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.

Association Between Oral Health and Airflow Limitation: Analysis Using a Nationwide Survey in Korea.

BACKGROUND: Although poor oral health is a common comorbidity in individuals with airflow limitation (AFL), few studies have comprehensively evaluated this association. Furthermore, the association between oral health and the severity of AFL has not been well elucidated. METHODS: Using a population-based nationwide survey, we classified individuals according to the presence or absence of AFL defined as pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity < 0.7. Using multivariable logistic regression analyses, we evaluated the association between AFL severity and the number of remaining teeth; the presence of periodontitis; the Decayed, Missing, and Filled Teeth (DMFT) index; and denture wearing. RESULTS: Among the 31,839 participants, 14% had AFL. Compared with the control group, the AFL group had a higher proportion of periodontitis (88.8% vs. 79.4%), complete denture (6.2% vs. 1.6%), and high DMFT index (37.3% vs. 27.8%) (P < 0.001 for all). In multivariable analyses, denture status: removable partial denture (adjusted odds ratio [aOR], 1.12; 95% confidence interval [95% CI], 1.04-1.20) and complete denture (aOR, 1.52; 95% CI, 1.01-2.05), high DMFT index (aOR, 1.13; 95% CI, 1.02-1.24), and fewer permanent teeth (0-19; aOR, 1.32; 95% CI, 1.12-1.52) were significantly associated with AFL. Furthermore, those with severe to very severe AFL had a significantly higher proportion of complete denture (aOR, 2.41; 95% CI, 1.11-3.71) and fewer remaining teeth (0-19; aOR, 2.29; 95% CI, 1.57-3.01). CONCLUSION: Denture wearing, high DMFT index, and fewer permanent teeth are significantly associated with AFL. Furthermore, a reduced number of permanent teeth (0-19) was significantly related to the severity of AFL. Therefore, physicians should pay attention to oral health in managing patients with AFL, such as chronic obstructive pulmonary disease.

Altered Lung Heat Shock Protein-70 Expression and Severity of Sepsis-Induced Acute Lung Injury in a Chronic Kidney Disease Rat Model.

Enhanced heat shock protein-70 (HSP-70) expression in the lungs is associated with attenuated acute lung injury (ALI) in a sepsis model. Chronic kidney disease (CKD) significantly contributes to the poor prognosis of patients with sepsis. This study examined the relationship between sepsis-induced ALI severity and altered lung HSP-70 expression in CKD. Experimental rats underwent a sham operation (control group) or 5/6 nephrectomy (CKD group). Sepsis was induced with cecal ligation and puncture (CLP). Laboratory tests and lung harvest were performed in the control group (without CLP and after 3, 12, 24, and 72 h of CLP) and in the CKD group (without CLP and after 72 h of CLP). ALI was the most severe after 12 h of sepsis. The mean lung injury score at 72 h after sepsis was significantly higher in the CKD group than in the control group (4.38 versus 3.30, p < 0.01). Nonetheless, enhanced lung HSP-70 expression was not observed in the CKD group. This study shows that altered lung HSP-70 expression is associated with the worsening of sepsis-induced ALI in patients with CKD. Enhancing lung HSP-70 is a novel treatment target for patients with CKD and sepsis-induced ALI.

Comparison of Postextubation Outcomes Associated with High-Flow Nasal Cannula vs. Conventional Oxygen Therapy in Patients at High Risk of Reintubation: a Randomized Clinical Trial.

BACKGROUND: Liberation and extubation are important for patients supported by mechanical ventilation. Extubation success is related to the duration of an intensive care unit (ICU) stay and mortality rate. High-flow nasal cannula (HFNC) oxygen therapy has physiological and clinical benefits in respiratory care. The present study compared clinical outcomes associated with HFNC and conventional oxygen therapy (COT) among patients at high risk for reintubation. METHODS: A single-center randomized clinical trial was conducted between March 2018 and June 2019. Sixty adults admitted to the ICU and who were at high-risk of reintubation and met the inclusion criteria were enrolled in this study. "High risk" for reintubation was defined as having at least one of the following risk factors: age > 65 years, Acute Physiology and Chronic Health Evaluation II score > 12 points on extubation day, obesity, poor expectoration, airway patency problems, difficult or prolonged weaning, and more than one comorbidity. The primary outcome of interest was reintubation within 72 hours. Secondary outcomes included duration of ICU and hospital stay, mortality rate, and time to reintubation. RESULTS: Of 60 patients, 31 received HFNC and 29 received COT (mean age, 78 ± 7.8 vs. 76 ± 6.5 years, respectively). Reintubation rate within 72 hours did not differ between the groups (3 patients [9.7%] vs. 1 patient [3.4%], respectively). Reintubation time was shorter among patients who received COT than among patients who received HFNC (0.5 hour vs. 25 hours), but this difference was not statistically significant. Duration of ICU did not differ between the groups (14.7 ± 9.6 days vs. 13.8 ± 15.7 days, for HFNC and COT, respectively). CONCLUSION: Among patients at high risk for reintubation, compared with COT, HFNC did not reduce the risk of reintubation within 72 hours.

Factors Associated With Quality of Death in Korean ICUs As Perceived by Medical Staff: A Multicenter Cross-Sectional Survey.

OBJECTIVES: Facilitating a high quality of death is an important aspect of comfort care for patients in ICUs. The quality of death in ICUs has been rarely reported in Asian countries. Although Korea is currently in the early stage after the implementation of the "well-dying" law, this seems to have a considerable effect on practice. In this study, we aimed to understand the status of quality of death in Korean ICUs as perceived by medical staff, and to elucidate factors affecting patient quality of death. DESIGN: A multicenter cross-sectional survey study. SETTING: Medical ICUs of two tertiary-care teaching hospitals and two secondary-care hospitals. PATIENTS: Deceased patients from June 2016 to May 2017. INTERVENTIONS: Relevant medical staff were asked to complete a translated Quality of Dying and Death questionnaire within 48 hours after a patient's death. A higher Quality of Dying and Death score (ranged from 0 to 100) corresponded to a better quality of death. MEASUREMENTS AND MAIN RESULTS: A total of 416 completed questionnaires were obtained from 177 medical staff (66 doctors and 111 nurses) of 255 patients. All 20 items of the Quality of Dying and Death received low scores. Quality of death perceived by nurses was better than that perceived by doctors (33.1 ± 18.4 vs 29.7 ± 15.3; p = 0.042). Performing cardiopulmonary resuscitation and using inotropes within 24 hours before death were associated with poorer quality of death, whereas using analgesics was associated with better quality of death. CONCLUSIONS: The quality of death of patients in Korean ICUs was considerably poorer than reported in other countries. Provision of appropriate comfort care, avoidance of unnecessary life-sustaining care, and permission for more frequent visits from patients' families may correspond to better quality of death in Korean medical ICUs. It is also expected that the new legislation would positively affect the quality of death in Korean ICUs.

Solid part size is an important predictor of nodal metastasis in lung cancer with a subsolid tumor.

BACKGROUND: Candidates for preoperative or intraoperative nodal assessment among patients with non-small cell lung cancer (NSCLC) manifesting as a subsolid tumor are not established. The present study was conducted to demonstrate the distribution of nodal metastasis rate according to newly proposed T categories for subsolid tumors, and we further aimed to identify radiologic parameters that can be predictive of nodal metastasis. METHODS: We retrospectively reviewed cases of NSCLC manifesting as a subsolid tumor in computed tomography scans in a university-affiliated tertiary hospital between April 2013 and August 2016. All patients underwent mediastinal lymph node dissection during resection surgery. Multivariate analysis was performed among clinical and radiologic parameters. RESULTS: Of the 269 eligible patients, T-categories were classified as cTis (n = 23, 8.6%), cT1 (n = 203, 75.5%), and cT2 (n = 43, 16.0%). Ten patients (3.7%) had nodal metastasis: pN1 (n = 5, 1.9%), pN2 (n = 5, 1.9%). Nodal metastasis was not observed in tumors with a solid part ≤1.0 cm (cT1mi and cT1a) or in nonsolid tumors ≤3.0 cm (cTis). The nodal metastasis rate in cT1b, cT1c, and cT2 tumors was 6.1% (4/65), 8.3% (1/12), and 11.7% (5/43), respectively. Multivariate analysis showed that a solid part size > 1.5 cm [odds ratio, 5.89; 95% confidence interval, 1.25-27.68, p = 0.025] was significantly associated with nodal metastasis. CONCLUSIONS: We observed nodal metastasis from cT1b tumors (solid part size > 1 cm) among proposed T categories for subsolid tumors and a solid part size is an important radiologic parameter predictive of nodal metastasis in NSCLC manifesting as a subsolid tumor. Considering the low rate of nodal metastasis, pathologic nodal assessment may be unnecessary in early T category tumors with a small solid part size.

Tuberculosis survivors and the risk of cardiovascular disease: analysis using a nationwide survey in Korea.

Background: Although the association between tuberculosis (TB) and cardiovascular disease (CVD) has been reported in several studies and is explained by mechanisms related to chronic inflammation, few studies have comprehensively evaluated the association between TB and CVD in Korea. Methods: Using the Korea National Health and Nutrition Survey, we classified individuals according to the presence or absence of previous pulmonary TB was defined as the formal reading of a chest radiograph or a previous diagnosis of pulmonary TB by a physician. Using multivariable logistic regression analyses, we evaluated the association between the 10-year atherosclerotic cardiovascular disorder (ASCVD) risk and TB exposure, as well as the 10-year ASCVD risk according to epidemiological characteristics. Results: Among the 69,331 participants, 4% (n = 3,101) had post-TB survivor group. Comparing the 10-year ASCVD risk between the post-TB survivor and control groups, the post-TB survivor group had an increased 10-year ASCVD risk in the high-risk group (40.46% vs. 24.00%, P < 0.001). Compared to the control group, the intermediate- and high-risk groups had also significantly increased 10-year ASCVD risks (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04-1.23 and OR 1.69, 95% CI 1.59-1.78, respectively) in the post-TB survivor group. In the association of CVD among post-TB survivors according to epidemiologic characteristics, age [adjusted OR (aOR) 1.10, 95% CI 1.07-1.12], current smoking (aOR 2.63, 95% CI 1.34-5.14), a high family income (aOR 2.48, 95% CI 1.33-4.62), diabetes mellitus (aOR 1.97, 95% CI 1.23-3.14), and depression (aOR 2.06, 95% CI 1.03-4.10) were associated with CVD in the post-TB survivor group. Conclusions: Our study findings suggest a higher 10-year ASCVD risk among TB survivors than healthy participants. This warrants long-term cardiovascular monitoring and management of the post-TB population.

Characteristics and intrasubject variation in the respiratory microbiome in interstitial lung disease.

Recent studies have reported that the lower airway microbiome may play an essential role in the development and progression of interstitial lung disease (ILD). The aim of the current study was to evaluate the characteristics of the respiratory microbiome and intrasubject variation in patients with ILD. Patients with ILD were recruited prospectively for 12 months. The sample size was small (n = 11) owing to delayed recruitment during the COVID-19 pandemic. All subjects were hospitalized and were evaluated by a questionnaire survey, blood sampling, pulmonary function test, and bronchoscopy. Bronchoalveolar lavage fluid (BALF) was obtained at 2 sites, the most and least disease-affected lesions. Sputum collection was also performed. Furthermore, 16S ribosomal RNA gene sequencing was performed using the Illumina platform and indexes of α- and ß-diversity were evaluated. Species diversity and richness tended to be lower in the most-affected lesion than in the least-affected lesion. However, taxonomic abundance patterns were similar in these 2 groups. The phylum Fusobacteria was more prevalent in fibrotic ILD than in nonfibrotic ILD. Inter-sample differences in relative abundances were more prominent in BALF versus sputum specimens. Rothia and Veillonella were more prevalent in the sputum than in BALF. We did not detect site-specific dysbiosis in the ILD lung. BALF was an effective respiratory specimen type for evaluating the lung microbiome in patients with ILD. Further studies are needed to evaluate the causal links between the lung microbiome and the pathogenesis of ILD.

Safety and efficacy of remimazolam compared with midazolam during bronchoscopy: a single-center, randomized controlled study.

Although remimazolam is an ultra-short-acting benzodiazepine with a shorter elimination half-life and faster recovery time than midazolam, studies evaluating its safety and efficacy during bronchoscopy are limited. This study aimed to compare the safety and efficacy of remimazolam with those of midazolam for bronchoscopy. This prospective randomized parallel-group study was conducted at a single institution. The primary outcome was the time from the end of the procedure to full alertness. Other procedural time parameters, satisfaction profiles, and adverse effects were thoroughly evaluated. The time taken to reach peak sedation and the time from the end of the procedure to full alertness was significantly shorter in the remimazolam group than in the midazolam group (median [interquartile range], 2 min [1-4] vs. 3 min [2-5], P = 0.006; and median, 2 min [1-5] vs. 5 min [1-12], P = 0.035, respectively). In patients with non-biopsy procedures (n = 79), participant satisfaction was significantly higher in the remimazolam group than in the midazolam group (median rated scale, 10 vs. 7, P = 0.042). Physician satisfaction and willingness to repeat the procedure were similar between groups. Although the incidence of adverse effects was similar between the groups and there was no significant difference, the midazolam group had a higher antidote administration rate than the remimazolam group (15.7% vs. 4.1%, P = 0.092). Remimazolam is effective and safe for achieving adequate sedation, with a shorter onset time and faster neuropsychiatric recovery than midazolam. It may be a new option for sedation during bronchoscopy.Trial registration: The trial registration number is NCT05994547, and the date of first registration is 16/08/2023.

Effectiveness of the use of an oscillating positive expiratory pressure device in bronchiectasis with frequent exacerbations: a single-arm pilot study.

Impaired airway clearance in patients with non-cystic fibrosis bronchiectasis causes frequent bacterial infection, chronic inflammation, and progressive tissue destruction. We aimed to evaluate whether an oscillating positive expiratory pressure (OPEP) device could allow effective sputum expectoration and prevent acute exacerbations in patients with bronchiectasis who had frequent acute exacerbations. This open-label, single-arm, prospective study included 17 patients who experienced three or more acute exacerbations in the past year. We evaluated the prevention of acute exacerbations, subjective symptom improvement, and change in sputum amount during the use of the Aerobika (Trudell Medical International, London, ON) OPEP device twice daily for 6 months. Of all enrolled patients, only two acute exacerbations occurred during the study period, indicating a significant decrease compared with the number of acute exacerbations before the device use (p < 0.001). Additionally, Bronchiectasis Health Questionnaire score changed from 58.7 to 66.6, showing significant improvement over the treatment period (p < 0.001). The largest sputum volume was observed 3 months after OPEP device use (baseline: 10 ml, 3rd month 25 ml, p = 0.325). There were no major adverse events related to the use of OPEP devices. Twice-daily physiotherapy with OPEP device in patients with bronchiectasis who have frequent exacerbations may facilitate symptomatic improvement and prevention of acute exacerbations without serious adverse events.

A case report of nilotinib-induced irreversible interstitial lung disease.

RATIONALE: Nilotinib is a second line tyrosine kinase inhibitor to treat patients with chronic myeloid leukemia after imatinib resistance or intolerance. Drug related pulmonary complication is known to be rare. We discuss a case of nilotinib-induced interstitial lung disease presenting with nonspecific interstitial pneumonia on the unilateral lung. PATIENT CONCERNS: A 46-year-old man with chronic-phase chronic myeloid leukemia presented with cough and weight loss for 2 months. He had been treated with nilotinib for 52 months. DIAGNOSIS: Computed tomography scan showed right lung dominant consolidations, ground glass opacities and traction bronchiectasis. Bronchoalveolar lavage fluid analysis revealed no evidence of infection or malignancy. Surgical lung biopsy specimen was consistent with fibrosing nonspecific interstitial pneumonia. The patient was diagnosed with nilotinib induced interstitial lung disease. INTERVENTIONS: Corticosteroid treatment was initiated with prednisolone (50 mg daily) and slowly tapered down for 2 months. OUTCOMES: Cough improved after the course of corticosteroid treatment. However, fibrotic lung lesions persisted. Reinitiation of nilotinib resulted in the worsening of lung lesions. LESSONS: We report a case of irreversible interstitial lung disease that caused by nilotinib. Clinicians should have suspicion of this potential pulmonary complication in patients with respiratory symptoms and abnormal radiologic findings during nilotinib treatment, albeit rarely.

Which factors are helpful for the early determination of treatment level in patients with interstitial lung disease in the intensive care unit to minimize the suffering in their end of life?: A retrospective study.

Interstitial lung disease (ILD) is widely known to be associated with high mortality and poor prognosis, especially in patients admitted to the intensive care unit (ICU). The objective of this study was to investigate clinical predictors for assisting relatively early decision of treatment level in the ICU. We retrospectively investigated patients with ILD who were admitted to the ICU between January 1, 2014, and September 30, 2019. A total of 64 patients were analyzed. We found the ICU and hospital mortality rates to be 67.2% and 69.8%, respectively. Nonsurvivors had a higher fraction of inspired oxygen (FiO2) on days 1 (79 ±â€…21 vs 60% ±â€…21%, P = .001) and 3 (61 ±â€…31 vs 46% ±â€…19%, P = .004). They showed lower partial pressure of oxygen/FiO2 (PF) ratio on days 1 (134 ±â€…80 vs 173 ±â€…102, P = .049) and 3 (147 ±â€…74 vs 235 ±â€…124, P = .003) than the survivor group. The lactic acid levels obtained on day 1 and PF ratio measured on day 3 were associated with mortality (odds ratio, 1.89; 95% confidence interval 1.03-3.47 and odds ratio, 0.99; 95% confidence interval 0.98-1.00, respectively). Among the 31 ICU survivors, 10 patients died in the general ward, 12 patients died after hospital discharge; only 9 patients survived after 1 year. We suggest that these clinical predictors could be used to determine the level of further treatment or withdrawal on day 3 of admission in patients with ILD admitted to the ICU to minimize the prolonged suffering in a relatively early period.

Trend of lung cancer surgery, hospital selection, and survival between 2005 and 2016 in South Korea.

BACKGROUND: Studies on the clinical implication of hospital selection for patients with lung cancer are few. Therefore, this study aimed to analyze 2005-2016 data from the Korean national database to assess annual trends of lung cancer surgery and clinical outcomes according to hospital selection. METHODS: Data of 212 554 patients with lung cancer who underwent upfront surgery were screened. Trends according to sex, age, residence, and income were examined. Descriptive statistics were performed, and ptrend values were estimated. The association between survival and hospital selection was assessed using the log-rank test. A multivariate Cox regression analysis was also performed. RESULTS: A total of 49 021 patients were included in this study. Surgery was prevalent among men, patients aged 61-75 years, capital area residents, and high-income patients. However, with the increasing rate of surgery among women, patients aged ≥76 years, city residents, and middle-income patients, the current distribution of lung cancer surgery could change. The rate of lobectomy among these groups increased. All patients, except those in capital areas, preferred a hospital outside their area of residence (HOR); the number of patients with this tendency also increased. However, this trend was not observed among low-income patients and those aged ≥76 years. There were significant differences in survival according to hospital selection. CONCLUSIONS: The trend of lung cancer surgery is changing. The current medical system is effective in providing lobectomy for patients including women, aged ≥76 years, city residents, and middle-income. Increasing tendency to choose an HOR requires further study.

Clinical characteristics, radiological features, and disease severity of bronchiectasis according to the spirometric pattern.

Bronchiectasis show various ventilatory disorders in pulmonary function. The characteristics and severity of patients with bronchiectasis according to these pulmonary dysfunctions are still very limited. This study aimed to evaluate the clinical, radiologic feature and the disease severity of patients with bronchiectasis according to spirometric patterns. We retrospectively evaluated 506 patients with bronchiectasis who underwent pulmonary lung function test (PFT) at a referral hospital between 2014 to 2021. The results showed that cylindrical type was the most common (70.8%) type of bronchiectasis on chest Computed tomography (CT), and 70% of patients had bilateral lung involvement. On the other hand, obstructive ventilatory disorder was the most common (51.6%), followed by normal ventilation (30%) and restrictive ventilatory disorder (18.4%). The modified Medical Research Council (mMRC) was highest in patients with obstructive ventilatory disorders, Modified Reiff score [median (interquartile range)] [6 (3-10), P < 0.001], FACED (FEV1, Age, Chronic colonization, Extension, and Dyspnea) score [3 (1-4), P < 0.001], and Bronchiectasis Severity (BSI) score [8 (5-11), P < 0.001] showed significantly highest values of obstructive ventilatory disorder rather than restrictive ventilatory disorder and normal ventilation. More than half of patients with bronchiectasis had obstructive ventilatory disorder. Bronchiectasis with obstructive ventilatory disorders has more dyspnea symptom, more disease severity and more radiologic severity. There was no significant association between spirometric pattern and radiologic type, but the more severe the radiologic severity, the more severe the lung function impairment.

Multidisciplinary team approach on tracheoesophageal fistula in a patient with home ventilator.

A 68-year-old man was transferred to our tertiary hospital. Ten years ago, he received radiation therapy for tonsil cancer, and while there was no evidence of recurrence, he suffered from recurrent aspiration. We treated his aspiration pneumonia in the intensive care unit. Prior to his discharge, he received percutaneous dilatational tracheostomy (PDT) before he was transferred to a nursing hospital. Nine months later, he was readmitted owing to tracheoesophageal fistula (TEF). However, he was considered unsuitable for conservative intervention after a multidisciplinary team discussion. Esophageal stent insertion was impossible due to the high level of TEF in the esophagus. Additionally, the size of the TEF could not be covered by an endosponge and endoluminal vacuum therapy, and there was no tracheal stent that could cover his large trachea. The preceding percutaneous enteral gastrostomy (PEG) procedure was required for the primary closure operation of the esophagus; however, family's consent could not be obtained. After 1month, the patient and his family changed their minds and agreed to the procedure and we attempted to perform PEG procedure. However, we could not proceed with PEG owing to stenosis in the inlet of the esophagus. Then, the patient deteriorated clinically and died due to pneumonia with septic shock.

Change in perception of the quality of death in the intensive care unit by healthcare workers associated with the implementation of the "well-dying law".

PURPOSE: The importance of dying with dignity in the intensive care unit (ICU) has been emphasized. The South Korean government implemented the "well-dying law" in 2018, which enables patients to refuse futile life-sustaining treatment (LST) after being determined as terminally ill. We aimed to study whether the well-dying law is associated with a significant change in the quality of death in the ICU. METHODS: The Quality of Dying and Death (QODD) questionnaires were prospectively collected from the doctors and nurses of deceased patients of four South Korean medical ICUs after the law was passed (January 2019 to May 2020). Results were compared with those of our previous study, which used the same metric before the law was passed (June 2016 to May 2017). We compared baseline characteristics of the deceased patients, enrolled staff, QODD scores, and staff opinions about withdrawing LST from before to after the law was passed. RESULTS: After the well-dying law was passed, deceased patients (N = 252) were slightly older (68.6 vs. 66.6, p = 0.03) and fewer patients were admitted to the ICU for post-resuscitation care (10.3% vs. 20%, p = 0.003). The mean total QODD score significantly increased after the law was passed (36.9 vs. 31.3, p = 0.001). The law had a positive independent association with the increased QODD score in a multiple regression analysis. CONCLUSION: Our study is the first to show that implementing the well-dying law is associated with quality of death in the ICU, although the quality of death in South Korea remains relatively low and should be further improved.

Clinical profiles and outcomes of pulmonary tuberculosis patients with delayed treatment at a tertiary hospital in South Korea.

BACKGROUND: Data on the clinical characteristics of delayed treatment initiation among pulmonary tuberculosis (TB) patients are lacking. Thus, this study aimed to identify the factors associated with delayed treatment in culture-confirmed pulmonary TB and to assess outcomes of delayed treatment. METHODS: We retrospectively evaluated 151 patients with culture-confirmed pulmonary TB between 2015 and 2017. Delayed and timely treatment was defined as initiation of anti-TB treatment after and before the identification of Mycobacterium tuberculosis complex isolate, respectively. Factors related to delayed treatment, such as comorbidities, clinical presentation, and patterns of initial healthcare use, were collected. We analyzed whether delayed treatment was associated with all-cause mortality using a multivariate binary logistic regression model adjusted for age, sex, cardiovascular disease, and malignancy. RESULTS: In total, 55 (36.4%) patients had delayed treatment. The median length between the first medical visit and treatment initiation was 9 days. Compared with timely treatment, delayed treatment was associated with no initial visit to a non-pulmonary department [adjusted odds ratio (aOR) =10.49, 95% confidence interval (CI), 2.56-42.93] and absence of nucleic acid amplification test (aOR =7.54, 95% CI, 2.75-20.67). After adjusting for age, sex, cardiovascular disease, and solid malignancies, delayed treatment was significantly associated with all-cause mortality (aOR =3.79, 95% CI, 1.36-10.58). The most frequent possible cause of delayed treatment was the doctor's low suspicion of active TB disease. CONCLUSIONS: Given that delayed treatment is associated with worse outcomes in South Korea, targeted interventions to increase awareness on TB in the healthcare community are necessary for additional mycobacterial tests and consults of suspicious patients to TB specialists.

Analysis of avoidable cardiopulmonary resuscitation incidents with a part-time rapid response system in place.

BACKGROUND: Although a rapid response system (RRS) can reduce the incidence of cardiopulmonary resuscitation (CPR) in general wards, avoidable CPR cases still occur. This study aimed to investigate the incidence and causes of avoidable CPR. METHODS: We retrospectively reviewed the medical records of all adult patients who received CPR between April 2013 and March 2016 (35 months) at a tertiary teaching hospital where a part-time RRS was introduced in October 2012. Four experts reviewed all of the CPR cases and determined whether each event was avoidable. RESULTS: A total of 192 CPR cases were identified, and the incidence of CPR was 0.190 per 1,000 patient admissions. Of these, 56 (29.2%) were considered potentially avoidable, with the most common cause being doctor error (n=32, 57.1%), followed by delayed do-not-resuscitate (DNR) placement (n=12, 21.4%) and procedural complications (n=5, 8.9%). The percentage of avoidable CPR was significantly lower in the RRS operating time group than in the RRS non-operating time group (20.7% vs. 35.5%; P=0.026). Among 44 avoidable CPR events (excluding cases related to DNR issues), the rapid response team intervened in only three cases (6.8%), and most of the avoidable CPR cases (65.9%) occurred during the non-operating time. CONCLUSIONS: A significant number of avoidable CPR events occurred with a well-functioning, part-time RRS in place. However, RRS operation does appear to lower the occurrence of avoidable CPR. Thus, it is necessary to extend RRS operation time and modify RRS activation criteria. Moreover, policy and cultural changes are needed prior to implementing a full-time RRS.

Clinical Factors Associated with Cavitary Tuberculosis and Its Treatment Outcomes.

Cavitary pulmonary tuberculosis (TB) is associated with poor outcomes, treatment recurrence, higher transmission rates, and the development of drug resistance. However, reports on its clinical characteristics, associated factors, and treatment outcomes are lacking. Hence, this study sought to evaluate the clinical factors associated with cavitary pulmonary TB and its treatment outcomes. We retrospectively evaluated 410 patients with drug-susceptible pulmonary TB in a university hospital in Korea between 2014 and 2019. To evaluate the factors associated with cavitary TB, multivariable logistic regression was performed with adjustments for potential confounders. We also compared the treatment outcomes between patients with cavitary TB and those without cavitary TB. Of the 410 patients, 244 (59.5%) had non-cavitary TB and 166 (40.5%) had cavitary TB. Multivariable logistic analysis with forward selection method showed that body mass index (BMI) (adjusted OR = 0.88, 95% CI: 0.81-0.97), previous history of TB (adjusted OR = 3.45, 95% CI: 1.24-9.59), ex- or current smoker (adjusted OR = 1.77, 95% CI: 1.01-3.13), diabetes mellitus (adjusted OR = 2.72, 95% CI: 1.36-5.44), and positive results on the initial sputum acid-fast bacilli (AFB) smear (adjusted OR = 2.24, 95% CI: 1.26-3.98) were significantly associated with cavitary TB. Although treatment duration was significantly longer in patients with cavitary TB than in those with non-cavitary TB (248 (102-370 days) vs. 202 (98-336 days), p < 0.001), the recurrence rate after successful treatment was significantly higher in the patients with cavitary TB than in those with non-cavitary TB (0.4% vs. 3.0% p = 0.042). In conclusion, ex- or current smoker, lower BMI, previous history of TB, diabetes mellitus, and positivity of the initial AFB smear were associated with cavitary TB. The patients with cavitary TB had more AFB culture-positive results at 2 months, longer treatment duration, and higher recurrence rates than those with non-cavitary TB.

Genetic Features of Lung Adenocarcinoma with Ground- Glass Opacity: What Causes the Invasiveness of Lung Adenocarcinoma?

BACKGROUND: Lung adenocarcinoma (LUAD) with ground-glass opacity (GGO) can become aggravated, but the reasons for this aggravation are not fully understood. The goal of this study was to analyze the genetic features and causes of progression of GGO LUAD. METHODS: LUAD tumor samples and normal tissues were analyzed using an Illumina HiSeq 4000 system. After the tumor mutational burden (TMB) was calculated, the identified mutations were classified as those found only in GGO LUAD, those present only in non- GGO LUAD, and those common to both tissue types. Ten high-frequency genes were selected from each domain, after which protein interaction network analysis was conducted. RESULTS: Overall, 227 mutations in GGO LUAD, 212 in non-GGO LUAD, and 48 that were common to both tumor types were found. The TMB was 8.8 in GGO and 7.8 in non-GGO samples. In GGO LUAD, mutations of FCGBP and SFTPA1 were identified. FOXQ1, IRF5, and MAGEC1 mutations were common to both types, and CDC27 and NOTCH4 mutations were identified in the non-GGO LUAD. Protein interaction network analysis indicated that IRF5 (common to both tissue types) and CDC27 (found in the non-GGO LUAD) had significant biological functions related to the cell cycle and proliferation. CONCLUSION: In conclusion, GGO LUAD exhibited a higher TMB than non-GGO LUAD. No clinically meaningful mutations were found to be specific to GGO LUAD, but mutations involved in the epithelial-mesenchymal transition or cell cycle were found in both tumor types and in non-GGO tissue alone. These findings could explain the non-invasiveness of GGO-type LUAD.