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Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.
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Antígeno B7-H1 , Benzo(a)pireno , Progressão da Doença , Hiperglicemia , Fator de Crescimento Insulin-Like II , Neoplasias Pulmonares , Camundongos Endogâmicos C57BL , Proteínas Nucleares , Nucleofosmina , Receptor de Insulina , Animais , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Masculino , Humanos , Receptor de Insulina/metabolismo , Receptor de Insulina/genética , Camundongos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Hiperglicemia/metabolismo , Benzo(a)pireno/toxicidade , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like II/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Nitrosaminas/toxicidade , Macrófagos Associados a Tumor/metabolismo , Linhagem Celular Tumoral , Comunicação Parácrina , Regulação Neoplásica da Expressão Gênica , Fumar/efeitos adversos , Macrófagos/metabolismoRESUMO
This study aimed to assess the lung transplantation (LT) outcomes of patients with right ventricular dysfunction (RVD), focusing on the impact of various extracorporeal membrane oxygenation (ECMO) configurations. We included adult patients who underwent LT with ECMO as a bridge-to-transplant from 2011 to 2021 at a single center. Among patients with RVD (n = 67), veno-venous (V-V) ECMO was initially applied in 79% (53/67) and maintained until LT in 52% (35/67). Due to the worsening of RVD, the configuration was changed from V-V ECMO to veno-arterial (V-A) ECMO or a right ventricular assist device with an oxygenator (Oxy-RVAD) in 34% (18/67). They showed that lactic acid levels (2-6.1 mmol/L) and vasoactive inotropic score (6.6-22.6) increased. V-A ECMO or Oxy-RVAD was initiated and maintained until LT in 21% (14/67) of cases. There was no significant difference in the survival rates among the three configuration groups (V-V ECMO vs. configuration changed vs. V-A ECMO/Oxy-RVAD). Our findings suggest that the choice of ECMO configuration for LT candidates with RVD should be determined by the patient's current hemodynamic status. Vital sign stability supports the use of V-V ECMO, while increasing lactic acid levels and vasopressor needs may require a switch to V-A ECMO or Oxy-RVAD.
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Oxigenação por Membrana Extracorpórea , Transplante de Pulmão , Disfunção Ventricular Direita , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Disfunção Ventricular Direita/terapia , Disfunção Ventricular Direita/cirurgia , Adulto , Resultado do Tratamento , Coração Auxiliar , IdosoRESUMO
BACKGROUND: Although several trials were conducted to optimize the oxygenation range in intensive care unit (ICU) patients, no studies have yet reached a universal recommendation on the optimal a partial pressure of oxygen in arterial blood (PaO2) range in patients with sepsis. Our aim was to evaluate whether a relatively high arterial oxygen tension is associated with longer survival in sepsis patients compared with conservative arterial oxygen tension. METHODS: From the Korean Sepsis Alliance nationwide registry, patients treated with liberal PaO2 (PaO2 ≥ 80 mm Hg) were 1:1 matched with those treated with conservative PaO2 (PaO2 < 80 mm Hg) over the first three days after ICU admission according to the propensity score. The primary outcome was 28-day mortality. RESULTS: The median values of PaO2 over the first three ICU days in 1211 liberal and 1211 conservative PaO2 groups were, respectively, 107.2 (92.0-134.0) and 84.4 (71.2-112.0) in day 1110.0 (93.4-132.0) and 80.0 (71.0-100.0) in day 2, and 106.0 (91.9-127.4) and 78.0 (69.0-94.5) in day 3 (all p-values < 0.001). The liberal PaO2 group showed a lower likelihood of death at day 28 (14.9%; hazard ratio [HR], 0.79; 95% confidence interval [CI] 0.65-0.96; p-value = 0.017). ICU (HR, 0.80; 95% CI 0.67-0.96; p-value = 0.019) and hospital mortalities (HR, 0.84; 95% CI 0.73-0.97; p-value = 0.020) were lower in the liberal PaO2 group. On ICU days 2 (p-value = 0.007) and 3 (p-value < 0.001), but not ICU day 1, hyperoxia was associated with better prognosis compared with conservative oxygenation., with the lowest 28-day mortality, especially at PaO2 of around 100 mm Hg. CONCLUSIONS: In critically ill patients with sepsis, higher PaO2 (≥ 80 mm Hg) during the first three ICU days was associated with a lower 28-day mortality compared with conservative PaO2.
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Estado Terminal , Unidades de Terapia Intensiva , Oxigênio , Sepse , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estado Terminal/mortalidade , Estado Terminal/terapia , Idoso , Sepse/mortalidade , Sepse/sangue , Sepse/terapia , República da Coreia/epidemiologia , Estudos de Coortes , Oxigênio/sangue , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Pressão Parcial , Sistema de Registros/estatística & dados numéricos , Mortalidade Hospitalar , Gasometria/métodos , Gasometria/estatística & dados numéricosRESUMO
BACKGROUND: There is an argument whether the delayed intubation aggravate the respiratory failure in Acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). We aimed to investigate the effect of high-flow nasal cannula (HFNC) failure before mechanical ventilation on clinical outcomes in mechanically ventilated patients with COVID-19. METHODS: This retrospective cohort study included mechanically ventilated patients who were diagnosed with COVID-19 and admitted to the intensive care unit (ICU) between February 2020 and December 2021 at Asan Medical Center. The patients were divided into HFNC failure (HFNC-F) and mechanical ventilation (MV) groups according to the use of HFNC before MV. The primary outcome of this study was to compare the worst values of ventilator parameters from day 1 to day 3 after mechanical ventilation between the two groups. RESULTS: Overall, 158 mechanically ventilated patients with COVID-19 were included in this study: 107 patients (67.7%) in the HFNC-F group and 51 (32.3%) in the MV group. The two groups had similar profiles of ventilator parameter from day 1 to day 3 after mechanical ventilation, except of dynamic compliance on day 3 (28.38 mL/cmH2O in MV vs. 30.67 mL/H2O in HFNC-F, p = 0.032). In addition, the HFNC-F group (5.6%) had a lower rate of ECMO at 28 days than the MV group (17.6%), even after adjustment (adjusted hazard ratio, 0.30; 95% confidence interval, 0.11-0.83; p = 0.045). CONCLUSIONS: Among mechanically ventilated COVID-19 patients, HFNC failure before mechanical ventilation was not associated with deterioration of respiratory failure.
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COVID-19 , Insuficiência Respiratória , Humanos , Cânula , Respiração Artificial , COVID-19/terapia , Estudos Retrospectivos , Prognóstico , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/terapiaRESUMO
Chronic obstructive pulmonary disease (COPD) is a group of illnesses associated with unresolved inflammation in response to toxic environmental stimuli. Persistent exposure to PM is a major risk factor for COPD, but the underlying mechanism remains unclear. Using our established mouse model of PM-induced COPD, we find that repeated PM exposure provokes macrophage-centered chronic inflammation and COPD development. Mechanistically, chronic PM exposure induces transcriptional downregulation of HAAO, KMO, KYNU, and QPRT in macrophages, which are the enzymes of de novo NAD+ synthesis pathway (kynurenine pathway; KP), via elevated chromatin binding of the CCCTC-binding factor (CTCF) near the transcriptional regulatory regions of the enzymes. Subsequent reduction of NAD+ and SIRT1 function increases histone acetylation, resulting in elevated expression of pro-inflammatory genes in PM-exposed macrophages. Activation of SIRT1 by nutraceutical resveratrol mitigated PM-induced chronic inflammation and COPD development. In agreement, increased levels of histone acetylation and decreased expression of KP enzymes were observed in pulmonary macrophages of COPD patients. We newly provide an evidence that dysregulated NAD+ metabolism and consecutive SIRT1 deficiency significantly contribute to the pathological activation of macrophages during PM-mediated COPD pathogenesis. Additionally, targeting PM-induced intertwined metabolic and epigenetic reprogramming in macrophages is an effective strategy for COPD treatment.
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Material Particulado , Doença Pulmonar Obstrutiva Crônica , Animais , Camundongos , Humanos , Material Particulado/toxicidade , Material Particulado/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia , Histonas/metabolismo , NAD/metabolismo , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/genética , Macrófagos , Inflamação/metabolismo , Epigênese GenéticaRESUMO
BACKGROUND: Acute exacerbation of interstitial lung disease (AE-ILD) significantly impacts prognosis, leading to high mortality rates. Although lung transplantation is a life-saving treatment for selected patients with ILD, its outcomes in those presenting with AE-ILD have yielded conflicting results compared with those with stable ILD. This study aims to investigate the impact of pre-existing AE on the prognosis of ILD patients who underwent lung transplantation. METHOD: We conducted a single-center retrospective study by reviewing the medical records of 108 patients who underwent lung transplantation for predisposing ILD at Asan Medical Center, Seoul, South Korea, between 2008 and 2022. The primary objective was to compare the survival of patients with AE-ILD at the time of transplantation with those without AE-ILD. RESULTS: Among the 108 patients, 52 (48.1%) experienced AE-ILD at the time of lung transplantation, and 81 (75.0%) required pre-transplant mechanical ventilation. Although the type of ILD (IPF vs. non-IPF ILD) did not affect clinical outcomes after transplantation, AE-ILD was associated with worse survival outcomes. The survival probabilities at 90 days, 1 year, and 3 years post-transplant for patients with AE-ILD were 86.5%, 73.1%, and 60.1%, respectively, while those for patients without AE-ILD were higher, at 92.9%, 83.9%, and 79.6% (p = 0.032). In the multivariable analysis, pre-existing AE was an independent prognostic factor for mortality in ILD patients who underwent lung transplantation. CONCLUSIONS: Although lung transplantation remains an effective treatment option for ILD patients with pre-existing AE, careful consideration is needed, especially in patients requiring pre-transplant mechanical respiratory support.
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Doenças Pulmonares Intersticiais , Transplante de Pulmão , Humanos , Estudos Retrospectivos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/cirurgia , Prognóstico , Resultado do Tratamento , Transplante de Pulmão/efeitos adversos , Progressão da DoençaRESUMO
The efficacy of extended meropenem infusions in patients with nosocomial pneumonia is not well defined. Therefore, we compared the clinical outcomes of extended versus intermittent meropenem infusions in the treatment of nosocomial pneumonia. We performed a retrospective analysis of extended versus intermittent meropenem infusions in adult patients who had been treated for nosocomial pneumonia at a medical ICU between 1 May 2018 and 30 April 2020. The primary outcome was mortality at 14 days. Overall, 64 patients who underwent an extended infusion and 97 with an intermittent infusion were included in this study. At 14 days, 10 (15.6%) patients in the extended group and 22 (22.7%) in the intermittent group had died (adjusted hazard ratio (HR), 0.55; 95% confidence interval (CI): 0.23-1.31; p = 0.174). In the subgroup analysis, significant differences in mortality at day 14 were observed in patients following empirical treatment with meropenem (adjusted HR, 0.17; 95% CI: 0.03-0.96; p = 0.045) and in Gram-negative pathogens identified by blood or sputum cultures (adjusted HR, 0.01; 95% CI: 0.01-0.83; p = 0.033). Extended infusion of meropenem compared with intermittent infusion as a treatment option for nosocomial pneumonia may have a potential advantage in specific populations.
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BACKGROUND: The optimal strategy for fluid management during the first few days of ICU in sepsis patients remains controversial. We aimed to investigate the impact of cumulative fluid balance during the first three days of ICU on the mortality of patients with sepsis. METHODS: This study analyzed prospectively collected data from the Korean Sepsis Alliance Database, which registered 11,981 sepsis patients from 20 hospitals. We selected three propensity score-matched cohorts consisting of patients with a negative or positive cumulative fluid balance during the first three ICU days: from ICU admission to the first midnight as the D1 cohort, until the second midnight as the D2 cohort, and until the third midnight as the D3 cohort. The propensity score for fluid balance was calculated using covariates including the amount of fluid output during the first three ICU days. The primary outcome was mortality at day 28 in the ICU. RESULTS: From a total of 11,981 patients, 2516 patients were included for propensity score matching. After matching in a 1:1 ratio, there were 483, 373, and 392 matched pairs of patients assigned to the D1, D2, and D3 cohorts, respectively. In the D1 cohort, there were no significant differences in mortality at day 28 (hazard ratio [HR], 1.17; 95% confidence interval [CI] 0.85-1.60; P = 0.354) between the two groups. The positive fluid groups in both the D2 (HR, 2.13; 95% CI 1.48-3.06; P < 0.001) and D3 (HR, 1.56; 95% CI 1.10-2.22; P = 0.012) cohorts had significantly higher mortality rates than the negative fluid groups. CONCLUSIONS: In patients with sepsis, a positive fluid balance on the first ICU day was not associated with mortality at day 28. In contrast, cumulative positive fluid balances on the second and third ICU days were associated with higher mortality at day 28.
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OBJECTIVES: Changes in sedation levels over a long time in patients who are mechanically ventilated are unknown. Therefore, we investigated the long-term sedation levels of these patients by classifying them into different longitudinal patterns. DESIGN: This was a multicentre, prospective, longitudinal, and observational study. SETTING: Twenty intensive care units (ICUs) spanning several medical institutions in Korea. PARTICIPANTS: Patients who received mechanical ventilation and sedatives in ICU within 48 hours of admission between April 2020 and July 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary objective of this study was to identify the pattern of sedation practice. Additionally, we analysed the associations of trajectory groups with clinical outcomes as the secondary outcome. RESULTS: Sedation depth was monitored using Richmond Agitation-Sedation Scale (RASS). A group-based trajectory model was used to classify 631 patients into four trajectories based on sedation depth: persistent suboptimal (13.2%, RASS ≤ -3 throughout the first 30 days), delayed lightening (13.9%, RASS ≥ -2 after the first 15 days), early lightening (38.4%, RASS ≥ -2 after the first 7 days) and persistent optimal (34.6%, RASS ≥ -2 during the first 30 days). 'Persistent suboptimal' trajectory was associated with delayed extubation (HR: 0.23, 95% CI: 0.16 to 0.32, p<0.001), longer ICU stay (HR: 0.36, 95% CI: 0.26 to 0.51, p<0.001) and hospital mortality (HR: 13.62, 95% CI: 5.99 to 30.95, p<0.001) compared with 'persistent optimal'. The 'delayed lightening' and 'early lightening' trajectories showed lower extubation probability (HR: 0.30, 95% CI: 0.23 to 0.41, p<0.001; HR: 0.72, 95% CI: 0.59 to 0.87, p<0.001, respectively) and ICU discharge (HR: 0.44, 95% CI: 0.33 to 0.59, p<0.001 and HR: 0.80, 95% CI: 0.65 to 0.97, p=0.024) compared with 'persistently optimal'. CONCLUSIONS: Among the four trajectories, 'persistent suboptimal' trajectory was associated with higher mortality.
Assuntos
Hipnóticos e Sedativos , Respiração Artificial , Humanos , Estudos Prospectivos , Hipnóticos e Sedativos/uso terapêutico , Dor , Unidades de Terapia Intensiva , República da CoreiaRESUMO
BACKGROUND: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. METHODS: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation-Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. RESULTS: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death (P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.55-0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% CI, 0.56-0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79-1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65-2.17; P = 0.582). CONCLUSION: In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.
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Delírio , Hipnóticos e Sedativos , Humanos , Hipnóticos e Sedativos/uso terapêutico , Estudos de Coortes , Estudos Prospectivos , Mortalidade Hospitalar , Respiração Artificial , Delírio/epidemiologia , Unidades de Terapia Intensiva , República da CoreiaRESUMO
Airway complications may occur after lung transplantation and are associated with considerable morbidity and mortality. We investigated the incidence, risk factors, and clinical characteristics of these complications. We retrospectively reviewed the medical records of 137 patients who underwent lung transplantation between 2008 and 2021. The median follow-up period was 20 months. Of the 137 patients, 30 (21.9%) had postoperative airway complications, of which 2 had two different types of airway complications. The most common airway complication was bronchial stenosis, affecting 23 patients (16.8%). Multivariable Cox analysis revealed that a recipient's body mass index ≥ 25 kg/m2 (hazard ratio [HR], 2.663; p = 0.013) was a significant independent risk factor for airway complications, as was postoperative treatment with extracorporeal membrane oxygenation (ECMO; HR, 3.340; p = 0.034). Of the 30 patients who had airway complications, 21 (70.0%) were treated with bronchoscopic intervention. Survival rates did not differ significantly between patients with and without airway complications. Thus, our study revealed that one fifth of patients who underwent lung transplantation experienced airway complications during the follow-up period. Obesity and receiving postoperative ECMO are risk factors for airway complications, and close monitoring is warranted in such cases.
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Obstrução das Vias Respiratórias , Broncopatias , Transplante de Pulmão , Complicações Pós-Operatórias , Humanos , Broncopatias/etiologia , Incidência , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Obstrução das Vias Respiratórias/epidemiologia , Obstrução das Vias Respiratórias/etiologiaRESUMO
Continuous infusion of beta-lactam antibiotics has emerged as an alternative for the treatment of sepsis because of the favourable pharmacokinetics of continuous infusion. This study aimed to evaluate the survival benefits of continuous vs. intermittent infusion of piperacillin-tazobactam in critically ill patients with sepsis. We retrospectively conducted a single-centre study of continuous infusion vs. intermittent infusion of piperacillin-tazobactam for adult patients who met the Sepsis-3 criteria and were treated at a medical ICU within 48 h after hospitalisation between 1 May 2018 and 30 April 2020. The primary outcome was mortality at 28 days. A total of 157 patients (47 in the continuous group and 110 in the intermittent group) met the inclusion criteria for evaluation. The 28-day mortality rates were 12.8% in the continuous group and 27.3% in the intermittent group (p = 0.07). However, after adjustment for potential covariables, patients in the continuous group (12.8%) showed significantly lower mortality at 28 days than those in the intermittent group (27.3%; adjusted hazard ratio (HR), 0.31; 95% confidence interval (CI), 0.13-0.79; p = 0.013). In sepsis patients, continuous infusion of piperacillin-tazobactam may confer a benefit regarding the avoidance of mortality at 28 days compared with intermittent infusion.
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BACKGROUND: Hospital-onset sepsis is associated with a higher in-hospital mortality rate than community-onset sepsis. Many hospitals have implemented rapid response teams (RRTs) for early detection and timely management of at-risk hospitalized patients. However, the effectiveness of an all-day RRT over a non-all-day RRT in reducing the risk of in-hospital mortality in patient with hospital-onset sepsis is unclear. We aimed to determine the effect of the RRT's operating hours on in-hospital mortality in inpatient patients with sepsis. METHODS: We conducted a nationwide cohort study of adult patients with hospital-onset sepsis prospectively collected from the Korean Sepsis Alliance (KSA) Database from 16 tertiary referral or university-affiliated hospitals in South Korea between September of 2019 and February of 2020. RRT was implemented in 11 hospitals, of which 5 (45.5%) operated 24-h RRT (all-day RRT) and the remaining 6 (54.5%) had part-day RRT (non-all-day RRT). The primary outcome was in-hospital mortality between the two groups. RESULTS: Of the 405 patients with hospital-onset sepsis, 206 (50.9%) were admitted to hospitals operating all-day RRT, whereas 199 (49.1%) were hospitalized in hospitals with non-all-day RRT. A total of 73 of the 206 patients in the all-day group (35.4%) and 85 of the 199 patients in the non-all-day group (42.7%) died in the hospital (P = 0.133). After adjustments for co-variables, the implementation of all-day RRT was associated with a significant reduction in in-hospital mortality (adjusted odds ratio 0.57; 95% confidence interval 0.35-0.93; P = 0.024). CONCLUSIONS: In comparison with non-all-day RRTs, the availability of all-day RRTs was associated with reduced in-hospital mortality among patients with hospital-onset sepsis.
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Equipe de Respostas Rápidas de Hospitais , Sepse , Adulto , Estudos de Coortes , Hospitais , Humanos , Estudos Prospectivos , Sepse/terapiaRESUMO
BACKGROUND: Central venous blood gas (cVBG) values are correlated with arterial blood gas (ABG) values. However, the substitution of cVBG values for ABG values in critically ill patients remains uninvestigated. Thus, we investigated the reliability between cVBG and ABG values and sought to define the conditions that could improve the reliability of cVBG values as a substitute. METHODS: We conducted a prospective comparison of 292 sets of cVBG values and ABG values from 82 subjects admitted to the medical ICU between October 2017-July 2018. Paired cVBG and ABG samples were collected daily during the first 5 d of ICU treatment and on days 8, 15, 22, and 29. Intraclass correlation coefficient (ICC) and Bland-Altman limits of agreement (LOA) were obtained. RESULTS: The ICC between ABG and cVBG was 0.626 for pH, 0.696 for PCO2 , 0.869 for bicarbonate, 0.866 for base excess, and 0.989 for lactic acid. Bland-Altman plots showed clinically unacceptable LOA between all parameters. Subgroup analysis indicated a significant increase in the ICCs of PCO2 in samples with mechanical ventilation (0.0574-0.735, P = .02) and central venous oxygen saturation (ScvO2) ≥ 70% (0.611-0.763, P = .008). After adjustment, the 95% LOA between ABG and cVBG was -0.06 to 0.07 for pH and -7.09 to 7.05 for PCO2 in mechanically ventilated subjects with ScvO2 ≥ 70%. CONCLUSIONS: ABG and cVBG values showed clinically acceptable agreements and improved reliability in mechanically ventilated subjects with ScvO2 ≥ 70%. cVBG analysis may be a substitute for ABG analysis in mechanically ventilated patients once tissue perfusion is restored.
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Dióxido de Carbono , Estado Terminal , Gasometria , Humanos , Concentração de Íons de Hidrogênio , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
Mutations of the mitochondrial genome (mtDNA) cause a range of profoundly debilitating clinical conditions for which treatment options are very limited. Most mtDNA diseases show heteroplasmy - tissues express both wild-type and mutant mtDNA. While the level of heteroplasmy broadly correlates with disease severity, the relationships between specific mtDNA mutations, heteroplasmy, disease phenotype and severity are poorly understood. We have carried out extensive bioenergetic, metabolomic and RNAseq studies on heteroplasmic patient-derived cells carrying the most prevalent disease related mtDNA mutation, the m.3243 A > G. These studies reveal that the mutation promotes changes in metabolites which are associated with the upregulation of the PI3K-Akt-mTORC1 axis in patient-derived cells and tissues. Remarkably, pharmacological inhibition of PI3K, Akt, or mTORC1 reduced mtDNA mutant load and partially rescued cellular bioenergetic function. The PI3K-Akt-mTORC1 axis thus represents a potential therapeutic target that may benefit people suffering from the consequences of the m.3243 A > G mutation.
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DNA Mitocondrial/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , DNA Mitocondrial/genética , Feminino , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Mutação/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genéticaRESUMO
BACKGROUND: According to the rapid response system's team composition, responding teams were named as rapid response team (RRT), medical emergency team (MET), and critical care outreach. A RRT is often a nurse-led team, whereas a MET is a physician-led team that mainly plays the role of an efferent limb. As few multicenter studies have focused on physician-led METs, we comprehensively analyzed cases for which physician-led METs were activated. METHODS: We retrospectively analyzed cases for which METs were activated. The study population consisted of subjects over 18 years of age who were admitted in the general ward from January 2016 to December 2017 in 9 tertiary teaching hospitals in Korea. The data on subjects' characteristics, activation causes, activation methods, performed interventions, in-hospital mortality, and intensive care unit (ICU) transfer after MET activation were collected and analyzed. RESULTS: In this study, 12,767 cases were analyzed, excluding those without in-hospital mortality data. The subjects' median age was 67 years, and 70.4% of them were admitted to the medical department. The most common cause of MET activation was respiratory distress (35.1%), followed by shock (11.8%), and the most common underlying disease was solid cancer (39%). In 7,561 subjects (59.2%), the MET was activated using the screening system. The commonly performed procedures were arterial line insertion (17.9%), intubation (13.3%), and portable ultrasonography (13.0%). Subsequently, 29.4% of the subjects were transferred to the ICU, and 27.2% died during hospitalization. CONCLUSIONS: This physician-led MET cohort showed relatively high rates of intervention, including arterial line insertion and portable ultrasonography, and low ICU transfer rates. We presume that MET detects deteriorating patients earlier using a screening system and begins ICU-level management at the patient's bedside without delay, eventually preventing the patient's condition from worsening and transfer to the ICU.
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Serviço Hospitalar de Emergência , Equipe de Respostas Rápidas de Hospitais , Médicos , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Avaliação de Resultados em Cuidados de Saúde , República da CoreiaRESUMO
BACKGROUND: The current early warning scores may be insufficient for medical emergency teams (METs) to use in assessing the severity and the prognosis of activated patients. We evaluated the predictive powers of the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS) for 28-day mortality and to analyze predictors of 28-day mortality in general ward patients who activate the MET. METHODS: Adult general ward inpatients who activated the MET in a tertiary referral teaching hospital between March 2009 and December 2016 were included. The demographic and clinical characteristics and physiologic parameters at the time of MET activation were collected, and MEWS and NEWS were calculated. RESULTS: A total of 6,729 MET activation events were analyzed. Patients who died within 28 days were younger (mean age 60 vs 62 years), were more likely to have malignancy (72% vs 53%), were more likely to be admitted to the medical department rather than the surgical department (93% vs 80%), had longer intervals from admission to MET activation (median, 7 vs 5 days), and were less likely to activate the MET during nighttime hours (5 PM to 8 AM) (61% vs 66%) compared with those who did not die within 28 days (P < 0.001 for all comparisons). The areas under the receiver operating characteristic curves of MEWS and NEWS for 28-day mortality were 0.58 (95% CI, 0.56-0.59) and 0.60 (95% CI, 0.59-0.62), which were inferior to that of the logistics regression model (0.73; 95% CI, 0.72-0.74; P < 0.001 for both comparisons). CONCLUSIONS: Both the MEWS and NEWS had poor predictive powers for 28-day mortality in patients who activated the MET. A new scoring system is needed to stratify the severity and prognosis of patients who activated the MET.
Assuntos
Escore de Alerta Precoce , Equipe de Respostas Rápidas de Hospitais , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Quartos de Pacientes , Valor Preditivo dos Testes , República da Coreia/epidemiologia , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Vitamin C has shown several beneficial effects on sepsis in preclinical studies. However, clinical data supporting these reports are scarce. This study aimed to evaluate whether adjunctive intravenous vitamin C therapy could reduce hospital mortality in patients with severe sepsis or septic shock requiring mechanical ventilation. METHODS: For this retrospective cohort study, consecutive medical ICU patients with severe sepsis or septic shock requiring mechanical ventilation were included. The study patients were classified into the vitamin C or control groups depending on the administration of intravenous vitamin C (2 g every 8 hours). The primary outcome was hospital mortality. RESULTS: Thirty-five patients in the vitamin C group and 40 patients in the control group were included. The two groups were comparable in regards to the baseline characteristics at ICU admission. The hospital mortality was 46% (16 of 35 patients) in the vitamin C group and 40% (16 of 40 patients) in the control group, showing a statistically nonsignificant difference (P=0.62). The mortality at 90 days after ICU admission (60% vs. 48%) did not significantly differ between groups. The median time to shock reversal was 3 days [interquartile range (IQR), 2 to 5 days] in both groups. The changes in the Sepsis-related Organ Failure Assessment (SOFA) scores during the first 4 ICU days were -1.4±3.3 and -1.4±3.0 in the vitamin C and control groups, respectively. CONCLUSIONS: Adjunctive intravenous vitamin C therapy alone did not reduce hospital mortality in mechanically ventilated patients with severe sepsis or septic shock.
RESUMO
BACKGROUND: Bronchiolitis obliterans syndrome (BOS) can occur after hematopoietic stem cell transplantation (HSCT) and is associated with significant mortality. We investigated the role of forced expiratory volume in one s (FEV1 ) as a prognostic marker in BOS after HSCT. METHODS: Among all patients who underwent HSCT between December 1993 and November 2013 at a tertiary center in South Korea, 1187 patients were enrolled. Patient medical records were retrospectively analyzed to evaluate the prognostic factors associated with survival in these cases. RESULTS: During a median follow-up period of 30.7 months after HSCT, 82 patients (6.9%) were diagnosed with BOS. The mean FEV1 of the BOS patients was 34.7% of predicted, and the mean FEV1 of 31 of these patients (37.8%) was <30% of predicted. The estimated overall survival rate for BOS patients excluding three patients who received lung transplantation was 74% at three yr from BOS diagnosis. Multivariate analysis showed that diagnosis of BOS within six months and FEV1 < 30% of predicted at the time of BOS diagnosis were associated with shorter survival. CONCLUSIONS: An FEV1 < 30% of predicted at the time of diagnosis is significantly associated with an increased risk of death in patients with BOS after HSCT.