Continuous positive airway pressure versus high-flow nasal cannula oxygen therapy for acute hypoxemic respiratory failure: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: The relative effectiveness of initial non-invasive respiratory strategies for acute respiratory failure using continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) is unclear. METHODS: We conducted a multicenter, open-label, parallel-group randomized controlled trial to compare the efficacy of CPAP and HFNC on reducing the risk of meeting the prespecified criteria for intubation and improving clinical outcomes of acute hypoxemic respiratory failure. The primary endpoint was the time taken to meet the prespecified criteria for intubation within 28 days. RESULTS: Eighty-five patients were randomly assigned to the CPAP or HFNC group. Eleven (28.9%) in the CPAP group and twenty (42.6%) in the HFNC group met the criteria for intubation within 28 days. Compared with HFNC, CPAP reduced the risk of meeting the intubation criteria (hazard ratio [HR], 0.327; 95% CI, 0.148-0.724; p = 0.006). There were no significant between-group differences in the intubation rates, in-hospital and 28-day mortality rates, ventilator-free days, duration of the need for respiratory support, or duration of hospitalization for respiratory illness. Pulmonary oxygenation was significantly better in the CPAP group, with significantly lower pH and higher partial pressure of carbon dioxide, but there were no differences in the respiratory rate between groups. CPAP and HFNC were associated with few possibly causal adverse events. CONCLUSION: CPAP is more effective than HFNC at reducing the risk of meeting the intubation criteria in patients with acute hypoxemic respiratory failure.

Predictive performance of PD-L1 tumor proportion score for nivolumab response evaluated using archived specimens in patients with non-small cell lung cancer experiencing a postoperative recurrence.

OBJECTIVES: Postoperative recurrence in patients with non-small-cell lung carcinoma (NSCLC) is a major issue for life expectancy. Programmed cell death ligand 1 (PD-L1) expression on tumor cells is important in the prognosis of NSCLC. However, the predictive ability of PD-L1 evaluated with archived surgical specimens for nivolumab treatment have remained unknown. This study was aimed to analyze the predictive ability of the PD-L1 tumor proportion score (TPS) for nivolumab response in patients with NSCLC experiencing a postoperative recurrence using archived surgical specimens. MATERIALS AND METHODS: This retrospective cohort study involved patients with advanced NSCLC (N = 78) treated with nivolumab between April 2016 and September 2018. They were categorized into postoperative recurrence (N = 24) and non-postoperative recurrence (N = 54) groups. The predictive ability of PD-L1 TPS for response to nivolumab treatment in these two groups was determined using receiver operating characteristic (ROC) analysis. Additionally, we evaluated the predictive ability of PD-L1 TPS using rebiopsy specimens collected from the recurrent lesions in six patients of the postoperative recurrence group. RESULTS: PD-L1 TPS exhibited lower predictive performance in the postoperative recurrent group (area under the curve [AUC] = 0.58) compared with that in the non-post operative recurrent group (AUC = 0.81). Furthermore, PD-L1 TPS was significantly increased in rebiopsy specimens. The predictive performance of PD-L1 TPS in these specimens was higher (AUC = 0.90) than that in the archived surgical specimens. CONCLUSION: The study revealed that archived surgical specimens are inadequate for assessing the predictive ability of PD-L1 for nivolumab response, while rebiopsy specimens are adequate.

Home High-Flow Nasal Cannula Oxygen Therapy for Stable Hypercapnic COPD: A Randomized Clinical Trial.

Rationale: The long-term effects of using a high-flow nasal cannula for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease remain unclear. Objectives: To assess whether long-term high-flow nasal cannula use reduces the number of exacerbations and improves other physiological parameters in patients with chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease. Methods: We enrolled 104 participants (aged ⩾40 yr) with daytime hypercapnia (Global Initiative for Chronic Obstructive Lung Disease stages 2-4) receiving long-term oxygen therapy (⩾16 h/d for ⩾1 mo) and randomly assigned them to high-flow nasal cannula/long-term oxygen therapy and long-term oxygen therapy groups. The primary endpoint was the moderate or severe exacerbation rate. We compared changes from baseline in arterial blood gas values, peripheral oxygen saturation, pulmonary function, health-related quality-of-life scores, and the 6-minute-walk test. Measurements and Main Results: High-flow nasal cannula use significantly reduced the rate of moderate/severe exacerbations (unadjusted mean count 1.0 vs. 2.5, a ratio of the adjusted mean count between groups [95% confidence interval] of 2.85 [1.48-5.47]) and prolonged the duration without moderate or severe exacerbations. The median time to first moderate or severe exacerbation in the long-term oxygen therapy group was 25 (14.1-47.4) weeks; this was not reached in the high-flow nasal cannula/long-term oxygen therapy group. High-flow nasal cannula use significantly improved health-related quality of life scores, peripheral oxygen saturation, and specific pulmonary function parameters. No safety concerns were identified. Conclusions: A high-flow nasal cannula is a reasonable therapeutic option for patients with stable hypercapnic chronic obstructive pulmonary disease and a history of exacerbations. Clinical trial registered with www.umin/ac.jp (UMIN000028581) and www.clinicaltrials.gov (NCT03282019).

Reliability of the respiratory rate and oxygenation index for successful high-flow nasal cannula support in coronavirus disease pneumonia: a retrospective cohort study.

BACKGROUND: High-flow nasal cannula (HFNC) therapy is an important non-invasive respiratory support in acute respiratory failure, including coronavirus disease (COVID-19) pneumonia. Although the respiratory rate and oxygenation (ROX) index is a simple and useful predictor for HFNC failure and mortality, there is limited evidence for its use in patients with COVID-19 pneumonia. We aimed to evaluate the ROX index as a predictor for HFNC failure in patients with COVID-19 pneumonia. We also evaluated the ROX index as a predictor for 28-day mortality. METHODS: In this single-center, retrospective, cohort study, 248 patients older than 18 years of age with COVID-19 pneumonia received HFNC therapy for acute respiratory failure. The ROX index was evaluated within 4 h from the start of HFNC therapy. Past medical history, laboratory data, and the ROX index were evaluated as predictors for HFNC failure and 28-day mortality. RESULTS: The ROX index < 4.88 showed a significantly high risk ratio for HFNC failure (2.13 [95% confidence interval [CI]: 1.47 - 3.08], p < 0.001). The ROX index < 4.88 was significantly associated with 28-day mortality (p = 0.049) in patients with COVID-19 pneumonia receiving HFNC therapy. Age, chronic hypertension, high lactate dehydrogenase level, and low ROX index showed significantly high risk ratio for HFNC failure. C-reactive protein level and low ROX index were predictors of 28-day morality. CONCLUSION: The ROX index is a useful predictor for HFNC success and 28-day mortality in patients with COVID-19 pneumonia receiving HFNC therapy. TRIAL REGISTRATION: An independent ethics committee approved the study (Research Ethics Review Committee of Kobe City Medical Center General Hospital [number: zn220303; date: February 21, 2022]), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

Effect of high-flow nasal cannula oxygen therapy on exercise tolerance in patients with idiopathic pulmonary fibrosis: A randomized crossover trial.

BACKGROUND AND OBJECTIVE: Exercise capacity in idiopathic pulmonary fibrosis (IPF) is limited by exercise-induced hypoxaemia. This study aimed to examine the effect of high-flow nasal cannula oxygen therapy (HFNC) on exercise tolerance in patients with IPF. METHODS: We conducted a single-centre, open-label, randomized crossover trial to compare HFNC and Venturi mask (VM) therapy in terms of exercise tolerance. Patients underwent constant-load symptom-limited exercise testing at 80% peak work rate with HFNC or a VM in a randomized order. The settings were 60 L/min and a 50% fraction of inspired oxygen (FiO2 ) for HFNC and 12 L/min and 50% FiO2 for VM. The primary outcome was endurance time, and the secondary outcomes were heart rate (HR), percutaneous oxygen saturation (SpO2 ), dyspnoea and leg fatigue, as determined by the modified Borg Scale at the isotime and endpoint, and the level of comfort while using the devices. RESULTS: Twenty-four participants (75.0% men; age, median [interquartile range]: 77.5 [68.8-83.0] years) were enrolled. Compared with VM, HFNC significantly improved the endurance time (647.5 s [454.0-1014.8] vs. 577.5 s [338.0-861.5]), minimum SpO2 (96.0% [95.0-98.0] vs. 94.0% [92.8-96.0]) and leg fatigue at the isotime (3.0 [1.6-4.0] vs. 5.0 [3.0-6.3]) and endpoint (4.0 [2.8-5.0] vs. 5.0 [3.8-6.3]). Differences in maximum HR, dyspnoea at the isotime and endpoint and comfort were non-significant between HFNC and VM therapy. CONCLUSION: HFNC increased exercise tolerance in patients with stable IPF experiencing exercise-induced hypoxaemia.

Dissociated response and clinical benefit in patients treated with nivolumab monotherapy.

Immune checkpoint inhibitors (ICIs) are effective for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, an unconventional response pattern is sometimes encountered. A dissociated response (DR), characterized by some lesions shrinking and others growing, has been recognized with ICI treatment. In this study, we examined the characteristics and treatment outcomes of DR in previously treated NSCLC patients, receiving nivolumab monotherapy. We conducted a retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab. We assessed the tumor response of each organ using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at the first radiologic evaluation. We investigated treatment outcome and compared overall survival using the Kaplan-Meier Method and log-rank tests. Further, we conducted the same analysis in patients who had previously received chemotherapy or tyrosine kinase inhibitor therapy in our hospital. Between April 2016 and September 2018, 107 patients who received nivolumab fulfilled the inclusion criteria. Of them, 5 (5%) patients showed a DR. There were no specific differences in characteristics between DR and non-DR cases. Patients showing DR had significantly longer overall survival than those showing concordant progressive disease (46.9 vs. 8.2 months, p = 0.038). The frequencies of DR in the ICI, chemotherapy, and tyrosine kinase inhibitor-treated cohorts were 5%, 1%, and 4%, respectively. DR was uncommon, but this presented a distinctive pattern of nivolumab response. Some patients might benefit from continuing nivolumab therapy and may achieve a longer overall survival.

Tumour content ratio matters for detecting epidermal growth factor receptor mutation by cobas test in small biopsies; a retrospective study.

BACKGROUND: Recent studies indicate the benefit of treatment with osimertinib over that with conventional epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for untreated EGFR-mutated non-small cell lung cancer (NSCLC). Cobas ver2 is the only companion diagnostic method for detecting EGFR mutations with osimertinib treatment. We clinically experience false negative cases with this test, but its actual sensitivity is unknown. Moreover, no study has suggested the importance of tumour dissection, and most facilities do not routinely perform them on small biopsies. The purpose of this study was to evaluate the sensitivity of cobas in clinical practice and clarify the role of dissection as a component of the cobas testing. METHODS: We examined 132 patients with EGFR-mutated NSCLC diagnosed by bronchoscopy and confirmed with PCR clamp. Patients were tested with cobas and the EGFR-positive rate was calculated. Samples with undetected EGFR mutations were retested after tumour dissection and the rate of samples whose EGFR mutation was corrected to positive was assessed. To evaluate tumour cellularity, the tumour content ratio was assessed by calculating tumour cell count over the total cell count on the slide. RESULTS: The positive rate of EGFR mutation identification was 76% with cobas, although EGFR mutation-negative patients retained responses to TKI therapy equivalent to positive patients did; however, the tumour content ratio of negative samples was significantly lower than that of positive samples. Twenty-nine negative samples underwent dissection and 24% were corrected to positive. Moreover, 53% of the samples with a tumour content ratio below 10% was negative for cobas, but 33% of these turned positive after dissection. CONCLUSIONS: Cobas had a high false negative rate in clinical practice, and tumour content ratio might be associated with this rate. Dissection could improve the sensitivity of cobas, especially in samples with low tumour cellularity.

Early depth of tumor shrinkage and treatment outcomes in non-small cell lung cancer treated using Nivolumab.

Background It would be useful to have criteria for predicting long-term treatment responses to immune checkpoint inhibitors (ICIs). Maximum depth of response correlates with treatment outcomes among patients receiving programmed death protein 1 axis inhibitors for non-small cell lung cancer (NSCLC). We investigated associations between early depth of response and survival outcomes among patients receiving nivolumab for NSCLC. Methods Using records from prospective observational cohorts, we identified 83 previously treated advanced patients with NSCLC who received nivolumab during 2016-2017. Thirty-one patients who achieved disease control were analyzed. Tumor assessments followed the Response Evaluation Criteria in Solid Tumors (RECIST). Using Kaplan-Meier and receiver operating characteristic (ROC) curve analyses, treatment outcomes were compared with percent tumor reductions from baseline to the first evaluation (8-12 weeks after starting nivolumab). Results Early depth of response was predictive of 6-month progression-free survival (area under the ROC curve, 0.848). Based on ROC results, early tumor shrinkage was defined as a > 10% reduction by the first evaluation. Early tumor shrinkage was associated with significantly longer median progression-free survival (early tumor shrinkage: 16.6 months, 95% confidence interval [CI] 8.5 months-not reached; no early shrinkage: 5.1 months, 95% CI 3.9-6.8 months; P < 0.001) and significantly longer median overall survival (P = 0.046). Conclusions Early depth of tumor shrinkage was associated with outcomes after ICI treatment. Because of its simplicity and predictive ability, early tumor shrinkage may be a promising factor for use in clinical settings. However, confirmation of our results is needed.

Pulmonary artery enlargement predicts poor outcome during acute exacerbations of fibrotic interstitial lung disease.

BACKGROUND AND OBJECTIVE: In fibrotic interstitial lung disease (f-ILD), pulmonary artery diameter to ascending aorta diameter ratio (PA/A) ≥ 1 during the stable stage is associated with worse outcomes; however, the effect of acute exacerbation (AE) on the PA/A is unknown. METHODS: Patients with a diagnosis of AE of f-ILD and with a computed tomography (CT) scan performed during stable period to confirm background fibrosis, as well as a CT scan at admission, were included. The pulmonary arterial diameter, ascending aortic diameter and PA/A were measured using CT during AE and CT prior to AE, when available, to evaluate the changes. Demographic data, co-morbidities and clinical outcome (90-day mortality) were analysed. RESULTS: Of the 123 patients included, 45 had a PA/A ≥ 1 during AE and compared to the PA/A < 1 group, they were younger, had lower % vital capacity (VC) and % forced vital capacity (FVC), required more long-term oxygen therapy and other treatments, and had lower PaO2 /FiO2 (P/F) ratios. During AE, the PA/A increased from that during stable periods (P < 0.001), and a PA/A ≥ 1 was significantly associated with 90-day mortality both before and after adjustment for age, the P/F ratio at admission, long-term oxygen therapy usage and the type of background f-ILD (P = 0.018 and 0.025). CONCLUSION: To the best of our knowledge, this is the first longitudinal examination of the PA/A ratio and evaluation during AE of f-ILD. Our data show that a PA/A ≥ 1 during AE predicted poor survival outcome in f-ILD.

Natural history and clinical characteristics of multiple pulmonary nodules with ground glass opacity.

BACKGROUND AND OBJECTIVE: Ground glass nodules (GGNs) are frequently encountered in the lungs. We report the natural history and characteristics of multiple GGNs, and propose a management plan for patients with multiple GGNs. METHODS: We retrospectively analysed patients with GGNs that met the following criteria: (i) GGN diameter of 3 cm or less, (ii) ground glass opacity proportion of 50% or more and (iii) observation without treatment for ≥6 months. We evaluated size changes in computed tomography images. Two end points, 'incidence of growth at 36 months' and 'time to growth' were analysed using logistic regression models and Cox proportional hazards model. RESULTS: Between April 2008 and December 2014, 187 patients fulfilled the inclusion criteria (78 (42%) had multiple lesions). Among the multiple-GGN patients, the median observation period was 45.5 months, 25 patients (32%) experienced GGN progression at 36 months and 4 patients (5.1%) after 36 months. Between the multiple and single GGNs, there were no significant differences in growth incidence at 36 months (P = 0.1), after 36 months (P = 0.6) or in time to growth (P = 0.3). Among patients with multiple GGNs who experienced one GGN growth, 41% of patients experienced residual GGN growth afterwards. CONCLUSION: Patients with multiple GGNs showed a tendency to growth within the first 36 months, and a significant proportion of patients experienced multiple GGN progression. We suggest that the optimal observation period for patients with multiple GGNs is 36 months, but careful observation is needed after a lesion begins to grow.

The prognostic value of serum CA 19-9 for patients with advanced lung adenocarcinoma.

BACKGROUND: This study aimed to assess the prognostic accuracy of serum CA 19-9 in patients with advanced lung adenocarcinoma. METHODS: We retrospectively reviewed data of 246 patients who were diagnosed at our institute with advanced (stage IIIB or IV) lung adenocarcinoma between March 2006 and December 2012. We excluded patients who received no chemotherapy, or for whom we had no data on pre-treatment tumor markers. We also evaluated 116 consecutive resected specimens from patients with clinical stage I lung adenocarcinoma pathologically. RESULTS: The 76 (31 %) patients who were CA 19-9+ had shorter overall survival (OS) than CA 19-9- group (12.5 vs 26.2 months, P = 0.005). Cox's multivariate regression analysis identified Eastern Cooperative Oncology Group Performance Status 0 or 1 (P < 0.001), mutated epidermal growth factor receptor (EGFR) status (P < 0.001), stage IIIB (P < 0.001), CYFRA 21-1- (P < 0.001), CA 19-9- (P = 0.005) and use of platinum doublet therapy (P = 0.034) as independent predictors of longer OS. We stratified patients by CA 19-9 and CYFRA 21-1 as double positive (CA 19-9+/CYFRA 21-1+, n = 59), single positive (either CA19-9+ or CYFRA 21-1+, n = 113), or double negative (CA 19-9-/CYFRA 21-1-, n = 74). Their respective OS were 10.0, 23.3 and 31.8 months (P < 0.001). Pathological analysis also correlated CA 19-9 expression with malignant features such as vessel invasion, pleural invasion, cancer invasive factors and mucin production. CONCLUSIONS: CA 19-9 and CYFRA 21-1 are independent prognostic markers in patients with advanced lung adenocarcinoma. Combined use of CA 19-9 and CYFRA 21-1 provides further prognostic information in patients with advanced lung adenocarcinoma.

Analysis of advanced lung cancer patients diagnosed following emergency admission.

Data on prognosis and predictors of overall survival in advanced lung cancer patients diagnosed following emergency admission (DFEA) are currently lacking. We retrospectively analysed data from 771 patients with advanced nonsmall cell lung cancer between April 2004 and April 2012. Of the 771 patients, 103 (13%) were DFEA. DFEA was not an independent predictor of overall survival by multivariate Cox proportional hazard models, whereas good performance status (PS), epidermal growth factor receptor gene mutation, stage IIIB, adenocarcinoma and chemotherapy were independent predictors of overall survival (hazard ratio (95% CI) 0.36 (0.29-0.44), p<0.001; 0.49 (0.38-0.63), p<0.001; 0.64 (0.51-0.80), p<0.001; 0.81 (0.67-0.99), p=0.044; and 0.40 (0.31-0.52), p<0.001, respectively). Good PS just prior to opting for chemotherapy, but not at emergency admission, was a good independent predictor of overall survival in DFEA patients (hazard ratio (95% CI) 0.26 (0.12-0.55); p<0.001). DFEA is relatively common. DFEA and PS at emergency admission were not independent predictors of overall survival, but good PS just prior to opting for chemotherapy was an independent predictor of longer overall survival. Efforts to improve patient PS after admission should be considered vital in such circumstances.

Role of sedation for agitated patients undergoing noninvasive ventilation: clinical practice in a tertiary referral hospital.

BACKGROUND: Although sedation is often required for agitated patients undergoing noninvasive ventilation (NIV), reports on its practical use have been few. This study aimed to evaluate the efficacy and safety of sedation for agitated patients undergoing NIV in clinical practice in a single hospital. METHODS: We retrospectively reviewed sedated patients who received NIV due to acute respiratory failure from May 2007 to May 2012. Sedation level was controlled according to the Richmond Agitation Sedation Scale (RASS). Clinical background, sedatives, failure rate of sedation, and complications were evaluated by 1) sedative methods (intermittent only, switched to continuous, or initially continuous) and 2) code status (do-not-intubate [DNI] or non-DNI). RESULTS: Of 3506 patients who received NIV, 120 (3.4 %) consecutive patients were analyzed. Sedation was performed only intermittently in 72 (60 %) patients, was switched to continuously in 37 (31 %) and was applied only continuously in 11 (9 %). Underlying diseases in 48 % were acute respiratory distress syndrome/acute lung injury/severe pneumonia or acute exacerbation of interstitial pneumonia. In non-DNI patients (n = 39), no patient required intubation due to agitation with continuous sedation, and in DNI patients (n = 81), 96 % of patients could continue NIV treatment. PaCO2 level changes (6.7 ± 15.1 mmHg vs. -2.0 ± 7.7 mmHg, P = 0.028) and mortality in DNI patients (81 % vs. 57 %, P = 0.020) were significantly greater in the continuous use group than in the intermittent use group. CONCLUSIONS: According to RASS scores, sedation during NIV in proficient hospitals may be favorably used to potentially avoid NIV failure in agitated patients, even in those having diseases with poor evidence of the usefulness of NIV. However, with continuous use, we must be aware of an increased hypercapnic state and the possibility of increased mortality. Larger controlled studies are needed to better clarify the role of sedation in improving NIV outcomes in intolerant patients.

Detection of herpes viruses by multiplex and real-time polymerase chain reaction in bronchoalveolar lavage fluid of patients with acute lung injury or acute respiratory distress syndrome.

BACKGROUND: Human herpes viruses (HHVs) are important pathogens in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Rapid and efficient diagnostic tools are needed to detect HHVs in the lung in ALI/ARDS patients. OBJECTIVES: This study aimed to evaluate the usefulness of multiplex and real-time polymerase chain reaction (PCR) analysis of bronchoalveolar lavage fluid (BALF) for detecting HHV reactivation in ALI/ARDS patients. METHODS: Between August 2008 and July 2012, eighty-seven BALF samples were obtained from ALI/ARDS patients with unknown etiology and analyzed for HHVs. The types of HHVs in the BALF samples were determined using qualitative multiplex PCR followed by quantitative real-time PCR. RESULTS: Multiplex PCR identified herpes simplex virus type 1 (HSV-1) (n = 11), Epstein-Barr virus (EBV) (n = 16), cytomegalovirus (CMV) (n = 21), HHV type 6 (HHV-6) (n = 2), and HHV-7 (n = 1) genomic DNA in 35 (40%) of the BALF samples, including 14 (16%) samples containing 2 or 3 HHV types. CMV and EBV reactivation was rare in immunocompetent patients, whereas reactivation of HSV-1 was predominantly observed in intubated patients regardless of their immune status. Overall, HHVs were almost exclusively found in patients with immunosuppression or endotracheal intubation. Real-time PCR detected 0.95-1.59 × 10(6) copies of viral DNA/µg human genome DNA, and HSV-1 (n = 4), CMV (n = 9), and HHV-6 (n = 1) were identified as potentially pathogenic agents. CONCLUSIONS: The implementation of multiplex and real-time PCR of BALF was feasible in ALI/ARDS patients, which allowed efficient detection and quantification of HHV DNA.

Comparison of two transport systems available in Japan (TERUMO kenkiporter II and BBL Port-A-Cul) for maintenance of aerobic and anaerobic bacteria.

The kenkiporter II (KP II) transport system is commonly used in many hospitals in Japan for transporting bacterial specimens to microbiology laboratories. Recently, the BBL Port-A-Cul (PAC) fluid vial became available. However, no reports thus far have compared the effectiveness of these two transport systems. We chose 4 aerobic and facultative anaerobic bacteria as well as 8 anaerobic organisms, and prepared three strains of each bacterium in culture media for placement into PAC and KP II containers. We compared the effectiveness of each transport system for preserving each organism at 6, 24, and 48 h after inoculation at room temperature. Thirty-six strains out of 12 bacteria were used in this study. The PAC system yielded better recovery in quantity of organisms than the KP II system at 6, 24 and 48 h. More strains were significantly recovered with the PAC system than with the KP II at 24 h (36/36 vs. 23/36, P < 0.001) and 48 h (30/36 vs. 12/36, P < 0.001). The PAC system was better in the recovery of viable organisms counted at 24 and 48 h after inoculation compared with the KP II system. The PAC system may be recommended for the transfer of bacterial specimens in clinical settings.

Prognostic impact of cytokines and chemokines in bronchoalveolar lavage fluid on acute exacerbation of fibrosing interstitial lung disease.

BACKGROUND AND OBJECTIVE: Acute exacerbation of fibrosing interstitial lung disease (AE-FILD) is a serious condition with a high mortality rate. We aimed to comprehensively analyze cytokines in bronchoalveolar lavage fluid and their association with the clinical course of AE-FILD. METHODS: We retrospectively enrolled 60 patients with AE-FILD who underwent bronchoalveolar lavage. We comprehensively measured 44 cytokines and chemokines in the obtained bronchoalveolar lavage fluid using a Luminex analyzer. Patients were grouped into those who died within 90 days (non-survival group) and survived beyond 90 days (survival group) to investigate the association of the levels of cytokines and chemokines with mortality. RESULTS: The levels of matrix metalloproteinase 1 (p = 0.003), granulocyte-macrophage colony-stimulating factor (p = 0.040), interleukin 6 (p = 0.047), interleukin 8 (p = 0.050), monocyte chemoattractant protein-1 (p = 0.043), and eotaxin (p = 0.044) were significantly higher in the non-survival group than in the survival group. In the receiver operating characteristic analysis, their areas under the curve were 0.80, 0.68, 0.71, 0.70, 0.70, and 0.72, respectively. Using machine learning with these six cytokines and chemokines, the predictive accuracy for the survival group was 0.94. CONCLUSIONS: Our study demonstrated that several cytokines and chemokines in bronchoalveolar lavage fluid could be prognostic predictors in patients with AE-FILD.

Rebiopsy of non-small cell lung cancer patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor: Comparison between T790M mutation-positive and mutation-negative populations.

BACKGROUND: The secondary epidermal growth factor receptor (EGFR) mutation Thr790Met (T790M) accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitor (TKI). Recent reports have demonstrated that the emergence of T790M predicts a favorable prognosis and indolent progression. However, rebiopsy to confirm T790M status can be challenging due to limited tissue availability and procedural feasibility, and little is known regarding the differences among patients with or without T790M mutation. METHODS: The study investigated 78 EGFR-mutant patients who had undergone rebiopsy after TKI failure. The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method was used in EGFR mutational analyses. Various patient characteristics and postprogression survivals (PPSs) after initial TKI failure were retrospectively compared in patients with and without T790M. RESULTS: The T790M mutation was identified in 4 (17%) of 24 central nervous system lesions, and in 22 (41%) of 54 other lesions (P = .0417). No other characteristics had a statistical association with T790M prevalence. Median PPS was 31.4 months in 26 patients with T790M, and 11.4 months in 52 patients without T790M (P = .0017). In the multivariate analysis, statistically significant factors for longer PPS included T790M-positive, good performance status, and no carcinomatous meningitis. CONCLUSIONS: The emergence of T790M in central nervous system lesions was rare, compared with other lesions. Patients with T790M after TKI failure appear to have better prognoses than those without T790M. TKI rechallenge or continuous administration beyond progression may be effective after initial TKI failure.