. A follow-up chest computed tomography, however, revealed an appearance of a new nodule adjacent to the original nodule. TBLC and transbronchial forceps biopsy were done to rule out lung cancer and eventually, the eggs of Paragonimus westermani were found using TBLC. Praziquantel was prescribed, showing improvements in symptoms and chest X-ray findings. TBLC has more potential to be utilized as a diagnostic method than transbronchial forceps biopsy because it has a better chance to confirm pulmonary paragonimiasis, which can be initially suspected as pulmonary tuberculosis or lung cancer.

The Tri-iodothyronine (T3) Level Is a Prognostic Factor for Patients With Advanced NSCLC: Receiving Immune Checkpoint Inhibitors and Is Associated With Liver Metastasis.

Background: Endocrine hormones influence tumor progression and the response to treatment. Despite the importance of immune checkpoint inhibitors (ICIs) as treatments for advanced non-small cell lung cancer (NSCLC), few studies have explored the effects of hormone levels in NSCLC patients on the effectiveness of ICI therapies. We thus investigated the effects of baseline blood markers in patients with advanced NSCLC on ICI treatments. Methods: Patients with advanced NSCLC who received programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors at Chungnam National University Hospital between December 2016 and November 2020 and who lacked any history of thyroid gland-related diseases were analyzed retrospectively. We collected clinical information and baseline laboratory data, including the levels of endocrine hormones, cytokines, complete blood counts (CBCs), and peripheral blood chemistry panels. We explored the relationships of hormone levels with clinical outcomes (overall survival [OS], progression-free survival [PFS], and best response), liver metastasis, and blood markers using the Kaplan-Meier method, Cox's proportional hazards regression, and logistic regression. Results: A total of 113 patients were enrolled. A shorter PFS was independently associated with liver metastasis, higher cortisol levels, and lower hemoglobin (Hb) levels; a shorter OS was associated with liver metastasis, lower tri-iodothyronine (T3) levels, higher lactate dehydrogenase (LDH) levels, and lower albumin levels. Patients with low T3 levels exhibited a shorter PFS and OS, and a poorer best response. Patients with low T3 levels tended to have higher disease progression rates, lower levels of adrenocorticotropic hormone (ACTH), C-peptide, albumin, Hb, and neutrophil-to-lymphocyte ratio, and higher levels of interleukin (IL)-6, white blood cells, platelets, compared with those with normal T3 levels. We found a significant association between a low T3 level and liver metastasis. Conclusions: We found the baseline T3 level was associated with both prognosis and the response to ICIs in patients with advanced NSCLC, probably reflecting impaired liver function and systemic inflammation induced by the interaction of T3 with other biomarkers, such as IL-6, ACTH, cortisol, C-peptide, Hb, LDH, and albumin.

Pulmonary lymphangioleiomyomatosis and renal angiomyolipoma in a patient with systemic lupus erythematosus: A case report.

BACKGROUND: The co-incidence of systemic lupus erythematosus (SLE) and tuberous sclerosis with pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipoma (AML) is rare. In such patients, the rupture of renal AML may result in fatal circumstances, but this may be preventable. METHODS: A 22-year-old Asian woman with SLE was admitted to our hospital with severe left-flank pain. Imaging studies showed the bilateral rupture of multiple renal AMLs. RESULTS: The patient underwent emergency selective transcatheter embolization (TE) of the left renal artery. After TE and massive hydration, the patient complained of dyspnea and postembolization syndrome with fever. The chest computed tomography (CT) revealed pulmonary LAM, pulmonary edema with bilateral pleural effusions, and pneumonic consolidation. After the emergency procedure, the patient was treated with intravenous administration of antibiotics, diuretics, and nonsteroidal anti-inflammatory drugs for 10 days. The patient recovered favorably and was discharged 20 days after the treatment. She was diagnosed with renal AML and pulmonary LAM along with facial angiofibromas as well as tuberous sclerosis complex (TSC), although she had no TSC1 or TSC2 gene mutations. CONCLUSION: Although rare, SLE may coexist with TSC, along with LAM and AML, with a risk of AML rupture. The activation of the mTOR signaling pathway is shared between SLE and TSC. Thus, in patients with SLE, clinicians should consider imaging studies, such as kidney sonography and chest CT, to screen for possible manifestation of AML and LAM.

The rest period between chemotherapy and immunotherapy influences the efficacy of immune checkpoint inhibitors in lung cancer.

BACKGROUND: The use of immune checkpoint inhibitors (ICIs) as first-line treatment rather than as second-line treatment makes a big difference in the drug efficacy and progression-free survival. However, the mechanism for this is still not clear. This study aimed to analyze the effects of the rest period between chemotherapy and immunotherapy on the efficacy of ICIs. METHODS: This study included 100 patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between May 2016 and August 2019. The rest period was defined from the last dose of cytotoxic chemotherapy to the first dose of ICIs. We retrospectively reviewed patients' clinical data and blood test records and analyzed lymphocyte subsets using flow cytometry. RESULTS: The median rest period was 64 days. The long rest period group (≥36 days) showed significantly higher clinical benefits than the short rest period group (<36 days) (69.4% vs. 39.5%, p = 0.003). White blood cell (WBC) count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and neutrophil-lymphocyte ratio (NLR) just before chemotherapy were not different between the two groups. However, the blood test after chemotherapy immediately before immunotherapy showed significantly higher ANC and NLR in the short rest period group than in the long rest period group. The frequency of the Th1 subset and PD-1 + CD8+ T cells were significantly higher in the long rest period group than in the short rest period group. CONCLUSION: Time interval from chemotherapy to immunotherapy may affect immune cell status and efficacy of ICIs.

Early detection of delayed pneumothorax using lung ultrasound after transthoracic needle lung biopsy: A prospective pilot study.

OBJECTIVES: Delayed pneumothorax can cause an emergency room visit and be life-threatening in case of tension pneumothorax after transthoracic needle biopsy. We hypothesized that most delayed pneumothoraces are diagnosed by later enlargement of occult pneumothorax due to the low diagnostic accuracy of a chest X-ray. Lung ultrasound is a highly accurate tool for detection of pneumothorax. The aim of this study is to evaluate the diagnostic accuracy of lung ultrasound for prediction of delayed pneumothorax on chest X-ray. METHODS: This prospective pilot study was performed between April 2020 and July 2020 in Chungnam National University Hospital. The participants underwent chest X-rays and lung ultrasound before, immediately after, and 3 h after transthoracic needle biopsy, respectively. The presence or absence of lung sliding at each anterior BLUE-point on an ultrasound and pneumothorax on a chest X-ray was recorded. RESULTS: Pneumothorax occurred in 17 (35.4%) participants, and three of them underwent chest tube replacement. Of the 17 (35.4%) cases of pneumothorax, five participants (10.4%) were diagnosed with delayed pneumothorax. Three out of five participants showed loss of lung sliding on lung ultrasound before the diagnosis of delayed pneumothorax. Therefore, the sensitivity of lung sliding on lung ultrasound for early detection of delayed pneumothorax was 60%. Two undetected cases were asymptomatic, and the pneumothoraces were exceedingly small and recovered spontaneously. Thus, sensitivity for detection of clinically meaningful delayed pneumothorax requiring chest tube replacement was 100% (2/2). CONCLUSION: Lung ultrasound can probably predict clinically meaningful delayed pneumothorax after transthoracic needle lung biopsy.

Characteristics and outcomes of patients screened by rapid response team who transferred to the intensive care unit.

BACKGROUND: The utilization of a rapid response team (RRT) has influenced the clinical outcomes of patients in the general ward. However, the characteristics of RRT-screened patients who are transferred to the intensive care unit (ICU) are unknown. Therefore, the present study aimed to evaluate these factors. METHODS: We conducted a retrospective study using patient data from a tertiary medical center in Republic of Korea between January 2016 and December 2017. Multivariate logistic regression analyses were performed to assess the factors associated with the risk of in-hospital mortality. RESULTS: A total of 1,096 patients were included: 389 patients were transferred to the ICU, and 707 patients stayed in the ward. Patients in the ICU group were more likely to be admitted for medical reasons, hepatobiliary disease, and high heart rate. More interventions were performed, hospital stays were longer, and the 28-day and in-hospital mortality rates were higher in the ICU group than in the ward group. Multivariate logistic regression analyses showed that risk factors affecting ICU admission were higher Sequential Organ Failure Assessment (SOFA) score, National Early Warning Score (NEWS), platelet count, and lactate level. ICU transfer was not associated with in-hospital mortality. CONCLUSIONS: Among RRT-screened patients, those with higher SOFA score, NEWS, and lactate level were more likely to be transferred to the ICU. Therefore, these patients should be closely monitored and considered for ICU transfer.

Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. METHODS: This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. RESULTS: The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127loFoxP3+ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4+CD25+CD127loFoxP3+ Treg cells and PD-1+CD4+CD25+CD127loFoxP3+ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). CONCLUSION: Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.

Usefulness of presepsin in predicting the prognosis of patients with sepsis or septic shock: a retrospective cohort study.

BACKGRUOUND: The diagnosis and prediction of prognosis are important in patients with sepsis, and presepsin is helpful. In this study, we aimed to examine the usefulness of presepsin in predicting the prognosis of sepsis in Korea. METHODS: Patients diagnosed with sepsis according to the sepsis-3 criteria were recruited into the study and classified into surviving and non-surviving groups based on in-hospital mortality. A total of 153 patients (33 and 121 patients with sepsis and septic shock, respectively) were included from July 2019 to August 2020. RESULTS: Among the 153 patients with sepsis, 91 and 62 were in the survivor and non-survivor groups, respectively. Presepsin (p=0.004) and lactate (p=0.003) levels and the sequential organ failure assessment (SOFA) score (p<0.001) were higher in the non-survivor group. Receiver operating characteristic curve analysis revealed poor performances of presepsin and lactate in predicting the prognosis of sepsis (presepsin: area under the curve [AUC]=0.656, p=0.001; lactate: AUC=0.646, p=0.003). The SOFA score showed the best performance, with the highest AUC value (AUC=0.751, p<0.001). The prognostic cutoff point for presepsin was 1,176 pg/mL. Presepsin levels higher than 1,176 pg/mL (odds ratio [OR], 3.352; p<0.001), higher lactate levels (OR, 1.203; p=0.003), and higher SOFA score (OR, 1.249; p<0.001) were risk factors for in-hospital mortality. CONCLUSION: Presepsin levels were higher in non-survivors than in survivors. Thus, presepsin may be a valuable biomarker in predicting the prognosis of sepsis.

Severe mediastinitis and pericarditis after endobronchial ultrasound-guided transbronchial needle aspiration: A case report.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and minimally invasive diagnostic tool for mediastinal and hilum evaluation. However, infectious complications may occur after EBUS-TBNA. Among these, mediastinitis and pericarditis are rare. CASE SUMMARY: A 67-year-old woman was referred to our hospital due to paratracheal lymph node enlargement on chest computed tomography (CT). EBUS-TBNA was performed on the lymph node lesions, and prophylactic oral antibiotics were administered. Seven days after EBUS-TBNA, the patient visited the emergency room with a high fever and chest pain. Laboratory test results revealed leukocytosis with a left shift and elevated C-reactive protein level (25.7 mg/dL). Chest CT revealed the formation of a mediastinal abscess in the right paratracheal lymph node and pericardial and bilateral pleural effusions. The patient received intravenous antibiotic treatment, cardiac drainage through pericardiocentesis, and surgical management. The patient recovered favorably and was discharged 31 d after the operation. CONCLUSION: Mediastinitis and pericarditis after EBUS-TBNA are rare but should be considered even after the use of prophylactic antibiotics.