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BACKGROUND: Light-to-moderate alcohol consumption has been reported to be cardio-protective among apparently healthy individuals; however, it is unclear whether this association is also present in those with disease. To examine the association between alcohol consumption and prognosis in individuals with pre-existing cardiovascular disease (CVD), we conducted a series of meta-analyses of new findings from three large-scale cohorts and existing published studies. METHODS: We assessed alcohol consumption in relation to all-cause mortality, cardiovascular mortality, and subsequent cardiovascular events via de novo analyses of 14,386 patients with a previous myocardial infarction, angina, or stroke in the UK Biobank Study (median follow-up 8.7 years, interquartile range [IQR] 8.0-9.5), involving 1640 deaths and 2950 subsequent events, and 2802 patients and 1257 deaths in 15 waves of the Health Survey for England 1994-2008 and three waves of the Scottish Health Survey 1995, 1998, and 2003 (median follow-up 9.5 years, IQR 5.7-13.0). This was augmented with findings from 12 published studies identified through a systematic review, providing data on 31,235 patients, 5095 deaths, and 1414 subsequent events. To determine the best-fitting dose-response association between alcohol and each outcome in the combined sample of 48,423 patients, models were constructed using fractional polynomial regression, adjusting at least for age, sex, and smoking status. RESULTS: Alcohol consumption was associated with all assessed outcomes in a J-shaped manner relative to current non-drinkers, with a risk reduction that peaked at 7 g/day (relative risk 0.79, 95% confidence interval 0.73-0.85) for all-cause mortality, 8 g/day (0.73, 0.64-0.83) for cardiovascular mortality and 6 g/day (0.50, 0.26-0.96) for cardiovascular events, and remained significant up to 62, 50, and 15 g/day, respectively. No statistically significant elevated risks were found at higher levels of drinking. In the few studies that excluded former drinkers from the non-drinking reference group, reductions in risk among light-to-moderate drinkers were attenuated. CONCLUSIONS: For secondary prevention of CVD, current drinkers may not need to stop drinking. However, they should be informed that the lowest risk of mortality and having another cardiovascular event is likely to be associated with lower levels of drinking, that is up to approximately 105g (or equivalent to 13 UK units, with one unit equal to half a pint of beer/lager/cider, half a glass of wine, or one measure of spirits) a week.
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Doenças Cardiovasculares , Infarto do Miocárdio , Consumo de Bebidas Alcoólicas/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , MorbidadeRESUMO
BACKGROUND: Heavy menstrual bleeding (HMB) has been shown to have a profound negative impact on women's quality of life and lead to increases in health care costs; however, data on HMB among Chinese population is still rather limited. The present study therefore aimed to determine the current prevalence and risk factors of subjectively experienced HMB in a community sample of Chinese reproductive-age women, and to evaluate its effect on daily life. METHODS: We conducted a questionnaire survey in 2356 women aged 18-50 years living in Beijing, China, from October 2014-July 2015. A multivariate logistic regression model was used to identify risk factors for HMB. RESULTS: Overall, 429 women experienced HMB, giving a prevalence of 18.2%. Risk factors associated with HMB included uterine fibroids (adjusted odds ratio [OR] =2.12, 95% confidence interval [CI] = 1.42-3.16, P < 0.001) and multiple abortions (≥3) (adjusted OR = 3.44, 95% CI = 1.82-6.49, P < 0.001). Moreover, women in the younger age groups (≤24 and 25-29 years) showed higher risks for HMB, and those who drink regularly were more likely to report heavy periods compared with never drinkers (adjusted OR = 2.78, 95% CI = 1.20-6.46, P = 0.017). In general, women experiencing HMB felt more practical discomforts and limited life activities while only 81 (18.9%) of them had sought health care for their heavy bleeding. CONCLUSIONS: HMB was highly prevalent among Chinese women and those reporting heavy periods suffered from greater menstrual interference with daily lives. More information and health education programs are urgently needed to raise awareness of the consequences of HMB, encourage women to seek medical assistance and thus improve their quality of life.
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Atividades Cotidianas/psicologia , Menorragia/epidemiologia , Qualidade de Vida/psicologia , Adulto , Pequim/epidemiologia , Feminino , Humanos , Menorragia/psicologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Data to date is far from sufficient to describe the recent epidemiology of ventilator-associated pneumonia (VAP) in mainland China. This study aimed to estimate the overall incidence of VAP, with a special focus on its temporal trend and associated factors. METHODS: Meta-analyses of 195 studies published from 2010 to 2015 were conducted, followed by subgroup analyses by methodological quality, pre-defined setting characteristics and attributes of populations. RESULTS: The overall cumulative VAP incidence in mainland China was 23.8% (95% confidence interval (CI) 20.6-27.2%), with the results showing high heterogeneity. The pooled incidence densities were 24.14 (95% CI 21.19-27.51) episodes and 22.83 (95% CI 19.88-26.23) patients per 1000 ventilator-days. A decline in the cumulative incidence was observed from 2006 (49.5%, 95% CI 40.0-59.0%) to 2014 (19.6%, 95% CI 10.4-31.0%); differences in the incidence rates were also documented according to Chinese provinces and diagnostic criteria (p < 0.001). Older age (≥60 years), coma, re-intubation, tracheotomy and prolonged ventilation were the factors significantly associated with the occurrence of VAP. CONCLUSIONS: The incidence of VAP remains high in mainland China but has decreased since 2006. The reported rates vary considerably across individual studies, probably due to variations in diagnosis and geographical region. More studies using standard definitions and cut-off points are needed to better clarify the epidemiology of VAP across the country.
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Pneumonia Associada à Ventilação Mecânica/epidemiologia , China/epidemiologia , Humanos , IncidênciaRESUMO
BACKGROUND: Hormone replacement therapy (HRT) has been proven highly effective for menopausal symptoms caused by radical surgery. However, the impact of postoperative HRT on the clinical outcomes of patients previously treated for epithelial ovarian cancer (EOC) remains unclear. OBJECTIVE: To determine whether postoperative HRT use has any positive or negative impacts on prognosis and recurrence among EOC survivors. METHODS: Studies that provided an assessment of postoperative HRT use and prognosis or recurrence in EOC patients were included for analysis. Two reviewers independently evaluated the eligibility of identified studies and abstracted the data. A fixed effects model was used to pool study-specific estimates of hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Two randomized controlled trials (RCTs) and four cohort studies included 419 EOC survivors who used HRT and 1029 non-users. The aggregated HR of overall survival (OS) suggested that HRT use after surgery for EOC had a favorable impact on OS (HR=0.69, 95% CI: 0.61-0.79), but when these studies were categorized into cohort study and RCT subgroups, not all of them demonstrated positive results (HR=0.63, 95% CI: 0.49-0.81 and HR=1.03, 95% CI: 0.58-1.83, respectively). The meta-analysis of EOC recurrence of three available studies demonstrated that postoperative HRT use was not associated with an increased risk of recurrence in EOC survivors (RR=0.83, 95% CI: 0.64-1.07). This pattern also emerged in the subgroup analysis for the stage and type of HRT. CONCLUSIONS: In EOC patients, postoperative HRT does not have a negative effect on overall survival and tumor recurrence. However, well-designed and large-scale RCTs are needed to verify this relationship in the future.
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Terapia de Reposição de Estrogênios/métodos , Menopausa , Recidiva Local de Neoplasia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Ovariectomia , Carcinoma Epitelial do Ovário , Feminino , Terapia de Reposição Hormonal , Humanos , Ovariectomia/métodos , Cuidados Pós-Operatórios , Prognóstico , Modelos de Riscos Proporcionais , Taxa de SobrevidaRESUMO
The valorization of electroplating sludge (ES) for high added value presents greater economic and environmental benefits than conventional treatment methods such as thermal processing, solidification, and landfill. Inspired by the mechanism of chemical looping combustion (CLC), this study developed a novel cost-effective method for denitrification by preparing FeNi-OCs from ES to achieve the synergistic reduction of CO and NO emissions. The phase structure, micromorphology, and valence state changes of the FeNi-OC catalyst during the CO-catalyzed reduction of NO and the pathway for catalytic denitrification using FeNi-OCs were analyzed. Results showed that CO could reduce FeNi-OCs to FeNi, and the reduced FeNi was subsequently oxidized back to FeNi-OCs by NO, a process analogous to CLC. During experiments, the simultaneous consumption of CO and NO gases was observed at 350 °C. This phenomenon was highly pronounced at 600 °C, where the CO and NO concentrations decreased from initial values of 8550 and 470 ppm, respectively, to 6719 and 0 ppm, respectively, with conversion rates of 21.41 % and 100 %, respectively. Hence, synergistic emission reduction was achieved. Further experiments also indicated that the addition of 1.5 % ES during iron ore sintering could substantially reduce the CO and NO concentrations in the sintering flue gas from 1268.32 and 244.81 ppm, respectively, to 974.51 and 161.11 ppm, respectively.
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Alcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in UK Biobank. Binge and heavy binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), with higher genetic predisposition further amplifying the risk. Further, we demonstrate a pronounced interaction between heavy binge drinking and high PRS, resulting in a relative excess risk due to interaction (RERI) of 6.07. Diabetes consistently elevates ARC risk across all drinking and PRS categories, and showed significant interaction with both binge patterns and genetic risk. Overall, we demonstrate synergistic effects of binge drinking, genetics, and diabetes on ARC, with potential to identify high-risk individuals for targeted interventions.
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Consumo Excessivo de Bebidas Alcoólicas , Diabetes Mellitus , Hepatopatias , Adulto , Humanos , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Consumo Excessivo de Bebidas Alcoólicas/genética , Etanol , Predisposição Genética para DoençaRESUMO
BACKGROUND AND AIMS: Research into alcohol consumption and cardiovascular disease (CVD) patients' prognosis has largely ignored the longitudinal dynamics in drinking behaviour. This study measured the association between alcohol consumption trajectories and mortality risk in CVD patients. DESIGN: Prospective cohort study. SETTING: UK-based Whitehall II Study. PARTICIPANTS: A total of 1306 participants with incident non-fatal CVD (coronary heart disease/stroke) events. MEASUREMENTS: Up to eight repeated measures of alcohol intake were available for each patient from the most recent assessment phase pre-incident CVD and all subsequent phases post-incident CVD, spanning up to three decades. Six trajectory groups of alcohol consumption were identified using group-based trajectory modelling and related to the risk of all-cause mortality, adjusting for demographics and changes in life-style and health status. FINDINGS: Three hundred and eighty deaths were recorded during a median follow-up of 5 years after patients' last alcohol assessment. Compared with patients who consistently drank moderately (≤ 14 units/week), former drinkers had a greater risk of mortality (hazard ratio = 1.74, 95% confidence interval = 1.19-2.54) after adjustment for covariates. There was no significantly increased risk of mortality in long-term abstainers, reduced moderate drinkers, stable or unstable heavy drinkers. Cross-sectional analyses based only on drinking information at patients' last assessment found no significant differences in mortality risk for abstainers, former or heavy drinkers versus moderate drinkers. CONCLUSIONS: Cardiovascular disease patients who consistently drink ≤ 14 units/week appear to have a similar risk of mortality to those who are long-term abstainers, which does not support a protective effect of moderate drinking on total mortality. Cardiovascular disease patients who stop drinking appear to have increased mortality risk compared with continuous moderate drinkers, but this may be linked to poor self-rated health before cardiovascular disease onset.
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Doenças Cardiovasculares , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos Transversais , Humanos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de RiscoRESUMO
Guideline developers consider cost-effectiveness evidence in decision making to determine value for money. This consideration in the guideline development process can be informed either by formal and dedicated economic evaluations or by systematic reviews of existing studies. To inform the American Society of Hematology guideline on the diagnosis of venous thromboembolism (VTE), we conducted a systematic review focused on the cost-effectiveness of diagnostic strategies for VTE within the guideline scope. We systematically searched Medline (Ovid), Embase (Ovid), National Health Service Economic Evaluation Database, and the Cost-effectiveness Analysis Registry; summarized; and critically appraised the economic evidence on diagnostic strategies for VTE. We identified 49 studies that met our inclusion criteria, with 26 on pulmonary embolism (PE) and 24 on deep vein thrombosis (DVT). For the diagnosis of PE, strategies including d-dimer to exclude PE were cost-effective compared with strategies without d-dimer testing. The cost-effectiveness of computed tomography pulmonary angiogram (CTPA) in relation to ventilation-perfusion (V/Q) scan was inconclusive. CTPA or V/Q scan following ultrasound or d-dimer results could be cost-effective or even cost saving. For DVT, studies supporting strategies with d-dimer and/or ultrasound were cost-effective, supporting the recommendation that for patients at low (unlikely) VTE risk, using d-dimer as the initial test reduces the need for diagnostic imaging. Our systematic review informed the American Society of Hematology guideline recommendations about d-dimer, V/Q scan and CTPA for PE diagnosis, and d-dimer and ultrasound for DVT diagnosis.
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Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Análise Custo-Benefício , Humanos , Embolia Pulmonar/diagnóstico , Medicina Estatal , Tromboembolia Venosa/diagnóstico , Trombose Venosa/diagnósticoRESUMO
BACKGROUND: To examine the longitudinal trajectories of alcohol consumption prior to and following the diagnosis of cardiovascular diseases (CVD). METHODS: We conducted a case-control study of 2501 incident cases of angina, myocardial infarction or stroke and 10 001 matched controls without the condition. Repeated measures of alcohol were centred on the date of diagnosis, spanning up to 30 years before and after CVD onset. Mean trajectories of weekly consumption were estimated using growth curve models. RESULTS: For trajectories prior to diagnosis, mean volume of alcohol consumed among male cases increased over time, peaking at around 8 years before diagnosis at 95 (95% CI 60 to 130) g/week and declining afterwards. Trajectories following diagnosis showed mean consumption in male cases dropped from 87 (95% CI 54 to 120) g/week to 74 (95% CI 45 to 102) g/week after the date of diagnosis and then slightly rose to 78 (95% CI 40 to 116) g/week at the subsequent 3.5 years, before gradually declining to 31 (95% CI 2 to 61) g/week at 30 years after diagnosis. Mean consumption among female cases remained stable prior to diagnosis (at about 30 g/week), fell marginally to 25 (95% CI 20 to 30) g/week after the date of diagnosis and kept decreasing afterwards. Similar trajectories were obtained in cases and controls. CONCLUSIONS: This is the first attempt to show how patients with CVD change their drinking volume over such a wide time span. Future research needs to establish insight into drinking behaviour in other ways (such as frequency and context) and address the impact of changes in drinking on patients with CVD.
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BACKGROUND: Trial and observational evidence is conflicting in terms of the association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment in the general population. It is uncertain whether the associations occur in stroke patients, who are at known higher risk of cognitive decline. This systematic review was to synthesize the evidence for these associations among stroke patients. METHODS: MEDLINE, EMBASE, the Cochrane Library and trial registries were searched. We included randomized controlled trials (RCTs) or observational cohort studies conducted among patients with stroke and reported on the association of blood lipids, atherosclerosis or statin use with dementia or cognitive impairment. Meta-analysis was conducted separately for crude and maximally adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: Of 18,026 records retrieved, 56 studies (one RCT and 55 cohort studies) comprising 38,423 stroke patients were included. For coronary heart disease, the pooled OR of dementia and cognitive impairment was 1.32 (95%CI 1.10-1.58, nâ¯=â¯15 studies, I2â¯=â¯0%) and 1.23 (95%CI 0.99-1.54, nâ¯=â¯14, I2â¯=â¯26.9%), respectively. Peripheral artery disease was associated with dementia (OR 3.59, 95%CI 1.47-8.76, nâ¯=â¯2, I2â¯=â¯0%) and cognitive impairment (OR 2.70, 95%CI 1.09-6.69, nâ¯=â¯1). For carotid stenosis, the pooled OR of dementia and cognitive impairment was 2.67 (95%CI 0.83-8.62, nâ¯=â¯3, I2â¯=â¯77.9%) and 3.34 (95%CI 0.79-14.1, nâ¯=â¯4, I2â¯=â¯96.6%), respectively. For post-stroke statin use, the pooled OR of dementia and cognitive impairment was 0.89 (95%CI 0.65-1.21, nâ¯=â¯1) and 0.56 (95%CI 0.46-0.69, nâ¯=â¯3, I2â¯=â¯0%), respectively. No association was observed for hypercholesterolemia. These results were mostly consistent with adjusted ORs or HRs, which were reported from limited evidence. CONCLUSION: Atherosclerosis was associated with an increased risk of post-stroke dementia. Post-stroke statin use was associated with decreased risk of cognitive impairment. To confirm whether or not statins confer advantages in the post-stroke population in terms of preventing cognitive decline over and above their known effectiveness in reducing risk of further vascular events, further stroke trials including cognitive assessment and observational analyses adjusted for key confounders, focusing on key subgroups or statin use patterns are required.
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Disfunção Cognitiva/prevenção & controle , Demência/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Aterosclerose , Disfunção Cognitiva/etiologia , Demência/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Values and preferences relate to the importance that patients place on health outcomes (eg, bleeding, having a deep venous thrombosis) and are essential when weighing benefits and harms in guideline recommendations. To inform the American Society of Hematology guidelines for management of venous thromboembolism (VTE) disease, we conducted a systematic review of patients' values and preferences related to VTE. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature from inception to April of 2018 (PROSPERO-CRD42018094003). We included quantitative and qualitative studies. We followed Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance for rating the certainty and presenting findings for quantitative research about the relative importance of health outcomes and a grounded theory approach for qualitative thematic synthesis. We identified 14 quantitative studies (2465 participants) describing the relative importance of VTE-related health states in a widely diverse population of patients, showing overall small to important impact on patients' lives (certainty of the evidence from low to moderate). Additionally, evidence from 34 quantitative studies (6424 participants) and 15 qualitative studies (570 participants) revealed that patients put higher value on VTE risk reduction than on the potential harms of the treatment (certainty of evidence from low to moderate). Studies also suggested a clear preference for oral medication over subcutaneous medication (moderate certainty). The observed variability in health state values may be a result of differences in the approaches used to elicit them and the diversity of included populations rather than true variability in values. This finding highlights the necessity to explore the variability induced by different approaches to ascertain values.
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Hematologia , Neoplasias , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular , Humanos , Estados Unidos , Tromboembolia Venosa/tratamento farmacológicoRESUMO
PURPOSE: Metabolic syndrome (MetS) has been extensively studied for its long-term health effects, typically through conventional Cox proportional hazards regression modeling of the overall association of MetS with a single outcome. Such an approach neglects the inherent links between MetS-related disease outcomes and fails to provide sufficient insights into the impact of each component of MetS over time. METHODS: We therefore conducted a retrospective cohort study of 63,680 individuals who received health check-ups at the MJ Health Screening Center in Taiwan from 1997-2005 to study the subsequent risks of hypertension, type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) simultaneously for MetS and its components. Multivariate-adjusted hazard ratios (HRs) were calculated using Cox models for multiple failure outcomes. RESULTS: At baseline, MetS was identified in 7835 participants. Over a median follow-up of 3 years, 8252, 1634, and 6714 participants developed hypertension, T2DM and CKD, respectively. The HR for MetS was 2.41 (95% CI 2.29-2.53) for hypertension, 5.17 (95% CI 4.68-5.71) for T2DM and 1.22 (95% CI 1.15-1.31) for CKD. Three MetS components showed the strongest association with each of the outcomes: elevated blood pressure with hypertension (HR = 3.62, 95% CI 3.46-3.79), raised fasting plasma glucose with T2DM (HR = 8.89, 95% CI 7.86-10.06) and elevated triglycerides with CKD (HR = 1.14, 95% CI 1.08-1.21). CONCLUSIONS: MetS may help identify individuals with metabolic profiles that confer incremental risks for multiple diseases. Additionally, several components of the syndrome should be considered by clinicians, as they show stronger associations with specific diseases than MetS.
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Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão/epidemiologia , Síndrome Metabólica/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Idoso , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Hipertensão/etiologia , Incidência , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Medição de Risco , Taiwan/epidemiologiaRESUMO
OBJECTIVE: To estimate the prevalence of Pseudomonas aeruginosa and antimicrobial-resistant P. aeruginosa in ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP), and community-acquired pneumonia (CAP) in mainland China. METHODS: Meta-analyses of 50 studies published from 2010 to 2014 were conducted, followed by pre-defined subgroup analyses and meta-regressions. RESULTS: P. aeruginosa accounted for 19.4% (95% confidence interval (CI) 17.6-21.2%) of all isolates in VAP, which was similar to the proportion in HAP of 17.8% (95% CI 14.6-21.6%), but significantly greater than the proportion in CAP of 7.7% (15/195, p<0.001). Regarding VAP, the prevalence of P. aeruginosa has decreased since 2007. P. aeruginosa exhibited varying resistance to agents recommended for the initial management of VAP, with a high level of resistance to gentamicin (51.1%, 95% CI 37.7-64.4%) and a low level of resistance to amikacin (22.5%, 95% CI 14.3-33.6%). The prevalence of P. aeruginosa isolates resistant to agents recommended for the treatment of HAP ranged from 22.2% (95% CI 13.8-33.6%) for amikacin to 50.0% (95% CI 30.2-69.8%) for cefoperazone. CONCLUSIONS: P. aeruginosa was highly prevalent among patients with VAP and HAP in mainland China. The initial empirical treatment of these patients remains challenging because of the strikingly high prevalence of antimicrobial resistance.
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Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Pneumonia Bacteriana/microbiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Farmacorresistência Bacteriana , Humanos , Prevalência , Pseudomonas aeruginosa/efeitos dos fármacosRESUMO
GPRC5A is a G-protein-coupled receptor expressed in lung tissue but repressed in most human lung cancers. Studies in Gprc5a(-/-) mice have established its role as a tumor-suppressor function in this setting, but the basis for its role has been obscure. Here, we report that GPRC5A functions as a negative modulator of EGFR signaling. Mouse tracheal epithelial cells (MTEC) from Gprc5a(-/-) mice exhibited a relative increase in EGFR and downstream STAT3 signaling, whereas GPRC5A expression inhibited EGFR and STAT3 signaling. GPRC5A physically interacted with EGFR through its transmembrane domain, which was required for its EGFR inhibitory activity. Gprc5a(-/-) MTEC were much more susceptible to EGFR inhibitors than wild-type MTEC, suggesting their dependence on EGFR signaling for proliferation and survival. Dysregulated EGFR and STAT3 were identified in the normal epithelia of small and terminal bronchioles as well as tumors of Gprc5a(-/-) mouse lungs. Moreover, in these lungs EGFR inhibitor treatment inhibited EGFR and STAT3 activation along with cell proliferation. Finally, overexpression of ectopic GPRC5A in human non-small cell lung carcinoma cells inhibited both EGF-induced and constitutively activated EGFR signaling. Taken together, our results show how GPRC5A deficiency leads to dysregulated EGFR and STAT3 signaling and lung tumorigenesis. Cancer Res; 75(9); 1801-14. ©2015 AACR.