Cytokine profiling identifies circulating IL-6 and IL-15 as prognostic stratifiers in patients with non-small cell lung cancer receiving anti-PD-1/PD-L1 blockade therapy.

Whether circulating levels of specific cytokines at baseline link with treatment efficacy of immune checkpoint blockade (ICB) therapy in patients with non-small cell lung cancer remains unknown. In this study, serum samples were collected in two independent, prospective, multicenter cohorts before the initiation of ICB. Twenty cytokines were quantified, and cutoff values were determined by receiver operating characteristic analyses to predict non-durable benefit. The associations of each dichotomized cytokine status with survival outcomes were assessed. In the discovery cohort (atezolizumab cohort; N = 81), there were significant differences in progression-free survival (PFS) in accordance with the levels of IL-6 (log-rank test, P = 0.0014), IL-15 (P = 0.00011), MCP-1 (P = 0.013), MIP-1ß (P = 0.0035), and PDGF-AB/BB (P = 0.016). Of these, levels of IL-6 and IL-15 were also significantly prognostic in the validation cohort (nivolumab cohort, N = 139) for PFS (log-rank test, P = 0.011 for IL-6 and P = 0.00065 for IL-15) and overall survival (OS; P = 3.3E-6 for IL-6 and P = 0.0022 for IL-15). In the merged cohort, IL-6high and IL-15high were identified as independent unfavorable prognostic factors for PFS and OS. The combined IL-6 and IL-15 status stratified patient survival outcomes into three distinct groups for both PFS and OS. In conclusion, combined assessment of circulating IL-6 and IL-15 levels at baseline provides valuable information to stratify the clinical outcome of patients with non-small cell lung cancer treated with ICB. Further studies are required to decipher the mechanistic basis of this finding.

Increased serum cholesterol and long-chain fatty acid levels are associated with the efficacy of nivolumab in patients with non-small cell lung cancer.

BACKGROUND: Lipids have immunomodulatory functions and the potential to affect cancer immunity. METHODS: The associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab. RESULTS: When each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P < 0.001), high-density lipoprotein (HDL)-cholesterol (P = 0.014), total cholesterol (P = 0.007), lauric acid (P = 0.015), myristic acid (P = 0.022), myristoleic acid (P = 0.035), stearic acid (P = 0.028), linoleic acid (P = 0.005), arachidic acid (P = 0.027), eicosadienoic acid (P = 0.017), dihomo-γ-linolenic acid (P = 0.036), and behenic acid levels (P = 0.032) were associated with longer PFS independent of programmed death ligand 1 (PD-L1) expression. Meanwhile, increased LDL-cholesterol (P < 0.001), HDL-cholesterol (P = 0.009), total cholesterol (P = 0.036), linoleic acid (P = 0.014), and lignoceric acid levels (P = 0.028) were associated with longer OS independent of PD-L1 expression. When multiple lipids were evaluated simultaneously, LDL-cholesterol (P = 0.003), HDL-cholesterol (P = 0.036), and lauric acid (P = 0.036) were independently predictive of PFS, and LDL-cholesterol (P = 0.008) and HDL-cholesterol (P = 0.031) were predictive of OS. ORR was not associated with any serum lipid. CONCLUSIONS: Based on the association of prolonged survival in patients with increased serum cholesterol and long-chain fatty acid levels, serum lipid levels may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.

Blood eosinophil count and FeNO to predict benralizumab effectiveness in real-life severe asthma patients.

OBJECTIVE: Benralizumab is a promising drug for severe uncontrolled asthma. This study aimed to clarify the effectiveness of benralizumab in a real-life setting. METHODS: Subjects included 24 patients with severe type 2 asthma who received benralizumab between April 2018 and July 2019. Changes in parameters, exacerbation frequency, and oral corticosteroid (OCS) use after 4 and 24 weeks of administration were examined. The parameters included the Global Evaluation of Treatment Effectiveness (GETE) scale, Asthma Control Questionnaire (ACQ), Asthma Control Test (ACT), blood eosinophils, fractional exhaled nitric oxide (FeNO), and spirometry. The response to treatment was defined as follows: for patients with exacerbations or OCS use before treatment initiation, a reduction of ≥50% in exacerbation frequency or OCS use; and for patients without exacerbations or OCS use, an improvement of ≥0.5 in ACQ scores and ≥3 in ACT scores, or of ≥10.38% in FEV1. RESULTS: Twenty-one patients completed the treatment for 24 weeks. Excellent and good GETE scales and ACQ and ACT improvement were found in 67% of the patients at 4 weeks, and the effect continued until 24 weeks. The patients' rate with exacerbations was significantly reduced compared to the previous 24 weeks before administration. In 17 patients receiving OCS, the use could be reduced or quit in 14 patients. Overall, 16 patients (76.2%) met the responder definition and could be predicted by the baseline eosinophil count and FeNO levels with the best cutoff values of 100/µL and 40 ppb, respectively. CONCLUSIONS: Blood eosinophil and FeNO could predict benralizumab effectiveness.

Erlotinib and bevacizumab in elderly patients ≥75 years old with non-small cell lung cancer harboring epidermal growth factor receptor mutations.

The efficacy and safety of combination therapy with erlotinib and bevacizumab in elderly patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations are unknown. Elderly patients aged ≥75 years old with advanced or recurrent NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) received erlotinib (150 mg, daily) and bevacizumab (15 mg/kg on day 1 of a 21-day cycle) until disease progression or the occurrence of unacceptable toxicities. The primary endpoint was progression-free survival from enrollment. Twenty-five patients were enrolled in this study, and the median age was 80 years. Fifteen (60.0%) and 10 patients (40.0%) had exon 21 L858R mutations and exon 19 deletions, respectively. The median progression-free survival from enrollment was 12.6 months [95% confidence interval (CI): 8.0-33.7 months]. The objective response rate was 88.0% [95% CI: 74.0%-99.0%], and the disease control rate was 100% [95% CI: 88.7%-100%]. Grade 3 or higher adverse events occurred in 12 patients (48.0%), and rash and nausea were the most common. Grade 3 or higher bevacizumab-related toxicities occurred in 4 (16.0%) patients, including proteinuria (n = 2), gastrointestinal perforation (n = 1) and pneumothorax (n = 1). A dose reduction of erlotinib and cessation of bevacizumab was required in 16 (64.0%) and 18 patients (72.0%), respectively. Erlotinib and bevacizumab combination therapy showed a minimal survival benefit with frequent dose reductions and/or treatment discontinuations in elderly patients with EGFR-positive NSCLC.

Clinical utility of liquid biopsy for EGFR driver, T790M mutation and EGFR amplification in plasma in patients with acquired resistance to afatinib.

BACKGROUND: Cell-free DNA (cfDNA) genotyping in plasma using the cobas EGFR Mutation Test v2 (cobas) is the first liquid biopsy as a companion diagnosis to identify the EGFR T790M mutation (T790M) after the failure of treatment of EGFR-tyrosine kinase inhibitors (TKIs) (1st generation, gefitinib [G] and erlotinib [E] and 2nd generation, afatinib [A]). This study investigated the clinical utility of a liquid biopsy for patients who acquired resistance to afatinib. METHODS: We prospectively collected plasma from 51 patients who had acquired resistance to afatinib between April 2015 and November 2016 to evaluate the frequency of T790M by cobas and digital droplet PCR (UMIN000025112). Additionally, we retrospectively reviewed 38 patients who tested by cobas in plasma after G/E failure to compare for T790M detection between A and with G/E. RESULTS: The detection rate of EGFR-driver and T790M in plasma in patients treated with A (A group) as a first-line EGFR-TKI was lower than with G/E followed by A (G/E→A group), although the differences were not significant (EGFR-driver: 41% [A] vs. 67% [G/E→A], P=0.1867; and T790M: 8% [A] vs. 17% [G/E→A], P=0.5798). In first-line setting, the detection rate for EGFR-driver and T790M in plasma by cobas was lower in A group than in G/E group, although there was no significant difference (EGFR-driver: 34% [A] vs. 52% [G/E], P=0.2072; and T790M: 10% [A] vs. 27% [G/E], P=0.1161). CONCLUSION: The detection of EGFR-driver and T790M in plasma by cobas in patients treated with afatinib might be lower than with G/E in a real-world setting.

Effectiveness of a 23-valent pneumococcal polysaccharide vaccine for the prevention of pneumococcal pneumonia in the elderly with chronic respiratory diseases: a case-control study of a single center.

BACKGROUND: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial. METHODS: To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case-control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department. RESULTS: There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12). CONCLUSION: This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases.

Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with uncommon histology: a propensity-score-matched analysis.

BACKGROUND: Clinical efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with uncommon histology (uNSCLC) is unknown. METHODS: Patients with NSCLC treated with ICI monotherapy between January 2014 and December 2018 in 10 Japanese hospitals were retrospectively evaluated. The patients were divided into: (1) NSCLC with common histology (cNSCLC), defined as adenocarcinoma and squamous cell carcinoma; and (2) uNSCLC, defined as incompatibility with morphological and immunohistochemical criteria for adenocarcinoma or squamous cell carcinoma. Propensity score matching was performed to balance the two groups. RESULTS: Among a total of 175 patients included, 44 with uNSCLC (10 pleomorphic carcinomas, 9 large cell neuroendocrine carcinomas, 2 large cell carcinomas, and 23 not otherwise specified) and 44 with matched cNSCLC (32 adenocarcinomas and 12 squamous cell carcinomas) were selected for analyses. Median progression-free survival (PFS) (4.4 months, 95% confidence interval [CI] 1.8-7.7 months) and overall survival (OS) (11.4 months, 95% CI 7.4-27.4 months) in the uNSCLC patients were not significantly different from those in matched cNSCLC patients (5.4 months, 95% CI 3.1-7.6 months, p = 0.761; and 14.1 months, 95% CI 10.6-29.6 months, p = 0.381). In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-1 and programmed death ligand-1 (PD-L1) expression were predictive for PFS and OS in uNSCLC. CONCLUSIONS: ICIs had similar clinical efficacy for treatment of uNSCLC and cNSCLC. Good ECOG-PS and PD-L1 expression were predictive for efficacy of ICIs in uNSCLC.

Propensity score analysis of overall survival between first- and second-generation EGFR-TKIs using real-world data.

We constructed a data set of EGFR-mutant non-small-cell lung carcinoma (NSCLC) patients, and compared the overall survival of first-generation (1G), and second-generation (2G) EGFR-tyrosine kinase inhibitors (TKIs) in clinical practice using a propensity score. We reviewed the clinical data of consecutive EGFR-mutated NSCLC patients who received EGFR-TKI therapy between January 2008 and August 2017 at 11 institutions in Japan. The primary endpoint was overall survival (OS). When comparing OS between 1G and 2G EGFR-TKIs, propensity score analyses were performed using 2 methods: matching and inverse probability of treatment weighting (IPTW). (Clinical Trial information: UMIN000030121) In total, 1400 patients from 11 institutions were enrolled in this study, and the data from the 1366 patients who received only EGFR-TKI therapy were analyzed (gefitinib [GEF], N = 732; erlotinib [ERL], N = 416; afatinib, N = 218). Median OS times (months [95%CI]) were 29.7 [27.5-33.5] in the 1G group (gefitinib, 32.0 [28.1-35.8]; erlotinib, 27.5 [23.9-31.7]), and 38.6 [32.2-NR] in the 2G group (afatinib), respectively. The trend of longer OS for afatinib against 1G EGFR-TKIs remained, even after adjusted by propensity score. (unadjusted, hazard ratio [HR] 0.676, P = .0023; adjusted by IPTW, HR 0.685 P < .0001; adjusted by matching, HR 0.725, P = .0418). Exploratory analysis showed that OS using the 2G EGFR-TKI was superior to that of the 1G EGFR-TKIs, suggesting the potential of sequential therapy of 2G EGFR-TKI followed by osimertinib. (HR 0.419, P = .0519) Real-world data analysis using 1354 data records, using propensity scoring, indicated that 2G EGFR-TKI had a trend of longer OS compared with 1G EGFR-TKIs.

Oscillometry as a Predictor of Exercise Tolerance in COPD.

The usefulness of the oscillometry, known as forced oscillation technique, for predicting exercise tolerance in subjects with COPD is unknown. To test the hypothesis, we investigated whether oscillometry could predict a 6-minute walking distance (6MWD) <350 m in the 6-minute walk test (6MWT).This was a prospective, observational study. Fifty-seven subjects with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between April 2015 and April 2016 (54 males; median age, 70 years; and %FEV1, 61.0%). Modified MRC dyspnea scale (mMRC), COPD Assessment Test (CAT), oscillometry, spirometry, and 6MWT were performed in a stable condition. The participants were classified into subjects with 6MWD ≥350 m or 6MWD <350 m, and the predictor of 6MWD <350 m was assessed.Of the 57 total subjects, 43 (75.4%) had a 6MWD ≥350 m, and 14 (24.6%) had a 6MWD <350 m. Between the two groups, there were significant differences in mMRC scale, GOLD stages, CAT scores, FEV1, IC, 6MWD, lowest SpO2, maximum Borg scale, respiratory resistance (Rrs), and reactance (Xrs). In multivariate regression analysis, a 6MWD <350 m was independently predicted by CAT scores (OR 1.15, 95% CI: 1.01-1.30) and inspiratory R5 (OR 6.01, 95% CI: 1.09-33.30). In receiver operating characteristic curves, the area under the curve was 0.76, 0.78, and 0.85 for CAT scores, R5, and CAT scores + R5, respectively, with the best cutoff value of 17 and 2.82 cmH20/L/s. In conclusion, the oscillatory parameter, inspiratory R5, predicted low exercise tolerance in COPD subjects.

Switch maintenance therapy with S-1 after induction therapy with carboplatin and nanoparticle albumin-bound paclitaxel in advanced lung squamous cell carcinoma.

Background Optimal maintenance therapy for lung squamous cell carcinoma (SCC) has not been established. The aim of this study was to evaluate the efficacy and safety of switch maintenance therapy with S-1, an oral fluoropyrimidine, after induction therapy with carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in chemotherapy-naïve patients with advanced SCC. Methods Chemotherapy-naïve patients with advanced SCC received induction therapy with four cycles of carboplatin (at an area under the curve of 6, day 1 of a 28-day cycle) and nab-paclitaxel (100 mg/kg, days 1, 8, and 15). Patients who achieved disease control after induction therapy received maintenance therapy with S-1 (80 mg/m2, days 1-14 of a 21-day cycle) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) from the start of maintenance therapy. Results Seventy-two patients with SCC were enrolled to the study. After four cycles of induction therapy, 35 (48.6%) patients achieved disease control, and 31 (43.1%) of these patients received maintenance therapy. Median PFS from the start of maintenance therapy was 3.0 months (95% confidence interval: 2.1-3.8 months). The most common toxicities of grade 3 or higher during maintenance therapy were nausea (13.3%), neutropenia (10.0%), and diarrhea (6.7%). Conclusions Switch maintenance therapy with S-1 after induction therapy with carboplatin and nab-paclitaxel was associated with moderate efficacy and acceptable safety and may represent a feasible treatment option for patients with advanced SCC.

Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung.

BACKGROUND: There are few reports about the factor influencing the prognosis of high-grade neuroendocrine carcinoma. In this study, we evaluated surgical outcome of clinical stage I high-grade neuroendocrine carcinoma. METHODS: Patients who underwent curative surgery for high-grade neuroendocrine tumors of the lung in clinical stage I were included in this study. We retrospectively analyzed 27 consecutive patients. The aim of this study was to clarify the clinical course of the disease after surgery and what factors influence the prognosis. RESULTS: Twenty-two patients have small cell carcinoma, and 5 patients have large cell neuroendocrine carcinoma. Patients who could undergo surgery within 60 days after the first visit (p < 0.01) and undergo lobectomy (p < 0.01) and whose pro-gastrin-releasing peptide ≦ 72 pg/ml (p = 0.04) performed good prognosis after surgery. In multivariate analysis, surgery within 60 days and operative procedure were independent factors associated with OS. CONCLUSION: Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung should be performed as early as possible, and better outcome can be obtained with lobectomy than partial resection.

Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

Management of brain metastasis with magnetic resonance imaging and stereotactic irradiation attenuated benefits of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer.

BACKGROUND: Magnetic resonance imaging (MRI) enables a more sensitive detection of brain metastasis and stereotactic irradiation (SRI) efficiently controls brain metastasis. In limited-stage small cell lung cancer (LS-SCLC), prophylactic cranial irradiation (PCI) in patients with good responses to initial treatment is recommended based on the survival benefit shown in previous clinical trials. However, none of these trials evaluated PCI effects using the management of brain metastasis with MRI or SRI. This study aimed to determine the effects of MRI and SRI on the benefits of PCI in patients with LS-SCLC. METHODS: The clinical records of pathologically proven SCLC from January 2006 to June 2013 in facilities equipped with or had access to SRI in Japan were retrospectively reviewed. Patients with LS-SCLC and complete or good partial responses after initial treatment were included in the study and analyzed by the Kaplan-Meier method. RESULTS: Of 418 patients with SCLC, 124 met criteria and were divided into patients receiving PCI (PCI group; n = 29) and those without PCI (non-PCI groups; n = 95). At baseline, ratios of patients with stage III were significantly advantageous for the non-PCI group, although younger age and high ratios of complete response and MRI confirmed absence of brain metastasis were advantageous for the PCI group. Neither median survival times (25 vs. 34 months; p = 0.256) nor cumulative incidence of brain metastasis during 2 years (45.5 vs. 30.8%; p = 0.313) significantly differed between the two groups. Moreover, these factors did not significantly differ among patients with stage III disease (25 vs. 26 months; p = 0.680, 42.3 vs. 52.3%; p = 0.458, respectively). CONCLUSION: PCI may be less beneficial in patients with LS-SCLC if the management with MRI and SRI is available.

Real-world effect of gastroesophageal reflux disease on cough-related quality of life and disease status in asthma and COPD.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and often coexists with asthma or chronic obstructive pulmonary disease (COPD); however, it is unknown whether there are differences in the effect of GERD on these diseases. The purpose of this study was to assess the difference in the effect of GERD on cough-related quality of life and disease status in asthma and COPD in a real-world setting. METHODS: Subjects were 132 patients with overall controlled asthma and 102 patients with stable COPD. They completed the frequency scale for symptoms of GERD (FSSG), a validated Japanese questionnaire for GERD, the Leicester Cough Questionnaire (LCQ), and the Asthma Control Test (ACT) or COPD assessment test (CAT) questionnaires. RESULTS: We found that 29 (22.0%) patients with asthma and 22 (21.6%) patients with COPD had GERD. There was no difference in the FSSG scale between the diseases. The patients with GERD, regardless of having asthma or COPD, had lower LCQ scores affecting all health domains and lower ACT or higher CAT scores than those without GERD. Overall, the patients with COPD had lower LCQ scores regardless of the presence or absence of GERD. The FSSG scale was negatively correlated with the LCQ total score in asthma and in COPD. In contrast, the FSSG scale was positively correlated with the CAT score but not with the ACT score. CONCLUSIONS: Patients with GERD had impaired cough-related quality of life, poor asthma control or more symptoms and impacts of COPD.

Predictors of expiratory flow limitation measured by forced oscillation technique in COPD.

BACKGROUND: Expiratory flow limitation (EFL) during tidal breathing is common in patients with severe COPD, and a major determinant of dynamic hyperinflation and exercise limitation. EFL can be measured by the forced oscillation technique (FOT); however, the relevance to clinical parameters is not fully understood. We hypothesized that emphysema extent and pulmonary function would contribute independently to the degree of EFL. METHODS: Broadband frequency FOT and pulmonary function tests were performed in 74 patients with COPD to derive respiratory system resistance (Rrs) and reactance (Xrs), and the EFL index as expressed by the differences between inspiratory and expiratory phases of Xrs at 5 Hz (ΔX5). Emphysema extent was measured by high-resolution computed tomography and scored. RESULTS: On the basis of the median value of ΔX5 (0.55 cmH2O/L/s), patients were classified into a high or low EFL index group. In multivariate regression analyses, a high EFL index was independently predicted by emphysema score, peripheral airway obstruction (forced expiratory flow between 25% and 75% of forced vital capacity), hyperinflation (functional residual capacity), and airway caliber (whole-breath Rrs at 5 Hz). CONCLUSIONS: EFL measured by FOT is a global measure of COPD that has separable etiologies and is useful for evaluating the disease condition.

Olanzapine Plus Triple Antiemetic Therapy for the Prevention of Carboplatin-Induced Nausea and Vomiting: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial.

PURPOSE: We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone for preventing chemotherapy-induced nausea and vomiting in patients receiving carboplatin-containing chemotherapy. PATIENTS AND METHODS: Chemotherapy-naïve patients scheduled to receive carboplatin (AUC ≥5) were randomly assigned to receive either olanzapine 5 mg once daily (olanzapine group) or placebo (placebo group) in combination with aprepitant, a 5-HT3 RA, and dexamethasone. The primary end point was the complete response (CR; no vomiting and no rescue therapy) rate in the overall phase (0-120 hours). Secondary end points included the proportion of patients free of nausea and safety. RESULTS: In total, 355 patients (78.6% male, median age 72 years, 100% thoracic cancer), including 175 and 180 patients in the olanzapine and placebo groups, respectively, were evaluated. The overall CR rate was 86.9% in the olanzapine group versus 80.6% in the placebo group. The intergroup difference in the overall CR rate was 6.3% (95% CI, -1.3 to 13.9). The proportions of patients free of chemotherapy-induced nausea in the overall (88.6% in the olanzapine group v 75.0% in the placebo group) and delayed (89.7% v 75.6%, respectively) phases were significantly higher in the olanzapine group than in the placebo group (both P < .001). Somnolence was observed in 43 (24.6%) and 41 (22.9%) patients in the olanzapine and placebo groups, respectively, and no events were grade ≥3 in severity. CONCLUSION: The addition of olanzapine was not associated with a significant increase in the overall CR rate. Regarding the prevention of nausea, adding olanzapine provided better control in patients receiving carboplatin-containing chemotherapy, which needs further exploration.

Impaired cough-related quality of life in patients with nontuberculous mycobacteriosis.

BACKGROUND: Cough and sputum are the significant symptoms of nontuberculous mycobacteriosis (NTM) and impair quality of life (QOL). However, the relationship between these symptoms and clinical features is not fully understood. This study aimed to investigate cough-related QOL in NTM patients. METHODS: The study subjects included 78 patients with NTM at our hospital from October to December 2015. They completed the Leicester Cough Questionnaire (LCQ) and the Cough and Sputum Assessment Questionnaire (CASA-Q) (both questionnaires: the higher, the better); the Frequency Scale for the Symptoms of gastroesophageal reflux disease (GERD) (FSSG), a validated Japanese questionnaire for GERD (the higher, the worse), was also assessed. The FSSG consists of 12 items, including the reflux-related symptoms and dysmotility symptoms domains, each of which is quantified on a scale of 0-4 points, and the cut-off score for GERD is set at 8 points. Associations between these scores and clinical parameters were assessed. RESULTS: The total LCQ score was reduced-the physical domain was dominant. The total LCQ and CASA-Q scores were reduced, with dominance in the physical and symptoms domains, respectively. The reflux-related symptoms score was higher than the dysmotility symptoms score. A multivariate linear regression analysis revealed that the mean total LCQ score was independently associated with current smoking, fibrocavitary type, bilateral cavitary lesion, and FSSG total score. CONCLUSIONS: Cough-related QOL was impaired in NTM patients who currently smoked, had radiological characteristics, and had GERD.

The liver-to-spleen ratio is a risk factor predicting oxygen demand in COVID-19 patients.

Background: We aimed to investigate risk factors predicting oxygen demand in COVID-19 patients. Methods: Patients admitted to Shizuoka General Hospital with COVID-19 from August 2020 to August 2021 were included. First, we divided patients into groups with and without oxygen demand. Then, we compared patients' clinical characteristics and laboratory and radiological findings to determine factors predicting oxygen demand. Results: One hundred seventy patients with COVID-19 (aged 58±15 years, 57 females) were enrolled. Common comorbidities were cardiovascular diseases (47.6%), diabetes mellitus (28.8%), and dyslipidemia (26.5%). Elder age, higher body mass index, cardiovascular diseases, diabetes mellitus, lower lymphocyte count, albumin, hepatic attenuation value, and the liver-to-spleen ratio (L/S), higher D-dimer, aspartate aminotransferase, lactate dehydrogenase, troponin-T, C-reactive protein, KL-6, chest and abdominal circumference, and visceral fat were found in patients with oxygen demand. According to the multivariate logistic regression analysis, L/S, lymphocyte count, D-dimer, and abdominal circumference under the diaphragm were independent risk factors predicting oxygen demand in COVID-19 patients. Conclusions: On admission, L/S, lymphocyte count, D-dimer, and abdominal circumference were predictive factors for oxygen demand. These factors may help in the appropriate triage of COVID-19 patients in the decision to admit them to the hospital.