Chest CT findings in severe acute respiratory distress syndrome requiring V-V ECMO: J-CARVE registry.

BACKGROUND: Chest computed tomography findings are helpful for understanding the pathophysiology of severe acute respiratory distress syndrome (ARDS). However, there is no large, multicenter, chest computed tomography registry for patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to describe chest computed tomography findings at V-V ECMO initiation and to evaluate the association between the findings and outcomes in severe ARDS. METHODS: This multicenter, retrospective cohort study enrolled patients with severe ARDS on V-V ECMO, who were admitted to the intensive care units of 24 hospitals in Japan between January 1, 2012, and December 31, 2022. RESULTS: The primary outcome was 90-day in-hospital mortality. The secondary outcomes were the successful liberation from V-V ECMO and the values of static lung compliance. Among the 697 registry patients, of the 582 patients who underwent chest computed tomography at V-V ECMO initiation, 394 survived and 188 died. Multivariate Cox regression showed that traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality (hazard ratio [95% confidence interval] 1.77 [1.19-2.63], p = 0.005 and 1.97 [1.02-3.79], p = 0.044, respectively). The presence of traction bronchiectasis was also associated with decreased successful liberation from V-V ECMO (odds ratio: 0.27 [0.14-0.52], p < 0.001). Lower static lung compliance was associated with some chest computed tomography findings related to changes outside of pulmonary opacity, but not with the findings related to pulmonary opacity. CONCLUSIONS: Traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality in patients with severe ARDS who required V-V ECMO.

Relationship between critical care nutrition and post-intensive care syndrome in surviving ventilated patients with COVID-19: a multicenter prospective observational study.

The impact of nutrition therapy in the acute phase on post-intensive care syndrome (PICS) remains unclear. We conducted a multicenter prospective study on adult patients with COVID-19 who required mechanical ventilation for more than three days. The questionnaire was mailed after discharge. Physical PICS, defined as less than 90 points on the Barthel index (BI), was assigned as the primary outcome. We examined the types of nutrition therapy in the first week that affected PICS components. 269 eligible patients were evaluated 10 months after discharge. Supplemental parenteral nutrition (SPN) >400 kcal/day correlated with a lower occurrence of physical PICS (10% vs 21.92%, p = 0.042), whereas the amounts of energy and protein provided, early enteral nutrition, and a gradual increase in nutrition delivery did not, and none correlated with cognitive or mental PICS. A multivariable regression analysis revealed that SPN had an independent impact on physical PICS (odds ratio 0.33, 95% CI 0.12-0.92, p = 0.034), even after adjustments for age, sex, body mass index and severity. Protein provision ≥1.2 g/kg/day was associated with a lower occurrence of physical PICS (odds ratio 0.42, 95% CI 0.16-1.08, p = 0.071). In conclusion, SPN in the acute phase had a positive impact on physical PICS for ventilated patients with COVID-19.

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.

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron.

Streptococcal Toxic Shock Syndrome Due to Invasive Coloproctitis Caused by Group G Streptococcus: A Case Report and Literature Review.

Streptococcus dysgalactiae subsp. equisimillis (SDSE) is classified as a group G streptococcus (GGS). In systemic SDSE infection, septic shock is easily induced and has a high mortality of 44%. The case was a 78-year-old man presented with fever and chills of 20 hours duration. He was in shock at the presentation and developed melena on day nine. CT images showed bowel wall thickening with emphysema and bedside colonoscopy showed active bleeding in the descending colon and rectum. Blood cultures were positive for Streptococcus dysgalactiae and a diagnosis of streptococcal toxic shock syndrome (STSS) due to SDSE was made. Urgent Hartmann procedure with laparotomy for removal of descending and rectal colon was performed to relieve his shock status. His shock status was reversed after surgery. Surgical specimens confirmed the presence of SDSE on the intestinal mucosa. This is the first case of STSS due to SDSE infection of the intestinal wall. Resection of infected tissue in the setting of multiple organ dysfunction syndrome and necrotizing enterocolitis is indicated in such cases.

High versus low positive end-expiratory pressure setting in patients receiving veno-venous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome: study protocol for the multicentre, randomised ExPress SAVER Trial.

INTRODUCTION: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay. ETHICS AND DISSEMINATION: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals. TRIAL REGISTRATION NUMBER: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022. PROTOCOL VERSION: 28 March 2023, version 4.0.

Prevalence and Risk Factor Analysis of Post-Intensive Care Syndrome in Patients with COVID-19 Requiring Mechanical Ventilation: A Multicenter Prospective Observational Study.

INTRODUCTION: Post-intensive care syndrome (PICS) is an emerging problem in critically ill patients and the prevalence and risk factors are unclear in patients with severe coronavirus disease 2019 (COVID-19). This multicenter prospective observational study aimed to investigate the prevalence and risk factors of PICS in ventilated patients with COVID-19 after ICU discharge. METHODS: Questionnaires were administered twice in surviving patients with COVID-19 who had required mechanical ventilation, concerning Barthel Index, Short-Memory Questionnaire, and Hospital Anxiety and Depression Scale scores. The risk factors for PICS were examined using a multivariate logistic regression analysis. RESULTS: The first and second PICS surveys were obtained at 5.5 and 13.5 months (mean) after ICU discharge, with 251 and 209 patients completing the questionnaires and with a prevalence of PICS of 58.6% and 60.8%, respectively, along with the highest percentages of cognitive impairment. Delirium (with an odds ratio of (OR) 2.34, 95% CI 1.1-4.9, and p = 0.03) and the duration of mechanical ventilation (with an OR of 1.29, 95% CI 1.05-1.58, and p = 0.02) were independently identified as the risk factors for PICS in the first PICS survey. CONCLUSION: Approximately 60% of the ventilated patients with COVID-19 experienced persistent PICS, especially delirium, and required longer mechanical ventilation.

Relation between nutrition therapy in the acute phase and outcomes of ventilated patients with COVID-19 infection: a multicenter prospective observational study.

BACKGROUND: Optimal nutrition therapy has not yet been established for the acute phase of severe coronavirus disease 2019 (COVID-19) infection. OBJECTIVES: We aimed to examine the effects of nutrition delivery in the acute phase on mortality and the long-term outcomes of post-intensive care syndrome (PICS). METHODS: A multicenter prospective study was conducted on adult patients with COVID-19 infection requiring mechanical ventilation during an intensive care unit (ICU) stay. Daily total energy (kcal/kg) and protein (g/kg) deliveries in the first week of the ICU stay were calculated. The questionnaire for PICS evaluation was mailed within a median of 6 mo after hospital discharge. The primary outcome was in-hospital mortality, and secondary outcomes were the PICS components of physical impairment, cognitive dysfunction, and mental illness. RESULTS: Among 414 eligible patients, 297 who received mechanical ventilation for 7 d or longer were examined. PICS was evaluated in 175 patients among them. High protein delivery on days 4-7 correlated with a low in-hospital mortality rate. In contrast, high protein delivery on days 1-3 correlated with physical impairment. A multivariate logistic regression analysis adjusted for age, sex, BMI, and severity revealed that average energy and protein deliveries on days 4-7 correlated with decreased in-hospital mortality (OR: 0.94; 95% CI: 0.89, 0.99; P = 0.013 and OR: 0.40; 95% CI: 0.17, 0.93; P = 0.031, respectively). Nutrition delivery did not correlate with PICS outcomes after adjustments. In the multivariate regression using a restricted cubic spline model, in-hospital mortality monotonically decreased with increases in average nutrition delivery on days 4-7. CONCLUSIONS: In patents with COVID-19 on mechanical ventilation for ≥7 d, nutrition delivery in the late period of the acute phase was monotonically associated with a decrease in in-hospital mortality. Adequate protein delivery is needed on days 4-7.This trial was registered at https://www.umin.ac.jp as UMIN000041276.

Prognostic significance of serum cytokines during acute exacerbation of idiopathic interstitial pneumonias treated with thrombomodulin.

BACKGROUND: Acute exacerbation (AE) has been reported to herald a poor prognosis in idiopathic pulmonary fibrosis and is now thought to do so in idiopathic interstitial pneumonias (IIPs). However, the pathophysiology of AE-IIPs is not sufficiently understood. In our previously reported SETUP trial, we found better survival in patients with AE-IIPs treated with corticosteroids and thrombomodulin than in those treated with corticosteroids alone. In that study, we collected serum samples to evaluate changes in cytokine levels and retrospectively examined the prognostic significance and pathophysiological role of serum cytokines in patients with AE-IIPs. METHODS: This study included 28 patients from the SETUP trial for whom serial serum samples had been prospectively obtained. AE-IIPs were diagnosed using the Japanese Respiratory Society criteria. All patients were treated with intravenous thrombomodulin and corticosteroids from 2014 to 2016. Serum levels of 27 cytokines were measured using Bio-Plex. The high-resolution CT pattern at the time of diagnosis of AE was classified as diffuse or non-diffuse. RESULTS: Univariate analysis revealed that higher serum levels of interleukin (IL)-2, IL-7, IL-9, IL-12, IL13, basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, interferon-γ inducible protein-10, platelet-derived growth factor and regulated on activation, normal T cell expressed and secreted (RANTES) at AE were significant predictors of 90-day survival. The HRCT pattern was also a significant clinical predictor of 90-day survival. Multivariate analysis with stepwise selection identified a higher serum RANTES level at AE to be a significant predictor of 90-day survival, including after adjustment for HRCT pattern. Multivariate analysis with stepwise selection suggested that a marked increase in the serum IL-10 level on day 8 could predict 90-day mortality. CONCLUSIONS: A higher serum RANTES level at AE the time of diagnosis predicted a good survival outcome, and an elevated serum IL-10 level on day 8 predicted a poor survival outcome. TRIAL REGISTRATION NUMBER: UMIN000014969.

Efficacy of recombinant thrombomodulin for poor prognostic cases of acute exacerbation in idiopathic interstitial pneumonia: secondary analysis of the SETUP trial.

BACKGROUND: Acute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP. METHODS: In this study, we included 85 patients, in whom fibrin degradation product (FDP)/d-dimer was evaluated at AE, from the 100 patients in the SETUP trial. The AE-IIP patients in the rhTM arm (n=39) were diagnosed using the Japanese criteria from 2014 to 2016 and treated with intravenous rhTM for 6 days in addition to the conventional therapy. The AE-IIP patients in the control arm (n=46) were treated with the conventional therapy without rhTM between 2011 and 2013. The subjects were classified into higher and lower FDP/d-dimer groups based on the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation scoring system. A multivariate Cox proportional hazard regression analysis with stepwise selection was performed to reveal the prognostic factors of AE-IIP. RESULTS: We developed a prognostic scoring system using two significant prognostic factors, higher FDP/d-dimer at AE and prednisolone therapy before AE, with 3 and 2 points assigned for each parameter, respectively. The prognostic scores ranged from 0 to 5. Survival of AE-IIP patients with a prognostic score=0 was significantly better than that of patients with score ≥2. Survival was improved with the rhTM therapy (p<0.05) in the poor prognostic cases (score ≥2), but not in the good prognostic cases (score=0). CONCLUSIONS: Treatment with rhTM might improve survival in AE-IIP cases with poor prognoses.Trial registration numberUMIN000014969, date: 28 August 2014.

Recombinant thrombomodulin for acute exacerbation in idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) or other idiopathic interstitial pneumonias (IIP) is a poor prognostic event despite conventional therapy with corticosteroids and/or immunosuppressants. We aimed to evaluate the efficacy and safety of recombinant human soluble thrombomodulin (rhTM) for AE-IIP. METHODS: For this prospective single-arm open-label multicentre cohort study, we retrospectively registered 61 cases of AE-IIP treated with conventional therapy between 2011 and 2013 (control arm), and prospectively enrolled 39 cases of AE-IIP treated with conventional therapy and rhTM (380 U/kg/day for 6 days) between 2014 and 2016 (rhTM arm). To reduce potential confounding in treatment comparisons, an adjusted mortality analysis for 90-day survival was conducted with weighted Cox proportional hazards regression models using inverse probability of treatment weighting. Weights were derived from propensity scores estimated using a multivariable logistic regression analysis including potential confounders. RESULTS: The 90-day survival rates of AE-IIP patients treated with/without rhTM were 66.7% (26/39) and 47.5% (29/61), respectively. After adjusting for imbalances, rhTM therapy was significantly associated with reduced mortality (adjusted hazard ratio (HR): 0.453; 95% CI: 0.237-0.864; P = 0.0163). The frequencies of adverse events with/without rhTM were 17.9% (7/39) and 19.7% (12/61), which were similar in both arms (P = 1.0). Two bleeding-related adverse events occurred in the rhTM arm. CONCLUSION: Safety and efficacy were observed for rhTM treatment of AE-IIP. A future randomized controlled trial is required to draw final conclusions.

Pretreatment Glasgow prognostic score and prognostic nutritional index predict overall survival of patients with advanced small cell lung cancer.

BACKGROUND: Various biomarkers have been shown to predict prognosis in various types of cancers. However, these biomarkers have not been studied in advanced small cell lung cancer (SCLC). The modified Glasgow prognostic score (mGPS) is based on serum albumin level and C-reactive protein (CRP). The prognostic nutritional index (PNI) is a combination of serum albumin level and absolute lymphocyte count. This study aimed to evaluate the prognostic value of mGPS and PNI in SCLC. METHODS: We retrospectively reviewed and calculated mGPS and PNI for patients with stage IIIB or IV SCLC who initiated platinum-based combination chemotherapy between November 2007 and June 2016. We compared overall survival (OS) and progression-free survival (PFS) between high and low groups of these two biomarkers. Univariate and multivariate Cox hazard analyses assessed the prognostic value of these biomarkers. RESULTS: We reviewed 97 SCLC patients. The OS of patients with mGPS 0-1 and higher PNI was significantly longer than that of those with mGPS 2 and lower PNI. The PFS of mGPS 0-1 was significantly longer than that of mGPS 2, while there was no significant difference in PFS according to PNI. Multivariate analyses found mGPS 0-1 (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.27-4.31, P<0.01) and higher PNI (HR 0.50, 95% CI 0.31-0.78, P<0.01) as prognostic factors for longer OS. However, neither biomarker was predictive of PFS. CONCLUSION: Our study was a small retrospective study; however, the data demonstrate that pretreatment mGPS and PNI are independent predictors of OS in patients with advanced SCLC. The pretreatment assessment of mGPS and PNI may be useful for identification of patients with poor prognosis. We recommend pretreatment measurement of serum albumin, C-reactive protein, and absolute lymphocyte count.

Diffuse Alveolar Hemorrhage Induced by Irinotecan for a Patient with Metastatic Thymic Carcinoma: A Case Report and Literature Review.

We herein report a 73-year-old Japanese woman with metastatic thymic carcinoma who developed diffuse alveolar hemorrhage (DAH) during irinotecan chemotherapy. She presented with a mild fever and exertional dyspnea after the second cycle of weekly irinotecan monotherapy. Chest images showed diffuse ground-glass opacities. The diagnosis of DAH was based on the findings of the bronchoalveolar lavage fluid, which was bloody and contained hemosiderin-laden macrophages. The discontinuation of irinotecan and introduction of oral prednisolone improved her symptoms and chest abnormal shadows. This is the first case of DAH caused by irinotecan.

Trajectory of chemotherapy for patients with EGFR wild-type advanced pulmonary adenocarcinoma: a single-institution retrospective study.

BACKGROUND: Pulmonary adenocarcinoma, recently benefited by new cytotoxic and molecularly targeted drugs, has been classified by driver mutations, such as EGFR mutations. The aim of this study was to research the proportions of patients treated with first- to third-line chemotherapy and to find influential factors for the introduction of chemotherapy and survival benefit from chemotherapy. MATERIALS AND METHODS: Data were collected retrospectively on patients who met the following criteria: adenocarcinoma, diagnosed between June 2007 and March 2015 at our hospital, stage IIIB or IV, and EGFR wild type. A nonchemotherapy group of patients who did not receive chemotherapy was compared with a chemotherapy group of patients who received it. The patients who had received first- to third-line chemotherapy between June 2007 and November 2015 at our hospital were also analyzed. RESULTS: During the study period, 46 patients did not receive chemotherapy, while 148, 89, and 48 received first-, second- and third-line chemotherapy, respectively. As predictive factors for unlikely chemotherapy, multivariate logistic analysis detected Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, hemoglobin <13.2 g/dL, creatinine clearance (Ccr) <50.4 mL/min, and CRP ≥0.53 mg/dL. As factors predicting shorter survival after chemotherapy, multivariate Cox proportional-hazard analyses detected age ≥75 years, ECOG PS ≥2, lower lymphocyte counts, and higher CRP for the first line; female, higher neutrophil counts, lower lymphocyte counts, reduced Ccr, hyponatremia, and shorter interval between first- and second-line chemotherapy for the second line; and age ≥75 years, body mass index <18.5 kg/m2, higher neutrophil counts, lower lymphocyte counts, hyponatremia, higher lactate dehydrogenase, and higher CRP for the third line. CONCLUSION: Approximately 76% of patients were treated with first-line chemotherapy. Of those patients, 61% and 34% proceeded to second- and third-line chemotherapy, respectively. For patients with poor PS, anemia, reduced Ccr, and higher CRP, it is difficult to introduce chemotherapy.

Neutrophil-to-Lymphocyte Ratio Predicts Overall Survival of Advanced Non-Small Cell Lung Cancer Harboring Mutant Epidermal Growth Factor Receptor.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be prognostic biomarkers in various cancers, including non-small cell lung cancer (NSCLC). However, little has been known about these two ratios for a specific population of NSCLC harboring active epidermal growth factor receptor (EGFR) mutation. METHODS: We retrospectively reviewed electrical medical records of 152 patients who met the following criteria: NSCLC harboring mutant EGFR, EGFR-tyrosine kinase inhibitor (EGFR-TKI) monotherapy initiated between October 2007 and February 2017 at our hospital, stage III-IV or post-surgical recurrence. We compared overall survival (OS) and progression-free survival (PFS) between dichotomized groups by the optimal cut-off points of the two biomarkers. Univariate and multivariate Cox hazard analyses also searched for prognostic factors of survival time. RESULTS: OSs of NLR < 2.11 (median 38.6 vs. 24.1 months, P < 0.01) and LMR ≥ 5.09 (median 39.4 vs. 26.4 months, P < 0.01) were significantly longer than those of NLR ≥ 2.11 and LMR < 5.09. Multivariate analyses found lower NLR (hazard ratio (HR) 1.07, 95% CI: 1.01 - 1.14; P = 0.03) as an independent prognostic factor for longer OS, in addition to Eastern Cooperative Oncology Group performance status 0 - 1, first-line EGFR-TKI, higher serum sodium concentration and lower lactate dehydrogenase. However, LMR was not detected as a significant prognostic factor for OS. None of these two biomarkers was selected as an independent prognostic factor for PFS. CONCLUSIONS: This study demonstrated that elevated NLR is an independent prognostic factor for poor survival of patients with EGFR mutant NSCLC. NLR is a useful and simple biomarker for these patients.

Good's Syndrome Accompanied by Agranulocytosis Following a Rapid Clinical Course.

Good's syndrome is an immunodeficiency disease involving thymoma accompanied by hypogammaglobulinemia. We encountered a case of Good's syndrome accompanied by agranulocytosis that followed a rapid clinical course. A 72-year-old man visited our hospital with a two-week history of a sore throat. Candida albicans was detected in the pharynx, and hypogammaglobulinemia was detected in addition to granulocytopenia. The patient subsequently developed septic shock and followed a rapid clinical course which ended in death. Good's syndrome with agranulocytosis was diagnosed at autopsy. Good's syndrome accompanied by agranulocytosis can follow a rapid clinical course and some cases remain asymptomatic until old age. Its prompt treatment is crucial.

Retrospective analysis of outcomes and prognostic factors of chemotherapy for small-cell lung cancer.

BACKGROUND: Small-cell lung cancer (SCLC) is responsive to initial chemotherapy but becomes resistant to cytotoxic drugs. The aim of this study was to evaluate what proportion of patients with SCLC had received the first- and further-line chemotherapy and which patients had benefited from chemotherapy. METHODS: We retrospectively reviewed medical records of patients with SCLC who had been treated with the best supportive care alone and the first-, second-, or third-line chemotherapy at the Osaka Police Hospital from June 2007 until March 2015. RESULTS: Among 145 patients diagnosed with SCLC and eligible for analysis, 118 patients received chemotherapy. We added five patients who initiated the second-line chemotherapy during the study period at our institution. Sixty-five and 31 patients received the second- and third-line chemotherapies, respectively. Multivariate logistic regression analysis detected age ≥75 years (odds ratio, 2.80; 95% confidence interval, 1.01-7.75; P=0.047) and European Clinical Oncology Group Performance Status (ECOG PS) 3-4 (14.3; 4.86-41.9; P<0.01) as factors disturbing the introduction of chemotherapy. Multivariate Cox hazard analyses also detected ECOG PS 2-4 (3.34; 2.00-5.58; P<0.01) as a factor decreasing overall survival after the first-line chemotherapy, and C-reactive protein level ≥1.0 mg/dL (2.67; 1.30-5.47; P<0.01) and progression-free survival after the first-line chemotherapy ≥6 months (2.85; 1.50-5.43; P<0.01) as factors influencing overall survival after the second-line chemotherapy. CONCLUSION: Approximately two-thirds and one-third of the patients who receive chemotherapy proceed to the second- and third-line chemotherapies, respectively. Several factors, such as age, ECOG PS, C-reactive protein level, and progression-free survival after previous treatment may be useful when considering the introduction of further-line chemotherapy.

Outcomes and prognostic factors of chemotherapy for patients with locally advanced or metastatic pulmonary squamous cell carcinoma.

BACKGROUND: Pulmonary squamous cell carcinoma has not benefited from improvements in chemotherapy over the past decade, compared with non-squamous non-small-cell lung cancer. Nowadays, treatment strategies differ between squamous and non-squamous non-small-cell lung cancers. This study aimed to investigate the percentage of patients treated with first-, second-, or third-line chemotherapy and the characteristics of patients for whom chemotherapy has been beneficial. METHOD: Data on patients with stage IIIB or IV squamous cell carcinoma diagnosed between June 2007 and March 2015, and on patients who had received first-, second-, or third-line chemotherapy between June 2007 and November 2015 at our hospital, were retrospectively extracted from our institutional medical charts. We also compared patients who were treated with chemotherapy (chemotherapy group) and patients who were not (non-chemotherapy group) using multivariate logistic regression and multivariate Cox hazard analyses, respectively. RESULTS: During the study period, 103, 63, and 32 patients received first-, second-, and third-line chemotherapy, respectively. Fifty-one patients did not receive chemotherapy. Factors predicting unlikely chemotherapy included age ≥75 years, Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ≥2, Charlson comorbidity index ≥2, hemoglobin <12.2 g/dL, red cell distribution width ≥13.9%, and serum sodium <140 mEq/L. Factors predicting survival for each line of chemotherapy included the following: ECOG-PS ≥2 for first-line; ECOG-PS ≥2 and lymphocyte count for second-line; and ECOG-PS ≥2, body mass index <18.5 kg/m2, and hemoglobin and lactate dehydrogenase levels for third-line. CONCLUSION: Approximately 66% of patients received first-line chemotherapy. Of those, 66% and 33% received second- and third-line chemotherapy, respectively. ECOG-PS was always an essential prognostic factor when considering introducing chemotherapy and proceeding with additional chemotherapy. Other markers, such as lymphocyte count, body mass index, anemia, and lactate dehydrogenase level, may be useful depending on the patient and line of chemotherapy.

Influence of indacaterol on daily physical activity in patients with untreated chronic obstructive pulmonary disease.

BACKGROUND: Indacaterol, a once-daily, long-acting ß2-agonist, may improve not only respiratory function, dyspnea symptoms, and quality of life, but also physical activity for patients with chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the effect of 12-week indacaterol therapy on daytime physical activity in patients with untreated COPD. METHODS: The subjects were stable and untreated COPD outpatients with a percent predicted forced expiratory volume in 1 second (%FEV1) below 80%. Baseline assessments included clinical assessment, respiratory function testing, arterial blood gas analysis, the COPD assessment test (CAT™), and the Medical Outcomes Study 36-Item Short-Form Health Survey, Japanese version 2 (SF-36v2(®)). Patients underwent monitoring by uniaxial accelerometer before and after 12 weeks once-daily inhalation of indacaterol 150 µg/day. RESULTS: Eighteen patients were evaluable. Patient characteristics included a mean age of 74.2 years, and three patients were current smokers. Indacaterol improved mean (± standard deviation [SD]) %FEV1 from 55.2% (±17.9%) to 61.0% (±17.3%) (P=0.003), CAT scores from 16.4 (±10.2) points to 12.4 (±8.2) points (P=0.04), some scales of the SF-36v2 (physical component summary, 41.6±9.7 points to 45.1±7.9 points, P=0.03), and number of daily steps (3,311.5±2,103.3 steps/day to 3,841.8±2,096.8 steps/day, P=0.02), but did not affect daily energy expenditure (85.0±77.2 kcal change to 90.9±56.8 kcal, P=0.29) or exercise duration of an intensity of level 1 or more (36.4±23.9 minutes increase to 40.8±21.6 minutes, P=0.12). CONCLUSION: Twelve weeks of indacaterol improved respiratory function and quality of life, but did not significantly affect physical activity in patients with moderate-to-severe COPD.

Opioids have no negative effect on the survival time of patients with advanced lung cancer in an acute care hospital.

PURPOSE: The purpose of this study is to determine whether or not opioid administration influenced the survival time of patients with advanced lung cancer in an acute care hospital setting. METHODS: This was a single institutional and retrospective study. We reviewed patients with advanced lung cancer who had died from January 2008 to December 2013 at the Osaka Police Hospital. We compared survival times, calculated from the time of the last hospitalization or the last chemotherapy, between patients who had not used any opioids, those who had used a low dose of opioids (< 60 mg/day), and those who had used a higher dose of opioids (≥ 60 mg/day). RESULTS: A total of 369 patients, of which 284 had received chemotherapy, were analyzed. Opioid users were generally younger than nonusers. There was no significant difference in survival time after the last hospitalization in terms of opioid dose at the last admission and mean daily opioid dose; there was also no significant difference in survival time after the last chemotherapy in terms of the mean daily opioid dose and the opioid dose at death. Univariate and multivariate Cox proportional hazard analysis regarding survival time after the last hospitalization or the last chemotherapy did not reveal any opioid-related variables as a significant predictive factor. CONCLUSIONS: Opioids were found to have no negative influence on survival time even in an acute care hospital.