Major adverse cardiovascular events and hyperuricemia during tuberculosis treatment.

BACKGROUND: Hyperuricemia is common during tuberculosis (TB) treatment, especially in association with pyrazinamide (PZA). This study investigated the relationship between major adverse cardiovascular events (MACEs) and hyperuricemia during TB treatment. METHODS: We conducted a single-center retrospective cohort study. From January 2010 through June 2017, we assessed all consecutive TB patients at Chonnam National University Hospital in South Korea. Hyperuricemia was defined as serum uric acid levels exceeding 7.0 mg/dL (men) and 6.0 mg/dL (women). RESULTS: Of the 1,143 patients included, PZA was administered to 1,081 (94.6%), and hyperuricemia was detected in 941 (82.3%). Eight patients experienced MACEs. Multivariate analysis using logistic regression indicated that prior ischemic heart disease was associated with MACE development (OR,14.087; 95% CI,3.304-60.061; P < 0.000), while hyperuricemia was not (OR, 1.505; 95% CI, 0.184-12.299; P = 0.703). For patients without drug-resistant TB, the absence of hyperuricemia was associated with higher mortality (OR, 2.609; 95% CI, 1.066-6.389; P = 0.036), whereas hyperuricemia was associated with less worse outcomes (OR,0.316; 95% CI,0.173-0.576; P < 0.000). CONCLUSIONS: Although most patients treated with PZA developed hyperuricemia, it was not associated with MACE development. Hyperuricemia during TB treatment was associated with better outcomes, possibly due to consistent adherence to TB treatment.

Serum KL-6 levels predict the occurrence and severity of treatment-related interstitial lung disease in lung cancer.

In this study, we aimed to investigate the feasibility of serum Krebs von den Lungen-6 (KL-6) as a potential biomarker for treatment-related ILD (TR-ILD) in lung cancer. We recruited patients with lung cancer in whom KL-6 was measured to differentiate between pneumonia and ILD (category 1), diagnose and assess the severity of suspicious ILD (category 2), or evaluate baseline levels before cancer treatment (category 3). Among 1,297 patients who underwent KL-6 testing, 422 had lung cancer, and TR-ILD was detected in 195 patients. In categories 1-2, median KL-6 level was higher in drug-induced ILD or acute exacerbation of underlying ILD than in no ILD or radiation-induced pneumonitis, and it was correlated with the severity of TR-ILD. High KL-6 level (cut-off: > 436U/mL) was an independent risk factor for severe TR-ILD, and low KL-6 level with high procalcitonin level (> 0.5 ng/mL) could exclude severe TR-ILD. Patients with severe TR-ILD had worse overall survival than those without, whereas high baseline KL-6 level was associated with worse survival, especially in patients without severe TR-ILD. Therefore, serum KL-6 may be a surrogate marker for predicting the occurrence and assessing the severity of TR-ILD at the time of suspected ILD and before lung cancer treatment.

Nontuberculous mycobacterial pulmonary disease in a patient with unilateral pulmonary artery agenesis: Case report.

Nontuberculous mycobacteria (NTM) are ubiquitous organisms, but can cause a chronic pulmonary infection in some patients. Therefore, there could be host factors susceptible to this disease. A structural lung disease including damages of lungs caused by previous respiratory infection has been suggested as a host factor. Here we presented a case of NTM pulmonary disease which developed in a structural lung disease caused by a rare congenital lung disease. A 46-year-old male, was transferred to our hospital with an unexpandable lung after a closed thoracostomy due to spontaneous pneumothorax. His chest computed tomography showed an absence of left pulmonary artery at the time of admission. Mycobacterial culture in sputum, bronchial washing fluid, and pleural fluid showed the growth of NTM. Mycobacterium intracellulare was isolated from all positive cultures in the specimens. Combinations of drugs for M. intracellulare pulmonary disease including azithromycin, rifampin, and ethambutol were administered for 16 months. Amikacin intra venous treatment used for 6 months after treatment initiation. Culture conversion was achieved at 4 months of treatment. There was no evidence of recurrence of NTM pulmonary disease for 6 months after treatment. In conclusion, patients who have structural lung disease need to be careful monitoring about development of NTM pulmonary disease.

Risk factors and clinical outcomes associated with acquired hypofibrinogenemia in patients administered hemocoagulase batroxobin for hemoptysis.

Background: Hemocoagulase batroxobin is used to prevent hemostasis or bleeding in surgical and trauma patients; however, the role of batroxobin in patients with hemoptysis is not well understood. We evaluated the risk factors and prognosis of acquired hypofibrinogenemia in hemoptysis patients treated systemically with batroxobin. Methods: We retrospectively reviewed the medical charts of hospitalized patients who were administered batroxobin for hemoptysis. Acquired hypofibrinogenemia was defined as a plasma fibrinogen level >150 mg/dL at baseline, decreasing to <150 mg/dL after batroxobin administration. Results: Overall, 183 patients were enrolled, of whom 75 had acquired hypofibrinogenemia after the administration of batroxobin. There was no statistical difference in the median age of the patients in the non-hypofibrinogenemia and hypofibrinogenemia groups (72.0 vs. 74.0 years, respectively). The patients in the hypofibrinogenemia group showed a higher rate of intensive care unit (ICU) admission (11.1% vs. 22.7%; P=0.041) and tended to have more massive hemoptysis than those in the non-hyperfibrinogenemia group (23.1% vs. 36.0%; P=0.068). The patients in the hypofibrinogenemia group further showed a higher requirement for transfusion (10.2% vs. 38.7%; P<0.000) than those in the non-hyperfibrinogenemia group. Low levels of baseline plasma fibrinogen and a prolonged and higher total dose of batroxobin were associated with the development of acquired hypofibrinogenemia. Acquired hypofibrinogenemia was associated with increased 30-day mortality [hazard ratio (HR), 4.164; 95% confidence interval (CI), 1.318-13.157]. Conclusions: The plasma fibrinogen levels in patients who were administered batroxobin for hemoptysis should be monitored, and batroxobin should be discontinued if hypofibrinogenemia occurs.

Usefulness of Mycobacterium tuberculosis-polymerase chain reaction with bronchial washing samples in predicting discontinuation of airborne infection isolation in patients hospitalized with suspected pulmonary tuberculosis.

OBJECTIVE: In-hospital tuberculosis (TB) transmission remains a concern. Airborne infection isolation (AII) can be discontinued in hospitalized patients with suspected active pulmonary TB when the results of three consecutive sputum acid-fast bacilli (AFB) smears are negative. However, fiberoptic bronchoscopy can be performed in patients who may have difficulty in producing sputum samples. This study aimed to investigate the usefulness of Mycobacterium tuberculosis-polymerase chain reaction (MTB-PCR) with bronchial washing specimens in predicting AII discontinuation in hospitalized patients with suspected active pulmonary TB. METHODS: We reviewed the medical charts of patients admitted to a tertiary hospital who were isolated and underwent fiberoptic bronchoscopy for suspicious pulmonary TB from January 2016 to December 2019. Patients with positive MTB-PCR results in the initial sputum examination were excluded. Criteria for discontinuing AII were defined as negative results for three consecutive AFB smears from respiratory specimens, or cases diagnosed other than TB. The study patients were divided into two groups: TB group and non-TB group. RESULTS: In total, 166 patients were enrolled in the study. Of them, 35 patients were diagnosed with TB. There was no significant difference between the number of males in the TB (81; 61.8%) and non-TB (21; 60.0%) group. Though 139 patients had negative results on MTB-PCR using washing specimens, eight showed positive AFB culture. Of the 139 patients with negative MTB-PCR results, 138 had negative results for three consecutive AFB smears or were established to not have pulmonary TB. Therefore, the predictive accuracy of MTB-PCR with bronchial washing samples for discontinuing AII was 99.2%. CONCLUSION: Although a negative result from MTB-PCR with bronchial washing samples cannot exclude pulmonary TB, it can predict AII discontinuation in hospitalized patients with suspected active pulmonary TB.

Risk factors for cerebral complications in patients with pulmonary arteriovenous malformations: A multicenter retrospective cohort study.

OBJECTIVE: Pulmonary arteriovenous malformation (PAVM) is a rare pulmonary disease. Although most patients with PAVMs are asymptomatic, cerebral complications associated with PAVMs are often fatal. This study aimed to evaluate the risk factors for cerebral complications in patients with PAVMs. METHODS: We retrospectively reviewed the medical charts of patients with PAVMs between 2003 and 2021 at two tertiary referral hospitals and one secondary hospital. RESULTS: Fifty-five patients diagnosed with PAVMs were enrolled in this study. Most patients were female (89.1%), and the median age was 53 years. Thirty patients (54.5%) had incidentally detected PAVMs without symptoms. Twenty-four patients (43.7%) with PAVMs were treated with embolotherapy or surgery. Thirteen patients (23.6%) had cerebral complications. There was no significant difference in the development of cerebral complications according to treatment; however, older age (≥ 65 years) was associated with the development of new cerebral complications in untreated patients with PAVMs (odds ratio, 17.09; 95% confidence interval, 1.16-250.31; P = 0.038). CONCLUSION: Older age (≥ 65 years) was a risk factor for the development of cerebral complications in patients with PAVMs; therefore, treatment should be considered in older patients with PAVMs.

Three cases of rigid bronchoscopic removal of carinal masses: Case report.

Tracheal tumors are rare diseases. They can cause narrowing of a central airway, a severe respiratory distress, and death. The objective of this case series is to highlight the role of rigid bronchoscopy in diagnosing and treating carina masses which are difficult to remove surgically. Tumor excision was performed by the rigid bronchoscopic intervention. Additional treatment was administered according to the diagnosis of each individual patient. After the procedure, patients' symptoms were improved and stenotic central airways were reopened. Rigid bronchoscopy can be a good therapeutic option to reestablish airway patency and a bridge treatment for further definitive treatment.

Altered distribution, activation and increased IL-17 production of mucosal-associated invariant T cells in patients with acute respiratory distress syndrome.

OBJECTIVE: Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that are engaged in a number of diseases, but their roles in acute respiratory distress syndrome (ARDS) are not fully examined yet. This study aimed to examine levels and functions of MAIT cells in patients with ARDS. METHODS: Peripheral blood samples from patients with ARDS (n=50) and healthy controls (HCs, n=50) were collected. Levels of MAIT cells, cytokines, CD69, programmed cell death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) were measured by flow cytometry. RESULTS: Circulating MAIT cell levels were significantly reduced in patients with ARDS than in HCs. MAIT cell levels were inversely correlated with disease severity and mortality. Cytokine production profiles in MAIT cells showed that percentages of interleukin (IL)-17 producing MAIT cell were significantly higher in patients with ARDS than in HCs. Patients with ARDS exhibited higher expression levels of CD69, PD-1 and LAG-3 in circulating MAIT cells. Moreover, levels of MAIT cells and expression levels of CD69, PD-1 and IL-17 in MAIT cells were higher in bronchoalveolar lavage fluid samples than in peripheral blood samples. Our in vitro experiments showed that MAIT cells triggered macrophages to produce proinflammatory cytokines such as tumour necrosis factor-α, IL-1ß and IL-8. CONCLUSIONS: This study demonstrates that circulating MAIT cells are numerically deficient in patients with ARDS. In addition, MAIT cells were found to be activated, migrate into lung, secrete IL-17 and then stimulate macrophages. These findings suggest that MAIT cells contribute to the worsening of inflammation in the lung of patients with ARDS.

Life-threatening Mycobacterium intracellulare pleuritis in an immunocompetent host: Case reports.

RATIONALE: Nontuberculous mycobacteria (NTM)-associated pleuritis is a very rare disease. Here, we describe 2 cases of life-threatening Mycobacterium intracellulare-associated pleuritis in immunocompetent hosts. PATIENT CONCERNS: A 78-year-old man with sudden onset-onset dyspnea (case 1) and an 80-year-old man with cough, sputum and fever (case 2) presented to our emergency room. DIAGNOSES: Both the patients were diagnosed with Mycobacterium intracellulare-associated pleuritis. INTERVENTION: In case 1, the patient underwent intubation with mechanical ventilation due to hypoxemic respiratory failure. Daily azithromycin, rifampin and ethambutol, and intravenous amikacin 3 times a week was administered. In case 2, the patient received daily azithromycin, rifampin and ethambutol, and intravenous amikacin 3 times a week. OUTCOMES: In case 1, after receiving NTM treatment for 14 months, NTM-associated pleuritis was cured, with radiologic improvement. In case 2, however, bronchopleural fistula was developed. Despite tube drainage, air leak continued. The patient refused surgical management and eventually died of respiratory failure. LESSONS: Pleural effusion arising from NTM lung disease located in the subpleural area should be considered a possible cause of NTM-associated pleuritis. Drainage and a multidrug regimen are required to treat NTM, and surgical treatment should be considered when complications occur.

Efficacy and dose of afatinib in patients with non-small cell lung cancer after failure of prior gefitinib or erlotinib treatment.

BACKGROUND: We report a subgroup analysis of afatinib with respect to its efficacy, safety, and the long-term survival of patients in a Named Patient Use program at a single institution. METHODS: We analyzed 60 patients with stage IV non-small cell lung cancer (NSCLC) who had been treated with ≥1 line of platinum-based chemotherapy and had activating epidermal growth factor receptor (EGFR) mutations or disease control for ≥6 months with prior EGFR inhibitors. Afatinib was started on a daily dose of 50 mg, which was decreased according to the adverse events and tolerability. RESULTS: A total of 13 patients achieved partial remission, whereas 33, 12, and two showed stable disease, had progression, and were not evaluable, respectively, resulting in an objective response rate and disease control rate of 21.7% and 76.7%, respectively. The median progression-free survival (PFS) was 5.4 (95% confidence interval [CI]: 4.0-7.7) months and median overall survival (OS) was 10.1 (8.5-13.6) months. Toxicities leading to drug discontinuation were experienced by four patients (6.7%). Grade 3 diarrhea occurred in 10 patients (16.7%), and afatinib dose reductions were required in 35 patients. The PFS and OS were significantly longer for patients whose dose was reduced to 40 or 30 mg than for those without dose reduction (7.0 vs 3.1 months and 13.5 vs 8.1 months, respectively, p < 0.05). CONCLUSIONS: The efficacy of afatinib was similar to that identified in the global data without unexpected adverse events. Survival analyses support the currently approved dose of afatinib as first-line treatment for NSCLC.

Paradoxical pulmonary hemorrhage associated with hemocoagulase batroxobin in a patient with hemoptysis: A CARE-compliant case report.

RATIONAL: Hemocoagulase, a hemostatic, is used in patients with trauma, gastrointestinal bleeding, or pulmonary hemorrhage or those undergoing surgery. However, paradoxical bleeding after hemocoagulase administration is not considered a clinically significant adverse effect. Here, we report a case of paradoxical pulmonary hemorrhage associated with hypofibrinogenemia after administration of the hemocoagulase batroxobin in a patient with hemoptysis. PATIENT CONCERNS: An 86-year-old woman complained of hemoptysis during hospitalization with organophosphate poisoning. Hemocoagulase was administered to manage bleeding; however, bleeding signs, such as hemoptysis, massive epistaxis, and ecchymosis, recurred. DIAGNOSES: The patient was diagnosed with acquired hypofibrinogenemia on the basis of the reduced plasma fibrinogen level after hemocoagulase administration and lack of other causes of bleeding. INTERVENTION: Hemocoagulase administration was discontinued, and fibrinogen-containing plasma products were administered. OUTCOMES: The plasma fibrinogen level normalized and bleeding signs did not recur. LESSONS: It is necessary to measure plasma fibrinogen levels regularly in patients undergoing hemocoagulase administration and discontinue its administration when acquired hypofibrinogenemia is detected.

Clinical characteristics and prognosis of patients with Pneumocystis jirovecii pneumonia without a compromised illness.

OBJECTIVE: Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP. METHODS: We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC). RESULTS: The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016). CONCLUSIONS: Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.

Efficacy of an inpatient smoking cessation program at a single regional cancer center: A prospective observational study.

ABSTRACT: Smoking is the leading cause of preventable death and a risk factor for cancer, but smoking cessation is difficult even in patients who need hospitalization. This study aimed to investigate the usefulness of an inpatient smoking cessation consultation program and to analyze the clinical factors associated with abstinence. In this observational study, patients received regular counseling for 6 months, and abstinence was objectively assessed via urine and exhaled carbon monoxide testing. Cessation rates were assessed at 4 weeks and 6 months, and clinical characteristics associated with cessation success were investigated. Of the 571 patients referred to participate in the program, 170 (29.8%) were enrolled, and only 2 (1.2%) used smoking cessation drugs in addition to counseling. The smoking cessation rate was 77.6% after 4 weeks and 59.1% after 6 months. The cessation rates were significantly higher in patients with cancer than in those without cancer at both timepoints (63.8% vs 21.9%, P < .001, 53.6% vs 12.5%, P < .001), and they were also higher in the first admission group than in the re-admission group (87.4% vs 74.7%, P = .033, 88.5% vs 76.1%, P = .037). In patients with lung cancer, progression-free survival and overall survival tended to be better in those enrolled in the program (P = .158, P = .183). In conclusion, the inpatient smoking cessation program was associated with a high abstinence rate. Most patients maintained cessation without medication, suggesting that initial admission, along with a cancer diagnosis, can provide enough motivation to abstain from smoking. In addition, the smoking cessation effort showed potential to improve survival during lung cancer treatment.

Glutathione Peroxidase 3 as a Biomarker of Recurrence after Lung Cancer Surgery.

We aimed to examine the usefulness of serum glutathione peroxidase 3 (GPx3) as a biomarker of lung cancer recurrence after complete resection. We prospectively collected serial serum samples at the baseline, as well as 3, 6 and 12 months after surgery from complete resection cases in 2013. GPx3 levels were measured by enzyme-linked immunosorbent assay. Statistical tests including t-tests and Cox proportional hazard regression analyses were performed. Totally, 135 patients were enrolled, and 39 (28.9%) showed relapse during the median follow-up period (63.60 months; range, 0.167-81.867). The mean GPx3 change was significantly higher in the recurrence group at 6 months (0.32 ± 0.38 vs. 0.15 ± 0.29, p = 0.016) and 12 months (0.40 ± 0.37 vs. 0.13 ± 0.28, p = 0.001). The high GPx3 change group showed significantly higher 60-months recurrence rates than the low group (48.1% vs. 25.2% at 3 months, p = 0.005; 54.5% vs. 28.9% at 6 months, p = 0.018; 38.3% vs. 18.3% at 12 months, p = 0.035). High GPx3 change at 3 months were independent risk factors of recurrence (hazard ratio (HR) 3.318, 95% confidence interval (CI), 1.582-6.960, p = 0.002) and survival (HR 3.150, 95% CI, 1.301-7.628, p = 0.011). Therefore, serum GPx3 changes after surgery may be useful predictive biomarkers for recurrence in lung cancer. Larger-scale validation studies are warranted to confirm these findings.

Artificial intelligence and lung cancer treatment decision: agreement with recommendation of multidisciplinary tumor board.

BACKGROUND: IBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient's medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients. METHODS: We evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated 'recommended' by WFO. Concordance between MDT and WFO was analyzed by Cohen's kappa value. RESULTS: In total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P<0.001) of all cases, and concordance differed according to clinical stages. The strength of agreement was very good in stage IV non-small cell lung carcinoma (NSCLC) (100%, k=1.000) and extensive disease small cell lung carcinoma (SCLC) (100%, k=1.000). In stage I NSCLC, the agreement strength was good (92.4%, k=0.855). The concordance was moderate in stage III NSCLC (80.8%, k=0.622) and relatively low in stage II NSCLC (83.3%, k=0.556) and limited disease SCLC (84.6%, k=0.435). There were discordant cases in surgery (7/57, 12.3%), radiotherapy (2/12, 16.7%), and chemoradiotherapy (15/129, 11.6%), but no discordance in metastatic disease patients. CONCLUSIONS: Treatment recommendations made by WFO and MDT were highly concordant for lung cancer cases especially in metastatic stage. However, WFO was just an assisting tool in stage I-III NSCLC and limited disease SCLC; so, patient-doctor relationship and shared decision making may be more important in this stage.

Delayed diagnosis of lung cancer due to misdiagnosis as worsening of sarcoidosis: a case report.

BACKGROUND: The concurrence of sarcoidosis and primary lung cancer is very rare. We report a very rare case with a delayed diagnosis of primary lung cancer due to its misdiagnosis as worsening of pulmonary sarcoidosis. CASE PRESENTATION: A 68-year-old man presented to the outpatient department for evaluation of a mass in the right hilar area with lymphadenopathies in subcarinal and both interlobar areas on chest computed tomography (CT). Sufficient core samples were obtained from subcarinal and bilateral interlobar lymph nodes using endobronchial ultrasonography (EBUS) guided transbronchial needle aspiration (TBNA). EBUS could not reach the right hilar lymph node due to its high angle. The pathologic findings were consistent with sarcoidosis. After 5 months, chest CT revealed aggravation of the right upper paratracheal lymphadenopathy. Assuming worsening of sarcoidosis, he was prescribed an oral corticosteroid for 5 months. However, follow-up chest CT showed a newly developed right lower paratracheal lymphadenopathy and worsening right hilar lymphadenopathy. Bronchoscopy and EBUS were performed once again. Transbronchial lung biopsy from the right upper lobe and EBUS-TBNA from the right lower paratracheal lymph node revealed adenocarcinoma from the lung. CONCLUSIONS: Although coexistence of sarcoidosis and lung cancer is very rare, the clinician should consider the possibility of accompanying lung cancer in sarcoidosis patients who are not responding to initial corticosteroid therapy.

Necrotizing tracheobronchitis causing airway obstruction complicated by pandemic 2009 H1N1 influenza: A case report.

RATIONALE: Influenza is an infection caused by the influenza virus, and its symptoms are mostly mild and self-limiting. However, influenza can cause severe or fatal complications in high-risk patients. Although tracheobronchitis is one of the common complications of influenza, necrotizing tracheobronchitis is very rare. Herein, we describe a case of necrotizing tracheobronchitis causing airway obstruction complicated by pandemic 2009 H1N1 influenza. PATIENT CONCERNS: A 60-year-old man presented with fever and dyspnea. On arrival at the emergency room (ER), the patient received oxygen 4 L/minute via a nasal prolong owing to mild hypoxemia. And invasive mechanical ventilation was needed 5 hours after arrival at the ER due to progressive hypoxemia. DIAGNOSES: Fiberoptic bronchoscopy was performed owing to bloody secretion in the endotracheal tube and revealed diffuse tracheobronchitis with necrotic and hemorrhagic materials obstructing the trachea and bronchus. The pandemic 2009 H1N1 influenza virus was detected from the bronchial washing sample; no other microorganism was detected. INTERVENTION: He received peramivir plus oseltamivir and broad-spectrum antibiotics. OUTCOMES: The bloody secretion continued. He developed cardiac arrest due to airway obstruction on the 6th day of admission. After cardiac arrest, his condition progressed to multi-organ failure, and the patient died on the 10th day of admission. LESSONS: We suggest that necrotizing tracheobronchitis be considered in patients with influenza who present with unexplained hypoxemia.

Efficacy of immune checkpoint inhibitors according to PD-L1 tumor proportion scores in non-small cell lung cancer.

BACKGROUND: We correlated the tumor proportion score (TPS) of programmed cell death ligand 1 (PD-L1, SP263 or 22C3) expression with the disease control rate (DCR, partial remission and stable disease), and progression free survival (PFS) after nivolumab or pembrolizumab treatment. METHODS: A total of 70 case records (55 males, 15 females) of patients with non-small cell lung cancer (NSCLC, 46 adenocarcinoma, 22 squamous cell carcinoma, and two others) were reviewed. The PD-L1 expressions were divided into High (SP263 ≥ 30%, 22C3 ≥ 80%) and Low groups (SP263 < 30%, 22C3 < 80%). In the combined analysis, the PD-L1 group was defined as High if either of the two stains was classified as High and defined as Low if both stains were classified as Low. RESULTS: Among the patients treated with nivolumab (n = 37), the SP263 High group showed higher DCR compared to the SP263 Low group (52.6% vs. 11.1%, P = 0.024). In patients treated with pembrolizumab (n = 33), no significant difference in DCR and PFS according to PD-L1 expression was observed. In the combined analysis (n = 36), patients in the PD-L1 High group showed significantly higher DCRs than those in the PD-L1 Low group (56.1% vs. 24.1%, P = 0.028). PFS was significantly longer in the PD-L1 High group than in the Low group (medians 4.1 vs. 1.6 months, respectively, P = 0.04). CONCLUSION: A high expression level of PD-L1 was correlated with a significantly higher DCR and longer PFS in NSCLC patients treated with nivolumab or pembrolizumab.

Myasthenia gravis and myopathy after nivolumab treatment for non-small cell lung carcinoma: A case report.

Here, we report a case of myasthenia gravis and myopathy in a patient treated with nivolumab. A 76-year-old man who had been treated with four doses of nivolumab because of non-small cell lung cancer (NSCLC) presented with proximal-dominant muscle weakness and fluctuating ptosis and diplopia. Serologic studies revealed increased levels of muscle enzymes including creatine phosphokinase (2934 U/L), and acetylcholine receptor antibody was positive (1.31 nmol/L). Following electrodiagnostic study, he was diagnosed with myasthenia gravis and active stage of myopathy. After discontinuation of nivolumab, he was treated with corticosteroids, intravenous immunoglobulin G, and pyridostigmine. The neuromuscular symptoms and serologic abnormalities of the patient markedly improved. Currently, he is taking oral steroids and pyridostigmine without further immunotherapy.

Feasibility of liquid biopsy using plasma and platelets for detection of anaplastic lymphoma kinase rearrangements in non-small cell lung cancer.

PURPOSE: Fluorescence in situ hybridization (FISH) using tumor tissue is the gold standard for detection of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC). However, this method often is not repeatable due to difficulties in the acquisition of tumor tissues. Blood-based liquid biopsy using reverse transcription polymerase chain reaction (RT-PCR) is expected to be useful to overcome this limitation. Here, we investigated the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement and prediction of ALK inhibitor treatment outcomes. METHODS: ALK-FISH assays were performed in 1128 tumor specimens of NSCLC between January 2015 and June 2018. We retrospectively analyzed formalin-fixed paraffin-embedded (FFPE) tissues from previously confirmed FISH-positive (n = 199) and -negative (n = 920) cases. We recruited patients who had available tissue specimens and agreed to venous sampling. RNA was extracted from FFPE blocks, plasma, and platelets. Fusion RNA of echinoderm microtubule-associated protein-like 4 (EML4)-ALK was detected by quantitative PCR. RESULTS: Thirty-three FISH-positive and 28 FISH-negative patients were enrolled. In validation, data compared with FISH, RT-PCR using FFPE tissues showed 54.5% sensitivity, 78.6% specificity, and 75.5% accuracy. Liquid biopsy had higher sensitivity (78.8%), specificity (89.3%) and accuracy (83.6%). Higher positivity for liquid biopsy was shown in subgroups with delayed (≥ 6 months from diagnosis) blood sampling (plasma, 85.7%; platelets, 87.0%). In 26 patients treated with crizotinib, the platelet-positive subgroup showed longer median duration of treatment (7.2 versus 1.5 months), longer median progression-free survival (5.7 months versus 1.7 months), a higher overall response rate (70.6% versus 11.1%), and a higher disease control rate (88.2% versus 44.4%) than the platelet-negative subgroup. CONCLUSION: Liquid biopsy could have applications in the diagnosis of ALK-positive NSCLC, even when using RT-PCR, and platelets can be useful for predicting treatment outcomes of ALK inhibitors.