Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer.

BACKGROUND: The Cockcroft-Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non-small-cell lung cancer remain unknown. METHODS: We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin-pemetrexed. Glomerular filtration rate values in Calvert's formula were back-calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. RESULTS: Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression-free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76-1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65-1.17; p = 0.363), with higher grade 3-4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20-0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23-0.82; p = 0.010). CONCLUSIONS: Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.

Effect of pulmonary rehabilitation with assistive use of short-acting ß2 agonist in COPD patients using long-acting bronchodilators.

Background: Assistive use of short-acting ß2 agonists (SABAs) reportedly improves exercise tolerance, activities of daily living, and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD). However, the effect of SABA on physical activity (PA) is unclear.Objective: This study aimed to determine whether assistive use of SABA increases PA and whether additional pulmonary rehabilitation (PR) can aid further improvement.Methods: Twelve outpatients with COPD and dyspnea during daily activities despite regular use of long-acting bronchodilators were enrolled. This study comprised a 2-week pre-intervention investigation, a 12-week investigation of SABA effects, and an 8-week investigation of the additional effects of PR. Assistive use of SABA was allowed up to 4 times per day after the pre-intervention period. PA was measured for 14 consecutive days using an accelerometer sensor. Dyspnea, exercise tolerance, and HRQOL were evaluated at entry, at 4 and 12 weeks after initiating SABA use, and after completing PR.Results: Assistive use of SABA improved breathlessness during daily activities and increased PA (p < .001). PA and HRQOL were also improved following PR (p < .001 and p = .013, respectively).Conclusions: Combined therapy of SABA and PR can increase PA and HRQOL in COPD patients.

[Utility of the Predictive Score for Cisplatin-Induced Nephrotoxicity in Patients with Chemotherapy for Lung Cancer].

BACKGROUND: Cisplatin(CDDP)-induced nephrotoxicity(CIN)is a critical complication of chemotherapy. Among patients undergoing chemotherapy with CDDP, short-hydration, and magnesium supplementation for lung cancer, this study was conducted to evaluate the frequency of CIN and utility of the predictive score. METHODS: Patients who underwent chemotherapy with CDDP for lung cancer were retrospectively investigated. A multiple logistic regression analysis to detect the risk factors for CIN and receiver operating characteristic analysis to examine the discrimination of the predictive score were performed. RESULTS: A total of 111 patients were included, with a total count of chemotherapy courses of 402 and a median count of chemotherapy courses of 4. CIN occurred in 9.9% of the patients, with grade 2 and higher in 7.2% and 87% of the CIN cases detected in the initial course, respectively. The significantly independent risk factors for CIN included the number of chemotherapy courses, female gender, and predictive score. The discriminative power of the predictive score was moderate. CONCLUSION: The predictive score for CIN was simple and useful in patients undergoing chemotherapy for lung cancer with CDDP, short-hydration, and magnesium supplementation, even in late courses.

Comparison between stereotactic radiosurgery and whole-brain radiotherapy for 10-20 brain metastases from non-small cell lung cancer.

The efficacy and safety of stereotactic radiosurgery (SRS) in comparison with whole brain radiotherapy (WBRT) for brain metastases (BMs) remains unclear. The present study retrospectively reviewed 44 patients who received SRS or WBRT as an initial treatment for 10-20 BMs from non-small cell lung cancer between 2009 and 2016. Of the patients, 24 (54.5%) were treated with SRS and 20 (45.5%) were treated with WBRT. Overall survival (OS), time to intracranial progression (TTIP), neurological survival (NS), and prognostic factors were examined. OS did not significantly differ between the two groups: 7.3 months in the SRS group vs. 7.2 months in the WBRT group (P=0.502). Median TTIP was significantly shorter in the SRS group than in the WBRT group (7.1 vs. 19.1 months, P=0.009). In contrast, there were no significant differences in NS between the two groups (14.5 months in the SRS group vs. 12.9 months in the WBRT group, P=0.346). Univariate and multivariate analysis revealed that the type of initial treatment for BMs (WBRT or SRS) was not a significant prognostic factor (hazard ratio=0.80, 95% confidence interval: 0.42-1.52, P=0.502). However, histology, performance status, subsequent molecular targeted drugs, subsequent chemotherapy and salvage treatment were independent prognostic factors. There were no significant differences in OS and NS between treatment with SRS and treatment with WBRT in patients with 10-20 BMs, although TTIP was improved with WBRT. As an upfront treatment for 10-20 BMs, SRS may delay WBRT and the adverse events associated with WBRT.

Effects of Oral Morphine on Dyspnea in Patients with Cancer: Response Rate, Predictive Factors, and Clinically Meaningful Change (CJLSG1101).

BACKGROUND: Although the efficacy of parenteral morphine for alleviating dyspnea has been previously demonstrated in several studies, little is known regarding the efficacy of oral morphine for dyspnea among patients with cancer, including its response rate and predictive factors of effectiveness. Therefore, the aim of this study was to clarify the effectiveness of oral morphine on dyspnea in patients with cancer and elucidate the predictive factors of its effectiveness. SUBJECTS, MATERIALS, AND METHODS: In this multicenter prospective observational study, we investigated the change in dyspnea intensity in patients with cancer before and after the administration of oral morphine by using a visual analog scale (VAS). We also administered a self-assessment questionnaire to determine whether the patients believed oral morphine was effective. RESULTS: Eighty patients were enrolled in the study, and 71 of these patients were eligible. The least square mean of the VAS scores for dyspnea intensity was 53.5 at baseline, which decreased significantly to 44.7, 40.8, and 35.0 at 30, 60, and 120 minutes after morphine administration, respectively. Fifty-four patients (76.1%) reported that oral morphine was effective on the self-assessment questionnaire. Among the background factors, a high score for "sense of discomfort" on the Cancer Dyspnea Scale (CDS) and a smoking history of fewer pack-years were associated with greater effectiveness. CONCLUSION: Oral morphine was effective and feasible for treating cancer-related dyspnea. A higher score for "sense of discomfort" on the CDS and a smaller cumulative amount of smoking may be predictive factors of the effectiveness of oral morphine. IMPLICATIONS FOR PRACTICE: This study demonstrated that oral morphine was effective in alleviating cancer-related dyspnea due to multiple factors including primary lung lesions, airway narrowing, and pleural effusion. Approximately 76% of patients reported that oral morphine was effective. A higher score for "sense of discomfort" on the Cancer Dyspnea Scale and a lower cumulative amount of smoking may be predictive factors for the effectiveness of oral morphine. Interestingly, respiratory rates in patients who reported the morphine to be effective decreased significantly after oral morphine administration, unlike the respiratory rates in "morphine-ineffective" patients.

Factors influencing the physical activity in daily life of male patients with different levels of severity of chronic obstructive pulmonary disease.

[Purpose] Physical activity influences the prognosis of chronic obstructive pulmonary disease and is influenced by exercise tolerance, and environmental, psychological, and many other factors, but the influence of these factors on physical activity levels in each stage of chronic obstructive pulmonary disease is unknown. This study aimed to clarify this matter. [Participants and Methods] Seventy-one male patients with chronic obstructive pulmonary disease (aged 72.2 ± 4.5 years) participated in this study. We compared physical activity levels (determined as daily steps), presence or absence of daily routine (e.g., housework or hobby), 6-minute walking distance, psychological factors (using the Hospital Anxiety and Depression Scale), and health-related quality of life (Physical and Mental component summary of the 36-item short-form health survey) between patients in different stages of chronic obstructive pulmonary disease. [Results] When examined at each stage of chronic obstructive pulmonary disease, physical activity levels correlated with the presence or absence of daily routine, 6-minute walking distance, and Physical component summary in all stages, but the scores in the anxiety and depression components of the Hospital Anxiety and Depression Scale and Mental component summary correlated only with stage 4. [Conclusion] Physical functioning was related to physical activity levels at any stage of chronic obstructive pulmonary disease, although psychological functioning was related to the progress of disease severity. The approach to promote an active lifestyle must be selected depending on the stage of chronic obstructive pulmonary disease.

Comparison of Different Disease-Specific Health-Related Quality of Life Measurements in Patients with Long-Term Noninvasive Ventilation.

BACKGROUND: Two disease-specific questionnaires have been developed to assess health-related quality of life (HRQL) in patients with chronic respiratory failure: the Severe Respiratory Insufficiency (SRI) Questionnaire and the Maugeri Respiratory Failure (MRF) Questionnaire. We aimed to compare the characteristics of the SRI, MRF-26, and St. George's Respiratory Questionnaire (SGRQ) for use in patients with home noninvasive ventilation (NIV). METHODS: Fifty-six outpatients receiving long-term NIV were recruited and underwent assessments of pulmonary function, arterial blood gas, HRQL, dyspnea, and psychological status. RESULTS: Correlations of the SRI and MRF-26 with the SGRQ were modest. While pulmonary function was weakly related to only some domains of the SRI and MRF-26, the modified Medical Research Council (mMRC) dyspnea scale and Hospital Anxiety and Depression Scale (HADS) were significantly related to all domains of the SRI and MRF-26. Multiple regression analyses showed that HADS depression and mMRC accounted for 34% and 27% of the variance in the SRI, 24% and 37% in the MRF-26, and 17% and 46% in the SGRQ, respectively. CONCLUSIONS: The SRI and MRF-26 were reliable questionnaires for patients receiving long-term NIV. Dyspnea and psychological status were their main common determinants. The SRI covers more psychological health impairments than the MRF. This trial is registered with ClinicalTrials.gov Identifier: NCT00905476.

Validation of the Japanese Severe Respiratory Insufficiency Questionnaire in hypercapnic patients with noninvasive ventilation.

BACKGROUND: The Severe Respiratory Insufficiency (SRI) Questionnaire was originally developed in German to assess health-related quality of life (HRQL) and was validated as a multidimensional instrument with high psychometric properties in chronic hypercapnic respiratory failure (CHRF) patients receiving noninvasive ventilation (NIV). We aimed to investigate the intercultural adaptation of the Japanese SRI Questionnaire and whether it is a reliable and valid HRQL questionnaire to administer to those patients. METHODS: The SRI Questionnaire was adapted to Japanese using a translation and back-translation procedure, followed by equivalency assessment. It was validated in 56 stable outpatients receiving NIV for CHRF, primarily due to chronic obstructive pulmonary disease (COPD) and/or pulmonary tuberculosis sequelae. RESULTS: Examination of the frequency distribution of the Japanese SRI Questionnaire showed that the subscales and summary were approximately normally distributed and well balanced. There were no significant differences in SRI scores between patients with COPD and pulmonary tuberculosis sequelae. Cronbach׳s α values representing internal consistency of seven SRI subscales ranged from 0.56 to 0.80; attendant symptoms and sleep had the lowest values. Cronbach׳s α value was 0.92 for the SRI summary. The SRI summary score was significantly related to all eight subscales of the Medical Outcomes Study 36-item short form, with correlation coefficients of 0.41-0.66. CONCLUSIONS: The Japanese SRI Questionnaire was produced using a standardized procedure and an equivalency study. It has high psychometric properties with internal consistency and concurrent validity. The Japanese SRI Questionnaire can be used to assess HRQL in patients on NIV for CHRF.

Analysis of the relationship between health status and mortality in hypercapnic patients with noninvasive ventilation.

BACKGROUND: Health status and mortality are important outcomes in patients with advanced pulmonary diseases receiving noninvasive ventilation (NIV). However, their relationship has not been thoroughly investigated. METHODS: The present study prospectively recruited 56 stable outpatients treated with NIV for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease and/or pulmonary tuberculosis sequelae. At baseline, health status was measured by the Medical Outcomes Study 36-item short form, a generic questionnaire; the St. George's Respiratory Questionnaire (SGRQ), a respiratory-specific questionnaire; and two respiratory failure-specific questionnaires, the Maugeri Respiratory Failure questionnaire and the Severe Respiratory Insufficiency (SRI) questionnaire. Arterial blood gas, pulmonary function, dyspnea and psychological status were also measured. RESULTS: In cross-sectional comparisons of the four health status questionnaires, the SGRQ and SRI questionnaire had lower floor and ceiling effects. During the 3-year follow-up, 16 patients (29%) died. Health status shown by the SGRQ and SRI was significantly predictive of mortality, independently of the physiological measures of low body mass index (BMI), hypercapnia, and low pulmonary function. Stepwise multivariate analyses indicated that the SRI summary score was the most significant predictor of mortality (P = 0.0006) followed by BMI (P = 0.012). CONCLUSION: There was a significant relationship between health status and 3-year mortality in patients with NIV, independently of under-nutrition, hypercapnia and low pulmonary function. Health status measurement is important not only to comprehensively evaluate disease severity in relation to its close association with mortality, but also to elucidate factors that improve the survival of patients with advanced respiratory diseases.

A propensity score-matched comparison of the efficacies of OK-432 and talc slurry for pleurodesis for malignant pleural effusion induced by lung adenocarcinoma.

BACKGROUND: The choice of an optimal sclerosant for pleurodesis for malignant pleural effusion remains controversial. This retrospective clinical study compared the efficacy and safety of two sclerosants; talc slurry (talc-s) and OK-432. METHODS: We compared the characteristics, 30/90-day success rates, and adverse events in patients with lung adenocarcinoma who underwent pleurodesis by using either OK-432 or talc-s. Propensity score matching was used to compare the two scelrosants. RESULTS: Ninety-four patients (mean age=71.6±9.6 years) were included in this retrospective study, of whom 64 received OK-432 and 30 received talc-s. Seventy-three patients (77.6%) were initially diagnosed with clinical stage IV lung cancer, with a 28.7% epidermal growth factor receptor mutation frequency. The propensity score-matched cohort included 26 patients from each group. The 30-day success rates for OK-432 and talc-s were 80.7% and 76.9%, respectively (odds ratio: 1.26, 95% confidence interval: 0.33-4.77, p=0.73). Neither the overall incidence of adverse events nor the 90-day success rates differed significantly. Multivariate logistic regression revealed that the predictors of 30-day success were lower drainage volume on the previous day, particularly <250mL/day, the presence of full lung expansion, and pre-therapy with an epidermal growth factor receptor-tyrosine kinase inhibitor. The median post-pleurodesis survival time was 6.9 months, which was not significantly different between the study groups. CONCLUSIONS: Propensity score-matched analyses showed that pleurodesis using OK-432 and talc-s demonstrated comparable efficacy and safety profiles in patients with lung adenocarcinoma. This indicated that OK-432 could be a viable alternative to talc-s in this procedure.

Can we predict the development of serious adverse events (SAEs) and early treatment termination in elderly non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy?

PURPOSE: Predicting the feasibility of platinum-based chemotherapy remains an important issue in elderly (over 70 years) patients with non-small cell lung cancer (NSCLC). The aim of this study was to identify the risk factors for the early serious adverse events (SAEs) (during cycles 1-2) in elderly receiving platinum-based chemotherapy, and to explore the clinical characteristics of patients who require early treatment termination without progressive disease (PD). METHODS: One hundred and ninety-eight consecutive elderly NSCLC patients receiving platinum-based chemotherapy were retrospectively reviewed. RESULTS: The median age was 73 years (range 70-83). 161 (81 %) were males, and 190 (95 %) were PS 0-1. Fifty-one (29 %) and 39 (19 %) patients developed early non-hematological SAEs and hematological SAEs, respectively. Multivariate analysis identified low serum albumin (<3.0 g/dl) as an independent risk factor for non-hematological SAEs, while low creatinine clearance (<45 ml/min) for hematological SAEs. In all, 24 (12 %) patients needed early treatment termination without PD. The major reason for this event was the development of non-hematological SAEs (4.5 %), followed by grade 2 non-hematological adverse events (AEs) (3 %). In multivariate analysis, age over 75 years and low serum albumin were associated with this event. The median overall survival (OS) in patients with this event was only 6.0 months, while the development of early SAE was not associated with poor OS. CONCLUSION: Baseline serum albumin might be useful for predicting the feasibility of platinum-based chemotherapy, and the risk estimation of early treatment termination without PD might be beneficial for the treatment selection in elderly NSCLC patients.

[A Case of Acute Arterial Occlusion of the Lower Limb during Chemotherapy for Lung Cancer].

A 69-year-old man visited a clinic for left leg weakness. With suspicions of lung cancer and a metastatic brain tumor, he was referred to our hospital and was diagnosed with large cell neuroendocrine carcinoma, cT1bN0M1b (BRA), stage IV. After stereotactic radiosurgery for his brain metastasis, he was treated with chemotherapy containing cisplatin and irinotecan. A week after initiating chemotherapy, he suddenly developed severe right leg pain and adynamia. A computed tomography angiogram revealed occlusion of the right common femoral artery, and percutaneous thrombectomy was performed. The symptoms resolved completely, and he was discharged without any sequelae or recurrence. Acute arterial occlusion of the limbs during chemotherapy is uncommon and requires prompt diagnosis and treatment; hence, caution should be paid when it is clinically suspected.

Phase II Study of Carboplatin and Pemetrexed in Advanced EGFR-wild-type Non-squamous Non-small Cell Lung Cancer: The Central Japan Lung Study Group Trial 0906.

BACKGROUND: Several pre-clinical and clinical studies suggest a potential predictive role of epidermal growth factor receptor (EGFR) mutation in responsiveness to cytotoxic chemotherapy. The aim of this phase II study was to evaluate the efficacy and safety of pemetrexed-carboplatin combination as first-line chemotherapy in advanced non-squamous non-small cell lung cancer (NSCLC) limited to EGFR-wild-type cases. PATIENTS AND METHODS: In this single-arm, multicenter clinical trial, patients received pemetrexed (500 mg/m(2)) and carboplatin (area under the curve=6) intravenously on day 1 every 3 weeks for three to six cycles. The objective response rate (ORR) was the primary end-point; secondary end-points included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: A total of 54 patients were enrolled and 53 patients received therapy. No complete response was observed and partial response was observed in 19 (35.8%) cases, resulting in an ORR of 35.8% [95% confidence interval (CI)=23.1-50.2%]. Stable disease was observed in 20 (37.7%) patients and therefore the DCR was 73.6% (95% CI=59.7-84.7%). The median PFS was 5.4 months (95% CI=4.1-6.8 months) and the median OS was 12.7 months (95% CI=9.3-16.1 months). Treatment-related grade 3 or 4 hematological toxicities were neutropenia, leukopenia, anemia and thrombocytopenia in 35.8%, 11.3%, 30.2%, and 32.1% of patients, respectively. No grade 3 febrile neutropenia was observed, and grade 3 or 4 non-hematological toxicities were mild. There was no treatment-related death. CONCLUSION: The pemetrexed-carboplatin combination was effective and well-tolerated in patients with EGFR-wild-type non-squamous NSCLC (UMIN-CTR number: UMIN000003393).

Phase II study of erlotinib for previously treated patients with EGFR wild-type non-small-cell lung cancer, following EGFR mutation status reevaluation with the Scorpion Amplified Refractory Mutation System.

While assessing the efficacy of erlotinib in patients with epidermal growth factor receptor (EGFR) wild-type (WT) non-small-cell lung cancer (NSCLC), the sensitivity of the method used for the EGFR mutation analysis may affect the evaluation of the efficacy. We conducted a phase II study of erlotinib for previously treated patients with EGFR WT NSCLC screened by the peptide nucleic acid-locked nucleic acid (PNA-LNA) polymerase chain reaction (PCR) clamp method, which is known to be highly sensitive. The primary endpoint was the objective response rate (ORR). Preplanned reevaluation of the EGFR genotype as an exploratory endpoint was performed using the Scorpion Amplification Refractory Mutation System (S-ARMS) assay. Erlotinib was administered daily until disease progression or development of unacceptable toxicity. A total of 53 evaluable patients were enrolled. The histological subtypes were adenocarcinoma in 40 patients, squamous cell carcinoma in 9 patients and not otherwise specified NSCLC in 4 patients. Partial response (PR) was achieved in 6 patients (4 with adenocarcinoma and 2 with squamous cell carcinoma). The ORR was 11.3% [95% confidence interval (CI): 4.3-23.0]. The median progression-free survival (PFS) was 1.8 months (95% CI: 1.2-2.3). Samples from 26 of the 53 patients (49.0%) were available for EGFR mutation reanalysis with the S-ARMS assay. Of these 26 samples, only 1 sample of adenocarcinoma was found to be EGFR mutation-positive (exon 19 deletion) and the patient achieved a PR. The EGFR WT genotype was reconfirmed by the S-ARMS assay in the remaining 25 patients and 2 of these patients exhibited a PR. This study did not meet the primary endpoint, although erlotinib was found to be moderately effective in pretreated patients with EGFR WT NSCLC, even when the EGFR mutational status was confirmed by the highly sensitive PNA-LNA clamp PCR method.

First-line gefitinib therapy for elderly patients with non-small cell lung cancer harboring EGFR mutation: Central Japan Lung Study Group 0901.

BACKGROUND: The population of elderly patients with lung cancer is increasing worldwide. Although first-line gefitinib is one of the standard treatments for advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation, few data have been reported regarding gefitinib and elderly patients. PATIENTS AND METHODS: Chemotherapy-naïve patients aged 70 years or older with stage IIIB or IV NSCLC harboring EGFR-activating mutation were enrolled and treated with 250 mg of gefitinib daily until disease progression. The primary end point was response rate, and secondary end points were survival, safety, and quality of life. RESULTS: Twenty patients were enrolled, and the median age was 79.5 years (range 72-90). Overall response rate was 70% (95% CI 45.7-88.1%), and the disease control rate was 90% (95% CI 68.3-98.7%). The median progression-free survival and overall survival time were 10.0 and 26.4 months, respectively. The Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) scores improved significantly 4 weeks after the initiation of gefitinib (P = 0.037) and maintained favorably over a 12-week assessment period. Among the seven items of FACT-LCS, shortness of breath and cough improved significantly after 4 weeks of treatment (P = 0.046 and P = 0.008, respectively). The most common adverse events were rash and liver dysfunction. Although Grade 1 pneumonitis developed in one patient, no treatment-related death was observed. CONCLUSION: First-line gefitinib therapy is effective and feasible for elderly patients harboring EGFR mutation, and improves disease-related symptoms, especially pulmonary symptoms like shortness of breath and cough.

Predictors and impact of time to clinical stability in community-acquired pneumococcal pneumonia.

BACKGROUND: A clinical stability (CS) evaluation is thought to be important in community-acquired pneumonia (CAP) treatment, but evidence concerning the time to CS (TCS) remains lacking. METHODS: Among consecutive patients hospitalized with pneumococcal pneumonia, relationships between TCS and other clinical outcomes were examined, and predictors and a predictive TCS score were derived from patient characteristics on admission. RESULTS: A total of 144 patients were enrolled, including 46% and 27% with moderate and severe pneumonia, respectively, defined by the pneumonia severity index (PSI). The median TCS was 2 days, and was significantly correlated with the length of hospital stay (r = 0.595); a longer TCS was significantly associated with the more presence of poor clinical outcomes and ICU stays (adjusted odds ratios: 1.359 and 1.366, respectively). A multivariate Cox proportional hazard model revealed an absence of bilateral pneumonia (hazard rate (HR): 2.107) or bacteremia (HR: 2.520), and mild or moderate pneumonia (HR: 2.798 and 2.515, respectively, versus severe) as predictors of CS. A predictive score had moderate discriminating power for the prolonged TCS (area under the curve: 0.76), and provided similar predictive values for poor clinical outcomes and ICU stays. A score of 3 or more points indicated the prolonged TCS, with a sensitivity and specificity of 73.3% and 70.9%, respectively. CONCLUSIONS: Because TCS has a significant relationship with other clinical outcomes of pneumococcal CAP, the prediction of TCS might lead to the prevention of complications or an earlier transition to oral therapy. Future studies are warranted to validate these results.

Distinct features of distant metastasis and lymph node stage in lung adenocarcinoma patients with epidermal growth factor receptor gene mutations.

BACKGROUND: The influence of epidermal growth factor receptor (EGFR) mutation status on distant and lymph node metastasis is not fully understood. METHODS: Ninety-five consecutive patients with stage IV lung adenocarcinoma, who had been examined for the EGFR mutation status, were retrospectively analyzed with regard to numbers of distant metastasis and clinical stage of lymph node metastasis at the time of diagnosis. RESULTS: While EGFR mutation status did not influence the presence or absence of distant metastasis in the lung, brain, or liver, patients with EGFR mutations demonstrated a significantly greater number of metastatic lesions in the lung (median: 85 vs. 4, P=0.01) and the brain (11 vs. 3.5, P=0.04). On the other hand, patients with EGFR mutations showed a significantly lower lymph node staging (P<0.01). CONCLUSION: The presence of EGFR mutations in patients with lung adenocarcinoma correlates with lower lymph node stage and a greater number of metastatic lesions in the lung and brain.

Re-expansion pulmonary edema: evaluation of risk factors in 173 episodes of spontaneous pneumothorax.

BACKGROUND: The precise incidence and clinical features of re-expansion pulmonary edema (RPE) are unclear, and they vary among reports. In this study, we assessed the incidence, risk factors, and outcomes of patients with RPE over a 3-yr period in a general hospital, with the goal of proposing a primary intervention for pneumothorax. METHODS: We retrospectively reviewed records of inpatients with spontaneous pneumothorax treated by tube thoracostomy between October 2007 and December 2010. RESULTS: A total of 173 episodes of spontaneous pneumothorax occurred in 156 patients. The incidence of RPE was 27/173 (15.6%). Symptom duration and pneumothorax size were significant risk factors for RPE, and the occurrence of RPE was independent of primary treatment of spontaneous pneumothorax. Among the patients with RPE, 18 (67%) were symptomatic. Five patients (18.5%) were treated with temporary oxygen, however, 21 patients (78%) did not need any treatment. All patients survived and none required mechanical ventilation. The occurrence of RPE did not influence the clinical outcome. CONCLUSIONS: The risk of developing RPE increases with an increased duration or size of pneumothorax. Our results suggest that the methods of primary intervention, including prompt suction, do not affect the onset of RPE. Close observation is always required regardless of the intervention because of the potentially fatal complications.

Diagnostic management of patients with suspected ocular sarcoidosis.

BACKGROUND: Ophthalmologists often refer patients with suspected ocular sarcoidosis to pulmonologists for diagnostic examination of sarcoidosis. However, no recommendation has been proposed for managing such patients. This study aims to prospectively evaluate the diagnostic values of examinations and propose the management of patients with suspected ocular sarcoidosis. METHODS: Consecutive patients with suspected ocular sarcoidosis were prospectively investigated according to type of ocular lesions, measurement of serum ACE, and findings of chest radiography, chest CT, bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB). Diagnostic values were calculated on the basis of pathological results. RESULTS: Forty-two patients were included (female, 71.4%; mean age, 56.2±14.8 years), of whom 64.3% was diagnosed with sarcoidosis. Patient characteristics and ocular lesions did not differ significantly, regardless of the presence of sarcoidosis. Chest CT had low specificity and very high sensitivity for detecting sarcoidosis; in contrast, chest radiography and direct findings of bronchofiberscopy had high specificity and low sensitivity. Serum ACE and BAL did not have high diagnostic value. A flow chart was proposed to diagnose sarcoidosis, and this chart reduced the requirement of TBLB to 50% in our population. During the median follow-up of 51 months, 7 patients in the sarcoidosis group (25.9%) developed new lesions. CONCLUSIONS: Application of our flow chart appears to detect avoidable TBLB. Development of a more comprehensive flow chart including survey of ocular findings is warranted.

Paradoxical infarct in tuberculous meningitis: a case report.

We describe a case of 78-year-old woman with a 1-week history of fever and left hemiparesis. Head magnetic resonance imaging showed a small infarct. After admission, she showed altered consciousness and another small infarct. She finally had diagnoses of miliary tuberculosis (miliary-TB) and tuberculous meningitis (TBM). She recovered after receiving anti-tuberculous therapy (ATT) with prednisolone. However, 5 weeks later, we found another infarct. This is a rare case of TBM with recurrent infarcts in atypical lesions in spite of ATT. We suggest the possibility that the new infarct after ATT was due to a paradoxical reaction.