The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases.

Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.

A prospective, open-label, randomized clinical trial to evaluate the efficacy and safety of remimazolam in patients undergoing EBUS-TBNA: REST trial design.

BACKGROUND: Remimazolam is safe and effective for moderate sedation during flexible bronchoscopy, but its safety and efficacy during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains undetermined. The REST trial (NCT06275594) will be a prospective randomized study of remimazolam in patients undergoing EBUS-TBNA with conscious sedation. The primary aim is to evaluate whether remimazolam is safe and effective for moderate sedation during EBUS-TBNA compared to real-world midazolam and on-label midazolam. METHODS: The REST trial will recruit 330 patients from four university hospitals with mediastinal lesions suspected of being lung cancer who are eligible for EBUS-TBNA under moderate sedation. The participants will be randomized into groups using remimazolam, real-world midazolam, and on-label midazolam (US prescribing information dosage) to perform EBUS-TBNA for procedural sedation. The primary endpoint will be procedural success using composite measures. DISCUSSION: The REST trial will prospectively evaluate the efficacy and safety of remimazolam during EBUS-TBNA under moderate sedation. It will provide information for optimizing sedation modalities and contribute to practical benefits in patients undergoing EBUS-TBNA. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06275594). Prospectively registered on 15 February 2024.

Durvalumab Consolidation After Chemoradiotherapy in Elderly Patients With Unresectable Stage III NSCLC: A Real-World Multicenter Study.

BACKGROUND: The PACIFIC trial demonstrated survival benefit of durvalumab after concurrent chemoradiotherapy (CCRT) in unresectable stage III non-small-cell lung cancer. Data on the effectiveness and safety of durvalumab in elderly patients is lacking. METHODS: This retrospective study was conducted between September 2017 and September 2022. Progression-free survival (PFS), overall survival (OS), recurrence patterns, first subsequent treatment after recurrence, factors associated with survival outcomes, and adverse events (AEs) were compared. RESULTS: Of the 286 patients, 120 (42.0%) were ≥ 70 years and 166 (58.0%) were < 70 years. The median PFS (17.7 vs. 19.4 months; P = .43) and median OS (35.7 months vs. not reached; P = .13) were similar between 2 groups. Proportion of patients who completed durvalumab was lower in elderly patients (27.5% vs. 39.2%; P = .040). In elderly patients, ECOG PS 0 or 1 was associated with better PFS, and being male and having received a cisplatin-based regimen during CCRT were factors associated with better and worse OS, respectively. In patients aged < 70 years, a PD-L1 ≥ 50% was associated with improved PFS and OS. Elderly patients experienced more treatment-related AEs, grade 3/4 AEs, permanent discontinuation of durvalumab, and treatment-related deaths. Among the AEs leading to permanent discontinuation or death, pulmonary AE was significantly more common in elderly patients. CONCLUSION: Durvalumab demonstrated similar outcomes in elderly compared to younger patients. However, AEs were more common in elderly patients. Thus, judicious selection of patients and chemotherapy regimens, coupled with careful AE monitoring, are important factors for ensuring optimal durvalumab treatment.

Endobronchial Ultrasound Using Guide Sheath-Guided Transbronchial Lung Biopsy in Ground-Glass Opacity Pulmonary Lesions without Fluoroscopic Guidance.

Diagnosing ground-glass opacity (GGO) pulmonary lesions poses challenges. This study evaluates the utility of radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) in diagnosing GGO pulmonary lesions. A total of 1651 RP-EBUS procedures were performed during the study period. This study analyzed 115 GGO lesions. The EBUS visualization yield was 80.1%. Of 115 lesions, 69 (60%) were successfully diagnosed. The average size of diagnosed lesions was significantly larger than that of undiagnosed lesions (21.9 ± 7.3 vs. 17.1 ± 6.6 mm, p < 0.001). Diagnostic yield varied by lesion size: 50.0% for lesions <20 mm, 65.1% for 20-30 mm lesions, and 85.7% for lesions >30 mm. The mixed blizzard sign on EBUS appeared in 60.6% of mixed GGO lesions, with no cases in pure GGO lesions. Multivariable analyses showed that lesion size (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.00-1.16; p < 0.001) and mixed blizzard sign on EBUS (OR, 20.92; CI, 7.50-58.31; p < 0.001) were significantly associated with diagnostic success. Pneumothorax and hemoptysis occurred in 1.7% and 2.6% of patients, respectively. RP-EBUS-TBLB without fluoroscopic guidance is a viable diagnostic approach for GGO pulmonary lesions with acceptable complications.

Brain FDG PET for visualizing the relation between impaired lung function and cognitive decline in lung cancer: a preliminary study.

OBJECTIVE: Impaired lung function is associated with an increased risk for cognitive decline. F-18 fluorodeoxyglucose (FDG) PET is a well-known neurodegenerative biomarker for dementia. We investigated the association between lung and brain function using FDG PET in patients with lung cancer. METHODS: A random sub-sample of 102 patients with lung cancer and without a self-reported history of neuropsychiatric disorders were recruited and underwent both lung function tests and FDG PET scans before treatment. Lung function was analyzed as the percentage predicted value (% pred) of forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1). FDG uptake was measured as standardized uptake values (SUVs) in the frontal, parietal, temporal, and occipital cortices and cognition-related regions. Regional SUV ratios (SUVRs) were calculated by dividing the SUV in each region by the whole-brain SUV and were then evaluated against lung function indices and clinical variables. RESULTS: After excluding five patients with brain metastases, 97 patients were included in the final analysis (mean age, 67.7 ± 10.3 years). Mean FVC and mean FEV1 were 80.0% ± 15.4% and 77.6% ± 17.8%, respectively. Both FVC and FEV1 were positively correlated with SUVRs in all brain regions after adjusting the data for clinical variables. The degree of decrease in SUVRs related to lung function was not significantly different between cognition-related regions and other regions. CONCLUSION: Impaired lung function was associated with decreased glucose metabolism in all regions of the brain, indicating that cognitive decline related to decreased glucose metabolism may be due to reduced perfusion.

Low diffusion capacity predicts poor prognosis in extensive stage small cell lung cancer: a single-center analysis of 10 years.

BACKGROUND: Poor pulmonary function and chronic obstructive pulmonary disease (COPD) are associated with poorer overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. Few studies have investigated the association between pulmonary function and OS in small-cell lung cancer (SCLC) patients. We compared the clinical characteristics of extensive disease SCLC (ED-SCLC) with or without moderately impaired diffusion capacity for carbon monoxide (DLco) and investigated the factors associated with survival in ED-SCLC patients. METHODS: This retrospective single-center study was performed between January 2011 and December 2020. Of the 307 SCLC patients who received cancer therapy during the study, 142 with ED-SCLC were analyzed. The patients were divided into DLco < 60% group and DLco ≥ 60% groups. OS and predictors of poor OS were analyzed. RESULTS: The median OS of the 142 ED-SCLC patients was 9.3 months and the median age was 68 years. In total, 129 (90.8%) patients had a history of smoking, and 60 (42.3%) had COPD. Thirty-five (24.6%) patients were assigned to the DLco < 60% group. Multivariate analysis revealed that DLco < 60% (odds ratio [OR], 1.609; 95% confidence interval [CI], 1.062-2.437; P = 0.025), number of metastases (OR, 1.488; 95% CI, 1.262-1.756; P < 0.001), and < 4 cycles of first-line chemotherapy (OR, 3.793; 95% CI, 2.530-5.686; P < 0.001) were associated with poor OS. Forty (28.2%) patients received < 4 cycles of first-line chemotherapy; the most common reason for this was death (n = 22, 55%) from grade 4 febrile neutropenia (n = 15), infection (n = 5), or massive hemoptysis (n = 2). The DLco < 60% group had a shorter median OS than the DLco ≥ 60% group (10.6 ± 0.8 vs. 4.9 ± 0.9 months, P = 0.003). CONCLUSIONS: In this study, approximately one quarter of the ED-SCLC patients had DLco < 60%. Low DLco (but not forced expiratory volume in 1 s or forced vital capacity), a large number of metastases, and < 4 cycles of first-line chemotherapy were independent risk factors for poor survival outcomes in patients with ED-SCLC.

Endobronchial ultrasound-guided re-biopsy of non-small cell lung cancer with acquired resistance after EGFR tyrosine kinase inhibitor treatment.

BACKGROUND: Few studies assessed the use of endobronchial ultrasound (EBUS)-guided re-biopsy for detecting the T790M mutation after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure. METHODS: A total of 2996 EBUS procedures were performed during the study period (January 2019-June 2022). In total, 44 consecutive patients who underwent EBUS-guided re-biopsy (56 procedures) for detecting the T790M mutation were analyzed. The success rates and T790M mutation frequencies were analyzed according to the re-biopsy site and EBUS method. Multivariate logistic regression analyses were used to identify factors affecting the likelihood of the T790M mutation. RESULTS: The success rates for the mutation analyses using EBUS with a guide-sheath (EBUS-GS), EBUS guided transbronchial needle aspiration (EBUS-TBNA), and EBUS-GS with EBUS-TBNA for re-biopsy were 80.6% (29/36), 93.3% (14/15), and 100% (5/5), respectively. Patients who underwent lymph node biopsy using EBUS-TBNA had an increased rates of the T790M mutation compared with those undergoing lung biopsy using EBUS-GS (EBUS-TBNA, 60.0%; EBUS-GS with EBUS-TBNA, 40.0%; EBUS-GS, 11.1%; p < 0.001). In multivariate analysis, the use of a first-generation EGFR-TKI (odds ratio [OR], 4.29; 95% confidence interval [CI], 1.05-17.58; p = 0.043) was associated with occurrence of the T790M mutation. Re-biopsy of the metastatic site tended to be associated with a higher T790M mutation rate. Mild hemoptysis occurred in 3.6% (2/56) of the patients. CONCLUSIONS: EBUS-guided re-biopsy can be used for detecting the T790M mutation in patients who failed EGFR-TKI therapy. The T790M mutation frequency differed according to the re-biopsy site. The use of a first-generation EGFR-TKI was an independent predictor of the T790M mutation.

Cleavage-Responsive Biofactory T Cells Suppress Infectious Diseases-Associated Hypercytokinemia.

Severe infectious diseases, such as coronavirus disease 2019 (COVID-19), can induce hypercytokinemia and multiple organ failure. In spite of the growing demand for peptide therapeutics against infectious diseases, current small molecule-based strategies still require frequent administration due to limited half-life and enzymatic digestion in blood. To overcome this challenge, a strategy to continuously express multi-level therapeutic peptide drugs on the surface of immune cells, is established. Here, chimeric T cells stably expressing therapeutic peptides are presented for treatment of severe infectious diseases. Using lentiviral system, T cells are engineered to express multi-level therapeutic peptides with matrix metallopeptidases- (MMP-) and tumor necrosis factor alpha converting enzyme- (TACE-) responsive cleavage sites on the surface. The enzymatic cleavage releases γ-carboxyglutamic acid of protein C (PC-Gla) domain and thrombin receptor agonist peptide (TRAP), which activate endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1), respectively. These chimeric T cells prevent vascular damage in tissue-engineered blood vessel and suppress hypercytokinemia and lung tissue damages in vivo, demonstrating promise for use of engineered T cells against sepsis and other infectious-related diseases.

Utility of Radial Probe Endobronchial Ultrasound Guided Transbronchial Lung Biopsy in Bronchus Sign Negative Peripheral Pulmonary Lesions.

BACKGROUND: The presence of the bronchus sign on chest computed tomography is associated with an increased diagnostic yield of radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB). However, the utility of RP-EBUS-TBLB for bronchus sign negative peripheral pulmonary lesions (PPLs) remains unknown. We investigated the utility of RP-EBUS-TBLB in bronchus sign negative PPLs. METHODS: We retrospectively reviewed data from 109 patients who underwent RP-EBUS for bronchus sign negative PPLs from January 2019 to August 2020. TBLB was performed using RP-EBUS with a guide sheath and without fluoroscopy. The EBUS visualization and TBLB diagnostic yields were assessed. Multivariable logistic regression analyses were used to identify factors affecting the EBUS visualization and diagnostic yields. RESULTS: The EBUS visualization yield was 74.1% (68/109). Of the 109 lung lesions, 92 were definitively diagnosed. The overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 50.5% (55/109), 34.9% (29/83), 100% (26/26), 100% (29/29), and 32.5% (26/80), respectively. In multivariable analyses, the size of the lesion (≥ 20 mm; odds ratio [OR], 2.62; 95% confidence interval [CI], 1.16-5.93; P = 0.021) and the distance from the pleura (> 10 mm; OR, 2.37; 95% CI, 1.02-5.52; P = 0.045) were associated with EBUS visualization. Regarding diagnostic yield, having the probe within the lesion (OR, 28.50; 95% CI, 6.26-129.85; P < 0.001) and a solid lesion (OR, 14.58; 95% CI, 2.64-80.38; P = 0.002) were associated with diagnostic success. Pneumothorax and hemoptysis occurred in 3.7% (4/109) and 0.9% (1/109), respectively, of the patients. CONCLUSION: RP-EBUS-TBLB using a GS can be considered a diagnostic method in bronchus sign negative solid PPLs. Having the probe within the lesion and a solid lesion were important for diagnostic success. Complication rates were acceptable.

Radial Probe Endobronchial Ultrasound Using Guide Sheath-Guided Transbronchial Lung Biopsy in Peripheral Pulmonary Lesions without Fluoroscopy.

BACKGROUND: Radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) has improved the diagnostic yield of bronchoscopic biopsy of peripheral pulmonary lesions (PPLs). The diagnostic yield and complications of RP-EBUS-TBLB for PPLs vary depending on the technique, such as using a guide sheath (GS) or fluoroscopy. In this study, we investigated the utility of RP-EBUS-TBLB using a GS without fluoroscopy for diagnosing PPLs. METHODS: We retrospectively reviewed data from 607 patients who underwent RP-EBUS of PPLs from January 2019 to July 2020. TBLB was performed using RP-EBUS with a GS without fluoroscopy. The diagnostic yield and complications were assessed. Multivariable logistic regression analyses were used to identify factors affecting the diagnostic yields. RESULTS: The overall diagnostic accuracy was 76.1% (462/607). In multivariable analyses, the size of the lesion (≥20 mm; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.27-3.33; p=0.003), positive bronchus sign in chest computed tomography (OR, 2.30; 95% CI, 1.40-3.78; p=0.001), a solid lesion (OR, 2.40; 95% CI, 1.31-4.41; p=0.005), and an EBUS image with the probe within the lesion (OR, 6.98; 95% CI, 4.38-11.12; p<0.001) were associated with diagnostic success. Pneumothorax occurred in 2.0% (12/607) of cases and chest tube insertion was required in 0.5% (3/607) of patients. CONCLUSION: RP-EBUS-TBLB using a GS without fluoroscopy is a highly accurate diagnostic method in diagnosing PPLs that does not involve radiation exposure and has acceptable complication rates.

Incidence and Prognostic Factors of Respiratory Viral Infections in Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: Severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) that require hospitalization and emergency department visits are associated with considerable morbidity and mortality. Respiratory viral infection is an important cause of severe AECOPD. We evaluated the incidence and prognostic factors of viral infection in severe AECOPD. Patients and Methods: We performed a retrospective study of 262 cases of severe AECOPD in 192 patients who required hospitalization and emergency department visits at a tertiary teaching hospital in Daegu, Korea. A multiplex polymerase chain reaction panel using a nasopharyngeal swab sample was performed to detect viral infection. Results: Viral infection was detected in 108 events (41.2%) from 96 patients. The most common virus was rhinovirus/enterovirus (27.5%), followed by influenza virus (22.5%), respiratory syncytial virus (13.3%), parainfluenza virus (12.5%), coronavirus (12.5%), metapneumovirus (7.5%), and adenovirus (4.2%). Virus-positive exacerbations, compared to virus-negative exacerbations, had a higher frequency of symptoms of rhinopharyngitis, higher neutrophil count and C-reactive protein (CRP) level, and lower eosinophil count. Multivariate analysis demonstrated that elevated CRP levels (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.24-6.15), symptoms of rhinopharyngitis (OR, 1.98; 95% CI, 1.03-3.78), low eosinophil count (OR, 1.74; 95% CI, 1.03-2.92), and inhaled corticosteroid (ICS) use (OR, 1.70; 95% CI 1.04-2.80) were associated with viral infection in severe AECOPD. Conclusion: The incidence of viral infection in severe AECOPD was 41.2%, and the most commonly detected virus was rhinovirus/enterovirus. Increased CRP level, symptoms of rhinopharyngitis, low eosinophil count, and use of ICS were associated with viral infection in severe AECOPD.

Radial probe endobronchial ultrasound-guided transbronchial lung biopsy for the diagnosis of cavitary peripheral pulmonary lesions.

BACKGROUND: Cavitary peripheral pulmonary lesions (PPLs) are often diagnosed via transthoracic needle biopsy. However, today, radial probe endobronchial ultrasound (RP-EBUS) is widely used to diagnose PPLs. The efficacy and safety of RP-EBUS-guided transbronchial lung biopsy (RP-EBUS-TBLB) used to diagnose cavitary PPLs remain poorly known. We investigated the utility of RP-EBUS-TBLB using a guide sheath (GS) without fluoroscopy to diagnose PPLs. METHODS: Of 743 RP-EBUS procedures conducted to diagnose PPLs performed at our institution from January 2019 to October 2020, we analyzed 77 cavitary PPLs. TBLB was performed using RP-EBUS with a GS without fluoroscopy. The diagnostic accuracy and complications were assessed. All lung lesions with a definitive diagnosis were included in analyses. RESULTS: The overall diagnostic accuracy was 85.7% (66/77). Of malignant lesions (n = 34), 29 (85.3%) were diagnosed successfully. Of benign lesions (n = 43), 37 (86.0%) were diagnosed successfully. In multivariate analyses, a thicker cavity wall (≥10 mm, odds ratio [OR] 14.22, 95% confidence interval [CI] 2.58-78.35, p = 0.002) and EBUS imaging with the probe within the lesion (OR 12.02, 95% CI 1.91-75.53, p = 0.008) independently affected diagnostic success. The likelihood of success increased with increasing thickness of the cavity wall (p < 0.001, test for trend). The specimens obtained for molecular confirmation of malignancy were satisfactory. There were four cases of infection (5.2%) and three cases of pneumothorax (3.9%). CONCLUSIONS: RP-EBUS-TBLB of cavitary PPLs affords high diagnostic accuracy with acceptable complication rates.

Delayed sarcoidosis onset mimicking mediastinal lymphoma recurrence after complete remission of diffuse large B cell lymphoma: A case report.

Sarcoidosis-lymphoma syndrome describes a pathological state wherein both sarcoidosis and lymphoma are present. Sarcoidosis and lymphoma may occur concurrently, or sarcoidosis may precede lymphoma. There are few reports which have previously described the temporal progression from lymphoma to sarcoidosis. Here, we present a patient with stage II diffuse large B-cell lymphoma in the right breast. The patient achieved complete remission after chemotherapy. Five years after remission, the patient visited our clinic with newly developed enlarged mediastinal lymph nodes; lymphoma recurrence was suspected. However, mediastinal lymph node biopsy showed numerous noncaseating granulomas with no evidence of malignancy in the mediastinal lymph nodes. Consequently, a diagnosis of sarcoidosis was made. This case report highlights the need for pathological confirmation following biopsy when recurrence of lymphoma is suspected.

Delayed onset of mediastinitis with tracheomediastinal fistula following endobronchial ultrasound-guided transbronchial needle aspiration; A case report.

Infectious complications after endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are rare but serious. Here, we report a very rare case of delayed onset of mediastinitis with tracheomediastinal fistula after EBUS-TBNA. Surgical debridement was performed, antibiotics were administered, and the postoperative course of the patient was good. Careful monitoring is needed to prevent the possible development of infectious complications after EBUS-TBNA.

A rare case of primary solitary endobronchial plasmacytoma.

Extramedullary plasmacytoma (EMP) is a rare plasma cell tumor involving the organs but without bone marrow involvement or the characteristics of multiple myeloma. Primary solitary endobronchial plasmacytoma is extremely rare. Here we present the case of an 86-year-old male ex-smoker who visited our outpatient clinic for an endobronchial mass in the left upper lobe of the lung. Fiberoptic bronchoscopy revealed a protruding mass in the left upper lobar bronchus; based on the bronchoscopic biopsy findings, a primary solitary endobronchial plasmacytoma was diagnosed. After radiation therapy the patient was well and 6 months after treatment showed no evidence of disease recurrence. Extramedullary plasmacytoma should be considered in the differential diagnosis of an endobronchial mass.

Metastatic large cell carcinoma of the lung: A rare cause of acute small bowel obstruction.

Here, we report a case of acute intestinal obstruction as the initial presentation of primary lung cancer in a male patient. Abdominal computed tomography (CT) showed multiple polypoid masses and regional lymphadenopathy with small bowel obstruction. The patient underwent emergency surgery for multiple luminal malignancy with mesenteric masses. According to the various clinicopathological features, the tumor was confirmed to be metastatic large cell carcinoma originating from the lung. Large masses in the left lower lobe of the lung were identified on the chest CT after emergency surgery, and non-small cell lung cancer (NSCLC), not otherwise specified (NOS), was finally diagnosed on biopsy through bronchoscopy.

COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm.

Sterol regulatory element binding protein-2 (SREBP-2) is activated by cytokines or pathogen, such as virus or bacteria, but its association with diminished cholesterol levels in COVID-19 patients is unknown. Here, we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19. Intriguingly, we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients' blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity. We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression, while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients. Using an infectious disease mouse model, inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages. These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.

Successful osimertinib retreatment after extremely early onset severe pneumonitis in first-line treatment of lung adenocarcinoma.

Drug-induced pneumonitis is rare, and can result in death. Here, we present a report of a patient with adenocarcinoma harboring EGFR exon 19 deletion mutation treated with osimertinib as first-line treatment. After six days of treatment, extremely early onset severe pneumonitis was diagnosed. Discontinuation of osimertinib as well as administration of corticosteroid, and retreatment with osimertinib were successful. This case report highlights that extremely early onset severe pneumonitis can occur after osimertinib administration, and retreatment of osimertinib may be a useful treatment option after resolution of pneumonitis.

Reasons and Risk Factors for Readmission Following Hospitalization for Community-acquired Pneumonia in South Korea.

BACKGROUND: Limited studies have been performed to assess readmission following hospitalization for community-acquired pneumonia (CAP) in an Asian population. We evaluated the rates, reasons, and risk factors for 30-day readmission following hospitalization for CAP in the general adult population of Korea. METHODS: We performed a retrospective observational study of 1,021 patients with CAP hospitalized at Yeungnam University from March 2012 to February 2014. The primary end point was all-cause hospital readmission within 30 days following discharge after the initial hospitalization. Hospital readmission was classified as pneumonia-related or pneumonia-unrelated readmission. RESULTS: During the study period, 862 patients who survived to hospital discharge were eligible for inclusion and among them 72 (8.4%) were rehospitalized within 30 days. In the multivariable analysis, pneumonia-related readmission was associated with para/hemiplegia, malignancy, pneumonia severity index class ≥4 and clinical instability ≥1 at hospital discharge. Comorbidities such as chronic lung disease and chronic kidney disease, treatment failure, and decompensation of comorbidities were associated with the pneumonia-unrelated 30-day readmission rate. CONCLUSION: Rehospitalizations within 30 days following discharge were frequent among patients with CAP. The risk factors for pneumonia-related and -unrelated readmission were different. Aspiration prevention, discharge at the optimal time, and close monitoring of comorbidities may reduce the frequency of readmission among patients with CAP.

Pleural small cell carcinoma with massive pleural effusion: A case report.

RATIONALE: Small cell carcinoma (SCC) occurs mostly in the lung, and small cell lung cancer accounts for 13% of newly diagnosed lung cancers. Only 2.5% of SCC occurs in extrapulmonary sites, and SCC of pleural origin is especially very uncommon. PATIENT CONCERNS: An 85-year-old man presenting with progressive dyspnea for more than 7 days. DIAGNOSES: Computed tomography scan of the chest showed massive pleural effusion and diffuse nodular thickening of the pleura on the right chest. Sonography-guided needle biopsy of the pleural mass was performed and histologic and immunohistochemical findings revealed SCC. Since no parenchymal lung lesion was observed, the patient was finally diagnosed with SCC of the pleura (SCCP). INTERVENTIONS: Due to the patient's old age and poor performance status, chemotherapy was not performed and only drainage of pleural effusion was conducted for symptom relief. OUTCOMES: Dyspnea improved after pleural effusion drainage. The patient was discharged and transferred to a local medical center for hospice care. LESSONS: Although primary SCCP is extremely rare, SCCP should also be considered as well as mesothelioma in case of presence of a pleural-based mass with massive pleural effusion.