Disseminated Cryptococcosis Due to Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Absence of Pulmonary Alveolar Proteinosis.

INTRODUCTION: Autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) can cause acquired pulmonary alveolar proteinosis (PAP). Cases of acquired PAP susceptible to typical respiratory pathogens and opportunistic infections have been reported. Anti-GM-CSF autoantibodies have been reported in a few patients with cryptococcal meningitis. This study evaluated the presence of neutralizing anti-GM-CSF autoantibodies in patients without known congenital or acquired immunodeficiency with severe pulmonary or extrapulmonary cryptococcal infection but without PAP. METHODS: We took a clinical history and performed an immunologic evaluation and screening of anti-cytokine autoantibodies in patients with cryptococcal meningitis. The impact of autoantibodies to GM-CSF on immune function was assessed by intracellular staining of GM-CSF-induced STAT5 phosphorylation and MIP-1α production in normal peripheral blood mononuclear cells incubated with plasma from patients or normal control subjects. RESULTS: Neutralizing anti-GM-CSF autoantibodies were identified in four patients with disseminated cryptococcosis, none of whom exhibited PAP. Plasma from patients blocked GM-CSF signaling and inhibited STAT5 phosphorylation and production of MIP-1α. One patient died of disseminated cryptococcosis involving the central nervous system, which was associated with defective GM-CSF activity. CONCLUSIONS: Anti-GM-CSF autoantibodies increase susceptibility to cryptococcal infection in adults without PAP. Cryptococcal central nervous system infection associated with anti-GM-CSF autoantibodies could result in neurological sequelae or be life-threatening. Therefore, timely detection of neutralizing anti-GM-CSF autoantibodies and development of an effective therapy are necessary to prevent deterioration of cryptococcal infection in these patients.

Sleep disorders and an increased risk of Parkinson's disease in individuals with non-apnea sleep disorders: a population-based cohort study.

Sleep disorders are common non-motor symptoms in patients with Parkinson's disease. Our study aims to explore the relationship between non-apnea sleep disorders and future Parkinson's disease. This is a cohort study using a nationwide database. The participants were recruited from the Taiwan National Health Insurance Research Database between 2000 and 2003. A total of 91 273 adult patients who had non-apnea sleep disorders without pre-existing Parkinson's disease were enrolled. An age-, gender-, income-, urbanization- and Charlson comorbidity index score-matched control cohort consisting of 91 273 participants was selected for comparison. The two cohorts were followed for the occurrence of Parkinson's disease, death or until the end of 2010, whichever came first. The Kaplan-Meier analyses revealed patients with non-apnea sleep disorders tended to develop Parkinson's disease (log-rank test, P < 0.001). After a multivariate adjustment in a Cox regression model, non-apnea sleep disorders was an independent risk factor for the development of Parkinson's disease [crude hazard ratio: 1.63, 95% confidence interval (CI): 1.54-1.73, P < 0.001; adjusted hazard ratio: 1.18, 95% CI: 1.11-1.26, P < 0.001]. In the subgroup analysis, patients with chronic insomnia (lasting more than 3 months) had the greatest risk (crude hazard ratio: 2.91, 95% CI: 2.59-3.26, P < 0.001; adjusted hazard ratio: 1.37, 95% CI: 1.21-1.55, P < 0.001). In conclusion, this study revealed that non-apnea sleep disorders, especially chronic insomnia, are associated with a higher risk for future Parkinson's disease.

Effects of rapid ascent on the heart rate variability of individuals with and without acute mountain sickness.

PURPOSE: Through time- and frequency-domain analysis, we compared the effects of acute hypobaric hypoxia on the changes in heart rate variability (HRV) following night sleeping and morning awakening in individuals with and without acute mountain sickness (AMS). METHOD: Thirty-nine nonacclimatised healthy individuals were transported by bus from sea level to 3150 m within 3 h. Short-term HRV was measured two times a day-before sleeping (BS) and after awakening (AA)- at 3 days before ascent (T0), two consecutive nights at 3150 m (T1 and T2), and 2 days after descent (T3). AMS was diagnosed using the self-reported Lake Louise score questionnaire. RESULT: AMS developed in 19 of 39 participants (48.7%). At sea level, individuals had higher HRV at AA than at BS, and the trend of increased HRV at AA remained unchanged at high altitude, irrespective of AMS. At T1 BS, low-frequency power in normalised unit was significantly lower in participants with AMS than in those without AMS. Compared with those at T1 BS, the square root of the mean squared differences of successive normal-normal (NN) intervals, the number of interval differences of successive NN intervals more than 50 ms (NN50), and the proportion derived by dividing NN50 by the total number of NN intervals at T1 AA significantly increased in participants without AMS but nonsignificantly decreased in those with AMS. CONCLUSION: After rapid ascent, individuals with AMS did not demonstrate sympathetic hyperactivity but did exhibit withdrawal of cardiac vagal modulation in the morning following the first night's sleep.

Urinary Intestine Fatty Acid Binding Protein is Associated with Poor Outcome of Pneumonia Patients in Intensive Care Unit.

BACKGROUND: Urinary intestine fatty acid binding protein (U-IFABP) is a biomarker for gut injury. Previous studies showed that enterocyte damage in critically ill patients was common and appeared to be associated with poor prognosis. However, the impact of enterocyte damage on the outcome of critically ill patients with pneumonia has not yet been well investigated. The aim of the study is to evaluate the prognostic value of U-IFABP in critically ill patients with pneumonia. METHODS: A prospective observational study was performed in the intensive care unit (ICU) from September 1, 2013 to April 30, 2014. Pneumonia patients were divided into survival and non-survival groups. U-IFABP was measured using enzyme linked immunosorbent assay for 7 consecutive days after admission to ICU and expressed as U-IFABP/urine creatinine ratio. The prognostic value was tested by Receiver Operator Characteristic (ROC) curves and Kaplan-Meier curves. RESULTS: A total of 32 pneumonia patients with endotracheal intubation were enrolled. U-IFABP/Cr levels were significantly higher in non-survivors than in survivors at day 1 (p = 0.033), day 4 (p = 0.018), day 5 (p = 0.008), day 6 (p = 0.006) and day 7 (p = 0.008) after ICU admission. The areas under ROC curve in predicting mortality were 0.755 (D1), 0.781 (D4), 0.812 (D5), 0.823 (D6), and 0.812 (D7). Moreover, pneumonia patients with day 7 U-IFABP/Cr above the cutoff of 28.9 pg/100 µL had a significantly lower survival rate (p = 0.043). CONCLUSIONS: Enterocyte injury was common in critically ill patients with pneumonia. The severity of enterocyte injury, as evidenced by the U-IFABP/Cr, was associated with the patient's mortality. U-IFABP/Cr may serve as a significant prognostic factor for patients with pneumonia admitted to ICU. Further studies with larger populations are needed to verify these issues.

Brief left ventricular pressure overload reduces myocardial apoptosis.

BACKGROUND: Both apoptosis and necrosis contribute to cell death after myocardial ischemia and reperfusion. We previously reported that brief left ventricular pressure overload (LVPO) decreased myocardial infarct (MI) size. In this study, we investigated whether brief pressure overload reduces apoptosis and the mechanisms involved. MATERIALS AND METHODS: MI was induced by a 40-min occlusion of the left anterior descending coronary artery and 3-h reperfusion in male anesthetized Sprague-Dawley rats. Brief LVPO was achieved by two 10-min partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-min coronary artery occlusions and 10-min reperfusions. RESULTS: Brief LVPO and ischemic preconditioning significantly decreased MI size (P < 0.001). Brief pressure overload significantly reduced myocardial apoptosis, as evidenced by the decrease in the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei (P < 0.001), little or no DNA laddering, and reduced caspase-3 activation (P < 0.01). Moreover, brief pressure overload significantly increased Bcl-2 (P < 0.001) and decreased Bax (P < 0.001) and p53 (P < 0.01). Akt phosphorylation was significantly increased by brief pressure overload (P < 0.001), whereas c-Jun N-terminal kinase phosphorylation was significantly decreased (P < 0.001). Hemodynamics, area at risk, and mortality did not differ significantly among groups. CONCLUSIONS: Brief left LVPO significantly reduces myocardial apoptosis. The underlying mechanisms might be related to modulation of Bcl-2 and Bax, inhibition of p53, increased Akt phosphorylation, and suppressed c-Jun N-terminal kinase phosphorylation.

Sleep Apnea and Risk of Panic Disorder.

PURPOSE: Epidemiological studies have identified a trend in the development of depressive and anxiety disorders following a diagnosis of sleep apnea. The relationship between sleep apnea and subsequent panic disorder, however, remains unclear. METHODS: Using a nationwide database, the Taiwan National Health Insurance Research Database, patients with sleep apnea and age-, sex-, income-, and urbanization-matched control patients who did not have sleep apnea were enrolled between 2000 and 2010. Patients with a prior diagnosis of panic disorder before enrollment were excluded. The 2 cohorts were observed until December 31, 2010. The primary endpoint was occurrence of newly diagnosed panic disorder. RESULTS: A total of 8,704 sleep apnea patients and 34,792 control patients were enrolled. Of the 43,496 patients, 263 (0.60%) suffered from panic disorder during a mean follow-up period of 3.92 years, including 117 (1.34%) from the sleep apnea cohort and 146 (0.42%) from the control group. The Kaplan-Meier analysis revealed a predisposition of patients with sleep apnea to develop panic disorder (log-rank test, P <.001). After multivariate adjustment, the hazard ratio for subsequent panic disorder among the sleep apnea patients was 2.17 (95% confidence interval, 1.68-2.81; P <.001). CONCLUSIONS: Sleep apnea appears to confer a higher risk for future development of panic disorder.

Impact of rapid ascent to high altitude on sleep.

PURPOSE: Sleep disturbance at high altitude is common in climbers. In this study, we intended to evaluate the effect of rapid ascent on sleep architecture using polysomnography (PSG) and to compare the differences between subjects with and without acute mountain sickness (AMS). METHODS: The study included 40 non-acclimatized healthy subjects completing PSG at four time points, 3 days before the ascent (T0), two successive nights at 3150 m (T1 and T2), and 2 days after the descent (T3). All subjects were transported by bus from 555 to 3150 m within 3 h. AMS was diagnosed using self-reported questionnaire of Lake Louise score. RESULTS: Twenty of 40 (50%) subjects developed AMS. At high altitude, awakening percentages increased in AMS group but changed insignificantly in non-AMS group. Arousal index and apnea/hypopnea index (AHI) increased irrespective of AMS. The increases of AHI were more evident in non-AMS group than in AMS group. Compared to subjects without AMS, those with AMS had significantly lower sleep efficiency, lower central apnea index, and longer latencies to sleep and rapid eye movement (REM) sleep at T1 and lower REM sleep percentages at T1 and T2. Subjects with older age and lower minimum arterial oxygen saturation during sleep at sea level were prone to develop AMS. CONCLUSIONS: Higher AHI did not cause more frequent awakenings and arousals at high altitude. Central sleep apneas were observed in non-AMS but not in AMS group. Subjects unacclimatized to acute hypobaric hypoxia might have delayed and less REM sleep.

Nocturnal stem cell mobilization in patients with obstructive sleep apnoea: a pilot study.

BACKGROUND: Patients with obstructive sleep apnoea (OSA) experience repetitive cessation of breathing during sleep, leading to intermittent hypoxaemia, excessive oxidative stress and systemic inflammation. These insults may damage the vasculature and provoke the corresponding repair response, such as stem cell mobilization to peripheral blood. This study aimed to investigate nocturnal mobilization of stem cells in OSA. METHODS: Thirty-five patients with OSA and thirteen healthy controls were enrolled. Polysomnography was performed, and severity of OSA was defined by apnoea-hypopnoea index (AHI). Peripheral venous blood was drawn after and before sleep for measurement of CD34+ cell and SDF-1α level. Stem cell mobilization was gauged by ratios of the CD34+ level in the morning to that at night or by their difference. Correlation analysis was performed to identify factors related to stem cell mobilization. RESULTS: Compared to controls, the nocturnal ratios and difference of CD34+ cell levels were larger in patients with OSA (ratios: 1·141 vs. 0·896, P = 0·036; difference: 340 vs. -166/cc blood, P = 0·036), suggestive of stem cell mobilization. The mobilization ratios were related to AHI, body mass index (BMI), SpO2 nadir, oxygen desaturation index and time sustaining hypoxaemia. After adjusting age, gender and BMI, AHI (r = 0·357, P = 0·016) and hypoxaemia-related parameter remained significant. Paired nocturnal differences in CD34+ cell count (P = 0·009) and SDF-1α (P = 0·001) were also significant in patients with OSA, but not in controls. After CPAP therapy for 6 months, the elevated mobilization ratios in patients with OSA tended to decline (P = 0·059). CONCLUSION: CD34+ stem cell mobilization during sleep was observed in OSA.

Sleep apnoea patients have higher mortality when confronting sepsis.

BACKGROUND: Sleep is essential for the maintenance of an intact immune function. Patients with sleep apnoea experience frequent sleep interruption due to apnoea-related arousals, possibly adversely impacting their immunity and affecting their outcomes when confronting sepsis. This case-control study aimed to compare the outcomes of sepsis patients with and without sleep apnoea. METHODS: From 2000 to 2009, 168 sleep apnoea patients who were first admitted for sepsis were identified from the Taiwan National Health Insurance Research Database. Also, 672 sepsis patients without sleep apnoea, who were matched by age, gender and Charlson's comorbidity index scores, served as controls. Hospital outcomes of the two groups were compared. Binary logistic regression was employed for multivariate analysis. RESULTS: The mortality rates of sepsis patients with and without sleep apnoea were 60.1% and 47.9%, respectively (P = 0. 005). After multivariate adjustment, sleep apnoea (OR: 1.805, 95% CI: 1.227-2.656, P = 0.003), presence of shock (OR: 3.600, 95% CI: 2.144-6.046, P < 0.001) and number of organs with dysfunction (OR: 1.591, 95% CI: 1.087-2.329, P = 0.017) were found to be independently associated with mortality. Sleep apnoea patients who needed continuous positive airway pressure treatment had an even higher risk of mortality. CONCLUSIONS: Sepsis patients with sleep apnoea may have poorer hospital outcomes than those without sleep apnoea.

Sleep apnea and risk of pneumonia: a nationwide population-based study.

BACKGROUND: Evidence evaluating the risk of pneumonia in patients with obstructive sleep apnea is limited and mostly focuses on patients who receive continuous positive airway pressure (CPAP) therapy or on pediatric patients. We aimed to explore the risk of incident pneumonia among adults with sleep apnea, either with or without the need of CPAP therapy. METHODS: From Jan. 1, 2000, we identified adult patients with sleep apnea from the Taiwan National Health Insurance Research Database. A control cohort without sleep apnea, matched for age, sex and comorbidities, was selected for comparison. The 2 cohorts were followed until Dec. 31, 2010, and observed for occurrence of pneumonia. RESULTS: Of the 34,100 patients (6816 study patients and 27,284 matched controls), 2757 (8.09%) had pneumonia during a mean follow-up period of 4.50 years, including 638 (9.36%) study patients and 2119 (7.77%) controls. Kaplan-Meier analysis showed a higher incidence of pneumonia among patients with sleep apnea (log rank test, p < 0.001). After multivariate adjustment, patients with sleep apnea experienced a 1.20-fold (95% confidence interval 1.10-1.31) increase in incident pneumonia. The risk was even higher among patients who received CPAP therapy. INTERPRETATION: Sleep apnea appeared to confer a higher risk for future pneumonia, possibly in a severity-dependent manner.

The impact of concomitant pulmonary infection on immune dysregulation in Pneumocystis jirovecii pneumonia.

BACKGROUND: Concurrent infection may be found in Pneumocystis jirovecii pneumonia (PJP) of non-acquired immunodeficiency syndrome (AIDS) patients, however, its impact on immune dysregulation of PJP in non-AIDS patients remains unknown. METHODS: We measured pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-8, IL-17, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-ß1 and IL-1 receptor antagonist (IL-1RA) and inflammatory markers including high mobility group box 1, Krebs von den Lungen-6, receptor for advanced glycation end product, advanced glycation end product, surfactant protein D in bronchoalveolar lavage fluid (BALF) and blood in 47 pure PcP and 18 mixed PJP and other pulmonary infections (mixed PJP) in non-AIDS immunocompromised patients and explored their clinical relevance. The burden of Pneumocystis jirovecii in the lung was determined by counting number of clusters of Pneumocystis jirovecii per slide and the concentration of ß-D-glucan in BALF. PJP severity was determined by arterial oxygen tension/fraction of inspired oxygen concentration ratio, the need of mechanical ventilation and death. RESULTS: Compared with pure PJP group, mixed PJP group had significantly higher BALF levels of IL-1ß, TNF-α and IL-8 and significantly higher blood levels of IL-8. The BALF ratios of TNF-α/IL-10, IL-8/IL-10, IL-1ß/IL-10, TNF-α/TGF-ß1, IL-8/TGF-ß1, IL-1ß/TGF-ß1 and IL-1ß/IL-1RA were significantly higher in mixed than in pure PJP patients. There was no significant difference in clinical features and outcome between pure and mixed PJP groups, including inflammatory biomarkers and the fungal burden. In pure PJP patients, significantly higher BALF levels of IL-8 and the ratios of IL-8/IL-10, IL-1ß/TGF-ß1, MCP-1/TGF-ß1, MCP-1/IL1RA and IL-8/TGF-ß1 were found in the patients requiring mechanical ventilation and in non-survivors. CONCLUSIONS: In summary, concurrent pulmonary infection might enhance immune dysregulation of PJP in non-AIDS immunocompromised patients, but did not affect the outcome as evidenced by morbidity and mortality. Because of limited number of cases studied, further studies with larger populations are needed to verify these issues.

Cigarette smoking and hOGG1 Ser326Cys polymorphism are associated with 8-OHdG accumulation on mitochondrial DNA in thoracic esophageal squamous cell carcinoma.

BACKGROUND: We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-2'-deoxyguanosine [8-OHdG]) on mitochondrial DNA (mtDNA), whether the degree of 8-OHdG accumulation on mtDNA is related to the increased total mtDNA copy number, and whether human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphisms affect the degrees of 8-OHdG accumulation on mtDNA in thoracic esophageal squamous cell carcinoma (TESCC). METHODS: DNA extracted from microdissected tissues of paired noncancerous esophageal muscles, noncancerous esophageal mucosa, and cancerous TESCC nests (n = 74) along with metastatic lymph nodes (n = 38) of 74 TESCC patients was analyzed. Both the mtDNA copy number and mtDNA integrity were analyzed by quantitative real-time polymerase chain reaction (PCR). The hOGG1 Ser326Cys polymorphisms were identified by restriction fragment length polymorphism PCR and PCR-based direct sequencing. RESULTS: Among noncancerous esophageal mucosa, cancerous TESCC nests, and metastatic lymph nodes, the mtDNA integrity decreased (95.2 to 47.9 to 18.6 %; P < 0.001) and the mtDNA copy number disproportionally increased (0.163 to 0.204 to 0.207; P = 0.026). In TESCC, higher indexes of cigarette smoking (0, 0-20, 20-40, and >40 pack-years) were related to an advanced pathologic N category (P = 0.038), elevated mtDNA copy number (P = 0.013), higher mtDNA copy ratio (P = 0.028), and increased mtDNA integrity (P = 0.069). The TESCC mtDNA integrity in patients with Ser/Ser, Ser/Cys, and Cys/Cys hOGG1 variants decreased stepwise from 65.2 to 52.1 to 41.3 % (P = 0.051). CONCLUSIONS: Elevated 8-OHdG accumulations on mtDNA in TESCC were observed. Such accumulations were associated with a compensatory increase in total mtDNA copy number, indexes of cigarette smoking, and hOGG1 Ser326Cys polymorphisms.

The importance of pro-inflammatory and anti-inflammatory cytokines in Pneumocystis jirovecii pneumonia.

The role of pro-inflammatory and anti-inflammatory cytokines in Pneumocystis jirovecii pneumonia (PcP) of non-AIDS immunocompromised patients remains unclear. We measured the levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-ß1 in bronchoalveolar lavage fluid (BALF) and blood in 36 non-AIDS immunocompromised patients with PcP diagnosed by BAL and explored their clinical importance. The severity of PcP was determined by arterial oxygen tension/fraction of inspired oxygen concentration (PaO2/FiO2) ratio, the need of mechanical ventilation and the death. Twenty-five subjects without evidence of lung abnormality were included as control group. Compared with control group, PcP patients had significantly higher BALF levels of IL-1ß, TNF-α, IL-6, IL-8 and MCP-1 and significantly higher blood levels of IL-10, TGF-ß1, IL-8, IL-6 and MCP-1. For PcP patients, BALF levels of IL-8, IL-8/IL-10 ratio and IL-8/TGF-ß1 ratio and blood levels of IL-8 and IL-8/IL-10 ratio were significantly higher in the patients with PaO2/FiO2 < 200 mmHg than in those with PaO2/FiO2 > 200 mmHg. Similarly, significantly higher BALF levels of IL-8, IL-8/IL-10 ratio, IL-1ß/IL-10, IL-1ß/TGF-ß1 ratio, MCP-1/TGF-ß1 ratio and IL-8/TGF-ß1 ratio were found in the patients requiring mechanical ventilation and in non-survivors. In summary, an imbalance of pro-inflammatory and anti-inflammatory cytokines in BALF was found in PcP of non-AIDS immunocompromised patients. BALF levels of IL-8, IL-8/IL-10 ratio, IL-1ß/IL-10 ratio, IL-1ß/TGF-ß1 ratio, MCP-1/TGF-ß1 ratio and IL-8/TGF-ß1 ratio may be of value in assessing the severity of PcP and in predicting the outcome of the patients.

Bile acids increase alveolar epithelial permeability via mitogen-activated protein kinase, cytosolic phospholipase A2 , cyclooxygenase-2, prostaglandin E2 and junctional proteins.

BACKGROUND AND OBJECTIVE: Bile acid (BA) aspiration is associated with various lung diseases. It was hypothesized that BA may induce changes in alveolar epithelium permeability and contribute to the pathogenesis of lung injury. METHODS: Human alveolar epithelial cells were grown in monolayer and stimulated with a major component of BA, chenodeoxycholic acid (CDCA). Transepithelial electrical resistance (TER) and paracellular fluxes were measured to assess permeability alteration. Prostaglandin E2 ( PGE2 ) production was measured, and its effect on TER and junctional proteins (JP) was also examined. Reverse transcription polymerase chain reaction and Western blots were used to investigate the expression of messenger RNA and JP. RESULTS: CDCA induced significant p38 and c-Jun N-terminal kinase (JNK) phosphorylation, cytosolic phospholipase A2 (cPLA2 ) and cyclooxygenase-2 (COX-2) messenger RNA expression, PGE2 production, TER reduction and decay of JP (including occludin, zonula occludens-1 (ZO-1) and E-cadherin, in which ZO-1 had maximal change). CDCA also increased paracellular fluxes, which was abolished by dexamethasone. Both CDCA and PGE2 contributed to TER reduction in an identical trend and a dose-response manner. PGE2 also reduced ZO-1 expression, which was similar to that observed by CDCA stimulation. Pretreatment with inhibitors of p38 (SB203580), JNK (SP600125), cPLA2 (mepacrine) and COX-2 (NS398) as well as dexamethasone reversed the CDCA-induced PGE2 production, TER reduction and decay of ZO-1. CONCLUSIONS: The increase in alveolar permeability was associated with decay of JP. BA may induce permeability alteration through the upregulation of mitogen-activated protein kinase, cPLA2 , COX-2, PGE2 and JP, which may contribute to the pathogenesis of BA-associated lung injury.

Statin-induced lung injury: diagnostic clue and outcome.

BACKGROUND: Statin-induced lung injury (SILI) is an uncommon but serious complication of statins. The clinical features and outcome of patients with SILI vary widely. Clinical data relevant to diagnosis and outcome of patients with SILI were investigated in this study. METHOD: Four cases of SILI diagnosed at our institute and 12 cases reported in the English literature from 1995 to 2010 were studied. The patients were further divided into favourable and unfavourable outcome groups and compared. RESULTS: Compared with the 12 previously reported cases, fever (p=0.008) and consolidation (p=0.027) were more common and duration of statin treatment was significantly shorter (p=0.030) in our patients. Foamy alveolar macrophages in bronchoalveolar lavage fluid (BALF) were found in our four patients. Patients with cough (p=0.024), fever (p=0.026) and alveolar infiltrates (p=0.036), especially ground-glass opacity (GGO) (p=0.001) shown on thoracic high-resolution CT (HRCT), had a favourable outcome. Conversely, those with fibrosis shown on HRCT (p=0.008) had an unfavourable outcome. Stepwise logistic regression analysis demonstrated that cough (p=0.011), fever (p=0.005), and alveolar infiltrates (p=0.017), GGO (p<0.001) and fibrosis (p=0.002) shown on thoracic HRCT were independent factors affecting the outcome of SILI. CONCLUSIONS: For patients with SILI, pulmonary phospholipidosis, as shown by foamy alveolar macrophages in BALF, may be valuable in diagnosis, and clinical symptoms and thoracic HRCT findings are of value in predicting the outcome.

Temporal changes in biomarkers in individuals with and without acute mountain sickness following rapid ascent.

BACKGROUND: Field studies have reported conflicting results regarding changes in biomarkers at high altitude. This study measured temporal changes in biomarkers and compared the differences between individuals with and without acute mountain sickness (AMS). MATERIALS AND METHODS: This study included 34 nonacclimatized healthy participants. Ten-milliliters of blood were collected at four time points: 3 days before ascent (T0), on two successive nights at 3150 m (T1 and T2), and 2 days after descent (T3). Participants were transported by bus from 555 m to 3150 m within 3 hours. AMS was diagnosed using the self-reported Lake Louise Scoring (LLS) questionnaire. RESULTS: Compared with T0, significant increases in E-selectin and decreases in vascular endothelial growth factor (VEGF) levels were observed at high altitude. Significantly increased C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and S100 calcium-binding protein B (S100B) levels were observed at T2, and significantly decreased vascular cell adhesion molecule-1 (VCAM-1) levels were observed at T3. Eighteen (53%) participants developed AMS. Changes in E-selectin, CRP, MCP-1, and S100B levels were independent of AMS. Relative to individuals without AMS, those with AMS had significantly higher atrial natriuretic peptide (ANP) and VCAM-1 levels and lower plasminogen activator inhibitor-1 (PAI-1) levels at T1 and higher brain natriuretic peptide and lower VEGF and PAI-1 levels at T3. LLSs were positively correlated with ANP and VCAM-1 levels and negatively correlated with PAI-1 levels measured at T1. CONCLUSIONS: After acute ascent, individuals with and without AMS exhibited different trends in biomarkers associated with endothelial cell activation and natriuretic peptides.

Mouth opening/breathing is common in sleep apnea and linked to more nocturnal water loss.

BACKGROUND: Mouth opening/breathing during sleep is common in patients with obstructive sleep apnea (OSA), which is probably associated with more water loss and higher risk for nocturnal ischemic heart attack. This study aimed to evaluate nocturnal changes in hematocrit/hemoglobin levels and estimated plasma volume loss in OSA patients and its relation to their OSA severity and mouth open/breathing. METHODS: Sixty OSA patients and fifteen healthy controls were enrolled and underwent overnight polysomnography. Mouth status was evaluated via an infrared camera and nasal/mouth airflow. Hematocrit and hemoglobin levels in peripheral venous blood were measured before and after sleep to estimate the change of plasma volume. RESULTS: Compared to controls, OSA patients had a greater nocturnal increase in hematocrit (1.35% vs. 1.0%, p = 0.013), hemoglobin (0.50% vs. 0.30%, p = 0.002) and more estimated water loss (5.5% vs 3.7% of plasma volume, p < 0.013). The extent of increase was correlated to apnea-hypopnea index (AHI)_the marker of OSA severity (Spearman's ρ = 0.332, p = 0.004; ρ = 0.367, p = 0.001 for hematocrit, hemoglobin, respectively), which remained significant after serial multivariate adjustment. OSA patients had more sleep time with mouth open (96.7% vs 26.7% of total sleep time, p < 0.001) and time with complete mouth breathing (14.1% vs 2.7%, p < 0.001). The extent of mouth breathing was correlated to AHI (ρ=0.487, p < 0.001), nocturnal increase in hematocrit/hemoglobin levels (ρ = 0.236, p = 0.042; ρ = 0.304, p = 0.008, respectively) and estimated plasma volume loss (ρ = 0.262, p = 0.023). CONCLUSION: OSA patients had a greater increase in hematocrit/hemoglobin levels after sleep, which is probably linked to more water loss and more sleep time with mouth open/breathing.

Point-of-care application of diaphragmatic ultrasonography in the emergency department for the prediction of development of respiratory failure in community-acquired pneumonia: A pilot study.

Background: Early recognition of patients with community-acquired pneumonia (CAP) at risk of poor outcomes is crucial. However, there is no effective assessment tool for predicting the development of respiratory failure in patients with CAP. Diaphragmatic ultrasonography (DUS) is a novel technique developed for evaluating diaphragmatic function via measurements of the diaphragm thickening fraction (DTF) and diaphragm excursion (DE). This study evaluated the accuracy of DUS in predicting the development of respiratory failure in patients with CAP, as well as the feasibility of its use in the emergency department (ED) setting. Materials and methods: This was a single-center prospective cohort study. We invited all patients with ED aged ≥ 20 years who were diagnosed with CAP of pneumonia severity index (PSI) SIe diagnosed with CAP of pneumonia severe with respiratory failure or septic shock were excluded. Two emergency physicians performed DUS to obtain DTF and DE measurements. Data were collected to calculate PSI, CURB-65 score, and Infectious Diseases Society of America/American Thoracic Society severity criteria. Study endpoints were taken at the development of respiratory failure or 30 days post-ED presentation. Continuous variables were analyzed using T-tests, while categorical variables were analyzed using chi-square tests. Further logistic regression and receiver operating characteristic curve analyses were performed to examine the ability to predict the development of respiratory failure. Intra- and inter-rater reliability was examined with intraclass correlation coefficients (ICCs). Results: In this study, 13 of 50 patients with CAP enrolled developed respiratory failure. DTF was found to be an independent predictor (OR: 0.939, p = 0.0416). At the optimal cut-off point of 23.95%, DTF had 69.23% of sensitivity, 83.78% of specificity, 88.57% of negative predictive value, and 80% of accuracy. Intra- and inter-rater analysis demonstrated good consistency (intra-rater ICC 0.817, 0.789; inter-rater ICC 0.774, 0.781). Conclusion: DUS assessment of DTF may reliably predict the development of respiratory failure in patients with CAP presenting to the ED. Patients with DTF > 23.95% may be considered for outpatient management.

The minimum period of polysomnography required to confirm a diagnosis of severe obstructive sleep apnoea.

BACKGROUND AND OBJECTIVE: To combine the diagnosis of OSA with titration of positive airway pressure (PAP), current guidelines recommend that split-night polysomnography (PSG) be performed if an AHI of ≥40/h is recorded over 2h. However, the diagnostic validity of partial-night PSG is uncertain. This study aimed to test the validity of partial-night PSG and to determine the optimum AHI cut-off points. METHODS: Patients who visited the sleep centre at a tertiary medical centre between January and December 2008, for symptoms related to sleep disorders (sleepiness, snoring, sleep disturbance), and who completed full-night PSG, were evaluated for this study. Full-night PSG data were processed to obtain partial-night PSG data, from which AHI were computed as a reference for diagnosing severe OSA. Full-night and partial-night PSG data obtained over different recording times (expressed as x-h PSG, where xONL001831140 =1-6) were compared using receiver operating characteristic (ROC) curve analysis. The diagnostic validity of 2-h PSG with different AHI cut-off points (25/h to 45/h) was also calculated. RESULTS: Data from 198 PSG recordings was processed. For 2-h PSG, an AHI cut-off point of 30/h gave the highest accuracy of 90.9%. Comparing areas under the ROC curves (AUC), 2-h PSG (AUC=0.97) was as good as 2.5-h PSG (AUC=0.977, P=0.057) and 3-h PSG (AUC=0.978, P=0.125), but was better than 1.5-h PSG (AUC=0.955, P=0.016). CONCLUSIONS: Partial-night PSG is effective for diagnosing severe OSA. If there is an unabridged PSG recording indicating an AHI of ≥30/h for 2h, severe OSA can be diagnosed and PAP titration initiated.

Role of Doppler sonography in the diagnosis of pulmonary sequestration in an elderly patient: a case report.

An 83-year-old man presented with an asymptomatic mass-like lesion in left lower lobe on chest radiograph and CT, with no change over the past 7 years. Because of discrepancy between clinical and radiological manifestations, chest color Doppler sonography was done and identified a large tortuous pulsating vessel with systemic arterial waveform flowing toward the probe and entering the lesion at its apex. Subsequent contrast-enhanced reconstructed CT scans of the chest with angiography confirmed the diagnosis of intralobar pulmonary sequestration.