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Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS-associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013-September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality-related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42-day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42-day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non-antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826-0.884) and 0.778 (95% CI: 0.702-0.854) for SAPA onset and 42-day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14-day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS-endemic areas is crucial, with effective predictive tool.
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Aspergilose Pulmonar Invasiva , Febre Grave com Síndrome de Trombocitopenia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Aspergilose Pulmonar Invasiva/mortalidade , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Febre Grave com Síndrome de Trombocitopenia/complicações , Idoso , China/epidemiologia , AdultoRESUMO
Impairment of innate immune cell function and metabolism underlies immunosuppression in sepsis; however, a promising therapy to orchestrate this impairment is currently lacking. In this study, high levels of NOD-like receptor family CARD domain containing-3 (NLRC3) correlated with the glycolytic defects of monocytes/macrophages from septic patients and mice that developed immunosuppression. Myeloid-specific NLRC3 deletion improved macrophage glycolysis and sepsis-induced immunosuppression. Mechanistically, NLRC3 inhibits nuclear factor (NF)-κB p65 binding to nuclear factor of activated T cells 5 (NFAT5), which further controls the expression of glycolytic genes and proinflammatory cytokines of immunosuppressive macrophages. This is achieved by decreasing NF-κB activation-co-induced by TNF-receptor-associated factor 6 (TRAF6) or mammalian target of rapamycin (mTOR)-and decreasing transcriptional co-activator p300 activity by inducing NLRC3 sequestration of mTOR and p300. Genetic inhibition of NLRC3 disrupted the NLRC3-mTOR-p300 complex and enhanced NF-κB binding to the NFAT5 promoter in concert with p300. Furthermore, intrapulmonary delivery of recombinant adeno-associated virus harboring a macrophage-specific NLRC3 deletion vector significantly improved the defense of septic mice that developed immunosuppression upon secondary intratracheal bacterial challenge. Collectively, these findings indicate that NLRC3 mediates critical aspects of innate immunity that contribute to an immunocompromised state during sepsis and identify potential therapeutic targets.
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Tolerância Imunológica , Peptídeos e Proteínas de Sinalização Intercelular , Macrófagos , NF-kappa B , Sepse , Fatores de Transcrição , Animais , Camundongos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Macrófagos/imunologia , NF-kappa B/metabolismo , Sepse/imunologia , Sepse/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Hospedeiro ImunocomprometidoRESUMO
OBJECTIVE: To compare the efficacy and safety of remimazolam besylate and propofol for deep sedation in critically ill patients. METHODS: In this single-center, prospective, randomized, controlled pilot study, patients in the intensive care unit (ICU) requiring deep sedation were randomized to receive remimazolam besylate or propofol intravenously. Deep sedation was defined as a Richmond Agitation and Sedation Scale (RASS) score of - 4 or - 5. Sedation depth was monitored using RASS and Narcotrend Index (NI). The primary outcome was the percentage of time within the target sedation range without rescue sedation. The secondary outcomes included ventilator-free hours within 7 days, successful extubation, length of ICU stay, and 28-day mortality. Adverse events during the interventional period were also recorded. RESULTS: Thirty patients were assigned to each group. The median (IQR) RASS score was - 5.0 (- 5.0, - 4.0), and the median (IQR) NI value was 29.0 (21.0, 37.0) during the intervention period. Target RASS was reached a median of 100% of the sedation time in the two groups. No significant differences were observed in ventilator-free hours within 7 days, successful extubation, length of ICU stay, or 28-day mortality among groups. Hypotension occurred in 16 (53.3%) patients of remimazolam group and 18 (60.0%) patients of propofol group (p > 0.05). No patient experienced bradycardia. CONCLUSIONS: Remimazolam besylate appears to be an effective and safe agent for short-term deep sedation in critically ill patients. Our findings warrant large sample-sized randomized clinical trials.
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Sedação Profunda , Propofol , Humanos , Estado Terminal/terapia , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Projetos Piloto , Propofol/farmacologia , Propofol/uso terapêutico , Estudos Prospectivos , Respiração ArtificialRESUMO
OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of remimazolam besylate compared with propofol in maintaining mild-to-moderate sedation in patients receiving long-term mechanical ventilation. METHODS: In this single-centered randomized pilot study, adult patients mechanically ventilated longer than 24 h were randomized to receive remimazolam besylate or propofol. The target sedation range was - 3 to 0 on the Richmond Agitation and Sedation Scale (RASS). The primary outcome was the percentage of time in the target sedation range without rescue sedation. The secondary outcomes were ventilator-free days at day 7, the length of ICU stay and 28-day mortality. RESULTS: Thirty patients were assigned to each group. No difference was identified between the remimazolam group and propofol group in median age [60.0 (IQR, 51.5-66.3) years vs. 64.0 (IQR, 55.0-69.3) years, respectively, p = 0.437] or the median duration of study drug infusion [55.0 (IQR, 28.3-102.0) hours vs. 41.0 (IQR, 24.8-74.3) hours, respectively, p = 0.255]. The median percentage of time in the target RASS range without rescue sedation was similar in remimazolam and propofol groups [73.2% (IQR, 41.5-97.3%) vs. 82.8% (IQR, 65.6-100%), p = 0.269]. No differences were identified between the two groups in terms of ventilator-free days at day 7, length of ICU stay, 28-day mortality or adverse events. CONCLUSIONS: This pilot study suggested that remimazolam besylate was effective and safe for long-term sedation in mechanically ventilated patients compared with propofol.
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Propofol , Adulto , Idoso , Benzodiazepinas , Humanos , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Pessoa de Meia-Idade , Projetos Piloto , Propofol/efeitos adversos , Respiração ArtificialRESUMO
COVID-19 has inflicted the world for over two years. The recent mutant virus strains pose greater challenges to disease prevention and treatment. COVID-19 can cause acute respiratory distress syndrome (ARDS) and extrapulmonary injury. Dynamic monitoring of each patient's condition is necessary to timely tailor treatments, improve prognosis and reduce mortality. Point-of-care ultrasound (POCUS) is broadly used in patients with ARDS. POCUS is recommended to be performed regularly in COVID-19 patients for respiratory failure management. In this review, we summarized the ultrasound characteristics of COVID-19 patients, mainly focusing on lung ultrasound and echocardiography. Furthermore, we also provided the experience of using POCUS to manage COVID-19-related ARDS.
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COVID-19/diagnóstico por imagem , Ecocardiografia , Pulmão/diagnóstico por imagem , Testes Imediatos , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Terapia Respiratória/métodos , COVID-19/terapia , Humanos , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/virologiaRESUMO
BACKGROUND: Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI). METHODS: Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI. RESULTS: We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future. CONCLUSIONS: Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.
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Injúria Renal Aguda/genética , Choque Séptico/genética , Biomarcadores , Estudos de Casos e Controles , Biologia Computacional , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Mapas de Interação de ProteínasRESUMO
BACKGROUND: CD4+CD25+FoxP3+ T helper cells (Tregs), a subgroup of CD4+ T helper cells, are critical effectors that protect against acute lung injury (ALI) by contact-dependent suppression or releasing anti-inflammatory cytokines including interleukin-10 (IL-10), and transforming growth factor (TGF-ß). HMGB1 (High mobility group box 1 protein) was identified as a nuclear non-histone DNA-binding chromosomal protein, which participates in the regulation of lung inflammatory response and pathological processes in ALI. Previous studies have suggested that Tregs overexpresses the HMGB1-recognizing receptor. However, the interaction of HMGB1 with Tregs in ALI is still unclear. OBJECTIVE: To investigate whether HMGB1 aggravates ALI by suppressing immunosuppressive function of Tregs. METHODS: Anti-HMGB1 antibody and recombinant mouse HMGB1 (rHMGB1) were administered in lipopolysaccharide (LPS)-induced ALI mice and polarized LPS-primed Tregs in vitro. The Tregs pre-stimulated with or without rHMGB1 were adoptively transferred to ALI mice and depleted by Diphtheria toxin (DT). For coculture experiment, isolated Tregs were first pre-stimulated with or without rHMGB1 or anti-HMGB1 antibody, then they were cocultured with bone marrow-derived macrophages (BMMs) under LPS stimulation. RESULTS: Tregs protected against acute lung pathological injury. HMGB1 modulated the suppressive function of Tregs as follows: reduction in the number of the cells and the activity of Tregs, the secretion of anti-inflammatory cytokines (IL-10, TGF-ß) from Tregs, the production of IL-2 from CD4+ T cells and CD11c+ DCs, and the M2 polarization of macrophages, as well as inducing proinflammatory response of macrophages. CONCLUSIONS: HMGB1 could aggravate LPS induced-ALI through suppressing the activity and function of Tregs.
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Lesão Pulmonar Aguda/imunologia , Proteína HMGB1/imunologia , Linfócitos T Reguladores/imunologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Proteína HMGB1/metabolismo , Proteína HMGB1/fisiologia , Interleucina-10/imunologia , Lipopolissacarídeos/farmacologia , Pulmão/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/metabolismoAssuntos
Relação Dose-Resposta a Droga , Hipnóticos e Sedativos , Unidades de Terapia Intensiva , Propofol , Humanos , Propofol/administração & dosagem , Propofol/efeitos adversos , Propofol/análogos & derivados , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Adulto , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Sedação Consciente/métodos , Sedação Consciente/efeitos adversosAssuntos
Infecções por Coronavirus/fisiopatologia , Linfócitos/citologia , Linfopenia/virologia , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Betacoronavirus , COVID-19 , Estudos de Casos e Controles , China , Infecções por Coronavirus/sangue , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , SARS-CoV-2RESUMO
BACKGROUND: Early goal-directed therapy (EGDT) is used to reduce mortality from septic shock and could be used in early fluid resuscitation of acute respiratory distress syndrome (ARDS). The aim of the present study was to assess the effects of restrictive (RFR) and nonrestrictive fluid resuscitation (NRFR) on hemodynamics, oxygenation, pulmonary function, tissue perfusion, and inflammation in piglets with pulmonary or extrapulmonary ARDS (ARDSp and ARDSexp). MATERIAL AND METHODS: Chinese miniature piglets (6-8 weeks; 15 ± 1 kg) were randomly divided into 2 groups (n=12/group) for establishing ARDSp and ARDSexp models, and were further divided into 2 subgroups (n=6/subgroup) for performing RFR and NRFR. Piglets were anesthetized and hemodynamic, pulmonary, and oxygenation indicators were collected at different time points for 6 hours. The goal of EGDT was set for PiCCO parameters (mean arterial pressure (MAP), urine output and cardiac index (CI), and central venous oxygen saturation (ScvO2). RESULTS: Piglets under RFR had lower urine output compared with NRFR, as well as lower total fluid volume (P<0.05). EVLW was decreased in ARDSp+RFR and NRFR, as well as in ARDSexp+RFR, but EVLW increased in ARDSexp+NRFR (P<0.05). PaO2/FiO2 decreased in ARDSp using both methods, but was higher with RFR (P<0.05), and was increased in ARDSexp+RFR. Other pulmonary indicators were comparable. The anti-inflammatory cytokines IL-10 and LXA4 were increased in ARDSexp after RFR (P<0.05), but not in the other groups. CONCLUSIONS: RFR led to better oxygenation in ARDSp and ARDSexp compared with NRFR, but fluid restriction improved oxygenation in ARDSexp only.
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Hidratação , Oxigênio/sangue , Síndrome do Desconforto Respiratório/terapia , Animais , Modelos Animais de Doenças , Síndrome do Desconforto Respiratório/fisiopatologia , Suínos , Porco MiniaturaRESUMO
Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan-Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan-Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09), P < 0.001]. The relationship between log2-PIV and 28-day mortality was non-linear with a predicted inflection point at 8. To the right of the inflection point, high log2-PIV was associated with an increased 28-day mortality risk [HR (95% CI) 1.13 (1.09, 1.18), P < 0.001]. However, to the left of this point, this association was non-significant [HR (95% CI) 1.01 (0.94, 1.08), P = 0.791]. Similar results were found for 90-day mortality. Our study showed a non-linear relationship between PIV and 28-day and 90-day mortality risk in septic patients.
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Sepse , Humanos , Sepse/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Prognóstico , Inflamação/mortalidade , Estimativa de Kaplan-Meier , Biomarcadores , Unidades de Terapia Intensiva , Modelos de Riscos ProporcionaisRESUMO
STUDY OBJECTIVE: Fospropofol disodium is a propofol prodrug that is water-soluble and has a reduced risk of bacterial contamination and hypertriglyceridemia compared with propofol. Prior to implementing a large randomized trial, we investigated the feasibility, initial efficacy, and safety of fospropofol disodium compared with propofol in long-term mild-to-moderate sedation in intensive care units (ICUs). DESIGN: Single-centered, prospective, unblind, randomized, parallel-group clinical trial. SETTING: The general ICU of university-affiliated teaching hospital. PATIENTS: Adult patients (n = 60) expected to have mechanical ventilation for >24 h were enrolled and randomly assigned to the fospropofol or propofol group. INTERVENTIONS: The fospropofol group received continuous fospropofol disodium infusions and the propofol group received continuous propofol infusions. The sedation goal was a score of -3 to 0 on the Richmond Agitation and Sedation Scale (RASS). MEASUREMENTS: The primary outcome was the percentage of time spent in the target sedation range without rescue sedation. Safety outcomes were based on adverse events. Blood samples were collected to measure formate concentration in plasma. MAIN RESULTS: The median dose was 4.33 (IQR, 3.08-4.94) mg/kg/h in the fospropofol group and 1.96 (IQR, 1.44-2.94) mg/kg/h in the propofol group. The median percentage of time spent in the target RASS range without rescue sedation was identical in both groups, with 83.33% (IQR, 74.43%-100.00%) in the fospropofol group and 83.33% (IQR, 77.45%-100.00%) in the propofol group (p = 0.887). At least one adverse event was identifed in 23 (76.7%) fospropofol patients and 27 (90.0%) propofol patients. The most common adverse events were tachycardia and hypotension. No paresthesia, catheter-related bloodstream infection or propofol infusion syndrome in both groups was reported. Three patients in the fospropofol group had mild hypertriglyceridemia, and nine patients in propofol group had hypertriglyceridemia (mild in eight patients and moderate in one patient) (10% versus 30%, p = 0.104). The formate concentration in plasma was very low, and no significant difference was identified at any time point between the two groups. CONCLUSIONS: Fospropofol disodium appears to be a feasible, effective and safe sedative for patients receiving invasive mechanical ventilation with long-term sedation.
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Hipnóticos e Sedativos , Propofol , Propofol/análogos & derivados , Respiração Artificial , Humanos , Propofol/administração & dosagem , Propofol/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Projetos Piloto , Respiração Artificial/efeitos adversos , Estudos Prospectivos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Idoso , Unidades de Terapia Intensiva , Estudos de Viabilidade , Adulto , Sedação Consciente/métodos , Sedação Consciente/efeitos adversos , Infusões Intravenosas , Pró-Fármacos/administração & dosagem , Pró-Fármacos/efeitos adversosRESUMO
Sepsis is identified as a potentially lethal organ impairment triggered by an inadequate host reaction to infection (Sepsis-3). Viral sepsis is a potentially deadly organ impairment state caused by the host's inappropriate reaction to a viral infection. However, when a viral infection occurs, the metabolism of the infected cell undergoes a variety of changes that cause the host to respond to the infection. But, until now, little has been known about the challenges faced by cellular metabolic alterations that occur during viral infection and how these changes modulate infection. This study concentrates on the alterations in glucose metabolism during viral sepsis and their impact on viral infection, with a view to exploring new potential therapeutic targets for viral sepsis.
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Glucose , Sepse , Humanos , Glucose/metabolismo , Viremia , Metabolismo dos CarboidratosRESUMO
After aversive stress, people either choose to return to their previously familiar social environment or tend to adopt temporary social withdrawal to buffer negative emotions. However, which behavior intervention is more appropriate and when remain elusive. Here, we unexpectedly found that stressed mice experiencing social isolation exhibited less anxiety than those experiencing social contact. Within the first 24 h after returning to their previous social environment, mice experienced acute restraint stress (ARS) displayed low social interest but simultaneously received excessive social disturbance from their cage mates, indicating a critical time window for social isolation to balance the conflict. To screen brain regions that were differentially activated between the poststress social isolation and poststress social contact groups, we performed ΔFosB immunostaining and found that ΔFosB + signals were remarkably increased in the vDG of poststress social isolation group compared with poststress social contact group. There were no significant differences between the two groups in the other anxiety- and social-related brain regions, such as prelimbic cortex, infralimbic cortex, nucleus accumbens, etc. These data indicate that vDG is closely related to the differential phenotypes between the poststress social isolation and poststress social contact groups. Electrophysiological recording, further, revealed a higher activity of vDG in the poststress social isolation group than the poststress social contact group. Chemogenetically inhibiting vDG excitatory neurons within the first 24 h after ARS completely abolished the anxiolytic effects of poststress social isolation, while stimulating vDG excitatory neurons remarkably reduced anxiety-like behaviors in the poststress social contact group. Together, these data suggest that the activity of vDG excitatory neurons is essential and sufficient to govern the anxiolytic effect of poststress social isolation. To the best of our knowledge, this is the first report to uncover a beneficial role of temporal social isolation in acute stress-induced anxiety. In addition to the critical 24-h time window, activation of vDG is crucial for ameliorating anxiety through poststress social isolation.
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INTRODUCTION: Pulmonary fibrosis is a major cause of the poor prognosis of acute respiratory distress syndrome (ARDS). While mechanical ventilation (MV) is an indispensable life-saving intervention for ARDS, it may cause the remodeling process in lung epithelial cells to become disorganized and exacerbate ARDS-associated pulmonary fibrosis. Piezo1 is a mechanosensitive ion channel that is known to play a role in regulating diverse physiological processes, but whether Piezo1 is necessary for MV-exacerbated ARDS-associated pulmonary fibrosis remains unknown. OBJECTIVES: This study aimed to explore the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. METHODS: Human lung epithelial cells were stimulated with hydrochloric acid (HCl) followed by mechanical stretch for 48 h. A two-hitmodel of MV afteracidaspiration-inducedlunginjuryin mice was used. Mice were sacrificed after 14 days of MV. Pharmacological inhibition and knockout of Piezo1 were used to delineate the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. In some experiments, ATP or the ATP-hydrolyzing enzyme apyrase was administered. RESULTS: The stimulation of human lung epithelial cells to HCl resulted in phenotypes of epithelial-mesenchymal transition (EMT), which were enhanced by mechanical stretching. MV exacerbated pulmonary fibrosis in mice exposed to HCl. Pharmacologicalinhibitionorknockout of Piezo1 attenuated the MV-exacerbated EMT process and lung fibrosis in vivo and in vitro. Mechanistically, the observed effects were mediated by Piezo1-dependent Ca2+ influx and ATP release in lung epithelial cells. CONCLUSIONS: Our findings identify a key role for Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis that is mediated by increased ATP release in lung epithelial cells. Inhibiting Piezo1 may constitute a novelstrategyfor the treatment of MV-exacerbated ARDS-associated pulmonary fibrosis.
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Fibrose Pulmonar , Síndrome do Desconforto Respiratório , Camundongos , Humanos , Animais , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório/complicações , Canais Iônicos , Trifosfato de AdenosinaRESUMO
Contrast-induced encephalopathy (CIE) is an uncommon complication associated with contrast exposure during angiographic procedures that is usually transient but occasionally leads to permanent complications or death. Due to the low incidence of CIE, there are still insufficient reports. This study was used to summarize the clinical features of CIE through a case report and systematic review. We summarized and reviewed 127 patients with CIE, and we found that the total incidence of CIE between men and women had no difference (49.61 and 50.39%, respectively), but the average age in female patients with CIE was older than that in male patients (62.19 and 58.77 years, respectively). Interestingly, the incidence of female patients with CIE in the poor prognosis group was significantly higher than that in the good prognosis group (62.50 and 36.51%, respectively), and the average age of these female patients in the poor prognosis group was younger than that in the good prognosis group (61.39 and 62.82 years, respectively). The contrast medium types were mainly nonionic (79.69 and 73.02%, respectively) and low-osmolar (54.69 and 71.43%, respectively) in both groups. Importantly, the total contrast media administrated in patients with poor prognoses was greater than that administrated in patients with good prognoses (198.07 and 188.60 ml, respectively). In addition, comorbidities in both groups included hypertension (55.91%), diabetes mellitus (20.47%), previous contrast history (15.75%), renal impairment (11.81%), and hyperlipidemia (3.15%). The percentage of patients with cerebral angiography was significantly higher in the poor prognosis group than that in the good prognosis group (37.50 and 9.52%, respectively), whereas the percentage of patients with coronary angiography in both groups had the opposite results (35.94 and 77.78%, respectively). In conclusion, CIE may not always have a benign outcome and can cause permanent deficits. Female gender, younger age, the higher dose of contrast medium, and the procedure of cerebral angiography may be related to the patient's poor prognosis.
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Dysregulated host response to infection, which cause life-threatening organ dysfunction, was defined as sepsis. Sepsis can cause acute and long-term brain dysfunction, namely, sepsis-associated encephalopathy (SAE) and cognitive impairment. SAE refers to changes in consciousness without direct evidence of central nervous system infection. It is highly prevalent and may cause poor outcomes in sepsis patients. Cognitive impairment seriously affects the life quality of sepsis patients and increases the medical burden. The pathogenesis of sepsis-induced brain dysfunction is mainly characterized by the interaction of systemic inflammation, blood-brain barrier (BBB) dysfunction, neuroinflammation, microcirculation dysfunction, and brain dysfunction. Currently, the diagnosis of sepsis-induced brain dysfunction is based on clinical manifestation of altered consciousness along with neuropathological examination, and the treatment is mainly involves controlling sepsis. Although treatments for sepsis-induced brain dysfunction have been tested in animals, clinical treat sepsis-induced brain dysfunction is still difficult. Therefore, we review the underlying mechanisms of sepsis-induced brain injury, which mainly focus on the influence of systemic inflammation on BBB, neuroinflammation, brain microcirculation, and the brain function, which want to bring new mechanism-based directions for future basic and clinical research aimed at preventing or ameliorating brain dysfunction.
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Lesões Encefálicas , Encefalopatia Associada a Sepse , Sepse , Animais , Encéfalo/patologia , Lesões Encefálicas/complicações , Inflamação/patologia , Sepse/complicações , Sepse/diagnóstico , Sepse/tratamento farmacológico , Encefalopatia Associada a Sepse/complicações , Encefalopatia Associada a Sepse/diagnóstico , Encefalopatia Associada a Sepse/terapiaRESUMO
BACKGROUND: Acute respiratory distress syndrome (ARDS), a prevalent cause of admittance to intensive care units, is associated with high mortality. Prone positioning has been proven to improve the outcomes of moderate to severe ARDS patients owing to its physiological effects. Venovenous extracorporeal membrane oxygenation (VV ECMO) will be considered in patients with severe hypoxemia. However, for patients with severe hypoxemia supported with VV ECMO, the potential effects and optimal strategies of prone positioning remain unclear. This review aimed to present these controversial questions and highlight directions for future research. MAIN BODY: The clinically significant benefit of prone positioning and early VV ECMO alone was confirmed in patients with severe ARDS. However, a number of questions regarding the combination of VV ECMO and prone positioning remain unanswered. We discussed the potential effects of prone positioning on gas exchange, respiratory mechanics, hemodynamics, and outcomes. Strategies to achieve optimal outcomes, including indications, timing, duration, and frequency of prone positioning, as well as the management of respiratory drive during prone positioning sessions in ARDS patients receiving VV ECMO, are challenging and controversial. Additionally, whether and how to implement prone positioning according to ARDS phenotypes should be evaluated. Lung morphology monitored by computed tomography, lung ultrasound, or electrical impedance tomography might be a potential indication to make an individualized plan for prone positioning therapy in patients supported with VV ECMO. CONCLUSION: For patients with ARDS supported with VV ECMO, the potential effects of prone positioning have yet to be clarified. Ensuring an optimal strategy, especially an individualized plan for prone positioning therapy during VV ECMO, is particularly challenging and requires further research.
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INTRODUCTION: Remimazolam is a novel and ultra-short-acting benzodiazepine currently approved for procedural sedation and induction of general anaesthesia, with a possible indication for ICU sedation. This study aimed to evaluate the efficacy and safety of remimazolam and traditional sedatives for patients undergoing procedural sedation. EVIDENCE ACQUISITION: We systematically searched Cochrane Library, Embase, PubMed, Web of Science and ClinicalTrials.gov for randomized controlled trials of procedural sedation performed with remimazolam versus traditional sedatives. Data from the eligible studies were combined to calculate pooled risk ratio or standardized mean difference. EVIDENCE SYNTHESIS: Eleven studies of 2356 patients met the inclusion criteria. The results showed that remimazolam was associated with a higher procedure success rate (RR: 1.28, 95% CI: 1.07 to 1.52, P=0.006; I2=99%), a shorter duration of recovery after procedure (SMD: -0.56, 95% CI: -0.98, -0.14, P=0.009; I2=89%), and an earlier patient discharge after procedure (SMD: -0.37, 95% CI: -0.49, -0.25, P<0.00001; I2=0%) in comparison with traditional sedatives. There were no statistically significant differences in onset time, procedure time, and cognitive recovery between remimazolam and traditional sedatives groups. Remimazolam significantly decreased the rate of bradycardia (RR: 0.65, 95% CI: 0.43, 0.97, P=0.04; I2=0%), hypotension (RR: 0.57, 95% CI: 0.40, 0.80, P=0.001; I2=80%), and respiratory depression/hypoxia (RR: 0.46, 95% CI: 0.25, 0.83, P=0.01; I2=61%) compared to traditional sedatives. CONCLUSIONS: Remimazolam is a safe and effective sedative for procedural sedation on account of a higher success procedure rate, a faster recovery, a shorter discharge time, and a superior safety profile in comparison with traditional sedatives. Larger sample-sized and well-designed clinical trials are needed to verify our finding.
Assuntos
Sedação Consciente , Hipnóticos e Sedativos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Sedação Consciente/métodos , Benzodiazepinas/efeitos adversos , Anestesia GeralRESUMO
Intensive care unit (ICU)-acquired infection is a common cause of poor prognosis of sepsis in the ICU. However, sepsis-associated ICU-acquired infections have not been fully characterized. The study aims to assess the risk factors and develop a model that predicts the risk of ICU-acquired infections in patients with sepsis. Methods: We retrieved data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients were randomly divided into training and validation cohorts at a 7:3 ratio. A multivariable logistic regression model was used to identify independent risk factors that could predict ICU-acquired infection. We also assessed its discrimination and calibration abilities and compared them with classical score systems. Results: Of 16,808 included septic patients, 2,871 (17.1%) developed ICU-acquired infection. These patients with ICU-acquired infection had a 17.7% ICU mortality and 31.8% in-hospital mortality and showed a continued rise in mortality from 28 to 100 days after ICU admission. The classical Systemic Inflammatory Response Syndrome Score (SIRS), Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Charlson Comorbidity Index (CCI), and Acute Physiology Score III (APS III) scores were associated with ICU-acquired infection, and cerebrovascular insufficiency, Gram-negative bacteria, surgical ICU, tracheostomy, central venous catheter, urinary catheter, mechanical ventilation, red blood cell (RBC) transfusion, LODS score and anticoagulant therapy were independent predictors of developing ICU-acquired infection in septic patients. The nomogram on the basis of these independent predictors showed good calibration and discrimination in both the derivation (AUROC = 0.737; 95% CI, 0.725-0.749) and validation (AUROC = 0.751; 95% CI, 0.734-0.769) populations and was superior to that of SIRS, SOFA, OASIS, SAPS II, LODS, CCI, and APS III models. Conclusions: ICU-acquired infections increase the likelihood of septic mortality. The individualized prognostic model on the basis of the nomogram could accurately predict ICU-acquired infection and optimize management or tailored therapy.