3D airway geometry analysis of factors in airway navigation failure for lung nodules.

BACKGROUND: This study aimed to quantitatively reveal contributing factors to airway navigation failure during radial probe endobronchial ultrasound (R-EBUS) by using geometric analysis in a three-dimensional (3D) space and to investigate the clinical feasibility of prediction models for airway navigation failure. METHODS: We retrospectively reviewed patients who underwent R-EBUS between January 2017 and December 2018. Geometric quantification was analyzed using in-house software built with open-source python libraries including the Vascular Modeling Toolkit ( http://www.vmtk.org ), simple insight toolkit ( https://sitk.org ), and sci-kit image ( https://scikit-image.org ). We used a machine learning-based approach to explore the utility of these significant factors. RESULTS: Of the 491 patients who were eligible for analysis (mean age, 65 years +/- 11 [standard deviation]; 274 men), the target lesion was reached in 434 and was not reached in 57. Twenty-seven patients in the failure group were matched with 27 patients in the success group based on propensity scores. Bifurcation angle at the target branch, the least diameter of the last section, and the curvature of the last section are the most significant and stable factors for airway navigation failure. The support vector machine can predict airway navigation failure with an average area under the curve of 0.803. CONCLUSIONS: Geometric analysis in 3D space revealed that a large bifurcation angle and a narrow and tortuous structure of the closest bronchus from the lesion are associated with airway navigation failure during R-EBUS. The models developed using quantitative computer tomography scan imaging show the potential to predict airway navigation failure.

Features which discriminate between tuberculosis and haematologic malignancy as the cause of pleural effusions with high adenosine deaminase.

BACKGROUND: Adenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE). This study aimed to investigate the features that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L. METHODS: This was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the features associated with TBP and hMPE, respectively. RESULTS: Among 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 70 and 150 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95-4.95; P < 0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14-0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67-30.79; P < 0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD. A combination of lymphocytes ≥ 35%, LD/ADA < 18, and ADA < 150 IU/L demonstrated a sensitivity of 0.824 and specificity of 0.937 for predicting TBP. CONCLUSION: In patients with very high levels of pleural effusion ADA, hMPE should be considered. Several features in pleural effusion and serum may help to more effectively differentiate TBP from hMPE.

Clinical Course of Patients With Mediastinal Lymph Node Tuberculosis and Risk Factors for Paradoxical Responses.

BACKGROUND: Paradoxical responses (PR) occur more frequently in lymph node tuberculosis (LNTB) than in pulmonary tuberculosis and present difficulties in differential diagnosis of drug resistance, new infection, poor patient compliance, and adverse drug reactions. Although diagnosis of mediastinal LNTB has become much easier with the development of endosonography, limited information is available. The aim of this study was to investigate the clinical course of mediastinal LNTB and the risk factors associated with PR. METHODS: Patients diagnosed with mediastinal LNTB via endosonography were evaluated retrospectively between October 2009 and December 2019. Multivariable logistic regression was applied to evaluate the risk factors associated with PR. RESULTS: Of 9,052 patients who underwent endosonography during the study period, 158 were diagnosed with mediastinal LNTB. Of these, 55 (35%) and 41 (26%) concurrently had pulmonary tuberculosis and extrapulmonary tuberculosis other than mediastinal LNTB, respectively. Of 125 patients who completed anti-tuberculosis treatment, 21 (17%) developed PR at a median of 4.4 months after initiation of anti-tuberculosis treatment. The median duration of anti-tuberculosis treatment was 6.3 and 10.4 months in patients without and with PR, respectively. Development of PR was independently associated with age < 55 years (adjusted odds ratio [aOR], 5.72; 95% confidence interval [CI], 1.81-18.14; P = 0.003), lymphocyte count < 800/µL (aOR, 8.59; 95% CI, 1.60-46.20; P = 0.012), and short axis diameter of the largest lymph node (LN) ≥ 16 mm (aOR, 5.22; 95% CI, 1.70-16.00; P = 0.004) at the time of diagnosis of mediastinal LNTB. CONCLUSION: As PR occurred in one of six patients with mediastinal LNTB during anti-tuberculosis treatment, physicians should pay attention to patients with risk factors (younger age, lymphocytopenia, and larger LN) at the time of diagnosis.

10-Year Retrospective Review of the Etiologies for Meningitis With Elevated Adenosine Deaminase in Cerebrospinal Fluid: Etiologies Other Than TB.

Purpose: An elevated adenosine deaminase (ADA) level in the cerebrospinal fluid (CSF) is considered a reliable marker of tuberculous meningitis (TBM). However, CSF-ADA levels can also be elevated in other diseases. We aimed to find the most common diagnosis of patients with elevated CSF-ADA levels for the last 10 years. Methods: We retrospectively investigated the diagnoses of all patients with elevated CSF-ADA (ADA ≥ 10 IU/L) levels between 2010 and 2019 at the Samsung Medical Center. Definite TBM was defined based on microbiological evidence. Clinical TBM was defined based on the brain imaging and response to the standard TB treatment. We compared the laboratory characteristics of the three most common diagnoses. Results: CSF-ADA levels were elevated in 137 (5.6%) of 2,600 patients. The most common diagnoses included hematologic malignancy (HM; n = 36, 26.2%), TBM (n = 26, 19.0%), and viral meningitis (VM; n = 25, 18.2%). CSF-ADA levels did not differ significantly between TBM [median (interquartile range (IQR)), 20.2 IU/L (13.8-29.3)] and HM [16.5 (12.8-24.0)]. However, CSF-ADA levels were lower in VM [14.0 (11.0-16.1)] than in TBM (p = 0.027). Lymphocyte-dominant pleocytosis was more common in VM [77.0% (70.8-81.5)] than in TBM [16.0 (3.0-51.0), p = 0.015] or HM [36.0 (10.0-72.0); p = 0.032]. Interestingly, the CSF characteristics of clinical TBM were similar to those of VM but not definite TBM. Conclusion: The most common diagnoses with elevated CSF-ADA levels were HM, followed by TBM and VM. Clinicians should carefully consider the differential diagnoses in patients with elevated CSF-ADA levels, especially those in the early stage of meningitis without microbiological evidence for TBM.

Comparative Study on the Effect of Cidofovir Treatment for Severe Adenovirus Pneumonia.

BACKGROUND: Adenovirus infection can cause severe pneumonia even in immunocompetent adults. However, there is limited data on the benefits of cidofovir treatment in severe adenovirus pneumonia. The objective of this study was to evaluate the association of cidofovir treatment with clinical improvement in immunocompetent adult patients with severe adenovirus pneumonia. METHODS: We evaluated 22 male patients who admitted to intensive care unit (ICU) with severe adenovirus pneumonia between January 2014 and December 2019. The patients were divided into 2 groups, patients treated with cidofovir or not. Clinical outcomes including time to defervescence and stopping of oxygen supplement, length of stay in ICU and hospital, and the need for mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) were compared between the 2 groups. RESULTS: Among 22 patients, 13 patients (59%) were treated with cidofovir and 9 (41%) were not. The difference in mean time (95% confidence interval [CI]) to defervescence and stopping of oxygen supplement between cidofovir group and no cidofovir group was 2.1 (-5.7 to 10.0) and 1.0 (-14.9 to 16.8) days, respectively. The difference in mean length of stay (95% CI) in ICU and hospital between the 2 groups was 0.2 (-7.1 to 7.5) and -0.4 (-18.3 to 17.5) days, respectively. The differences in proportion of patients requiring MV and ECMO between the 2 groups was 28.2 (-17.4 to 73.8) % and -10.3 (-52.2 to 31.7) %, respectively. CONCLUSIONS: The treatment with cidofovir for severe adenovirus pneumonia in immunocompetent patients did not improve clinical outcomes. Further studies with larger samples with prospective design are warranted.

Exhaled Nitric Oxide in Patients with Stable Chronic Obstructive Pulmonary Disease: Clinical Implications of the Use of Inhaled Corticosteroids.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is regarded as a potential biomarker for identifying eosinophilic inflammation. We aimed to evaluate the clinical implication of FeNO and its influence on inhaled corticosteroids (ICS) prescription rate in Korean chronic obstructive pulmonary disease (COPD) patients. METHODS: FeNO level and its association with clinical features were analyzed. Changes in the prescription rate of ICS before and after FeNO measurement were identified. RESULTS: A total of 160 COPD patients were divided into increased (≥25 parts per billion [ppb], n=74) and normal (<25 ppb, n=86) FeNO groups according to the recommendations from the American Thoracic Society. Compared with the normal FeNO group, the adjusted odds ratio for having history of asthma without wheezing and with wheezing in the increased FeNO group were 2.96 (95% confidence interval [CI], 1.40-6.29) and 4.24 (95% CI, 1.37-13.08), respectively. Only 21 out of 74 patients (28.4%) with increased FeNO prescribed ICS-containing inhaler and 18 of 86 patients (20.9%) with normal FeNO were given ICS-containing inhaler. Previous exacerbation, asthma, and wheezing were the major factors to maintain ICS at normal FeNO level and not to initiate ICS at increased FeNO level. CONCLUSION: Increased FeNO was associated with the history of asthma irrespective of wheezing. However, FeNO seemed to play a subsidiary role in the use of ICS-containing inhalers in real-world clinics, which was determined with prior exacerbation and clinical features suggesting Th2 inflammation.

Inhalation with intravenous loading dose of colistin in critically ill patients with pneumonia caused by carbapenem-resistant gram-negative bacteria.

BACKGROUND: Despite the increasing use of colistin in clinical practice, the optimal dosing, and administration route have not been established. This study aimed to evaluate the clinical outcome and safety of intravenous (IV) colistin with a loading dose (LD) and adjunctive aerosolized (AS) colistin administration in critically ill patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) caused by carbapenem-resistant gram-negative bacteria (CRGNB). METHODS: We retrospectively reviewed 191 critically ill patients who received colistin for the treatment of HAP or VAP caused by CRGNB. Patients were divided into three groups: non-LD IV (patients received only IV colistin without LD), LD IV (patients received only IV colistin with LD), and AS-LD (patients received IV colistin with LD and adjunctive AS colistin). RESULTS: There was no difference in clinical response between the three groups. However, the rate of microbiological eradication was significantly higher in the AS-LD group (60%) than in the non-LD IV (31%), and LD IV (33%) groups (p = 0.010). Patients treated with adjunctive AS colistin in combination with LD IV had significantly lower 30-day mortality rates than patients treated with IV colistin alone (p = 0.027). After adjusting for potential confounding factors, adjunctive AS colistin was still significantly associated with lower mortality (adjusted OR 0.338, CI 95% 0.132-0.864, p = 0.024). However, nephrotoxicity did not change according to the use of LD regimen and AS colistin administration (p = 0.100). CONCLUSIONS: Adjunctive AS colistin in combination with IV colistin with LD was related to an improved 30-day mortality and microbiological outcome without an increase in nephrotoxicity in critically ill patients with HAP and VAP caused by CRGNB. The reviews of this paper are available via the supplemental material section.

Diagnostic Performance of Radial Probe Endobronchial Ultrasound without a Guide-Sheath and the Feasibility of Molecular Analysis.

BACKGROUND: Radial probe endobronchial ultrasound (R-EBUS), is effective for tissue diagnosis of lung lesions. We evaluated the diagnostic performance of R-EBUS both a guide-sheath and fluoroscopy and identified factors associated with accurate diagnosis. The feasibility of molecular and genetic testing, using specimens obtained by R-EBUS, was also investigated. METHODS: The study retrospectively reviewed 211 patients undergoing R-EBUS without a guide-sheath and fluoroscopy, June 2016-May 2017. After excluding 27 patients of which the target lesion was not reached, 184 were finally included. Multivariate logistic regression was used, to identify factors associated with accurate diagnosis. RESULTS: Among 184 patients, R-EBUS-guided biopsy diagnosed malignancy in 109 patients (59%). The remaining 75 patients (41%) with non-malignant results underwent additional work-ups, and 34 were diagnosed with malignancy. Based on final diagnosis, diagnostic accuracy was 80% (136/170), and sensitivity and specificity for malignancy were 76% (109/143) and 100% (27/27), respectively. In multivariate analysis, peripheral location (adjusted odds ratio [aOR], 3.925; 95% confidence interval [CI], 1.203-12.811; p=0.023), and central position of the probe (aOR, 2.435; 95% CI, 1.424-7.013; p=0.035), were associated with accurate diagnosis of malignancy. Molecular and genetic analyses were successful, in all but one case, with inadequate specimens. CONCLUSION: R-EBUS-guided biopsy without equipment, is effective for tissue diagnosis. Peripheral location and central position of the radial probe, were crucial for accurate diagnosis. Performance of molecular and genetic testing, using samples obtained by R-EBUS, was satisfactory.

Additional role of bronchial mucosal biopsy for ciliary structural abnormality in diagnosis of primary ciliary dyskinesia.

BACKGROUND: Transmission electron microscopy (TEM) is one of diagnostic tests for primary ciliary dyskinesia (PCD). The mucosal samples obtained for cilia examination are generally procured from the nasal turbinate, but these specimens often yield inadequate results. The bronchial mucosa is recognized as an alternative sample, but no study has examined the additional utility of bronchial mucosa compared with nasal mucosa in the diagnosis of PCD. METHODS: The medical records of 96 patients who underwent TEM for suspected PCD between April 1997 and June 2017 were reviewed. Patients were divided into three groups based on the site of mucosal biopsy: nasal biopsy (NB) group with nasal mucosal biopsy only; bronchial biopsy (BB) group with bronchial mucosal biopsy only; and nasal and bronchial biopsy (NBB) group with a combination of nasal and bronchial mucosal biopsies. RESULTS: The rate of PCD diagnosis was 28.8% (17/59) in the NB group, 41.2% (7/17) in the BB group, and 60.0% (12/20) in the NBB group. The yield of PCD diagnosis significantly increased in the NBB group compared with the NB group (P=0.012). In the NBB group, 25.0% (5/20) of patients were diagnosed with PCD by nasal mucosal biopsy, and 35.0% (7/20) of patients were additionally diagnosed by bronchial mucosal biopsy. The presence of sinusitis or bronchiectasis was not associated with prediction of PCD diagnosis from nasal or bronchial mucosal biopsy. CONCLUSIONS: The combination of nasal and bronchial mucosal biopsy for TEM showed higher yields of PCD diagnosis than nasal mucosal biopsy alone.

Treatment with a macrolide-containing regimen for Mycobacterium kansasii pulmonary disease.

BACKGROUND: Mycobacterium kansasii is a major pathogen associated with nontuberculous mycobacterial pulmonary disease. For treatment of M. kansasii pulmonary disease, daily therapy with isoniazid, rifampin, and ethambutol is traditionally recommended. Although a regimen containing a macrolide, instead of isoniazid, has been recently recommended, supporting data are limited. We compared the treatment outcomes of a macrolide-containing regimen (macrolide group) and an isoniazid-containing regimen (isoniazid group) on patients with M. kansasii pulmonary disease. METHODS: A total of 49 patients were identified between January 2002 and December 2016. Treatment outcomes for the isoniazid group (n = 24) and the macrolide group (n = 25) were compared. RESULTS: Baseline characteristics of the isoniazid and macrolide groups were similar. Favorable outcomes did not differ between the isoniazid group (79%, n = 19) and macrolide group (88%, n = 22, P = 0.463). Total treatment duration (median 17.9 months vs. 15.4 months; P = 0.712) and time to culture conversion (median 2.0 months vs. 1.2 months; P = 0.838) were also similar between the isoniazid and macrolide groups. Five patients who completed three-times-weekly intermittent treatment containing a macrolide for non-cavitary M. kansasii pulmonary disease achieved negative sputum culture conversion within 12 months of treatment. Only one patient experienced recurrence of M. kansasii pulmonary disease in the isoniazid group. CONCLUSIONS: A macrolide-containing regimen appears to be as effective as an isoniazid-containing regimen for treatment of M. kansasii pulmonary disease. Additionally, intermittent therapy containing a macrolide could be an alternative treatment option for non-cavitary M. kansasii pulmonary disease.

Unilateral pulmonary artery agenesis manifested by hemoptysis in pregnancy.

Unilateral pulmonary artery agenesis (UPAA) is a rare congenital anomaly which can be symptomatic or even asymptomatic. Most of patients with isolated UPAA have mild symptoms and it is difficult to be diagnosed, especially when abnormal findings of chest radiograph are the first presentation. It is often misdiagnosed and is not considered during differential diagnosis. To make a diagnosis of UPAA, various imaging modalities including chest radiograph, computed tomography (CT), and angiography are used. We report a 33-year-old woman in pregnancy presented recurrent hemoptysis whose CT was postponed due to her pregnancy. Although CT is a useful diagnostic tool, chest radiograph could be used instead in pregnancy suggesting UPAA with a lot of information.

A rare case of numerous thoracolithiasis with chest discomfort.

Thoracolithiasis is a rare benign condition with mobile free bodies in the pleural cavity. It is asymptomatic and mostly found incidentally. Up to our knowledge there is no report of symptomatic numerous thoracolithiasis. We report a very rare case of thoracolithiasis in a 36-year-old female with chest discomfort. Images from computed tomography presented a chain of small non-enhancing nodules in the left hemi-diaphragmatic pleura. Exploratory thoracoscopy was performed and twenty-five mobile pearl like thoracolithiasis were discovered. Histopathology showed extensive necrotic fatty tissue at its center surrounded by fibrosis. The patient was symptom-free after the surgical removal of numerous thoracolithiasis, suggesting thoracolithiasis was associated with chest discomfort.

Safety of endobronchial ultrasound-guided transbronchial needle aspiration in patients with lung cancer within a year after percutaneous coronary intervention.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) may be necessary for patients with incidental lung cancer during or after coronary intervention. Although EBUS-TBNA is quite safe, the safety in patients who recently received percutaneous coronary intervention (PCI) has not been demonstrated. The aim of this study was to assess the safety of EBUS-TBNA in patients with lung cancer who underwent PCI within one year. METHODS: We retrospectively reviewed the medical records of 24 patients who underwent EBUS-TBNA within one year after PCI between May 2009 and June 2017. Cardiovascular complications (death, myocardial infarction, arrhythmia, and acute heart failure) were assessed as primary outcomes. Procedural-related complications were assessed as secondary outcomes. RESULTS: The coronary artery diseases requiring PCI were: myocardial infarction (n = 10), unstable angina (n = 10), stable angina (n = 2), and silent ischemia (n = 2). The median interval between PCI and EBUS-TBNA was 125 days (interquartile range: 66-180). Atrial fibrillation with a rapid ventricular response temporarily occurred in one patient after EBUS-TBNA. No other significant cardiovascular complications were encountered. Fifteen patients were administered an anti-thrombotic agent the day of EBUS-TBNA, while four had ceased taking the agent < 4 days before EBUS-TBNA, however, there was no significant bleeding among those patients. CONCLUSION: EBUS-TBNA was safe and did not cause serious adverse events in patients with lung cancer who required tissue confirmation or mediastinal staging within one year after PCI. Incidental lung cancer found during or after a coronary intervention should be actively evaluated by EBUS-TBNA.

Nontuberculous Mycobacterial Lung Diseases Caused by Mixed Infection with Mycobacterium avium Complex and Mycobacterium abscessus Complex.

Mycobacterium avium complex (MAC) and M. abscessus complex (MABC) comprise the two most important human pathogen groups causing nontuberculous mycobacterial lung disease (NTM-LD). However, there are limited data regarding NTM-LD caused by mixed NTM infections. This study aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-LD caused by mixed infection with these two major NTM pathogen groups. Seventy-one consecutive patients who had been diagnosed with NTM-LD caused by mixed infection with MAC (M. avium or M. intracellulare) and MABC (M. abscessus or M. massiliense) between January 2010 and December 2015 were identified. Nearly all patients (96%) had the nodular bronchiectatic form of NTM-LD. Mixed infection with MAC and M. massiliense (n = 47, 66%) was more common than mixed infection with MAC and M. abscessus (n = 24, 34%), and among the 43 (61%) patients who were treated for NTM-LD for more than 12 months, sputum culture conversion rates were significantly lower in patients infected with MAC and M. abscessus (25% [3/12]) than in patients infected with MAC and M. massiliense (61% [19/31, P = 0.033]). Additionally, M. massiliense and M. abscessus showed marked differences in clarithromycin susceptibility (90% versus 6%, P < 0.001). Of the 23 patients who successfully completed treatment, 11 (48%) redeveloped NTM lung disease, with mycobacterial genotyping results indicating that the majority of cases were due to reinfection. Precise identification of etiologic NTM organisms could help predict treatment outcomes in patients with NTM-LD due to mixed infections.