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Background: The present study aimed to test if the temporal sequence between sleep apnea (SA) diagnosis and incident myocardial infarction (MI) was associated with the long-term mortality and cardiovascular event in a community-based cohort. Methods: We retrieved data from 9,453 incident MI patients between Jan. 1st 2000 and Dec. 31st 2012 from the Taiwan National Health Insurance Research Database. The study subjects included 207 MI patients with SA (SA-MI), further stratified into 110 with pre-existing SA before MI (SA-bMI) and 96 diagnosed with SA after MI (SA-pMI). The median follow-up period was 4.2 years. Propensity-score-matched controls were selected from 9,246 non-SA MI patients (non-SA-MI). The association of SA and outcomes including all-cause mortality and major adverse cardiac and cerebrovascular events (MACCEs) were analyzed by a Cox proportional hazards model. Results: The result showed that SA was not associated with mortality regardless of the timing of SA diagnosis. SA-pMI was associated with increased risk of MACCEs (Hazard ratio [HR]: 1.412, 95% confidence interval [CI]: 1.037~1.923, p = 0.029) including re-MI or revascularization and ischemic heart disease hospitalization. Such an association was most significant for SA diagnosed within one year after MI (HR: 2.029, 95% CI: 1.265~3.254, p = 0.003), which was not seen in patients treated with continuous positive airway pressure (CPAP). Conclusion: The temporal sequence and the time interval between SA diagnosis and incident MI was associated with the cardiovascular events after MI, especially within one year after MI. Early assessment for the presence of SA after incident MI and early CPAP intervention may reduce the risk of further adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the effect of combining positive airway pressure (PAP) therapy and mandibular advancement device (MAD) in patients with severe obstructive sleep apnea (OSA) who were pressure intolerant for PAP and were unresponsive to MAD. Methods: This retrospective study reviewed the medical records of severe OSA patients with apnea-hypopnea index (AHI) ≥ 30/hr who were diagnosed between October 1, 2008 and June 30, 2014. Patients were initially treated with 2 weeks of PAP, and those who were intolerant to high-pressure PAP (≥15 cm H2O) were switched to 12 weeks of MAD, which is a monobloc designed at 75% of maximum protrusion. Patients who had high residual AHI (≥15/hr) on MAD underwent 12 weeks of combination therapy (CT) with MAD and CPAP and were enrolled in the present study. Enrolled subjects who completed the 12-week CT were followed-up until June 30, 2016. Results: A total of 14 male patients were included. All three treatments effectively reduced AHI, oxygen desaturation index (ODI), and total sleep time with SpO2 <90% (% TST-SpO2<90%) compared to pretreatment values. The residual AHI and ODI on CT was lower than that on MAD or PAP. The residual % TST-SpO2<90% was lower than that on MAD and similar to that on PAP. The therapeutic pressure on CT was on average 9.2 cm H2O lower than that on PAP. For the 11 patients who completed CT, only CT reduced ESS compared to pretreatment value. No treatment had significant impact on % slow wave sleep or overnight change of blood pressure. For patients who completed CT, the average usage was 5.9±1.7 hr/night at 12th week and 6.4±1.5 hr/night at a median follow-up of 36.5-months. Conclusions: Combining MAD and CPAP showed additive effects on reducing AHI and ODI, and lowered the therapeutic pressures. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes is an autoimmune disease that destroys insulin-producing beta cells in the pancreas. Pancreatic islet transplantation could be an effective treatment option for type 1 diabetes once several issues are resolved, including donor shortage, prevention of islet necrosis and loss in pre- and post-transplantation, and optimization of immunosuppression. This study seeks to determine the cause of necrotic loss of isolated islets to improve transplant efficiency. Methodology: The oxygen tension inside isolated human islets of different sizes was simulated under varying oxygen environments using a computational in silico model. In vitro human islet viability was also assessed after culturing in different oxygen conditions. Correlation between simulation data and experimentally measured islet viability was examined. Using these in vitro viability data of human islets, the effect of islet diameter and oxygen tension of the culture environment on islet viability was also analyzed using a logistic regression model. Principal findings: Computational simulation clearly revealed the oxygen gradient inside the islet structure. We found that oxygen tension in the islet core was greatly lower (hypoxic) than that on the islet surface due to the oxygen consumption by the cells. The hypoxic core was expanded in the larger islets or in lower oxygen cultures. These findings were consistent with results from in vitro islet viability assays that measured central necrosis in the islet core, indicating that hypoxia is one of the major causes of central necrosis. The logistic regression analysis revealed a negative effect of large islet and low oxygen culture on islet survival. Conclusions/Significance: Hypoxic core conditions, induced by the oxygen gradient inside islets, contribute to the development of central necrosis of human isolated islets. Supplying sufficient oxygen during culture could be an effective and reasonable method to maintain isolated islets viable. [ABSTRACT FROM AUTHOR]

Background: Endobronchial ultrasound(EBUS)-guided transbronchial biopsy(TBB) is the preferred diagnostic tool for peripheral pulmonary lesions(PPLs) and mastering this procedure is an important task in the training of chest physicians. Little has been published about the learning experience of physicians with this technique, particularly at an institutional level. We aimed to establish a learning curve for EBUS-guided TBB for PPLs at a medical center. Methods: Between 2008 and 2015, consecutive patients with PPLs referred for EBUS-guided TBB at National Taiwan University Hospital were enrolled. To build the learning curve, the diagnostic yield of TBB (plus brushings and washings) was calculated and compared. Meanwhile, lesion characteristics, and procedure-related features and complications were obtained to analyze associations with TBB yield and safety profile. Results: A total of 2144 patients were included and EBUS-guided TBB was diagnostic for 1547(72%). The TBB yield was 64% in 2008 and reached a plateau of 72% after 2010. It took approximately 400 EBUS-guided procedures to achieve stable proficiency. Further analysis showed that improvement in diagnostic yield over time was mainly observed in PPLs, in cases in which the diameter was ≤2 cm or the EBUS probe could not be positioned within. Complication rates were low, with 1.8% and 0.5% for pneumothorax and hemorrhage, respectively. Conclusions: Even though EBUS-guided TBB is an easy-to-learn technique, it takes 3 years or around 400 procedures for a medical center to achieve a better and stable performance. In particular, the diagnostic yield for lesions without the probe within or those sized ≤2 cm could improve with time. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There is evidence to support a connection between COPD and diabetes mellitus (DM), another common medical disorder. However, additional research is required to improve our knowledge of these relationships and their possible implications. In this study, we investigated the impact of DM on patient outcomes through the clinical course of COPD. Methods: We conducted a cohort study in patients from the Taiwan Longitudinal Health Insurance Database between 2000 and 2013. Patients with COPD were identified and assessed for pre-existing and incident DM. A Cox proportional hazards model was built to identify factors associated with incident DM and to explore the prognostic effects of DM on COPD patients. A propensity score method was used to match COPD patients with incident DM to controls without incident DM. Results: Pre-existing DM was present in 332 (16%) of 2015 COPD patients who had a significantly higher hazard ratio (HR) [1.244, 95% confidence interval (CI) 1.010–1.532] for mortality than that of the COPD patients without pre-existing DM. During the 10-year follow-up period, 304 (19%) of 1568 COPD patients developed incident DM; comorbid hypertension (HR, 1.810; 95% CI, 1.363–2.403), cerebrovascular disease (HR, 1.517; 95% CI, 1.146–2.008) and coronary artery disease (HR, 1.408; 95% CI 1.089–1.820) were significant factors associated with incident DM. Survival was worse for the COPD patients with incident DM than for the matched controls without incident DM (Log-rank, p = 0.027). Conclusions: DM, either pre-existing or incident, was associated with worse outcomes in COPD patients. Targeted surveillance and management of DM may be important in clinical care of the COPD population. [ABSTRACT FROM AUTHOR]

Background: Severe sepsis is a potentially deadly illness and always requires intensive care. Do-not-resuscitate (DNR) orders remain a debated issue in critical care and limited data exist about its impact on care of septic patients, particularly in East Asia. We sought to assess outcome of severe sepsis patients with regard to DNR status in Taiwan. Methods: A retrospective cohort study was conducted in intensive care units (ICUs) between 2008 and 2010. All severe sepsis patients were included for analysis. Primary outcome was association between DNR orders and ICU mortality. Volume of interventions was used as proxy indicator to indicate aggressiveness of care. Results: Sixty-seven (9.4%) of 712 patients had DNR orders on ICU admission, and these patients were older and had higher disease severity compared with patients without DNR orders. Notably, DNR patients experienced high ICU mortality (90%). Multivariate analysis revealed that the presence of DNR orders was independently associated with ICU mortality (odds ratio: 6.13; 95% confidence interval: 2.66–14.10). In propensity score-matched cohort, ICU mortality rate (91%) in the DNR group was statistically higher than that (62%) in the non-DNR group (p <0.001). Regarding ICU interventions, arterial and central venous catheterization were more commonly used in DNR patients than in non-DNR patients. Conclusions: From the Asian perspective, septic patients placed on DNR orders on ICU admission had exceptionally high mortality. In contrast to Western reports, DNR patients received more ICU interventions, reflecting more aggressive approach to dealing with this patient population. The findings in some ways reflect differences between East and West cultures and suggest that DNR status is an important confounder in ICU studies involving severely septic patients. [ABSTRACT FROM AUTHOR]

Initiation and progression of cancer depend on many factors. Those on the genetic level are often considered crucial. To gain insight into the physical mechanisms of breast cancer, we construct a gene regulatory network (GRN) which reflects both genetic and environmental aspects of breast cancer. The construction of the GRN is based on available experimental data. Three basins of attraction, representing the normal, premalignant and cancer states respectively, were found on the phenotypic landscape. The progression of breast cancer can be seen as switching transitions between different state basins. We quantified the stabilities and kinetic paths of the three state basins to uncover the biological process of breast cancer formation. The gene expression levels at each state were obtained, which can be tested directly in experiments. Furthermore, by performing global sensitivity analysis on the landscape topography, six key genes (HER2, MDM2, TP53, BRCA1, ATM, CDK2) and four regulations (HER2⊣TP53, CDK2⊣BRCA1, ATM→MDM2, TP53→ATM) were identified as being critical for breast cancer. Interestingly, HER2 and MDM2 are the most popular targets for treating breast cancer. BRCA1 and TP53 are the most important oncogene of breast cancer and tumor suppressor gene, respectively. This further validates the feasibility of our model and the reliability of our prediction results. The regulation ATM→MDM2 has been extensive studied on DNA damage but not on breast cancer. We notice the importance of ATM→MDM2 on breast cancer. Previous studies of breast cancer have often focused on individual genes and the anti-cancer drugs are mainly used to target the individual genes. Our results show that the network-based strategy is more effective on treating breast cancer. The landscape approach serves as a new strategy for analyzing breast cancer on both the genetic and epigenetic levels and can help on designing network based medicine for breast cancer. [ABSTRACT FROM AUTHOR]

Background: Both procalcitonin (PCT) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have been investigated separately as indicators of infection in patients with autoimmune diseases. Our study simultaneously evaluated both PCT and sTREM-1 along with C-reactive protein (CRP) in febrile patients with autoimmune diseases. Methods: Fifty-nine patients were enrolled in the study. The patients were categorized into the infection group (n = 24) or the disease flare group (n = 35). sTREM-1, PCT and CRP concentrations at fever onset were compared between the two groups of patients. Results: sTREM-1 and CRP did not differ between the two groups. PCT [median (range), ng/ml] was higher in the infection group than in the disease flare group [0.53 (0.02–12.85) vs. 0.12 (0.02–19.23), p = 0.001]. The area under the receiver-operating characteristic (ROC) for diagnosis of infection was 0.75 for PCT (p = 0.001), 0.63 for CRP (p = 0.09) and 0.52 for sTREM-1 (p = 0.79). Using 0.2 ng/ml as the cutoff value for PCT, sensitivity was 0.75 and specificity was 0.77. Negative predictive values for PCT were 92%, 87% and 82% for a prevalence of infection of 20%, 30%, and 40%, respectively. Neither immunosuppressants nor biomodulators affected the level of the three biomarkers. However, in patients treated with corticosteroids, the levels of sTREM-1 and CRP were significantly decreased compared with the untreated patients. Conclusions: Setting PCT at a lower cutoff value could provide useful information on excluding infection in febrile patients with autoimmune diseases. The possible effect of corticosteroids on the level of sTREM-1 as an infection marker deserves further study. [ABSTRACT FROM AUTHOR]

We investigated the spatial variation of vitreous oxygen consumption in enucleated porcine eyes. A custom made oxygen source was fabricated that could be localized to either the mid or posterior vitreous cavity and steady state vitreous oxygen tension was measured as a function of distance from the source using a commercially available probe. The reaction rate constant of ascorbate oxidation was estimated ex vivo by measuring the change in oxygen tension over time using vitreous harvested from porcine eyes. Vitreous ascorbate from mid and posterior vitreous was measured spectrophotometrically. When the oxygen source was placed in either the mid-vitreous (N = 6) or the posterior vitreous (N = 6), we measured a statistically significant decrease in vitreous oxygen tension as a function of distance from the oxygen source when compared to control experiments without an oxygen source; (p<0.005 for mid-vitreous and p<0.018 for posterior vitreous at all distances). The mid-vitreous oxygen tension change was significantly different from the posterior vitreous oxygen tension change at 2 and 3mm distances from the respective oxygen source (p<0.001). We also found a statistically significant lower concentration of ascorbate in the mid-vitreous as compared to posterior vitreous (p = 0.02). We determined the reaction rate constant, k = 1.61 M-1s-1 ± 0.708 M-1s-1 (SE), of the oxidation of ascorbate which was modeled following a second order rate equation. Our data demonstrates that vitreous oxygen consumption is higher in the posterior vitreous compared to the mid-vitreous. We also show spatial variations in vitreous ascorbate concentration. [ABSTRACT FROM AUTHOR]

The ancestor of all modern domestic cats is the wildcat, Felis silvestris lybica, with archaeological evidence indicating it was domesticated as early as 10,000 years ago in South-West Asia. A recent study, however, claims that cat domestication also occurred in China some 5,000 years ago and involved the same wildcat ancestor (F. silvestris). The application of geometric morphometric analyses to ancient small felid bones from China dating between 5,500 to 4,900 BP, instead reveal these and other remains to be that of the leopard cat (Prionailurus bengalensis). These data clearly indicate that the origins of a human-cat ‘domestic’ relationship in Neolithic China began independently from South-West Asia and involved a different wild felid species altogether. The leopard cat’s ‘domestic’ status, however, appears to have been short-lived—its apparent subsequent replacement shown by the fact that today all domestic cats in China are genetically related to F. silvestris. [ABSTRACT FROM AUTHOR]

Background and Objective: Weaning parameters are commonly measured through an endotracheal tube in mechanically ventilated patients recovering from acute respiratory failure, however this practice has rarely been evaluated in tracheostomized patients. This study aimed to investigate changes in weaning parameters measured before and after tracheostomy, and to explore whether the data measured after tracheostomy were associated with weaning outcomes in difficult-to-wean patients. Methods: In a two-year study period, we enrolled orotracheally intubated patients who were prepared for tracheostomy due to difficult weaning. Weaning parameters were measured before and after the conversion to tracheostomy and compared, and the post-tracheostomy data were tested for associations with weaning outcomes. Results: A total of 86 patients were included. After tracheostomy, maximum inspiratory pressure (mean difference (Δ) = 4.4, 95% CI, 2.7 to 6.1, P<0.001), maximum expiratory pressure (Δ = 5.4, 95% CI, 2.9 to 8.0, P<0.001) and tidal volume (Δ = 33.7, 95% CI, 9.0 to 58.5, P<0.008) significantly increased, and rapid shallow breathing index (Δ = -14.6, 95% CI, -25.4 to -3.7, P<0.009) and airway resistance (Δ = -4.9, 95% CI, -5.8 to -4.0, P<0.001) significantly decreased. The patients who were successfully weaned within 90 days of the initiation of mechanical ventilation had greater increments in maximum inspiratory pressure (5.9 vs. 2.4, P = 0.04) and maximum expiratory pressure (8.0 vs. 2.0, P = 0.02) after tracheostomy than those who were unsuccessfully weaned. Conclusions: In conclusion, the conversion from endotracheal tube to tracheostomy significantly improved the measured values of weaning parameters in difficult-to-wean patients who subsequently weaned successfully from the mechanical ventilator. The change was significant only for airway resistance in patients who failed weaning. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

The performance of the BluePoint MycoID plus kit (Bio Concept Corporation, Taichung, Taiwan), which was designed to simultaneously detect Mycobacterium tuberculosis (MTB), rifampin- and isoniazid-resistant MTB, and nontuberculous mycobacteria (NTM) was first evaluated with 950 consecutive positive cultures in Mycobacterium Growth Indicator Tube (MGIT) system (BACTEC, MGIT 960 system, Becton-Dickinson, Sparks) from clinical respiratory specimens. The discrepant results between kit and culture-based identification were finally assessed by 16S rRNA gene sequencing and clinical diagnosis. The accuracy rate of this kit for identification of all Mycobacterium species was 96.3% (905/940). For MTB identification, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the kit were 99.7%, 99.3%, 99.0% and 99.8%, respectively. For rifampicin-resistant MTB identification, the sensitivity, specificity, PPV, and NPV of the kit were 100.0%, 99.4%, 91.3%, and 100.0%, respectively, while the corresponding values of isoniazid-resistant MTB identification were 82.6%, 99.4%, 95.0%, and 97.6%, respectively. In identifying specific NTM species, the kit correctly identified 99.3% of M. abscessus (147/148) complex, 100% of M. fortuitum (32/32), M. gordonae (38/38), M. avium (39/39), M. intracellulare (90/90), M. kansasii (36/36), and M. avium complex species other than M. avium and M. intracellulare (94/94). In conclusions, the diagnostic value of the BluePoint MycoID plus kit was superior to culture method for recoveries and identification of NTM to species level. In addition, the diagnostic accuracy of BluePoint MycoID plus kit in MTB identification was similar to conventional culture method with high accuracy rate of rifampicin-resistant M. tuberculosis identification. [ABSTRACT FROM AUTHOR]

Background: Patients with renal failure are vulnerable to tuberculosis, a common worldwide infectious disease. In the growing dialysis population, the risk for tuberculosis among the associated sub-groups is important but unclear. This study investigated latent tuberculosis infection (LTBI) in patients with severe chronic kidney disease (CKD) and among dialysis-unit staff caring for patients on dialysis. Methods: From January 2012 to June 2013, patients undergoing dialysis, those with severe CKD (estimated glomerular filtration rate <30ml/min/1.73 m2), and the dialysis-unit staff (nursing staff and doctors in hemodialysis units) in several Taiwan hospitals were prospectively enrolled. Interferon-gamma release assay (IGRA) through QuantiFERON-TB Gold In-tube was used to determine LTBI. Predictors for LTBI were analyzed. Results: Of the 599 participants enrolled, 106 (25%) in the dialysis group were IGRA positive. This was higher than the seven (11%) among severe CKD patients and 12 (11%) in the dialysis-unit staff. Independent predictors of LTBI in patient with renal dysfunction were old age (odds ratio [OR]: 1.03 [1.01–1.04] per year increment), prior TB lesion on chest radiograph (OR: 2.90 [1.45–5.83]), serum albumin (OR: 2.59 [1.63–4.11] per 1 g/dl increment), and need for dialysis (OR: 2.47, [1.02–5.95]). The QFT-GIT response was similar among the three groups. Malignancy (OR: 4.91 [1.84–13.10]) and low serum albumin level (OR: 0.22 [0.10–0.51], per 1 g/dl decrease) were associated with indeterminate IGRA results. Conclusions: More patients on dialysis have LTBI compared to those with severe CKD and the dialysis-unit staff. Old age, prior radiographic TB lesion, high serum albumin, and need for dialysis are predictors of LTBI in patients with renal failure. Patients with severe CKD are a lower priority for LTBI screening. The hemodialysis environment is not a risk for LTBI and dialysis-unit staff may be treated as general healthcare workers. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the long-term outcome of patients with a solitary large (>5 cm) hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage A who received liver resection (LR) or transarterial chemoembolization (TACE). Methods: Our study examined 128 patients treated by LR and 90 treated by TACE. To reduce bias in patient selection, we conducted propensity score analysis in the present study and 54 pairs of patients after propensity score matching were generated, their long-term survival was compared using the Kaplan–Meier method. Independent predictors of survival were identified by multivariate analysis. Results: Long-term survival was significantly better for the LR group by log-rank test (P<0.001). In multivariate analysis, tumor size, serum ALT level and TACE independently predicted survival. Despite similar baseline characteristics after propensity score matching, LR group still had significantly better survival (1 year, 68.5 vs. 55.0%; 3 years, 47.6 vs. 21.2%; 5 years, 41.3 vs. 18.5%; P = 0.007) than TACE group. The LR and TACE groups had comparable 30- and 90-day post-treatment mortality. Multivariate analysis showed that serum ALT level, serum AFP level and TACE independently predicted survival by multivariate analysis after propensity score matching. Conclusion: Our propensity-score-matched study suggested that LR provided significantly better long-term survival than TACE for a solitary large HCC of the BCLC stage A, regardless of tumor size. [ABSTRACT FROM AUTHOR]

Background and Objective: Several studies on diagnostic accuracy of pleural N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) for effusions from congestive heart failure (CHF) conclude that pleural NT-pro-BNP is a useful biomarker with high diagnostic accuracy for distinguishing CHF effusions. However, its applicability in critical care settings remains uncertain and requires further investigations. Methods: NT-proBNP was measured in pleural fluid samples of a prospective cohort of intensive care unit patients with pleural effusions. Receiver operating characteristic curve analysis was performed to determine diagnostic accuracy of pleural NT-proBNP for prediction of CHF effusions. Results: One hundred forty-seven critically ill patients were evaluated, 38 (26%) with CHF effusions and 109 (74%) with non-CHF effusions of various causes. Pleural NT-proBNP levels were significantly elevated in patients with CHF effusions. Pleural NT-pro-BNP demonstrated the area under the curve of 0.87 for diagnosing effusions due to CHF. With a cutoff of 2200 pg/mL, pleural NT-proBNP displayed high sensitivity (89%) but moderate specificity (73%). Notably, 29 (27%) of 109 patients with non-CHF effusions had pleural NT-proBNP levels >2200 pg/mL and these patients were more likely to experience septic shock (18/29 vs. 10/80, P<0.001) or acute kidney injury (19/29 vs. 9/80, P<0.001). Conclusions: Among critically ill patients, pleural NT-proBNP measurements remain a useful diagnostic aid in evaluation of pleural effusions. However, patients with non-CHF effusions may exhibit high pleural NT-proBNP concentrations if they suffer from septic shock or acute kidney injury. Accordingly, it is suggested that clinical context should be taken into account when interpreting pleural NT-proBNP values in critical care settings. [ABSTRACT FROM AUTHOR]

Introduction: Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes. Materials and Methods: A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted. Main outcomes were in-hospital mortality and one-year mortality after discharge. Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors. Results: The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization. In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03–1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01–1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38–0.98) and β blockers (OR: 0.63; 95% CI: 0.41–0.95) conferred a survival benefit. At one year after discharge, 22% (871/4029) of hospital survivors were dead. On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality. Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01–1.01) and ICU admission (HR: 1.33; 95% CI: 1.03–1.73) during the hospitalization were associated with higher mortality risks. Prescription of β blockers (HR: 0.79; 95% CI: 0.67–0.93) and statins (HR: 0.66; 95% CI: 0.47–0.91) on hospital discharge were protective against one-year mortality. Conclusions: Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients. Comorbidities play a crucial role in determining outcomes and should be carefully assessed. Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients. Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind. [ABSTRACT FROM AUTHOR]

Background: Profound alterations in immune responses associated with uremia and exacerbated by dialysis increase the risk of active tuberculosis (TB). Evidence of the long-term risk and outcome of active TB after acute kidney injury (AKI) is limited. Methods: This population-based-cohort study used claim records retrieved from the Taiwan National Health Insurance database. We retrieved records of all hospitalized patients, more than 18 years, who underwent dialysis for acute kidney injury (AKI) during 1999–2008 and validated using the NSARF data. Time-dependent Cox proportional hazards model to adjust for the ongoing effect of end-stage renal disease (ESRD) was conducted to predict long-term de novo active TB after discharge from index hospitalization. Results: Out of 2,909 AKI dialysis patients surviving 90 days after index discharge, 686 did not require dialysis after hospital discharge. The control group included 11,636 hospital patients without AKI, dialysis, or history of TB. The relative risk of active TB in AKI dialysis patients, relative to the general population, after a mean follow-up period of 3.6 years was 7.71. Patients who did (hazard ratio [HR], 3.84; p<0.001) and did not (HR, 6.39; p<0.001) recover from AKI requiring dialysis had significantly higher incidence of TB than patients without AKI. The external validated data also showed nonrecovery subgroup (HR = 4.37; p = 0.049) had high risk of developing active TB compared with non-AKI. Additionally, active TB was associated with long-term all-cause mortality after AKI requiring dialysis (HR, 1.34; p = 0.032). Conclusions: AKI requiring dialysis seems to independently increase the long-term risk of active TB, even among those who weaned from dialysis at discharge. These results raise concerns that the increasing global burden of AKI will in turn increase the incidence of active TB. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the association between obstructive sleep apnea (OSA) severity and pharyngeal parameters using sub-mental ultrasonography (US), and investigate the accuracy of US for identifying severe OSA patients. Methods: One hundred and five consecutive referrals for suspected OSA were enrolled. The diameters of the retro-glossal (RG) and retro-palatal (RP) regions were measured via sub-mental US upon expiration during tidal breathing, forced inspiration, and Müller maneuver (MM). Independent factors associated with severe OSA identified from two-thirds of randomly-selected patients (model-development group) were used to construct a model for predicting severe OSA. The accuracy of the model was validated in the remaining one-third of patients (validation group). Results: Fifty severe OSA patients, 30 with mild-moderate OSA, and 25 without OSA were enrolled. Compared to non-OSA and mild-moderate OSA patients, those with severe OSA had narrower RP diameter in all three maneuvers. Using the prediction model constructed with changes of RP diameters at MM and neck circumference, the independent predictors of severe OSA in the model-development group had 100% sensitivity and 65% specificity. Conclusion: Sub-mental US can accurately discriminate the severity of OSA and be used to identify patients with severe OSA. Trial Registration: ClinicalTrials.gov NCT00674076 [ABSTRACT FROM AUTHOR]

Background: There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature. Methods: Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months. Results: Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV1] <80% of predicted value). The mean FEV1 decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV1>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV1 decline. Initial FEV1>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062). Conclusions: NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors. [ABSTRACT FROM AUTHOR]

Background:Lung disease (LD) due to non-tuberculous mycobacteria is an important clinical concern. Mycobacterium avium complex (MAC) is one of the most common causative agents but the diagnosis of MAC-LD remains challenging. Detection of serum IgA antibody against MAC glycopeptidolipid (GPL) has recently been shown to improve the diagnosis of MAC-LD, but has yet to be validated worldwide. Methods:This prospective study was conducted in a tertiary referral center in northern Taiwan and enrolled patients with MAC-LD, MAC contamination, other lung diseases, and control subjects. Serum immunoglobulin A (IgA) antibody against MAC-GPL was detected in the participants and its specificity and sensitivity was assessed. Results:There were 56 patients with MAC-LD, 11 with MAC contamination, 13 M. kansasii-LD, 26 LD due to rapidly-growing mycobacteria (RGM), 48 pulmonary tuberculosis, and 42 household contacts of patients with TB. Patients with MAC-LD were older and 32% of them had an underlying co-morbidity. By logistic regression, serum MAC-GPL IgA level was an independent predictor of MAC-LD among the study subjects and those with culture-positive specimens for MAC. By the receiver operating characteristic curve, serum MAC-GPL IgA had a good power to discriminate MAC-LD from MAC contamination. Under the optimal cut-off value of 0.73 U/mL, its sensitivity and specificity were 60% and 91%, respectively. Among MAC-LD patients, presence of co-morbidity was associated with MAC-GPL <0.73 U/ml in logistic regression analysis. Conclusions:Measurement of serum anti-MAC-GPL IgA level is useful for the diagnosis of MAC-LD. However, its implement in clinical practice for immuno-compromised hosts needs careful consideration. [ABSTRACT FROM AUTHOR]

Introduction:The effect of hemoglobin levels on the weaning outcomes of mechanically ventilated patients remains under debate, particularly for the patients with difficult weaning. This study aims to evaluate the effect of hemoglobin levels on weaning outcomes in difficult-to-wean patients. Methods:This retrospective cohort study was conducted in a university-affiliated teaching hospital in Taiwan. Patients who fulfilled the criteria of difficult weaning were enrolled. Medical records were reviewed to obtain data on hemograms, biochemistry tests, transfusion records, comorbidities and weaning outcome. The association between hemoglobin levels and 30-day weaning outcomes was evaluated using a logistic regression model. Results:A total of 751 patients received mechanical ventilation during the study period, 138 of whom fulfilled the criteria of difficult weaning. Compared with the patients whose hemoglobin was <8 g/dL, those with higher hemoglobin levels were more likely to be successfully weaned (odds ratio [OR], 3.69; 95% CI, 1.22–11.15 for hemoglobin 8–10 g/dL and OR, 4.16, 95% CI, 1.30–13.29 for hemoglobin >10 g/dL). Multivariate analysis showed that the odds ratio for weaning success remained significant for hemoglobin levels of 8–10 g/dL (adjusted OR, 3.3; 95% CI, 1.07–10.15) with borderline significance for hemoglobin level > 10 g/dL (adjusted OR, 2.95, 95% CI, 0.88–9.96). Conclusions:Hemoglobin level is independently associated with weaning outcome in difficult-to-wean patients. Further studies are needed to evaluate whether a restrictive transfusion trigger for acute critical illness is also appropriate for such patients. [ABSTRACT FROM AUTHOR]