Association of Matrix Metalloproteinase-9 Genotypes With Lung Cancer Risk in Taiwan.

BACKGROUND/AIM: Matrix metalloproteinase-9 (MMP-9) expression is upregulated in various diseases, including lung cancer. However, the role of MMP-9 genotype in lung cancer susceptibility remains uncertain. This study aimed to clarify the contribution of MMP-9 promoter rs3918242 genotypes to the risk of lung cancer in Taiwan. MATERIALS AND METHODS: The MMP-9 rs3918242 genotypes of 358 lung cancer patients and 716 healthy controls were determined using polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: Individuals carrying the variant CT or TT genotype of MMP-9 rs3918242 did not demonstrate an increased risk of lung cancer compared to wild-type CC carriers [odds ratio (OR)=1.11 and 1.85, 95% confidence interval (95%CI)=0.82-1.48 and 0.91-3.76; p=0.5541 and 0.1280, respectively]. Moreover, individuals carrying the T allele did not show a higher lung cancer risk compared to those with the C allele (OR=1.21, 95%CI=0.95-1.54, p=0.1444). However, a significant association was observed between the MMP-9 rs3918242 TT genotype and lung cancer risk among non-smokers (OR=5.48, 95%CI=1.31-22.89, p=0.0181). CONCLUSION: The presence of the TT genotype for MMP-9 rs3918242 may indicate an elevated risk of lung cancer among non-smokers.

The Contribution of Double-strand Break Repair Radiation Sensitive Protein 51 Genotypes to Lung Cancer in Taiwan.

BACKGROUND/AIM: Numerous studies have reported the over-expression of the radiation-sensitive protein 51 (RAD51) in various types of cancer. However, the role of RAD51 genotypes in lung cancer remains largely unknown. This study aimed to assess the impact of the common variant RAD51 rs1801320 (G-135C) genotypes on the risk of lung cancer in Taiwan. MATERIALS AND METHODS: The contribution of RAD51 rs1801320 genotypes to lung cancer risk was investigated in a cohort comprising 358 lung cancer patients and 716 age- and sex-matched healthy controls, utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The analysis revealed that among the control subjects, the percentages of GG, CG, and CC genotypes of RAD51 rs1801320 were 73.2%, 24.3%, and 2.5%, respectively. Among the lung cancer patients, these percentages were 71.0%, 25.1%, and 3.9%, respectively (p for trend=0.4075). Allelic frequency distributions showed no significant association between the C allele of RAD51 rs1801320 and lung cancer risk determination (p=0.2987). Specifically, the RAD51 rs1801320 CC genotypes were associated with an elevated risk of lung cancer among males [adjusted odds ratio (aOR)=2.28, 95% confidence interval (95%CI)=1.03-4.87] and smokers (aOR=2.93, 95%CI=1.23-5.87), but not among females and non-smokers. CONCLUSION: The RAD51 rs1801320 CC genotype was identified as a risk factor for elevated lung cancer risk in males and smokers. This genotype may serve as a molecular biomarker at the DNA level for early detection and prediction of lung cancer in Taiwan.

Recommended assessment and management of sleep disordered breathing in patients with atrial fibrillation, hypertension and heart failure: Taiwan Society of Cardiology/Taiwan Society of sleep Medicine/Taiwan Society of pulmonary and Critical Care Medicine joint consensus statement.

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Association of Matrix Metalloproteinase-1 Promoter Polymorphisms With Asthma Risk.

BACKGROUND/AIM: Matrix metalloproteinase-1 (MMP-1) expression has been documented as an influential contributor to the intricate milieu of allergic airway inflammation, tissue remodeling, and the exacerbation of asthma's severity. However, the genetic role underlying MMP-1 in the context of asthma has remained enigmatic, with its full implications yet to be unveiled. Considering this, our research was designed to investigate the association of MMP-1 -1607 rs1799750 and the propensity for asthma severity. PATIENTS AND METHODS: As a case-control investigation, our study enrolled 198 individuals diagnosed with asthma and age- and sex-matched 453 non-asthmatic controls. The genotypes of MMP-1 rs1799750 were determined utilizing the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The frequency distributions of 2G/2G, 1G/2G and 1G/1G genotypes at MMP-1 rs1799750 were 49, 42.9, and 8.1%, respectively, among the patients with asthma. This pattern was not different from that of controls (43.7, 46.8, and 9.5%, respectively) (p for trend=0.4486). The allelic frequency pertaining to the variant 1G allele within the asthma group was 29.5%, with a non-significant disparity compared to the 32.9% in the control group (p=0.2596). Noticeably, there was a positive association between MMP-1 rs1799750 2G/1G and 1G/1G genotypes with asthma severity (p=0.0060). CONCLUSION: Our research indicated that the presence of MMP-1 rs1799750 1G allele might not be the sole arbiter of an individual's susceptibility to asthma, yet its potential to function as a discerning prognostic marker for the severity of asthma emerged as a noteworthy finding deserving attention and further exploration.

Novel genetic variants in long non-coding RNA MEG3 are associated with the risk of asthma.

Background: Asthma is the most common chronic inflammatory airway disease worldwide. Asthma is a complex disease whose exact etiologic mechanisms remain elusive; however, it is increasingly evident that genetic factors play essential roles in the development of asthma. The purpose of this study is to identify novel genetic susceptibility loci for asthma in Taiwanese. We selected a well-studied long non-coding RNA (lncRNA), MEG3, which is involved in multiple cellular functions and whose expression has been associated with asthma. We hypothesize that genetic variants in MEG3 may influence the risk of asthma. Methods: We genotyped four single nucleotide polymorphisms (SNPs) in MEG3, rs7158663, rs3087918, rs11160608, and rs4081134, in 198 patients with asthma and 453 healthy controls and measured serum MEG3 expression level in a subset of controls. Results: The variant AG and AA genotypes of MEG3 rs7158663 were significantly over-represented in the patients compared to the controls (P = 0.0024). In logistic regression analyses, compared with the wild-type GG genotype, the heterozygous variant genotype (AG) was associated with a 1.62-fold [95% confidence interval (CI) [1.18-2.32], P = 0.0093] increased risk and the homozygous variant genotype (AA) conferred a 2.68-fold (95% CI [1.52-4.83], P = 0.003) increased risk of asthma. The allelic test showed the A allele was associated with a 1.63-fold increased risk of asthma (95% CI [1.25-2.07], P = 0.0004). The AG plus AA genotypes were also associated with severe symptoms (P = 0.0148). Furthermore, the AG and AA genotype carriers had lower serum MEG3 expression level than the GG genotype carriers, consistent with the reported downregulation of MEG3 in asthma patients. Conclusion: MEG3 SNP rs7158663 is a genetic susceptibility locus for asthma in Taiwanese. Individuals carrying the variant genotypes have lower serum MEG3 level and are at increased risks of asthma and severe symptoms.

Update on guidelines for the treatment of COPD in Taiwan using evidence and GRADE system-based recommendations.

Chronic obstructive pulmonary disease (COPD) has significant contributions to morbidity and mortality world-wide. Early symptoms of COPD are not readily distinguishable, resulting in a low rate of diagnosis and intervention. Different guidelines and recommendatations for the diagnosis and treatment of COPD exist globally. The first edition of clinical practice guidelines for COPD was published in 2016 by the Ministry of Health and Welfare in Taiwan in collaboration with the Taiwan evidence-based medicine association and Cochrane Taiwan, and was revised in 2019 in order to update recent diagnostic and therapeutic modalities for COPD and its acute exacerbation. This revised guideline covered a range of topics highlighted in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report, including strategies for the diagnosis, assessment, monitoring, and management of stable COPD and exacerbations, with particular focus on evidence from Taiwan. The recommendations included in the revised guideline were formed based on a comprehensive systematic review or meta-analysis of specific clinical issues identified by an expert panel that surveyed relevant scientific evidence in the literature and guidelines published by the clinical communities and organizations nationally and internationally. The guidelines and recommendations are applicable to the clinical settings in Taiwan. We expect this revised guideline to facilitate the diagnosis, treatment and management of patients with COPD by physicians and health care professionals in Taiwan. Adaptations of the materials included herein for educational and training purposes is encouraged.

Significant Association of Cyclin D1 Promoter Genotypes With Asthma Susceptibility in Taiwan.

BACKGROUND/AIM: The molecular mechanisms underlying the association between cell cycle and asthma are poorly understood, and cyclin D1 (CCND1) is found to be upregulated in asthma airway smooth muscle. We investigated whether the most frequently examined functional variants in CCND1 determine asthma susceptibility. MATERIALS AND METHODS: We genotyped 651 participants for single-nucleotide polymorphisms (SNPs) at rs9344 and rs678653 on CCND1 and assessed the association of these SNPs with asthma risk. RESULTS: Significant differences were found in the distributions of genotypic (p=0.0064) and allelic (p=0.0021) frequencies of CCND1 rs9344. In addition, AG or GG carriers had 0.63- or 0.48-fold adjusted odds ratios for asthma risk (95%confidence intervals=0.48-0.92 and 0.22-0.78, respectively) than those who carried the AA wildtype. CONCLUSION: Our results suggest that cell cycle regulation may play a role in asthma initiation and development, and the CCND1 rs9344 genotype may serve as an early detection marker for asthma.

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.

Significant Association of MMP2 Promoter Genotypes to Asthma Susceptibility in Taiwan.

BACKGROUND/AIM: Matrix metalloproteinase 2 (MMP2) is reported to be overexpressed in asthma; however, its genotypic contribution to asthma is not well studied. Therefore, we examined the association of MMP2 genotypes with asthma risk among Taiwanese. MATERIALS AND METHODS: One hundred and ninety-eight asthma patients and 453 non-asthmatic subjects were determined with respect to their MMP2 -1306 (rs243845) and -735 (rs2285053) genotypes. RESULTS: CT and TT at MMP2 rs243845 are 17.7% and 1.5% among asthma cases, whereas their presence in healthy subjects is at 28.1% and 2.4%, respectively (p for trend=0.0118). In detail, the CT genotype in MMP2 rs243845 was associated with a decreased asthma risk [adjusted odds ratio (OR)=0.57, 95% confidence interval (CI)=0.37-0.78, p=0.0040], and the T allele conferred a significantly lower asthma risk compared to the wild-type C allele (adjusted OR=0.55, 95%CI=0.43-0.77, p=0.0042). No significance was found for MMP2 rs2285053. CONCLUSION: The genotype of CT in MMP2 rs243845 may serve as a novel biomarker in determining susceptibility to asthma in Taiwan.

The Significant Interaction of Excision Repair Cross-complementing Group 1 Genotypes and Smoking to Lung Cancer Risk.

BACKGROUND: The study aims to evaluate the contribution of excision repair cross-complementing group 1 (ERCC1), which plays an important role in genome integrity maintenance, to lung cancer risk. MATERIALS AND METHODS: ERCC1 rs11615 and rs3212986 genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and their association with lung cancer risk was examined among 358 lung cancer patients and 716 controls. RESULTS: The proportions of CC, CT and TT for the rs11615 genotype were 43.6%, 41.6% and 14.8% in the case group and 50.0%, 41.1% and 8.9% in the control group, respectively (p for trend=0.0082). Allelic analysis showed that ERCC1 rs11615 T-allele carriers have a 1.32-fold higher risk of lung cancer than wild-type C-allele carriers [95%confidence interval (CI)=1.09-1.60, p=0.0039]. In addition, a significant interaction between the rs11615 genotype and smoking status was observed. CONCLUSION: The T allele of ERCC1 rs11615 jointly with smoking habits may contribute to a higher lung cancer risk in Taiwan.

ADAM9 enhances CDCP1 by inhibiting miR-1 through EGFR signaling activation in lung cancer metastasis.

MicroRNAs (miRNAs), which are endogenous short noncoding RNAs, can regulate genes involved in important biological and pathological functions. Therefore, dysregulation of miRNAs plays a critical role in cancer progression. However, whether the aberrant expression of miRNAs is regulated by oncogenes remains unclear. We previously demonstrated that a disintegrin and metalloprotease domain 9 (ADAM9) promotes lung metastasis by enhancing the expression of a pro-migratory protein, CUB domain containing protein 1 (CDCP1). In this study, we found that this process occurred via miR-1 down-regulation. miR-1 expression was down-regulated in lung tumors, but increased in ADAM9-knockdown lung cancer cells, and was negatively correlated with CDCP1 expression as well as the migration ability of lung cancer cells. Luciferase-based reporter assays showed that miR-1 directly bound to the 3'-untranslated region of CDCP1 and inhibited its translation. Treatment with a miR-1 inhibitor restored CDCP1 protein levels and enhanced tumor cell mobility. Overexpression of miR-1 decreased tumor metastases and increased the survival rate in mice. ADAM9 knockdown reduced EGFR signaling and increased miR-1 expression. These results revealed that ADAM9 down-regulates miR-1 via activating EGFR signaling pathways, which in turn enhances CDCP1 expression to promote lung cancer progression.

Higher frequency but random distribution of EGFR mutation subtypes in familial lung cancer patients.

Despite the advancement of epidermal growth factor receptor (EGFR) inhibitors in lung cancer therapy, it remains unclear whether EGFR mutation status in familial lung cancers is different from that of sporadic cases. In this multicenter retrospective study, we compared both the EGFR mutation frequency and patterns between familial and sporadic cases. The results explored that family history of lung cancer is an independent predictor for higher EGFR mutation rate in 1713 lung adenocarcinoma patients (Odd ratio 1.68, 95% CI 1.06-2.67, P = 0.028). However, the distribution of EGFR mutation subtypes was similar to that of sporadic cases. Part of our study involved 40 lung cancer families with at least 2 tumor tissues available within each single family (n = 88) and there was no familial aggregation pattern in EGFR mutation subtypes. There were two families harboring the YAP1 R331W germline risk allele and EGFR mutation statuses among YAP1 family members also varied. These phenomena may hint at the direction of future research into lung carcinogenesis and EGFR mutagenesis.

EGFR mutation and lobar location of lung adenocarcinoma.

The objective of this study was to investigate the associations among lung cancer location, and epidermal growth factor receptor (EGFR) mutation status. Treatment-naive, pathologically confirmed lung adenocarcinomas with tumor specimens available for genetic analysis were included from 2011 through 2014. Overall, 1771 patients with lung adenocarcinoma were included for analysis, after excluding those with carcinoma not otherwise specified, or synchronous multiple primary lung cancers. The median age was 64 years, and the female:male and never smoker:ever smoker ratios were 930:855 (52:48%) and 1167:604 (65:35%), respectively. The EGFR mutation rate was 56%. Among patients, 1093 (62%) had primary tumors in the upper lobes. Compared with the characteristics of the EGFR wild-type, tumors with EGFR activating mutations were more common in women (P < 0.001), never smokers (P < 0.001), and in the upper lobes (P = 0.004). Among EGFR activating mutations, compared with the EGFR exon 19 deletion, L858R mutation were more common in women (P = 0.002), never smokers (P = 0.038), and the upper lobes P < 0.0005). The present study is the first to address that different pulmonary lobar locations might harbor different EGFR mutation subtypes. We demonstrated that adenocarcinomas with L858R mutation, rather than exon 19 deletion or wild-type EGFR gene, prefer to locate over the upper lungs. This phenomenon was more significant in females and never-smokers, implying the result of complex interactions between genetic susceptibility and environmental factors. Therefore, EGFR L858R mutation and exon 19 deletion may not be identical disease entity from the point of carcinogenesis.

ADAM9 enhances CDCP1 protein expression by suppressing miR-218 for lung tumor metastasis.

Metastasis is the leading cause of death in cancer patients due to the difficulty of controlling this complex process. MicroRNAs (miRNA), endogenous noncoding short RNAs with important biological and pathological functions, may play a regulatory role during cancer metastasis, but this role has yet to be fully defined. We previously demonstrated that ADAM9 enhanced the expression of the pro-migratory protein CDCP1 to promote lung metastasis; however, the regulatory process remains unknown. Here we demonstrate that endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 was associated with high migration ability in lung cancer cells. Direct interaction between miR-218 and the 3'-UTR of CDCP1 mRNAs was detected in luciferase-based transcription reporter assays. CDCP1 protein levels decreased as expression levels of miR-218 increased, and increased in cells treated with miR-218 antagomirs. Induction of miR-218 inhibited tumor cell mobility, anchorage-free survival, and tumor-initiating cell formation in vitro and delayed tumor metastases in mice. Our findings revealed an integrative tumor suppressor function of miR-218 in lung carcinogenesis and metastasis.

Identification of five driver gene mutations in patients with treatment-naïve lung adenocarcinoma in Taiwan.

BACKGROUND: It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations. METHODS: This prospective study was a multicenter project conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including EGFR, KRAS, BRAF, HER2 and EML4-ALK fusion mutations, were tested. EGFR, KRAS, BRAF and HER2 mutations were assessed by MALDI-TOF MS (Cohort 1). EML4-ALK translocation was tested by Ventana method in EGFR-wild type patients (Cohort 2). RESULTS: From August 2011 to November 2013, a total of 1772 patients with lung adenocarcinoma were enrolled. In Cohort 1 analysis, EGFR, KRAS, HER2 and BRAF mutations were identified in 987 (55.7%), 93 (5.2%), 36 (2.0%) and 12 (0.7%) patients, respectively. Most of these mutations were mutually exclusive, except for co-mutations in seven patients (3 with EGFR + KRAS, 3 with EGFR + HER2 and 1 with KRAS + BRAF). In Cohort 2 analysis, 29 of 295 EGFR-wild type patients (9.8%) were positive for EML4-ALK translocation. EGFR mutations were more common in female patients and non-smokers and KRAS mutations were more common in male patients and smokers. Gender and smoking status were not correlated significantly with HER2, BRAF and EML4-ALK mutations. EML4-ALK translocation was more common in patients with younger age. CONCLUSION: This was the first study in Taiwan to explore the incidence of five oncogenic drivers in patients with lung adenocarcinoma and the results could be valuable for physicians in consideration of targeted therapy and inclusion of clinical trials.

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.

An exploration of beliefs regarding exercise among Taiwanese patients with chronic obstructive pulmonary disease.

OBJECTIVES: To explore the beliefs regarding regular exercise among patients with chronic obstructive pulmonary disease (COPD). BACKGROUND: Low adherence to exercise has been observed in patients with COPD. It is important to identify factors regarding exercise from the patients' viewpoint. METHODS: Thirty-one patients were recruited from a medical center in Taiwan. Semi-structured, in-depth, one-on-one interviews were conducted to collect data. The narratives of the interviews were analyzed via content analysis. RESULTS: The majority of the participants affirmed the benefits of regular exercise; however, concerns about personal comfort and safety affected their actual exercise behavior. Five normative references were found to support exercise behavior, and several exercise promoters were identified. CONCLUSION: This study provides an understanding of exercise beliefs of Taiwanese patients with COPD stage II-IV and suggests several ideas for their exercise maintenance. There is a need to provide individualized exercise guides and reinforced programs for patients with chronic obstructive pulmonary disease.

Difference in upper airway collapsibility during wakefulness between men and women in response to lower-body positive pressure.

Fluid shift from the legs to the neck induced by LBPP (lower-body positive pressure) increases UA (upper airway) collapsibility in healthy men. Rostral fluid displacement during recumbency may therefore contribute to the pathogenesis of OSA (obstructive sleep apnoea). There is a higher prevalence of OSA in men than in women. We therefore hypothesized that UA collapsibility increases more in men in response to rostral fluid displacement than in women. UA collapsibility was assessed in healthy, non-obese men and women while awake by determining UA Pcrit (critical closing pressure) during application of different suction pressures to the UA. Subjects were randomized to 5 min control or LBPP arms after which they crossed-over into the other arm following a 30 min washout. LBPP was applied by inflating anti-shock trousers wrapped around both legs to 40 mmHg. Pcrit, leg fluid volume and neck circumference were measured at baseline and after 5 min of both control and LBPP periods. LBPP caused a decrease in leg fluid volume and an increase in neck circumference that did not differ between men and women. However, compared with the control period, LBPP induced a much greater increase in Pcrit in men than in women (7.2+/-1.8 compared with 2.0+/-1.5 cm H2O, P=0.035). We conclude that rostral fluid displacement by LBPP increases UA collapsibility more in healthy, non-obese men than in women. This may be one mechanism contributing to the higher prevalence of OSA in men than in women.

Clinical outcome and prognostic factors of patients with pyogenic liver abscess requiring intensive care.

OBJECTIVE: Despite improvements in diagnosis and treatment, pyogenic liver abscess remains a life-threatening disease. This study evaluated clinical outcome and prognostic factors in patients with pyogenic liver abscess admitted to the intensive care unit. DESIGN: Retrospective study. SETTING: Medical and surgical intensive care unit in a 1,700-bed university-based hospital. PATIENTS: Four hundred and thirty-six adult patients (> or = 18 yrs) with a diagnosis of pyogenic liver abscess were reviewed, and 72 patients with pyogenic liver abscess who required intensive care were enrolled in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty of 72 enrolled patients died, yielding an intensive care unit mortality rate of 28%. The most common underlying disease was diabetes mellitus (51%), and the most common microorganism was Klebsiella pneumoniae (74%). Compared with survivors, nonsurvivors had higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (22.2 +/- 9 vs. 13.7 +/- 6, p < .001), higher serum creatinine levels (2.9 +/- 2 vs. 1.9 +/- 2 mg/dL, p = .02), and longer prothrombin times (21 +/- 5 vs. 16 +/- 5 s, p = .01) on the first day of intensive care unit admission. In addition, factors associated with mortality included inadequate antibiotic therapy (p = .026), septic shock (p = .002), acute respiratory failure (p < .001), and acute renal failure (p = .043) on the first day of intensive care unit admission. On multivariate logistic regression analysis, factors that independently correlated with mortality were the presence of acute respiratory failure (p = .003, relative risk = 18.7) and APACHE II score > 16 (p = .026, relative risk = 7.43). CONCLUSIONS: In patients with pyogenic liver abscess requiring intensive care, variables including size of liver abscess, pathogens, comorbidity, and most laboratory data were not associated with mortality. Only the presence of acute respiratory failure and APACHE II score >16 on the first day of intensive care unit admission were significant prognostic factors.

Lower body positive pressure increases upper airway collapsibility in healthy subjects.

We previously showed that rostral fluid displacement by lower body positive pressure (LBPP) narrows the upper airway (UA) and increases UA resistance, but effects on UA collapsibility remained unknown. To test if LBPP increases UA collapsibility, 13 healthy men were randomized into a control or LBPP arm then crossed over into the other arm with a 30-min washout in between. LBPP was applied by inflating anti-shock trousers wrapped around both legs to 40 mmHg. UA collapsibility was assessed by determining UA critical closing pressure (P crit) during application of different negative airway pressures. P crit and leg fluid volume were measured at baseline and after 5 min during both periods. LBPP caused a significant increase in P crit associated with a reduction in leg fluid volume. We conclude that rostral fluid displacement by LBPP increases UA collapsibility in healthy men, suggesting that fluid shift into the neck could increase UA collapsibility during sleep and thereby predispose patients with fluid overload states to obstructive sleep apnea.