Effects of multilevel OSA surgery on patients with poor cardiopulmonary performance: A prospective pilot study.

OBJECTIVE: Multilevel airway surgery for obstructive sleep apnea/hypopnea syndrome (OSA) has benefits in improving sleep quality, but its effect on polysomnography (PSG) and 6-minute walk test (6MWT) parameters, including walking distance and cardiopulmonary performance, in patients with poor pre-operative cardiopulmonary performance remains understudied, which should be further investigated. METHODS: This prospective pilot study enrolled 27 consecutive OSA patients with poor pre-operative 6MWT results. All patients received multilevel OSA surgery, and the alterations of sleep parameters and 6MWT profiles were studied. The pre- and post-operative values of polysomnographic data and 6MWT profiles were analyzed using the Wilcoxon signed-rank tests. The relationships among changes of the indices of PSG and 6MWT were further investigated with the Spearman's correlations. RESULTS: After surgery, the sleep parameters and certain cardiopulmonary indices improved. When analyzing the correlations among changes of the indices of PSG and 6MWT, the improvement of daytime sleepiness (with ESS) was found related to farther walking distance (ρ=-0.414, p = 0.032) and higher percentage of "distance/target distance" (ρ=-0.435, p = 0.023). Moreover, the change of maximal expiratory pressure was the only index associated with the changes of AHI (apnea/hypopnea index, /hr.; ρ=-0.407, p = 0.035) and AHI in REM (ρ=-0.502, p = 0.009) among the cardiopulmonary performance parameters. CONCLUSION: This pilot study showed that OSA patients with poor pre-operative cardiopulmonary status undergoing multilevel sleep surgery could experience improvement in the sleep study and 6MWT to some extent. The relatively better walking distance and cardiopulmonary performance after the operation might potentially result from the improvement of daytime sleepiness and better respiration.

Comparison of mycology between different types of chronic rhinosinusitis.

BACKGROUND: The aim of this study was to culture fungi from the nasal discharge of patients with chronic rhinosinusitis (CRS) using both a traditional and Ponikau et al's method, and subsequently compare the culture results between CRS with nasal polyps (CRSwNPs) and without nasal polyps (CRSsNPs), and between eosinophilic and noneosinophilic CRS. METHODS: Eighty-one CRS patients with CRS who underwent functional endoscopic sinus surgery were enrolled. Before surgery, the severity of each patient's CRS was evaluated through an endoscopic examination and CT scan. Swab samples were collected from the middle meatus for traditional fungal cultures using cotton-tipped sticks. Afterward, the ipsilateral nasal cavity was irrigated, with the irrigated fluid processed using Ponikau et al's method for fungal culture. RESULTS: The endoscopic and CT scores were significantly higher in CRSwNPs than CRSsNPs, but were not different between eosinophilic CRS and noneosinophilic CRS. Using Ponikau et al's method, 61/81 (75.3%) of the specimens grew fungi. Among them, 20 of 32 (62.5%) CRSwNPs specimens and 41 of 49 (83.7%) CRSsNPs specimens grew fungi. For eosinophilic CRS specimens, 35 of 46 (76.1%) grew fungi, and 26 of 35 (74.3%) noneosinophilic CRS specimens grew fungi. The fungal culture rate was borderline significantly higher in CRSsNPs than CRSwNPs ( p = 0.058) but was not significantly different between eosinophilic CRS and noneosinophilic CRS ( p = 1). However, Cladosporium was significantly more common in CRSsNPs than CRSwNPs ( p = 0.048). CONCLUSION: Our results showed that the mycology of CRS was different between CRSwNPs and CRSsNPs.

Alternations of Blood Pressure Before and After OSA Surgery.

OBJECTIVE: To investigate the changes of blood pressure (BP) on patients with obstructive sleep apnea/hypopnea syndrome (OSA) before and after upper airway surgery. DESIGN: Case series with chart review. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: Patients with OSA who underwent upper airway surgery were enrolled. We retrospectively investigated the nighttime and daytime BP before and at least 3 months after OSA surgery. Paired t test was used to compare the changes of BP before and after surgery. Generalized estimating equation was used to examine the prognostic significance of the variables in predicting the changes of postoperative BP. RESULTS: In total, 176 patients with OSA (149 men, 27 women; mean age, 42.9 years; mean apnea/hypopnea index, 43.1/h) were enrolled in this study. The overall nighttime and daytime BP decreased significantly before and after OSA surgery (daytime systolic BP was reduced from 137.3 ± 14.0 mm Hg to 132.7 ± 17.0 mm Hg, P < .01; nighttime systolic BP was reduced from 138.7 ± 16.0 mm Hg to 133.7 ± 15.3 mm Hg, P < .01; daytime diastolic BP was reduced from 87.7 ± 14.7 mm Hg to 84.9 ± 10.6 mm Hg, P = .01; nighttime diastolic BP was reduced from 85.4 ± 12.9 mm Hg to 83.1 ± 11.1 mm Hg, P = .02). The changes of nighttime systolic and diastolic BP were significantly associated with the improvement of percentage of O2 saturation <90% during polysomnography. CONCLUSION: Surgical modifications of the upper airways for patients with OSA could benefit blood pressure.

Respiratory Muscle Training Improves Functional Outcomes and Reduces Fatigue in Patients with Myasthenia Gravis: A Single-Center Hospital-Based Prospective Study.

BACKGROUND: Myasthenia gravis (MG) is an immune-mediated disorder characterized by muscle fatigue and fluctuating weakness. Impairment in respiratory strength and endurance has been described in patients with generalized MG. We tested the hypothesis that respiratory muscle training (RMT) can improve functional outcomes and reduce fatigue in patients with MG. METHODS: Eighteen patients with mild to moderate MG participated in this study. The training group underwent home-based RMT three times a week for 12 weeks. Sixteen patients with MG without RMT were enrolled as a disease control group. Lung function, autonomic testing, Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), and functional outcome measurement by using quantitative myasthenia gravis (QMG) score and myasthenia gravis composite (MGC) scale were measured before and after the 12-week RMT. RESULTS: The 12-week RMT significantly increased forced vital capacity (FVC) from 77.9 ± 12.6% to 83.8 ± 17.7% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (. CONCLUSION: The home-based RMT is an effective pulmonary function training for MG patients. The RMT can not only improve short-term outcomes but also reduce fatigue in patients with mild to moderate generalized MG.

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling.

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes-including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4-were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

Effect of do-not-resuscitate orders on patients with sepsis in the medical intensive care unit: a retrospective, observational and propensity score-matched study in a tertiary referral hospital in Taiwan.

OBJECTIVE: The aim of this study was to determine whether do-not-resuscitate (DNR) orders affect outcomes in patients with sepsis admitted to intensive care unit (ICU). DESIGN: This is a retrospective observational study. PARTICIPANTS: We enrolled 796 consecutive adult intensive care patients at Kaohsiung Chang Gung Memorial Hospital, a 2700-bed tertiary teaching hospital in southern Taiwan. A total of 717 patients were included. MAIN MEASURES: Clinical factors such as age, gender and other clinical factors possibly related to DNR orders and hospital mortality were recorded. KEY RESULTS: There were 455 patients in the group without DNR orders and 262 patients in the group with DNR orders. Within the DNR group, patients were further grouped into early (orders signed on intensive care day 1, n=126) and late (signed after day 1, n=136). Patients in the DNR group were older and more likely to have malignancy than the group without DNR orders. Mortality at days 7, 14 and 28, as well as intensive care and hospital mortality, were all worse in these patients even after propensity-score matching. There were higher Charlson Comorbidity Index in the emergency room, but better outcomes in those with early-DNR orders compared with late-DNR orders. CONCLUSIONS: DNR orders may predict worse outcomes for patients with sepsis admitted to medical ICUs. The survival rate in the early-DNR order group was not inferior to the late-DNR order group.

Whole genome gene expression changes and hematological effects of rikkunshito in patients with advanced non-small cell lung cancer receiving first line chemotherapy.

It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC. These patients were randomized to receive combination chemotherapy (cisplatin and gemcitabine) with (n=9, CTH+R group) or without (n=8, CTH group) rikkunshito. The primary endpoint was the treatment response and the categories of the scales of anorexia, nausea, vomiting and fatigue; secondary endpoints included the hematological effect and whole genome gene expression changes. The results of the current study indicated that there were no significant differences in clinical outcomes, including treatment response and toxicity events, between the two groups. Median one-year overall survival (OS) was 12 months in the CTH group and 11 months in the CTH+R group (P=0.058 by log-rank test), while old age (>60 years old) was the only independent factor associated with one-year OS (hazard ratio 1.095, 95% confidence interval, 1.09-1.189, P=0.030). Patients in the CTH+R group experienced significantly greater maximum decreases in both white cell count (P=0.034) and absolute neutrophil count (P=0.030) from the baseline. A total of 111 genes associated with neutrophil apoptosis, the cell-killing ability of neutrophils, natural killer cell activation and B cell proliferation were up-regulated following rikkunshito treatment. A total of 48 genes associated with neutrophil migration, coagulation, thrombosis and type I interferon signaling were down-regulated following rikkunshito treatment. Rikkunshito may therefore affect the blood neutrophil count when used with combination chemotherapy in patients with NSCLC, potentially by down-regulating prostaglandin-endoperoxidase synthase 1, MPL, AMICA1 and junctional adhesion molecule 3, while up-regulating elastase, neutrophil expressed, proteinase 3, cathepsin G and cluster of differentiation 24.

Alternative Therapy for Patients With Obstructive Sleep Apnea/Hypopnea Syndrome: A 1-year, Single-blind, Randomized Trial of Tui Na.

Context • Obstructive sleep apnea/hypopnea syndrome (OSAHS) is among the most prevalent of sleep-related breathing disorders. No long-term follow-up studies have documented the continued success of lifestyle changes in treatment; oral appliances have an approximate 50% success rate; compliance with continuous positive airway pressure is poor, ranging from 50% to 89%; and the success rate of upper-airway surgery is only 66.4%. Therefore, some OSAHS patients seek alternative treatments. Objectives • The study intended to examine the efficacy of traditional Chinese therapeutic massage (tui na) for patients with OSAHS. Design • The research team designed a prospective study. Setting • The study took place at the outpatient clinic of the sleep center at the Kaohsiung Chang Gung Memorial Hospital (Kaohsiung, Taiwan), an academic tertiary medical center. Participants • Participants were 31 patients with moderate to severe OSAHS. Intervention • Each participant received a tui na treatment at multiple acupoints 2 ×/wk for 10 wk for approximately 15 min/session. Outcome Measures • At baseline and 3 mo after treatment, participants completed subjective measures, including (1) quality of life using a 36-item, short-form health survey (SF-36); (2) subjective snoring intensity indicated by bed-partners using a 0-10 visual analog scale (VAS); and (3) excessive daytime sleepiness (EDS) status, using a Chinese version of the Epworth Sleepiness Scale (CESS). The research team completed objective measures, including (1) polysomnography, (2) body mass index, and (3) neck circumference. Results • Twenty patients completed the full course of treatment. The apnea/hypopnea index per hour decreased from 43.8 ± 26.9 to 37.8 ± 31.7 after the treatments, with P = .049 (paired t test). The arousal index and rapid eye movement stage of sleep improved significantly. Statistically significant improvements were observed for the SF-36 on the score for the physical component summary, for its subscale for general health, for the mental component summary, and for 2 of its subscales: vitality and mental health. The VAS and the CESS showed that snoring intensity and EDS decreased significantly, respectively. No major complications occurred. Conclusions • Tui na is a feasible and safe treatment for patients with OSAHS. It can improve the quality of life, sleep architecture, snoring intensity, and EDS in patients with moderate-to-severe OSAHS. In the future, a controlled study should be considered to further investigate the effects of tui na for OSAHS.

Application of desaturation index in post-surgery follow-up in children with obstructive sleep apnea syndrome.

Adenotonsillectomy is recommended for children who need surgery for obstructive sleep apnea syndrome (OSAS). Overnight, polysomnography (PSG) is suggested for post-surgery follow-up, but this diagnostic technique is time consuming and inconvenient. Desaturation index (DI) has been reported as a good tool for predicting both the presence and severity of OSAS in children. The purpose of this study was to determine the usefulness of the DI for post-surgery follow-up of children with OSAS. This retrospective study enrolled 42 children, aged 3-12 years, who were snorers diagnosed with OSAS by overnight PSG and who underwent an adenotonsillectomy. Pre- and postoperative PSG parameters, nocturnal pulse oximetry data, and modified Epworth sleepiness scale scores were assessed. Previously determined cut-off DI values (2.05, 3.50, and 4.15 for mild, moderate, and severe OSAS, respectively) were used to predict residual OSAS. Of the 42 children, obvious improvements were observed in apnea-hypopnea index (AHI, decreased 45.5 %), arousal index (decreased 30.5 %), DI (decreased 40.4 %), and snore index (decreased 100.3 %) compared with the preoperative measurements. Among these objective PSG measures, DI had the strongest correlation with AHI both pre- and post-surgeries (r = 0.947 and r = 0.954, respectively; p all <0.001). The DI change, before and after surgery, also had the strongest positive correlation to the AHI change (r = 0.482 and p = 0.001). Using the previously determined DI cut-off values to predict postoperative residual OSAS, there was a good positive predictive value (92.6 %) for mild residual OSAS and a good negative predictive value for moderate and severe residual OSAS (85.2 and 89.7 %, respectively). These findings suggest that DI, as determined using a nocturnal pulse oximeter, may be an alternative tool for postoperative evaluation and follow-up of children with OSAS.

A Survival Scoring System for Non-Small Cell Lung Cancer Patients with De Novo Bone Metastases.

In the pre-tyrosine kinase inhibitors (TKIs) era, non-small cell lung cancer (NSCLC) patients with de novo bone metastases had a worse prognosis than those without. However, whether epidermal growth factor receptor (EGFR)-TKIs affect the outcomes of EGFR mutant NSCLC patients with de novo bone metastases has not been well studied thus far. We retrospectively studied the effect of EGFR mutation status and first-line EGFR-TKIs on patient outcomes and created a survival scoring system for NSCLC patients with de novo bone metastases. This retrospective study evaluated 1510 NSCLC patients diagnosed between November 2010 and March 2014. Among these patients, 234 patients had de novo bone metastases. We found that 121 of these 234 patients (51.7%) had positive EGFR mutation tests, and a positive EGFR mutation test significantly affected overall survival (OS) (EGFR mutant: 15.2 months, EGFR wild type: 6.5 months; p < 0.001). Other prognostic factors significant in the multivariable analysis for NSCLC with de novo bone metastases included Eastern Cooperative Oncology Group performance status (PS) (OS; PS 0-2: 11.2 months, PS 3-4: 4.9 months; p = 0.002), presence of extraosseous metastases (OS; with extraosseous metastases: 8.8 months, without extraosseous metastases: 14.0 months; p = 0.008), blood lymphocyte-to-monocyte ratio (LMR) (OS; LMR > 3.1: 17.1months, LMR ≤ 3.1: 6.9months; p < 0.001). A positive EGFR mutation status reversed the poor outcomes of NSCLC patients with de novo bone metastases. A simple and useful survival scoring system including the above clinical parameters was thus created for NSCLC patients with de novo bone metastases.

Impact of clinical parameters and systemic inflammatory status on epidermal growth factor receptor-mutant non-small cell lung cancer patients readministration with epidermal growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration to lung cancer patients is common owing to the few options available. Impact of clinical factors on prognosis of EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving EGFR-TKI readministration after first-line EGFR-TKI failure and a period of TKI holiday remains unclear. Through this retrospective study, we aimed to understand the impact of clinical factors in such patients. METHODS: Of 1386 cases diagnosed between December 2010 and December 2013, 80 EGFR-mutant NSCLC patients who were readministered TKIs after failure of first-line TKIs and intercalated with at least one cycle of cytotoxic agent were included. We evaluated clinical factors that may influence prognosis of TKI readministration as well as systemic inflammatory status in terms of neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Baseline NLR and LMR were estimated at the beginning of TKI readministration and trends of NLR and LMR were change amount from patients receiving first-Line TKIs to TKIs readministration. RESULTS: Median survival time since TKI readministration was 7.0 months. In the univariable analysis, progression free survival (PFS) of first-line TKIs, baseline NLR and LMR, and trend of LMR were prognostic factors in patients receiving TKIs readministration. In the multivariate analysis, only PFS of first-line TKIs (p < 0.001), baseline NLR (p = 0.037), and trend of LMR (p = 0.004) were prognostic factors. CONCLUSION: Longer PFS of first-line TKIs, low baseline NLR, and high trend of LMR were good prognostic factors in EGFR-mutant NSCLC patients receiving TKI readministration.

Advanced non-Small cell lung cancer patients at the extremes of age in the era of epidermal growth factor receptor tyrosine kinase inhibitors.

OBJECTIVES: The clinical characteristics and survival of very young (≤40 years) and very old (>80years) patients with advanced non-small cell lung cancer (NSCLC) are distinct. However, the benefits of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to patients at the extremes of age with NSCLC harboring EGFR mutation have not been well studied. We retrospectively studied the effect of extreme age on patients' clinical characteristics and prognosis. MATERIALS AND METHODS: Of 1510 lung cancer patients diagnosed between November 2010 and March 2014, 555 patients who were tested for EGFR mutations were included. Patients were divided into the following groups according to age: young (≤40 years), lower medium (41-60 years), higher medium (61-80years), and very old (>80years). RESULTS: Of the 555 patients, 20 (3.6%) patients were aged ≤40 years and 60 (10.8%) patients were aged >80years. Young NSCLC patients had a lower BMI (p=0.003), more brain (p=0.016) and bone metastases (p=0.002) Very young lung cancer patients still have poor prognosis even they were EGFR mutant. (EGFR mutant vs. wild type patients, OS: 12 vs. 7.3 months, p=0.215) Very old NSCLC patients had a lower BMI (p=0.003) and poor ECOG PS (p=0.028). Positive EGFR mutation test reverses poor prognosis of elderly NSCLC patients. (EGFR mutant vs. wild type patients, OS: 13.2 vs. 4.9 months, p=0.003) CONCLUSION: We observed EGFR mutations reverse the poor prognosis of old patients with NSCLC. However, young patients with lung cancer have a poor prognosis even if they harbor EGFR mutations.

Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

BACKGROUND: Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases. MATERIALS AND METHODS: This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users. RESULTS: Fifty-seven patients (57/269, 21.2%) were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234). However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002). Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041). Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases. CONCLUSION: Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.

The impact of clinical parameters on progression-free survival of non-small cell lung cancer patients harboring EGFR-mutations receiving first-line EGFR-tyrosine kinase inhibitors.

OBJECTIVES: In daily practice, some patients with certain clinical characteristics may have better responses to the administration of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). It is therefore reasonable to stratify and weigh the importance of these clinical parameters which may not only affect patients' responses to TKIs but also progression-free survival (PFS) other than the impact of EGFR mutation status per se. MATERIALS AND METHODS: This retrospective study evaluated EGFR-mutant, non-small cell lung cancer patients who received EGFR-TKIs as a first-line therapy between January 2011 and December 2013. Several potential prognostic factors were analyzed with respect to PFS, and the results of this analysis were validated in another time cohort. RESULTS: A total of 262 patients were included in the study. Age ≤ 40 years, uncommon EGFR mutations, poor performance status, more sites of distal metastasis, and blood lymphocyte to monocyte ratio ≤ 3 were independently associated with poor PFS. These five factors were included in a scoring system and three prognostic groups A, B, and C, were formed based on total scores of 0-1, 2, and ≥ 3, respectively. In the test group, the PFS was 15.7 month, 9.3 month, and 4.0 month in groups A, B, and C, respectively (p<0.001). Between the test and validation groups, no significant differences were found in each one of the three prognostic groups. CONCLUSIONS: The scoring system appears valid and reproducible for PFS prognosis in EGFR-mutant patients who received first-line EGFR-TKIs.

The impact of chronic rhinosinusitis on sleep-disordered breathing.

BACKGROUND: The nose plays an important role in sleep quality. Very little is known about sleep problems in patients with chronic rhinosinusitis (CRS). The aim of this study was to investigate the impact of CRS on sleep-disordered breathing. METHODOLOGY: CRS patients who underwent functional endoscopic sinus surgery were collected between July 2010 and May 2015. Before surgery, they filled 20-item Sino-Nasal Outcome Test and Epworth Sleepiness Scale questionnaires, were asked about the severity of nasal obstruction, and received acoustic rhinometry, smell test, an endoscopic examination, sinus computed tomography, and a one-night polysomnography. Sleep quality was evaluated in these patients and was correlated with the severity of rhinosinusitis. RESULTS: One hundred and thirty-nine CRS patients were enrolled in the study. Among them, 38.1% complained of daytime sleepiness, and this sleep problem was correlated with the symptom of nasal obstruction. Obstructive sleep apnea syndrome (OSAS) was diagnosed in 64.7% of the patients, but there was no correlation with the severity of rhinosinusitis. Nasal polyps did not worsen sleep problems in the CRS patients. CONCLUSIONS: This study showed that CRS patents had a high prevalence of OSAS, and worse OSAS in CRS patients was not correlated with the severity of rhinosinusitis.

Baseline and Trend of Lymphocyte-to-Monocyte Ratio as Prognostic Factors in Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer Patients Treated with First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

BACKGROUND: Patients with early-stage lung cancer who have a high baseline lymphocyte-to-monocyte ratio (LMR) have a favorable prognosis. However, the prognostic significance of LMR in patients with advanced-stage EGFR-mutant non-small cell lung cancer (NSCLC) receiving first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has not been established. We conducted a retrospective analysis to investigate the influence of LMR on clinical outcomes including progression-free survival (PFS) and overall survival (OS) in EGFR-mutant patients with NSCLC. MATERIALS AND METHODS: Of 1310 lung cancer patients diagnosed between January 2011 and October 2013, 253 patients receiving first-line EGFR-TKIs for EGFR-mutant NSCLC were included. The cut-off values for baseline and the 1-month-to-baseline ratio of LMR (MBR), determined by using receiver operating characteristic curves, were 3.29 and 0.63, respectively. Patients were divided into 3 prognostic groups: high LMR and MBR, high LMR or MBR, and low LMR and MBR. RESULTS: The mean patient age was 65.2 years, and 41% were men. The median PFS and OS were 10.3 and 22.0 months, respectively. The PFS in patients with high LMR and MBR, high LMR or MBR, and low LMR and MBR were 15.4, 7.1, and 2.0 months, respectively (p < 0.001), whereas the OS were 32.6, 13.7, and 5.1 months, respectively (p < 0.001). CONCLUSION: A combination of baseline and trend of LMR can be used to identify patients with a high mortality risk in EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs.

Impact of head and neck radiotherapy for patients with nasopharyngeal carcinoma on sleep-related breathing disorders.

IMPORTANCE: Little is known about the relationships between sleep-related breathing disorders (SRBDs) and nasopharyngeal carcinoma (NPC). OBJECTIVE: To clarify the impact of head and neck radiotherapy on SRBDs, we performed a pilot study to investigate the change of sleep architecture in patients with NPC before and after treatment. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of a prospective data set of 18 patients with NPC (15 men and 3 women; mean age, 49.8 years) and symptoms of SRBD, who completed radiotherapy and underwent polysomnography before and after treatment at a university-affiliated tertiary referral center. INTERVENTIONS: Radiotherapy and/or chemotherapy were applied based on the NPC stage. MAIN OUTCOMES AND MEASURES: Subjective SRBD symptoms, Epworth sleepiness scale score, snoring severity (visual analog scale, rated 0-10 by bed partner), and objective full-night polysomnographic parameters (apnea-hypopnea index [AHI], AHI in rapid eye movement [REM] sleep, central sleep apnea index, percentage of light sleep, percentage of deep sleep, percentage of REM sleep, sleep efficiency, sleep latency, arousal index, mean oxygen saturation, lowest oxygen saturation, desaturation index, and snoring index) were collected before and at least 6 months after treatment. RESULTS: After treatment, Epworth sleepiness scale and snoring severity scores significantly decreased from a mean (SD) of 11.0 (5.0) to 7.8 (2.3) (P = .005) and 6.0 (3.4) to 2.8 (2.3) (P < .001), respectively. The AHI changed from 26.2 (28.4) to 21.67 (24.15) (P = .28). However, AHI increased in 8 of 18 patients. A statistically significant increase was shown in mean oxygen saturation, from 95.3% (2.0%) to 97.1% (1.4%) (P < .001), though lowest oxygen saturation was not significantly altered. Percentage of light sleep increased significantly from 78.9% (8.8%) to 86.1% (9.6%) (P = .02), and percentage of REM sleep decreased from 17.5% (6.4%) to 12.7% (8.9%) (P = .10). Percentage of deep sleep was not significantly altered. CONCLUSIONS AND RELEVANCE: Although the severity of apnea and hypopnea events and snoring decreased in most of the patients with NPC after treatment, the sleep architecture became disrupted and 8 of 18 of the patients had an increased AHI after treatment. Identification and treatment of obstructive sleep apnea and hypopnea in patients with NPC may be important factors for improving the quality of life.

Validation of the applicability of the traditional Chinese version of the University of Pennsylvania Smell Identification Test in patients with chronic rhinosinusitis.

The 40-item University of Pennsylvania Smell Identification Test (UPSIT) is the most widely used smell test in the world. Presently, culturally modified versions of this test are available in multiple languages. A traditional Chinese version of the UPSIT (UPSIT-TC) has been developed for administration in Taiwan. The purpose of this study was to investigate the validity and reliability of the UPSIT-TC in Taiwanese patients with chronic rhinosinusitis (CRS). The phenylethyl alcohol (PEA) odor detection threshold test, the North American version of UPSIT (UPSIT-NA), and the UPSIT-TC were administered to 40 healthy subjects and to 100 CRS patients before and after functional endoscopic sinus surgery (FESS). The UPSIT-TC showed good internal consistency (Cronbach's alpha = 0.887, 0.886, and 0.870 at three test occasions) and test-retest reliability (p < 0.001). The scores of UPSIT-TC were significantly correlated to the PEA thresholds (p < 0.001). The UPSIT-TC scores were significantly higher than those of the UPSIT-NA (p = 0.028) when analysis was performed with logistic regression with independent variables including test occasions (before or after FESS), test methods (UPSIT-NA or UPSIT-TC), status of polyp (with or without), and PEA thresholds (improved or did not improve). In addition, there were significant between-group differences in UPSIT-TC scores including healthy versus CRS, CRS with polyps versus CRS without polyps, and PEA thresholds improved versus PEA thresholds which did not improve. The UPSIT-TC is reliable and valid for measuring olfactory function in Taiwanese patients with rhinosinusitis. In addition, the UPSIT-TC clearly resulted in better performance than that of UPSIT-NA.

Electrolyzed acid water nasal irrigation after functional endoscopic sinus surgery.

BACKGROUND: Electrolyzed acid water (EAW) has been recognized to have strong bactericidal activity, and the feasibility and safety of EAW irrigation in body cavities has been reported in the literature. This study was conducted to evaluate the effect of EAW nasal irrigation on the postoperative care of functional endoscopic sinus surgery (FESS). METHODS: Patients with chronic rhinosinusitis who received FESS for treatment were recruited and randomly assigned to three groups at 1 month postoperatively. Patients in group 1 received EAW for nasal irrigation daily for 2 months, those in group 2 received neutral normal saline (NS) daily for 2 months, and those in group 3 did not receive nasal irrigation after surgery. Before and 3 months after FESS, sinonasal symptoms were assessed by questionnaire and patients received endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and bacterial culture from middle meatus. RESULTS: There were 185 patients enrolled between May 2009 and March 2012. Among the patients who completed the study, 36 received EWA irrigation, 35 received NS irrigation, and 39 (group 3) received no irrigation. Patients with nasal irrigation had a better outcome based on questionnaire score and saccharine transit time. However, there was no difference in outcome between patients who received irrigation with EAW and NS. CONCLUSION: Our study showed that EWA irrigation did not confer a greater benefit than that of NS irrigation in post-FESS care.

Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy.

INTRODUCTION: Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy. METHODS: To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment. RESULTS: Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality. CONCLUSIONS: Our results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC.