Hibifolin protected pro-inflammatory response and oxidative stress in LPS-induced acute lung injury through antioxidative enzymes and the AMPK2/Nrf-2 pathway.

ALI is a grave medical ailment that manifests as abrupt inflammation of the lungs and diminished oxygen levels. It poses a considerable challenge to the medical fraternity, with elevated rates of morbidity and mortality. Our research endeavors to investigate the potential of hibifolin, a flavonoid glucuronide, imbued with potent antioxidant properties, and its molecular mechanism to combat LPS-induced ALI in mice. The study utilized ICR mice to create an ALI model induced by LPS. Prior to LPS administration, hibifolin was given at 10, 30, or 50 mg/kg, or dexamethasone was given at 1 mg/kg to assess its preventative impact. Changes in lung tissue, pulmonary edema, and lipid peroxidation were analyzed using H&E stain assay, lung wet/dry ratio assay, and MDA formation assay, respectively. Activity assay kits were used to measure MPO activity and antioxidative enzymes (SOD, CAT, GPx) activity in the lungs. Western blot assay was used to determine the phosphorylation of Nrf-2 and AMPK2 in the lungs. Hibifolin demonstrated a concentration-dependent improvement in LPS-induced histopathologic pulmonary changes. This treatment notably mitigated pulmonary edema, lipid peroxidation, and MPO activity in ALI mice. Additionally, hibifolin successfully restored antioxidative enzyme activity in the lungs of ALI mice. Moreover, hibifolin effectively promoted Nrf-2 phosphorylation and reinstated AMPK2 phosphorylation in the lungs of ALI mice. The results indicate that hibifolin could effectively alleviate the pathophysiological impact of LPS-induced ALI. This is likely due to its antioxidative properties, which help to restore antioxidative enzyme activity and activate the AMPK2/Nrf2 pathway. These findings are valuable in terms of enhancing our knowledge of ALI treatment and pave the way for further investigation into hibifolin as a potential therapeutic option for lung injuries.

Disulfiram/Copper Suppresses Cancer Stem Cell Activity in Differentiated Thyroid Cancer Cells by Inhibiting BMI1 Expression.

Differentiated thyroid carcinomas (DTCs), which have papillary and follicular types, are common endocrine malignancies worldwide. Cancer stem cells (CSCs) are a particular type of cancer cells within bulk tumors involved in cancer initiation, drug resistance, and metastasis. Cells with high intracellular aldehyde hydrogenase (ALDH) activity are a population of CSCs in DTCs. Disulfiram (DSF), an ALDH inhibitor used for the treatment of alcoholism, reportedly targets CSCs in various cancers when combined with copper. This study reported for the first time that DSF/copper can inhibit the proliferation of papillary and follicular DTC lines. DSF/copper suppressed thyrosphere formation, indicating the inhibition of CSC activity. Molecular mechanisms of DSF/copper involved downregulating the expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and cell cycle-related proteins, including cyclin B2, cyclin-dependent kinase (CDK) 2, and CDK4, in a dose-dependent manner. BMI1 overexpression diminished the inhibitory effect of DSF/copper in the thyrosphere formation of DTC cells. BMI1 knockdown by RNA interference in DTC cells also suppressed the self-renewal capability. DSF/copper could inhibit the nuclear localization and transcriptional activity of c-Myc and the binding of E2F1 to the BMI1 promoter. Overexpression of c-Myc or E2F1 further abolished the inhibitory effect of DSF/copper on BMI1 expression, suggesting that the suppression of c-Myc and E2F1 by DSF/copper was involved in the downregulation of BMI1 expression. In conclusion, DSF/copper targets CSCs in DTCs by inhibiting c-Myc- or E2F1-mediated BMI1 expression. Therefore, DSF is a potential therapeutic agent for future therapy in DTCs.

A case report of secondary synchronous diagnosis of multiple myeloma and systemic lupus erythematosus after breast cancer treatment: A CARE-compliant article.

INTRODUCTION: Breast cancer (BC) is the most diagnosed cancer worldwide. Multiple myeloma (MM) is a hematologic malignancy characterized by the overproduction of monoclonal antibodies in the bone marrow. Systemic lupus erythematosus (SLE) is distinguished by the aberrant activity of the immune system with heterogeneous clinical manifestations. The coexistence of more than one major illness in a patient can present a diagnostic challenge for clinical physicians, especially when the comorbid diseases share a similar clinical presentation. Herein, we report an unusual case of secondary synchronous diagnosis of MM and SLE after BC treatment. PATIENT CONCERNS: A 69-year-old female patient with breast cancer experienced severe skin itching and rashes on the face, anterior chest wall, back, and trunk for two days before admission. She had high levels of immunoglobulin and anti-nuclear antibodies; low levels of complements 3 and 4; positive anti-cardiolipin-IgM, anti-beta 2 glycoprotein-1 (anti-ß2GP1) antibodies, and lupus anticoagulant results at serological testing. DIAGNOSIS: The postoperative pathology report showed ductal carcinoma in situ in the right breast. SLE was confirmed based on the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria. IgG-κ type multiple myeloma was confirmed by bone marrow biopsy, and the patient was synchronously diagnosed with SLE and MM after BC treatment. INTERVENTIONS: Glucocorticoids and immunosuppressive agents, including intravenous hydrocortisone (5 g every 8 hours) and oral hydroxychloroquine (Plaquenil) (200 mg twice daily) were administered to treat SLE. One capsule of thalidomide 50 mg was administered orally every night at bedtime for MM. OUTCOMES: The patient died two days later, shortly after the administration of drugs, due to multiple organ failures secondary to pneumonia and respiratory failure. CONCLUSION: This is a case of MM and SLE after BC treatment. The present challenge was the early detection and accurate diagnosis of the secondary major illnesses, as the clinical manifestations were similar and non-specific between these two diseases. Awareness and prompt recognition of the common clinical symptoms of SLE and MM should be considered by clinical physicians to avoid delayed diagnoses and facilitate early treatment for a better prognosis.

Outcome of CPAP Titration for Moderate-to-Severe OSA Under Drug-Induced Sleep Endoscopy: A Randomized Controlled Crossover Trial.

Background: The titration pressure of continuous positive airway pressure (CPAP) is important in patients with obstructive sleep apnea (OSA). This study aimed to understand the difference between drug-induced sleep endoscopy (DISE)-guided CPAP titration and conventional sleep center (CSC) CPAP titration in patients with OSA. Methods: In this randomized, controlled, and single-blind crossover trial, we compared the effects of 1-month CPAP treatment in patients with OSA with either DISE-guided CPAP titration or CSC CPAP titration. Twenty-four patients with OSA were recruited for the study. All patients underwent polysomnography, DISE-guided CPAP titration, and accommodation. Initially, patients were randomly assigned to receive either DISE-guided CPAP titration or CSC CPAP treatment for the first month. They were then switched to other treatments in the second month. The Epworth sleepiness scale (ESS) score was recorded at baseline, 1 and 2 months. Results: The upper limit of the pressure of DISE-guided titration and CSC CPAP titration was not significantly different (13.9 ± 0.7 vs. 13.5 ± 0.5 cm H2O; P = 0.92). The residual apnea-hypopnea index and compliance were also not significantly different between the groups. ESS score significantly improved from baseline to 1 month after CPAP treatment in both groups. Both epiglottis (anterior-posterior collapse) and tongue base collapse were significantly associated with 95% CPAP pressure (P = 0.031 and 0.038, respectively). After multivariate regression analyses, the epiglottis (anterior-posterior collapse) was an independent factor for 95% CPAP pressure. The incidence rate of bradycardia was 58.3%, which is a safety concern for DISE. Despite the high incidence of bradycardia, all patients with bradycardia recovered with proper management. Conclusion: Both modalities were comparable in terms of establishing the pressure settings required to treat patients. Further large-scale studies are required to confirm these results. Trial registration: https://clinicaltrials.gov/, NCT03523013.

Large-scale assessment of consistency in sleep stage scoring rules among multiple sleep centers using an interpretable machine learning algorithm.

STUDY OBJECTIVES: Polysomnography is the gold standard in identifying sleep stages; however, there are discrepancies in how technicians use the standards. Because organizing meetings to evaluate this discrepancy and/or reach a consensus among multiple sleep centers is time-consuming, we developed an artificial intelligence system to efficiently evaluate the reliability and consistency of sleep scoring and hence the sleep center quality. METHODS: An interpretable machine learning algorithm was used to evaluate the interrater reliability (IRR) of sleep stage annotation among sleep centers. The artificial intelligence system was trained to learn raters from 1 hospital and was applied to patients from the same or other hospitals. The results were compared with the experts' annotation to determine IRR. Intracenter and intercenter assessments were conducted on 679 patients without sleep apnea from 6 sleep centers in Taiwan. Centers with potential quality issues were identified by the estimated IRR. RESULTS: In the intracenter assessment, the median accuracy ranged from 80.3%-83.3%, with the exception of 1 hospital, which had an accuracy of 72.3%. In the intercenter assessment, the median accuracy ranged from 75.7%-83.3% when the 1 hospital was excluded from testing and training. The performance of the proposed method was higher for the N2, awake, and REM sleep stages than for the N1 and N3 stages. The significant IRR discrepancy of the 1 hospital suggested a quality issue. This quality issue was confirmed by the physicians in charge of the 1 hospital. CONCLUSIONS: The proposed artificial intelligence system proved effective in assessing IRR and hence the sleep center quality.

Safrole-induced expression of proinflammatory responses is associated with phosphorylation of mitogen-activated protein kinase family and the nuclear factor-κB/inhibitor of κB pathway in macrophages.

OBJECTIVE: Safrole, also called shikimol and Sassafras, is the carcinogenic and phenylpropanoid compound extracted from Sassafras tree and anise, betel, and camphor. Moreover, a high concentration of safrole can be occur in the saliva because of betel nut or areca quid chewing which a common habit observed in Southern and Southeastern Asia. Notably, macrophages are crucial phagocytic cells of the immune system. Nonetheless, to date, no evidence has been reported regarding safrole-induced proinflammatory response and the corresponding mechanism in macrophages. MATERIALS AND METHODS: In the present study, the cytokines expression, NO generation, protein phosphorylation, and expression were assessed by enzyme-linked immunosorbent assay, Griess reagent, and Western blot assay, respectively. RESULTS: In this study, we determined that safrole induces the generation of nitric oxide and proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and IL-6 in RAW264.7 macrophages in a concentration-dependent manner. Furthermore, inhibitor of κB (IκB) degradation was caused by safrole in a concentration-dependent manner. In addition, the phosphorylation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) family, including p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase, was induced by safrole began to increase at 10 µM and attained a plateau at 100 µM. CONCLUSION: These results indicated that safrole induces the expression of proinflammatory responses in macrophages through the NF-κB/IκB pathway and its upstream factor, MAPK family phosphorylation.

A Simplified Screening Questionnaire for Detecting Severe OSA in Chronic Obstructive Airway Disease in Asian Population.

The aim of this study was to develop a simplified screening questionnaire to detect the existence of severe obstructive sleep apnea (OSA) in chronic obstructive pulmonary disease (COPD) patients to reduce mortality and hospitalization rates. Seventy-seven stable Asian COPD patients aged 69.2 ± 11.5 years were retrospectively analyzed into the development group. The simplified screening questionnaire was developed from factors identified from sleep surveys and demographic data to predict severe OSA. Receiver operating characteristic (ROC) curve analysis was used to validate the simplified screening questionnaire. Data from another 78 stable COPD patients were used for validation. The apnea-hypopnea index was similar between the development and validation groups (26.3 ± 21.9 and 27.6 ± 21.1, respectively). After logistic regression analysis in the development group, snoring, body mass index ≥27.5 kg/m2, witnessed apnea and coronary artery disease were incorporated into the screening questionnaire to predict OSA. When this questionnaire was applied to the validation group, the results were similar. The simplified screening questionnaire developed is useful in identifying severe OSA in COPD patients.

Nerolidol Suppresses the Inflammatory Response during Lipopolysaccharide-Induced Acute Lung Injury via the Modulation of Antioxidant Enzymes and the AMPK/Nrf-2/HO-1 Pathway.

Acute lung injury (ALI) is a life-threatening disease that is characterised by the rapid onset of inflammatory responses. Lipopolysaccharide (LPS) is an endotoxin that plays an important role in triggering ALI via pneumonia and sepsis. However, no effective therapeutic strategies are currently available to treat ALI. Nerolidol is an aliphatic sesquiterpene alcohol that is found in the essential oils of many flowers as well as floral plants. It has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties. Herein, we show that nerolidol pretreatment counteracted the histopathological hallmarks in LPS-induced ALI mice. Indeed, nerolidol pretreatment inhibited LPS-induced alveolar-capillary barrier disruption, lung edema, and lipid peroxidation. Moreover, nerolidol pretreatment prevented the LPS from decreasing the enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase. Importantly, nerolidol treatment enhanced phosphorylation of AMP-activated protein kinase (AMPK) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). Taken together, our study reveals the novel protective effects of nerolidol in LPS-induced ALI via the induction of antioxidant responses and activation of the AMPK/Nrf-2/HO-1 signalling pathway.

CHA2DS2-VASc scores predict major adverse cardiovascular events in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) frequently experience concurrent comorbidities; therefore, risk assessment for major adverse cardiovascular events (MACEs) is very important. OBJECTIVES: We explored the association between COPD and risk of MACEs with three common clinical events: acute myocardial infarction (AMI), ischemic stroke (IS), and cardiovascular death (CVD). METHODS: We evaluated the predictive value of the CHA2DS2-VASc score (congestive heart failure [C], hypertension [H], age [A], diabetes [D], stroke [S], and vascular disease [VASc]) for MACEs in COPD patients. In this observational study, we retrospectively reviewed the records of 29 258 patients with COPD between 2005 and 2009 in relation to MACE risk using the CHA2DS2-VASc score. We calculated the hazard ratios (HR) and 95% confidence intervals (CI) using a significance level of .05. RESULTS: Patients with COPD had significantly (P < .001) increased risk of MACEs, and a high prevalence of CHA2DS2-VASc scores ≥ 6, predicting MACEs (16.1%), AMI (3.3%), IS (8.7%), and CVD (4.0%). A good discrimination was found for MACEs, IS events, and CVD events (AUC = 0.740, 0.739, and 0.778, respectively) but poorer discrimination for AMI events (AUC = 0.697). CONCLUSION: Early lifestyle modifications and antithrombotic therapy may be essential for COPD patients at a high risk of MACEs, that is, those with CHA2DS2-VASc scores ≥ 6.

Snoring Sounds Predict Obstruction Sites and Surgical Response in Patients with Obstructive Sleep Apnea Hypopnea Syndrome.

Snoring sounds generated by different vibrators of the upper airway may be useful indicators of obstruction sites in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). This study aimed to investigate associations between snoring sounds, obstruction sites, and surgical responses (≥50% reduction in the apnea-hypopnea index [AHI] and <10 events/hour) in patients with OSAHS. This prospective cohort study recruited 36 OSAHS patients for 6-hour snoring sound recordings during in-lab full-night polysomnography, drug-induced sleep endoscopy (DISE), and relocation pharyngoplasty. All patients received follow-up polysomnography after 6 months. Fifteen (42%) patients with at least two complete obstruction sites defined by DISE were significantly, positively associated with maximal snoring sound intensity (40-300 Hz; odds ratio [OR], 1.25, 95% confidence interval [CI] 1.05-1.49) and body mass index (OR, 1.48, 95% CI 1.02-2.15) after logistic regression analysis. Tonsil obstruction was significantly, inversely correlated with mean snoring sound intensity (301-850 Hz; OR, 0.84, 95% CI 0.74-0.96). Moreover, baseline tonsil obstruction detected by either DISE or mean snoring sound intensity (301-850 Hz), and AHI could significantly predict the surgical response. Our findings suggest that snoring sound detection may be helpful in determining obstruction sites and predict surgical responses.

Bispectral Index in Evaluating Effects of Sedation Depth on Drug-Induced Sleep Endoscopy.

OBJECTIVE: To evaluate the effect of sedation depth on drug-induced sleep endoscopy (DISE). METHODS: Ninety patients with obstructive sleep apnea (OSA) and 18 snorers underwent polysomnography and DISE under bispectral index (BIS)-guided propofol infusion at two different sedation levels: BIS 65-75 (light sedation) and 50-60 (deep sedation). RESULTS: For the patients with OSA, the percentages of velopharynx, oropharynx, hypopharynx, and larynx obstructions under light sedation were 77.8%, 63.3%, 30%, and 33.3%, respectively. Sedation depth was associated with the severity of velopharynx and oropharynx obstruction, oropharynx obstruction pattern, tongue base obstruction, epiglottis anteroposterior prolapse and folding, and arytenoid prolapse. In comparison, OSA severity was associated with the severity of velopharynx obstruction, severity of oropharynx obstruction, and arytenoid prolapse (odds ratio (95% confidence interval); 14.3 (4.7-43.4), 11.7 (4.2-32.9), and 13.2 (2.8-62.3), respectively). A good agreement was noted between similar DISE findings at different times and different observers (kappa value 0.6 to 1, respectively). A high percentage of arytenoid prolapse (46.7% among the patients with OSA under light sedation) was noted. CONCLUSIONS: Greater sedative depth increased upper airway collapsibility under DISE assessment. DISE under BIS-guided propofol infusion, and especially a level of 65-75, offers an objective and reproducible method to evaluate upper airway collapsibility. Some findings were induced by drug sedation and need careful interpretation. Specific arytenoid prolapse patterns were noted for which further investigations are warranted. CLINICAL TRIALS REGISTRATION: http://www.clinicaltrials.gov, identifier: NCT01100554. COMMENTARY: A commentary on this article appears in this issue on page 965.

Potential therapeutic benefit of combining gefitinib and tamoxifen for treating advanced lung adenocarcinoma.

INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations are known as oncogene driver mutations and with EGFR mutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. Some studies have shown that activation of estrogen and estrogen receptor α or ß (ERα/ß) promote adenocarcinoma. We evaluated the relationship between the two receptors and the potential therapeutic benefit with Gefitinib and Tamoxifen. METHODS: We assessed the association between EGFR mutations as well as ERα/ß expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR exon 19 deletion mutant; Gefitinib-vulnerable cells) and A549 (EGFR wild type; Gefitinib-resistant cells) cancer cells were used to evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen. RESULTS: We found that the cytosolic but not the nuclear expression of ERß was associated with better OS in LAC tumors but not associated with EGFR mutation. The in vitro study showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ERß. In addition, combining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib. CONCLUSION: Tamoxifen enhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ERß in cytosol.

Chronic cough and obstructive sleep apnoea in a sleep laboratory-based pulmonary practice.

BACKGROUND: Obstructive sleep apnoea (OSA) has recently been identified as a possible aetiology for chronic cough. The aim of this study was to compare the incidence of chronic cough between patients with and without OSA and the impact of continuous positive airway pressure (CPAP) treatment in resolving chronic cough. METHODS: Patients referred to the sleep laboratory from January 2012 to June 2012 were retrospectively enrolled. Clinical data, treatment course and resolution of chronic cough were analysed. Specifically, gastro-oesophageal reflux (GERD), upper airway cough syndrome, asthma, apnoea-hypopnoea index and the impact of CPAP treatment on chronic cough were assessed. RESULTS: A total of 131 patients were reviewed. The incidence of chronic cough in the OSA group was significantly higher than the non-OSA group (39/99 (39.4%) vs. 4/32 (12.5%), p = 0.005). Both GERD and apnoea-hypopnoea index were significantly associated with chronic cough in univariate analysis. After multivariate logistic regression, GERD was the only independent factor for chronic cough. Moreover, the resolution of chronic cough was more significant in the OSA patients with CPAP treatment compared with those not receiving CPAP treatment (12/18 (66.7%) vs. 2/21 (9.5%), p = 0.010). CONCLUSION: The incidence of chronic cough was significantly higher in the OSA patients. In addition, CPAP treatment significantly improved chronic cough. Therefore, OSA may be a contributory factor to chronic cough.

Nocturnal CPAP improves walking capacity in COPD patients with obstructive sleep apnoea.

BACKGROUND: Exercise limitation is an important issue in patients with chronic obstructive pulmonary disease (COPD), and it often co-exists with obstructive sleep apnoea (overlap syndrome). This study examined the effects of nocturnal continuous positive airway pressure (CPAP) treatment on walking capacity in COPD patients with or without obstructive sleep apnoea. METHODS: Forty-four stable moderate-to-severe COPD patients were recruited and completed this study. They all underwent polysomnography, CPAP titration, accommodation, and treatment with adequate pressure. The incremental shuttle walking test was used to measure walking capacity at baseline and after two nights of CPAP treatment. Urinary catecholamine and heart rate variability were measured before and after CPAP treatment. RESULTS: After two nights of CPAP treatment, the apnoea-hypopnoea index and oxygen desaturation index significantly improved in both overlap syndrome and COPD patients, however these changes were significantly greater in the overlap syndrome than in the COPD group. Sleep architecture and autonomic dysfunction significantly improved in the overlap syndrome group but not in the COPD group. CPAP treatment was associated with an increased walking capacity from baseline from 226.4 ± 95.3 m to 288.6 ± 94.6 m (P < 0.05), and decreased urinary catecholamine levels, pre-exercise heart rate, oxygenation, and Borg scale in the overlap syndrome group. An improvement in the apnoea-hypopnoea index was an independent factor associated with the increase in walking distance (r = 0.564). CONCLUSION: Nocturnal CPAP may improve walking capacity in COPD patients with overlap syndrome. TRIAL REGISTRATION: NCT00914264.

The potential regimen of target-controlled infusion of propofol in flexible bronchoscopy sedation: a randomized controlled trial.

OBJECTIVES: Target-controlled infusion (TCI) provides precise pharmacokinetic control of propofol concentration in the effect-site (Ce), eg. brain. This pilot study aims to evaluate the feasibility and optimal TCI regimen for flexible bronchoscopy (FB) sedation. METHODS: After alfentanil bolus, initial induction Ce of propofol was targeted at 2 µg/ml. Patients were randomized into three titration groups (i.e., by 0.5, 0.2 and 0.1 µg/ml, respectively) to maintain stable sedation levels and vital signs. Adverse events, frequency of adjustments, drug doses, and induction and recovery times were recorded. RESULTS: The study was closed early due to significantly severe hypoxemia events (oxyhemoglobin saturation <70%) in the group titrated at 0.5 µg/ml. Forty-nine, 49 and 46 patients were enrolled into the 3 respective groups before study closure. The proportion of patients with hypoxemia events differed significantly between groups (67.3 vs. 46.9 vs. 41.3%, p = 0.027). Hypotension events, induction and recovery time and propofol doses were not different. The Ce of induction differed significantly between groups (2.4±0.5 vs. 2.1±0.4 vs. 2.1±0.3 µg/ml, p = 0.005) and the Ce of procedures was higher at 0.5 µg/ml titration (2.4±0.5 vs. 2.1±0.4 vs. 2.2±0.3 µg/ml, p = 0.006). The adjustment frequency tended to be higher for titration at 0.1 µg/ml but was not statistically significant (2 (0∼6) vs. 3 (0∼6) vs. 3 (0∼11)). Subgroup analysis revealed 14% of all patients required no further adjustment during the whole sedation. Comparing patients requiring at least one adjustment with those who did not, they were observed to have a shorter induction time (87.6±34.9 vs. 226.9±147.9 sec, p<0.001), a smaller induction dose and Ce (32.5±4.1 vs. 56.8±22.7 mg, p<0.001; 1.76±0.17 vs. 2.28 ±0.41, p<0.001, respectively), and less hypoxemia and hypotension (15.8 vs.56.9%, p = 0.001; 0 vs. 24.1%, p = 0.008, respectively). CONCLUSION: Titration at 0.5 µg/ml is risky for FB sedation. A subgroup of patients required no more TCI adjustment with fewer complications. Further studies are warranted to determine the optimal regimen of TCI for FB sedation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01101477.

Energy types of snoring sounds in patients with obstructive sleep apnea syndrome: a preliminary observation.

BACKGROUND: Annoying snore is the principle symptom and problem in obstructive sleep apnea syndrome (OSAS). However, investigation has been hampered by the complex snoring sound analyses. OBJECTIVE: This study was aimed to investigate the energy types of the full-night snoring sounds in patients with OSAS. PATIENTS AND METHOD: Twenty male OSAS patients underwent snoring sound recording throughout 6 hours of in-lab overnight polysomnogragphy. Snoring sounds were processed and analyzed by a new sound analytic program, named as Snore Map®. We transformed the 6-hour snoring sound power spectra into the energy spectrum and classified it as snore map type 1 (monosyllabic low-frequency snore), type 2 (duplex low-&mid-frequency snore), type 3 (duplex low- & high-frequency snore), and type 4 (triplex low-, mid-, & high-frequency snore). The interrator and test-retest reliabilities of snore map typing were assessed. The snore map types and their associations among demographic data, subjective snoring questionnaires, and polysomnographic parameters were explored. RESULTS: The interrator reliability of snore map typing were almost perfect (κ = 0.87) and the test-retest reliability was high (r = 0.71). The snore map type was proportional to the body mass index (r = 0.63, P = 0.003) and neck circumference (r = 0.52, P = 0.018). Snore map types were unrelated to subjective snoring questionnaire scores (All P>0.05). After adjustment for body mass index and neck circumference, snore map type 3-4 was significantly associated with severity of OSAS (r = 0.52, P = 0.026). CONCLUSIONS: Snore map typing of a full-night energy spectrum is feasible and reliable. The presence of a higher snore map type is a warning sign of severe OSAS and indicated priority OSAS management. Future studies are warranted to evaluate whether snore map type can be used to discriminate OSAS from primary snoring and whether it is affected by OSAS management.

Echoic features as predictors of diagnostic yield of endobronchial ultrasound-guided transbronchial lung biopsy in peripheral pulmonary lesions.

The endobronchial ultrasound (EBUS) features of peripheral pulmonary lesions (PPLs) are associated with histopathologic presentation. Certain histologic and radiologic characteristics of peripheral pulmonary lesions affect the diagnostic yield of transbronchial lung biopsies (TBLB). This study aimed to assess the feasibility of EBUS echoic features as predictors of diagnostic yield of TBLB. Four hundred and eight patients with PPLs underwent TBLB. The yields of TBLB in lesions with characteristic EBUS features were compared with those without such features. The overall diagnostic yield of TBLB was 64.2%. Lesion diameter (≥3 cm vs. <3 cm; 69.1% vs. 58.5%, p < 0.05), location of the EBUS probe (within vs. adjacent to lesions; 73.2% vs. 46.3%, p < 0.01) and lesion echogenicity (heterogeneous vs. homogeneous; 76.7% vs. 52.0%, p < 0.01) were associated with higher TBLB yields. In malignant PPLs, the echoic features associated with higher TBLB yields were lesion diameter (≥3 cm vs. <3 cm; 74.4% vs. 62.5%, p < 0.05), location of the EBUS probe (within vs. adjacent to lesions; 78.7% vs. 47.4%, p < 0.01), echoic feature of the margin (noncontinuous vs. continuous; 77.0% vs. 62.4%, p < 0.01) and lesion echogenicity (heterogeneous vs. homogeneous; 77.7% vs. 53.9%, p < 0.01). EBUS probe location, echoic feature of the margin and lesion echogenicity were independent predictors according to the results of multivariate analysis. In conclusion, EBUS features are feasible predictors of diagnostic yield of TBLB in peripheral lung lesions.

Low-dose weekly docetaxel is as tolerable as pemetrexed in previously treated advanced non-small-cell lung cancer.

OBJECTIVES: Docetaxel and pemetrexed have been validated as therapeutics for previously treated advanced non-small-cell lung cancer (NSCLC), but tolerability is a concern for standard treatment with docetaxel administered once every 3 weeks (tri-weekly 75-mg/m(2) schedule). We conducted this retrospective study to compare the efficacy and toxicity of weekly low-dose docetaxel versus tri-weekly pemetrexed for previously treated advanced NSCLC. METHODS: Consecutive patients who received low-dose single docetaxel (30 mg/m(2) on days 1 and 8 every 3 weeks) or pemetrexed (500 mg/m(2) every 3 weeks) at a single university-affiliated hospital following failure of previous treatment were retrospectively reviewed. Their outcomes and toxicity profiles were determined. RESULTS: 179 patients were included between 2005 and 2008 (docetaxel, n = 79; pemetrexed, n = 100). Both groups had similar hematologic (16.5 vs. 15.0%; p = 0.84) and non-hematologic (20.3 vs. 24%; p = 0.55) toxicities. After controlling for confounding factors, docetaxel remained superior to pemetrexed for progression-free survival (median 4.0 vs. 2.4 months; hazard ratio 0.64; 95% CI 0.47-0.87; p = 0.005) and overall survival (median 15.0 vs.8.5 months; hazard ratio 0.54; 95% CI 0.38-0.77; p <0.001). CONCLUSION: Although this study showed that weekly low doses of docetaxel were as tolerable as pemetrexed for previously treated advanced NSCLC, a prospective design is needed to confirm this finding.

Conscious sedation reduces patient discomfort and improves satisfaction in flexible bronchoscopy.

BACKGROUND: Conscious sedation for patients undergoing flexible bronchoscopy (FB) is suggested to alleviate discomfort and improve satisfaction despite controversy regarding its benefits. In Taiwan, the general FB practice involves local anesthesia only. This study aimed to assess the benefits and risks of conscious sedation in diagnostic FB. METHODS: This prospective case control study enrolled 44 non-sedated and 44 sedated patients who underwent diagnostic FB. All received the standard upper airway preparation, while sedated patients received clinically judged increments of midazolam and alfentanil for conscious sedation. Patient discomforts and the operator's opinions during FB were assessed using the verbal analogue score (VAS, 0-10 scale). Willingness to return was assessed as five scales to monitor patient satisfaction. Safety profiles throughout the procedures were also assessed. RESULTS: Compared to non-sedated patients, sedated ones expressed less discomfort, with lower VAS scores regarding scope insertion (3.5 [0-10] vs. 0 [0-5], p < 0.001), cough (5 [0-10] vs. 0 [0-5], p < 0.001), dyspnea (3 [0-10] vs. 0 [0-8], p < 0.001), pain (3 [0-10] vs. 0 [0-5], p < 0.001), and global tolerance of the procedures (5 [1-10] vs. 0 [0-9], p < 0.001). More sedated patients expressed willingness to return (70.5% vs. 36.4%, p = 0.001). The bronchoscopist also rated lower VAS scores on cough and dyspnea in sedated patients. Sedated patients had less hypertension but more hypoxemic episodes during the procedure, which were all transient and not life-threatening. CONCLUSIONS: Conscious sedation with clinically judged midazolam and alfentanil reduces discomforts, improves satisfaction, and carries slight, but manageable, hypoxemia risks in patients undergoing FB.

Endobronchial ultrasound increases the diagnostic yields of polymerase chain reaction and smear for pulmonary tuberculosis.

OBJECTIVES: Our objective was to determine the contribution of endobronchial ultrasound in the diagnostic yields of acid-fast bacillus smear, nucleic acid amplification tests, and culture in bronchoalveolar lavage fluid for pulmonary tuberculosis. METHODS: During a 1-year interval, 99 patients who had initial sputum-negative acid-fast bacillus smears or no sputum but were later proven to have a positive culture for Mycobacterium tuberculosis in their sputum or bronchoalveolar lavage fluid were retrospectively studied. Among them, 56 patients underwent bronchoscopy with endobronchial ultrasound (EBUS group) and 43 patients received conventional bronchoscopy for bronchoalveolar lavage (non-EBUS group). RESULTS: The diagnostic yields of the nucleic acid amplification tests (89.3%, 50/56; P = .006), acid-fast bacillus smear (30.4%, 17/56; P = .013), and M tuberculosis culture in bronchoalveolar lavage fluid (67.9%, 38/56; P = .041) were significantly higher in the EBUS group of patients. The results of those who underwent conventional bronchoscopy were 65.1% (28/43), 9.3% (4/43), and 46.5% (20/43), respectively. Combining bronchoalveolar lavage fluid smear and nucleic acid amplification tests, we made a rapid diagnosis of pulmonary tuberculosis in 51 (91.1%) of the 56 EBUS patients and 29 (67.4%; P = .004) of the 43 non-EBUS patients. CONCLUSIONS: The introduction of endobronchial ultrasound increases the diagnostic yield of the nucleic acid amplification tests, acid-fast bacillus smear, and M tuberculosis culture from bronchioalveolar lavage fluid in patients with pulmonary tuberculosis who have negative sputum smear or no sputum production.