The role of disseminated intravascular coagulation (DIC) has not been extensively studied in patients with sepsis. A prospective study was performed in a single university hospital. The incidences of ...DIC at day 1 (<24 hours post-sepsis diagnosis) and day 3 (48 to 72 hours) were investigated among patients with sepsis. The International Society of Thrombosis and Haemostasis criteria for DIC were used. Among 381 patients initially screened, 219 were enrolled in this study and the incidences of overt DIC were 27.9% and 30.1% on day 1 and day 3, respectively. Patients with pneumonia had a lower incidence of DIC on day 1, but a higher hospital mortality rate compared to those with non-pneumonia sepsis. In multivariate models, although day 1 and day 3 DIC scores were not associated with hospital mortality after adjusting for existing severity scores, the change in DIC scores (odds ratio 1.862; 95% confidence interval 1.061 to 3.266) exhibited a significant association. Day 3 DIC scores were more accurate in predicting hospital mortality than day 1 DIC scores (P <0.001), especially in patients with non-pneumonia sepsis. However, DIC scores did not give additional discriminative power to the existing prognostic scores in predicting mortality of patients with sepsis. In conclusion, the change in DIC score was significantly associated with hospital mortality. Patients with pneumonia sepsis had a lower incidence of DIC on day 1, despite their higher disease severity and mortality rate, compared to those with other sources of sepsis.
Despite quality assurance standards, Papanicolaou (Pap) test characteristics remain less than optimal.
To compare the societal costs and benefits of human papillomavirus (HPV) testing, Pap testing, ...and their combination to screen for cervical cancer.
A simulation model of neoplasia natural history was used to estimate the societal costs and quality-adjusted life expectancy associated with 18 different general population screening strategies: Pap plus HPV testing, Pap testing alone, and HPV testing alone every 2 or 3 years among hypothetical longitudinal cohorts of US women beginning at age 20 years and continuing to 65 years, 75 years, or death.
Discounted costs per quality-adjusted life-year (QALY) saved of each screening strategy.
Maximal savings in lives were achieved by screening every 2 years until death with combined HPV and Pap testing at an incremental cost of $76 183 per QALY compared with Pap testing alone every 2 years. Stopping biennial screening with HPV and Pap testing at age 75 years captures 97.8% of the benefits of lifetime screening at a cost of $70 347 per QALY. Combined biennial HPV and Pap testing to age 65 years captures 86.6% of the benefits achievable by continuing to screen until age 75 years. Human papillomavirus screening alone was equally effective as Pap testing alone at any given screening interval or age of screening cessation but was more costly and therefore was dominated. In sensitivity analyses, HPV testing would be more effective and less costly than Pap testing at a cost threshold of $5 for an HPV test.
Screening with HPV plus Pap tests every 2 years appears to save additional years of life at reasonable costs compared with Pap testing alone. Applying age limits to screening is a viable option to maintain benefits while reducing costs.
Germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene cause VHL disease, a rare and autosomal-dominant genetic syndrome. Because VHL protein (pVHL) is the master regulator of ...hypoxia-inducible factor alpha (HIFα), the most prominent feature of VHL disease is the deregulation of HIFα proteins. However, the precise mechanism by which the loss of pVHL function contributes to tumorigenesis is not fully understood. Here, we show that pVHL destabilizes the F-box protein Skp2, a chief component of Skp, Cullin, F-box-containing complex that promotes DNA synthesis in the S phase. The β-domain of pVHL interacts with Skp2, stimulating proteasome-dependent Skp2 degradation, but the destabilization of Skp2 does not depend on the E3 ubiquitin ligase activity of pVHL. Notably, the generation of DNA damage induces Skp2 degradation, which is attenuated by the suppression of endogenous pVHL expression. One possible mechanism of pVHL-dependent Skp2 degradation entails the antagonizing of Akt-mediated Skp2 phosphorylation, which maintains Skp2 stability. Reintroduction of VHL into VHL-null renal cell carcinoma (RCC) cells decreased Skp2 levels and restored DNA damage-dependent Skp2 degradation. These results identify the tumor suppressor function of pVHL in delaying the S-phase progression to inhibit cell proliferation on DNA damage. Clinically, this report explains as to why Skp2 accumulates abnormally in RCC tissues.
The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player ...in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-l-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.
Data regarding the relationship between microbiologic features and comorbidities in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are limited. The aim of this ...study was to correlate microbiologic findings with comorbidities in patients with moderate to severe AECOPD.
This multicenter observational study included patients with AECOPD seen at 28 hospitals in South Korea between January 2015 and December 2018, and the data were retrospectively collected. Pathogens were examined in patients with either pulmonary or extrapulmonary comorbidities, and compared to those of patients without comorbidities. The relationship between pathogen type and the number of comorbidities was also evaluated.
Bacterial infections (178 37.2% vs 203 28.7%, p = 0.002) and co-infections with bacteria and viruses (65 13.6% vs 57 8.1%, p = 0.002) were more prevalent in patients with pulmonary comorbidities. Bacterial pathogens (280 34.7% vs 101 26.7%, p=0.006) were detected at a higher rate in patients with extrapulmonary comorbidities. Previous pulmonary tuberculosis (PTB), bronchiectasis, and diabetes mellitus were risk factors for bacterial infection, and congestive heart failure was a risk factor for bacterial and viral co-infection. As the number of comorbidities increased, the risk of bacterial infection increased considerably.
was more frequently identified in patients with previous PTB (57 15.3% vs 59 7.4%, p < 0.001) and bronchiectasis (33 19.6% vs 83 8.3%, p < 0.001).
AECOPD patients with comorbidities were more likely to experience infection-related exacerbations compared to those without comorbidities. As the overall number of comorbidities increased, the risk of bacterial infection increased significantly.
The efficacy of inhaled corticosteroids (ICSs)/long-acting beta2-agonist (LABA) treatment in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) compared to ...patients with COPD alone has rarely been examined. This study aimed to evaluate the clinical efficacy for the improvement of lung function after ICS/LABA treatment in patients with ACOS compared to COPD alone patients.
Patients with stable COPD were selected from the Korean Obstructive Lung Disease (KOLD) cohort. Subjects began a 3-month ICS/LABA treatment after a washout period. ACOS was defined when the patients had 1) a personal history of asthma, irrespective of age, and wheezing in the last 12 months in a self-reported survey and 2) a positive bronchodilator response.
Among 152 eligible COPD patients, 45 (29.6%) fulfilled the criteria for ACOS. After a 3-month treatment with ICS/LABA, the increase in forced expiratory volume in 1 second (FEV
) was significantly greater in ACOS patients than in those with COPD alone (240.2±33.5 vs 124.6±19.8 mL,
=0.002). This increase in FEV
persisted even after adjustment for confounding factors (adjusted
=0.002). According to severity of baseline FEV
, the ACOS group showed a significantly greater increase in FEV
than the COPD-alone group in patients with mild-to-moderate airflow limitation (223.2±42.9 vs 84.6±25.3 mL,
=0.005), whereas there was no statistically significant difference in patients with severe to very severe airflow limitation.
This study provides clinical evidence that ACOS patients with mild-to-moderate airflow limitation showed a greater response in lung function after 3 months of ICS/LABA combination treatment.
We performed a double‐blinded, genotype‐based stratification study to explore the pharmacokinetics and pharmacodynamics of amitriptyline according to CYP2C19 and CYP2D6 genotype in Korean subjects. ...Twenty‐four healthy adults were grouped by genotype of CYP2C19 and CYP2D6. After a single dose of 25 mg of amitriptyline, blood samples were collected and anticholinergic effects were measured. The extent of N‐demethylation of amitriptyline significantly decreased in subjects carrying two nonfunctional alleles of CYP2C19. The extent of hydroxylation of amitriptyline or nortriptyline was significantly reduced in subjects carrying two CYP2D6 decreased functional alleles compared with those with no or one decreased functional allele. The overall metabolic pathway of amitriptyline was more likely to be dominated by CYP2C19 than CYP2D6. The gene variations of CYP2C19 and CYP2D6 did not change the pharmacodynamic effect. The findings of this study will provide useful information on individualized drug treatment with amitriptyline considering both CYP2D6 and CYP2C19 gene variations.
This study examines whether market participants react to the announcements of corporate governance ranking exercises. As a regulatory innovation, the Financial Supervisory Commission in Taiwan ...initiated and administered two ranking exercises, one in 2015 and the other in 2016, on all publicly listed companies. Adopting anchoring‐and‐adjustment theory, the study predicts that market participants will react strongly to the second announcement if the ranking obtained in the second exercise turns out to be better than the ranking in the first round. Employing an event study methodology, the study shows that market participants react positively and significantly to firms ranked in the top 50% in the second corporate governance exercise. Their reactions to the announcement are even stronger among those that did not list in the top 20% in the first exercise, but made it into the top 50% in the second one. Overall, our analyses support that anchoring‐and‐adjustment theory effectively explains market participants’ behaviour. Since the monitoring of the board of directors and investors may not effectively mitigate the potential moral hazard committed by family owners/executives, our empirical evidence demonstrates that a ranking exercise probably can be employed to supplement routine corporate governance disclosures made in annual reports, in order to strengthen the check‐and‐balance mechanism and reduce the risk of principal–principal conflicts. In conclusion, we discuss the implications of the research findings and propose directions for future studies.
A new sensing technique for rapidly detecting ethanol concentration in aqueous solutions based on electromagnetic resonance is discussed. The sensor has two substrate layers and operates at ...5G-mm-wave frequencies. An experimental study of the new resonator's configuration determines the sensor's sensitivity. During the measurements, 6 samples were modeled with varying amounts of ethanol concentration in the water. The results showed that
S
11
resonance moves linearly towards higher frequencies as the ethanol content increases. The resonant frequency shifted at 0.178 GHz per 10% increase in ethanol towards higher frequencies. As a result, the proposed 5G-mm-wave-sensing technique based on a replaceable sensing layer was proved to be suitable for rapid, accurate, and low-cost alcohol content detection in liquids.
Maintaining adequacy in chronic obstructive pulmonary disease (COPD) care is essential to sustain an adequate level of care. We aimed to assess the current status of COPD quality control and the ...influence of inhaler changes on disease-related health care utilization.
The Health Insurance Review and Assessment Service (HIRA) nationwide database for reimbursed insurance claims from all medical institutions in South Korea from May 2014 to April 2017 was investigated. COPD care quality was assessed by the performance rate of spirometry, the percentage of persistent visit patients and patients prescribed a bronchodilator. The number of severe exacerbations was evaluated.
A total of 68,942 COPD patients were included for 3 years of longitudinal analyses. The overall spirometry enforcement rate was just over 50%, the percentage of regular follow-up patients was over 85%, and bronchodilators were prescribed to over 80% of the patients. COPD-related hospitalization or ER visit rates were 16.6%, 15.3%, and 17.8% for three consequent assessments, respectively. Inhaler changes were analyzed between the first and second assessments: 57.1% were maintained, 0.4% were changed to another class, 9% were escalated, and 5.2% were de-escalated. Only in the escalated group, especially those who changed from the mono to dual inhaler and dual to triple inhaler, had fewer hospitalizations or ER visits.
Adequacy of COPD care status was not that high considering the low-enforcement rate of spirometry, but most patients were prescribed a bronchodilator and regularly followed up. Those who escalated inhaler treatment experienced less health care utilization.
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