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BACKGROUND: Red blood cell distribution width (RDW) is related to sepsis-related mortality. Hemophagocytic lymphohistiocytosis (HLH) is a syndrome caused by severe infection, tumors, or autoimmunity without a specific diagnosis. OBJECTIVE: To explore the correlation between RDW and mortality in patients with HLH. DESIGN AND SETTING: A retrospective study conducted in a hospital in China. METHODS: A total of 101 inpatients with HLH from January 1, 2017 to December 31, 2021 were divided into non-survivor (n = 52) and survivor (n = 49) groups. A non-parametric test was used to analyze demographic, clinical, and laboratory data between groups. Independent variables with P < 0.05 were analyzed using binary logistic regression to screen out mortality-related variables. Selected variables were subjected to multivariate logistic regression analysis, and those with strong correlations were screened. Receiver operating characteristic (ROC) curves of strongly correlated variables and area under curve (AUC) values were obtained. RESULTS: The APACHE II score, RDW, and platelet (PLT) and fibrinogen (FIB) levels (P < 0.05) different significantly. RDW, PLT, FIB were correlated with mortality. The AUC values of RDW, PLT, and FIB were 0.857, 0.797, and 0.726, respectively. RDW was associated with mortality in patients with HLH (P < 0.01, cut-off value: 16.9). The sensitivity and specificity of predicting mortality were 97.96% and 96.1%, respectively. CONCLUSION: Logistic regression analysis showed a correlation between RDW and patients' mortality. Therefore, RDW can be used to predict mortality in patients with HLH.
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Linfo-Histiocitose Hemofagocítica , Sepse , Humanos , Estudos Retrospectivos , Índices de Eritrócitos , Curva ROC , Prognóstico , EritrócitosRESUMO
ABSTRACT BACKGROUND: Red blood cell distribution width (RDW) is related to sepsis-related mortality. Hemophagocytic lymphohistiocytosis (HLH) is a syndrome caused by severe infection, tumors, or autoimmunity without a specific diagnosis. OBJECTIVE: To explore the correlation between RDW and mortality in patients with HLH. DESIGN AND SETTING: A retrospective study conducted in a hospital in China. METHODS: A total of 101 inpatients with HLH from January 1, 2017 to December 31, 2021 were divided into non-survivor (n = 52) and survivor (n = 49) groups. A non-parametric test was used to analyze demographic, clinical, and laboratory data between groups. Independent variables with P < 0.05 were analyzed using binary logistic regression to screen out mortality-related variables. Selected variables were subjected to multivariate logistic regression analysis, and those with strong correlations were screened. Receiver operating characteristic (ROC) curves of strongly correlated variables and area under curve (AUC) values were obtained. RESULTS: The APACHE II score, RDW, and platelet (PLT) and fibrinogen (FIB) levels (P < 0.05) different significantly. RDW, PLT, FIB were correlated with mortality. The AUC values of RDW, PLT, and FIB were 0.857, 0.797, and 0.726, respectively. RDW was associated with mortality in patients with HLH (P < 0.01, cut-off value: 16.9). The sensitivity and specificity of predicting mortality were 97.96% and 96.1%, respectively. CONCLUSION: Logistic regression analysis showed a correlation between RDW and patients' mortality. Therefore, RDW can be used to predict mortality in patients with HLH.
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BACKGROUND: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. METHODS: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. RESULTS: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups. CONCLUSIONS: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. TRIAL REGISTRATION: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.
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Estado Terminal , Apoio Nutricional , China , Estado Terminal/terapia , Humanos , Unidades de Terapia Intensiva , Fatores de TempoRESUMO
A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.
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COVID-19/imunologia , SARS-CoV-2/fisiologia , Idoso , Autopsia , COVID-19/diagnóstico , COVID-19/genética , COVID-19/virologia , China , Diagnóstico , Feminino , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Terapia de Imunossupressão , Ativação Linfocitária , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Células Mieloides/imunologia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , SARS-CoV-2/imunologia , Carga ViralRESUMO
BACKGROUND: Gas gangrene is usually manifested as myonecrosis and subcutaneous gas accumulation, but rarely manifested as arterial occlusion or pneumatosis in the right ventricle and the pulmonary artery. CASE PRESENTATION: We report a case of gas gangrene caused by Clostridium septicum. The patient developed gas gangrene after being pecked by a chicken but turned for the better following antibiotic treatment and debriment. Imaging test revealed a rare occlusion of the right femoral artery and pneumatosis in the right ventricle and the main pulmonary artery. CONCLUSIONS: In the presence of gas gangrene, special care must be taken to prevent against the formation of circulatory air embolism. The gas gangrene-induced gangrene in the limb of this patient might be attributed to the combined action of infection and arterial occlusion. MDT (Multidisciplinary team)-Green Channel mode is conductive to treatment success of gas gangrene.
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Clostridium septicum , Gangrena Gasosa , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/cirurgia , Gangrena/etiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Extremidade Inferior , Artéria Pulmonar/diagnóstico por imagemRESUMO
Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.
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COVID-19/patologia , Pulmão/virologia , SARS-CoV-2/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Autopsia , COVID-19/virologia , China , Estudos de Coortes , Estado Terminal , Feminino , Fibrose , Hospitalização , Humanos , Rim/patologia , Rim/virologia , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/virologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , RNA Viral/metabolismo , SARS-CoV-2/genética , Baço/patologia , Baço/virologia , Traqueia/patologia , Traqueia/virologiaRESUMO
OBJECTIVE: This study is the largest clinical study of noninvasive Abdominal wall tension (AWT) measurement with a tensiometer to date. It also initially applies a polynomial regression equation to analyze the correlation between AWT measurement and intravesical pressure (IVP) measurement and remarkably finds interesting changes between different IVP intervals and AWT. METHODS: Critically ill patients who were treated in the intensive care unit (ICU) of Daping Hospital, Army Medical University, from August 30, 2018, to June 30, 2020, and met the inclusion criteria were prospectively included in this study. The patients were divided into an intra-abdominal hypertension group and a non-intra-abdominal hypertension group and an abdominal infection group and no abdominal infection group. AWT and IVP were measured at 9 points on the abdominal wall on the first day after admission to the ICU. The correlations between AWTs and IVP were analyzed, and the role of AWT in the diagnosis of complications of abdominal infection and the prediction of adverse prognosis were analyzed. RESULTS: A total of 127 patients were included. The average AWT and IVP were 2.77±0.38 N/mm and 12.31±7.01 mmHg, respectively, on the first day of admission. There was a positive correlation between AWT and IVP (correlation coefficient r = 0.706, p < 0.05). The polynomial regression model was AWT= -1.616×10-3 IVP2 +8.323×10-2 IVP+2.094. The cutoff value of the sensitivity and specificity of AWT for the diagnosis of abdominal infection was 2.57 N/mm. Furthermore, AWT = 2.57 N/mm had the best diagnostic efficiency, which was better than that of IAH and lactate. CONCLUSION: There was a correlation between AWT and IVP. AWT measurement was helpful in the diagnosis of IAH and abdominal infection complications and can therefore serve as a new method for the clinical diagnosis of IVP and abdominal infection.
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OBJECTIVE: To determine the association of post-traumatic acute respiratory distress syndrome (ARDS) on poor prognosis, and provide a theoretical basis for the treatment of patients with post-traumatic ARDS in clinical practice. Methods: This was a retrospective study including trauma victims in the intensive care unit (ICU) of Daping Hospital. The patients were classified as having ARDS or non-ARDS, according to the Berlin definition. Subsequently, these patients were divided into subgroups, according to age, gender and injury site. The relationship between ARDS and prognosis was analyzed, including mechanical ventilation days, length of ICU stay, length of hospital stay, infection, sepsis, multiple organ dysfunction syndrome (MODS) and death. RESULTS: There were 507 trauma patients, out of which 287 (56.61%) cases were with ARDS. The duration of mechanical ventilation, ICU stay and hospital stay in the ARDS group was significantly longer than that in the non-ARDS group (5 days vs 3 days, 10 days vs 4 days, 30 days vs 27 days, respectively). In addition, ARDS was associated with an increased risk of nfection (p<0.05; OR=4.17; 95%CI=2.72-6.41), sepsis (p<0.05; OR=3.45; 95%CI=2.28-5.22), and MODS (p<0.05; OR=2.82; 95% CI=1.67-4.72), but had no significant association with mortality (p>0.05). Similar results were found in the subgroup analyses. Conclusion: In conclusion, the prognosis of the patients with post-traumatic ARDS was worse; however, ARDS had little effect on death.
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Síndrome do Desconforto Respiratório , Humanos , Unidades de Terapia Intensiva , Prognóstico , Respiração Artificial , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/etiologia , Estudos RetrospectivosRESUMO
Sepsis, which is characterized by multiple organ dysfunctions as a result of an unbalanced host-inflammatory response to pathogens, is potentially a life-threatening condition and a major cause of death in the intensive care units (ICUs). However, effective treatment or intervention to prevent sepsis-associated lethality is still lacking. Human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation has been shown to have potent immunomodulatory properties and improve tissue repair yet lacks direct antibacterial and endotoxin clearance activities. In this study, we engineered hUC-MSCs to express a broad-spectrum antibacterial fusion peptide containing BPI21 and LL-37 (named BPI21/LL-37) and confirmed that the BPI21/LL-37 modification did not affect the stemness and immunoregulatory capacities of hUC-MSCs but remarkably, enhanced its antibacterial and toxin-neutralizing activities in vitro. Furthermore, we showed that administration of BPI21/LL-37-engineered hUC-MSCs significantly reduces serum levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6, whereas increases that of IL-10 in cecal ligation and puncture (CLP)-induced sepsis mouse model. Administration of BPI21/LL-37-engineered hUC-MSCs significantly reduced systemic endotoxin (lipopolysaccharide [LPS]) levels and organ bacterial load, ameliorated damage to multiple organs, and improved survival. Taken together, our study demonstrates that BPI21/LL-37-engineered hUC-MSCs might offer a novel therapeutic strategy to prevent or treat sepsis via enhanced antimicrobial and anti-inflammatory properties to preserve organ functions better.
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Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Proteínas Recombinantes de Fusão/farmacologia , Sepse/terapia , Cordão Umbilical/citologia , Animais , Terapia Combinada , Modelos Animais de Doenças , Endotoxinas/imunologia , Engenharia Genética , Humanos , Imunomodulação/efeitos dos fármacos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Camundongos , Sepse/etiologia , Sepse/mortalidadeRESUMO
OBJECTIVE: To analyze the risk factors of patients with trauma in intensive care unit (ICU), a new warning scoring system is established for predicting the incidence of sepsis in traumatic patients; and to provide a new simple method of clinical score, which could provide a reference for clinical prevention and treatment of sepsis. METHODS: The clinical data of 591 patients with trauma in the ICU of the Army Specialized Medical Center of Army Medical University and Affiliated Hospital of Zunyi Medical University from January 2012 to December 2017 were retrospectively analyzed. The patients were divided into sepsis group (n = 382) and non-sepsis group (n = 209) according to their clinical outcome. The basic clinical data of all ICU trauma patients were collected, and the differences in gender, age, underlying diseases, and vital signs, critical illness scores, blood culture results and laboratory biochemical examinations within 24 hours of ICU admission between the two groups were analyzed. Univariate Logistic regression analysis was used to screen the related factors leading to sepsis. The indexes with P < 0.12 analyzed by univariate Logistic regression analysis were included in multivariate Logistic regression analysis. The risk factors of sepsis in traumatic patients were screened and assigned, and the total score was sepsis early warning score. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of the warning score of sepsis in patients with trauma. RESULTS: The incidence of sepsis in ICU trauma patients was 64.6% (382/591), and the ICU mortality was 10.5% (40/382). The traffic accident was a common cause of ICU trauma patients. Compared with non-sepsis patients, Glasgow coma score (GCS), proportion of past history, red blood cell (RBC), platelet (PLT), albumin (Alb) were lower in patients with sepsis, and body temperature, pulse, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), injury severity score (ISS), new injury severity score (NISS), fraction of inspired oxygen (FiO2), blood sodium, activated partial thromboplastin time (APTT), prothrombin time (PT), procalcitonin (PCT), C-reactive protein (CRP) levels were higher, blood transfusion, central venous catheterization, mechanical ventilation, shock, multiple organ dysfunction syndrome (MODS), open injury and multiple injuries were more common, the duration of mechanical ventilation, ICU days and total hospital days were longer, and all the differences were statistically significant. Most of the traumatic patients with sepsis were undergone with multiple trauma. Compared with non-sepsis patients, the proportion of multiple position trauma was significantly higher than patients without sepsis. And most traumatic patients were insulted in head, face and neck. The risk factors were screened by univariate and multivariate Logistic stepwise regression analysis, the indexes into the regression model were pulse > 100 bpm [odds ratio (OR) = 1.617, 95% confidence interval (95%CI) = 0.992-2.635, P = 0.044], APTT > 36 s (OR = 2.164, 95%CI = 1.056-4.435, P = 0.035), shock (OR = 1.798, 95%CI = 1.056-3.059, P = 0.031), mechanical ventilation (OR = 5.144, 95%CI = 2.302-11.498, P < 0.001), APACHE II > 21 (OR = 3.348, 95%CI = 1.724-6.502, P < 0.001), NISS > 25 (OR = 3.332, 95%CI = 1.154-9.624, P = 0.026), assigning scores were 0.5, 1.0, 0.5, 1.5, 1.5, 1.5, respectively, which were included in the new warning score of sepsis. ROC curve analysis showed that the area under ROC curve (AUC) of warning score for predicting sepsis in patients with trauma was 0.782, which was significantly higher than the APACHE II (AUC = 0.672), APTT (AUC = 0.574) and NISS (AUC = 0.515) with significant difference (all P < 0.01). When the cut-off value of sepsis warning score was 4.0, the sensitivity and specificity were 71.7% and 61.9%, respectively. CONCLUSIONS: Close monitoring and stabilization of vital signs of traumatic patients within 24 hours of ICU admission and reduction of unreasonable invasive mechanical ventilation time are expected to reduce the incidence of sepsis in traumatic patients. New warning score of sepsis consisted of six factors: pulse, APTT, shock, mechanical ventilation, APACHE II and NISS. Rational use of warning score of sepsis would help us to assess the prognosis of traumatic patients more easily and effectively, and the predicted effect is much better than APACHE II, APTT and NISS.
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Monitorização Fisiológica/métodos , Sepse/diagnóstico , Ferimentos e Lesões/fisiopatologia , APACHE , Humanos , Unidades de Terapia Intensiva , Valor Preditivo dos Testes , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Cardiovascular complications, especially myocardial infarctions (MIs), are the leading mortality cause in diabetic patients. The transplantation of stem cells into damaged hearts has had considerable success as a treatment for MI, although whether antidiabetic drugs affect the therapeutic efficacy of stem cell transplantation is still unknown. This study aims to understand whether and how metformin, one of the first-line drugs used to treat type 2 diabetes mellitus (T2DM), induces mesenchymal stromal cell (MSC) apoptosis and dampens their cardioprotective effect after transplantation into infarcted hearts. METHODS: A mouse MI model was generated via permanent ligation of the left anterior descending (LAD) coronary artery. MSCs with or without metformin treatment were transplanted after MI in diabetic mice. Echocardiography was used to assess cardiac function and determine cardiac remodeling, and TTC staining was performed to evaluate infarction size. A mouse gavage model was performed to evaluate bone marrow MSCs for flow cytometry assay. RESULTS: Metformin dampened MSC therapeutic efficacy, which increased infarct size and restricted functional cardiac recovery. Specifically, metformin induced the activation of AMP-activated protein kinase (AMPK)-mediated apoptosis through the inhibition of S6K1-Bad-Bcl-xL cell survival signaling, resulting in the upregulated expression of apoptosis-associated proteins and increased MSC apoptosis. Accordingly, counteracting AMPK attenuated metformin-induced apoptosis in MSCs and partially restored their cardioprotective effects in diabetic mice with MI. Furthermore, a decrease in peripheral blood MSCs was found in patients with T2DM who had a metformin medication history. CONCLUSIONS: Our results highlight an unexpected adverse effect of metformin-induced MSC apoptosis through AMPK-mediated mTOR suppression, which is attenuated by an AMPK inhibitor. Moreover, AMPK inhibition may be a novel strategy for enhancing the effectiveness of stem cell therapy after MI in diabetes.
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Apoptose/efeitos dos fármacos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Metformina/farmacologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Adenilato Quinase/metabolismo , Animais , Cardiotônicos/metabolismo , Diabetes Mellitus Experimental , Feminino , Humanos , Masculino , Camundongos , Resultado do TratamentoRESUMO
BACKGROUND: There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. METHODS: This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. RESULTS: A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2-19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2-3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353-0.599; p < 0.001). AGI 4 was significantly associated with lower hazard of EN administration (HR 0.056; 95% CI 0.008-0.398; p = 0.004). In a linear regression model, greater Sequential Organ Failure Assessment scores (coefficient - 0.002, 95% CI - 0.008 to - 0.001; p = 0.024) and male gender (coefficient - 0.144, 95% CI - 0.203 to - 0.085; p < 0.001) were found to be associated with lower EN proportion. As compared with AGI 1, AGI 2-3 was associated with lower EN proportion (coefficient - 0.206, 95% CI - 0.273 to - 0.139; p < 0.001). CONCLUSIONS: The study showed that EN delivery was suboptimal in Chinese ICUs. More attention should be paid to EN use in the early days after ICU admission.
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Nutrição Enteral/normas , Resultado do Tratamento , APACHE , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , China , Estudos Transversais , Nutrição Enteral/métodos , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Modelos de Riscos ProporcionaisRESUMO
The aim of this phase 1 clinical trial was to test the safety and feasibility of a single dose of allogeneic umbilical cord-derived mesenchymal stem cells (MSCs) in patients with severe sepsis. This is a single-center, open-label, dose-escalation phase 1 clinical trial of a single dose of intravenous MSCs in patients with severe sepsis. We enrolled 15 patients who averagely divided into low (1â¯×â¯106 cells/kg), intermediate (2â¯×â¯106 cells/kg), and high (3â¯×â¯106 cells/kg) dosing cohorts. Primary outcomes included the incidence of infusion-associated events and serious adverse events. Secondary outcomes included systemic endpoints, mortality, and inflammation biologic markers. A historical case-matched comparison group was set as the control. This study enrolled 15 patients (10 male and 5 female), with a median age of 58. Compared to those in the historical, case-matched group, neither there were infusion-associated serious events or treatment-related adverse events in any of the 15 patients in this trial, nor were there any safety or efficacy signals for serious adverse events or the measured cytokines. A single intravenous infusion of allogeneic MSCs up to a dose of 3â¯×â¯106 cells/kg was safe and well tolerated in 15 patients with severe sepsis.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Sepse/terapia , Cordão Umbilical/citologia , APACHE , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Coortes , Citocinas/sangue , Feminino , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Pessoa de Meia-Idade , Sepse/sangue , Sepse/mortalidade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: To explore the mechanism of the different clinical efficacies of mesenchymal stem cell transplantation (MSCT) and identify a possible serum biomarker for predicting the therapeutic effect of MSCT in rheumatoid arthritis (RA) patients. METHODS: A total of 105 patients with persistently active RA and poor responses to traditional medication were randomly divided into MSCT and control groups. Outcomes were evaluated according to the 28-joint Disease Activity Score and Health Assessment Questionnaire, serological indicators, regulatory T cell (Treg) to T helper 17 (Th17) cell ratio, and inflammatory cytokine levels. Twelve weeks after MSCT, the outcomes of the MSCT group were evaluated according to the European League against Rheumatism response criteria. Patients with a good or moderate response were added to the response group, and those with no response were added to the no-response group. RESULTS: No serious adverse events were reported for either MSCT subgroup (28 in the response group and 24 in the no-response group). The therapeutic effects lasted for 48 weeks without continuous administration. Notably, a transient increase in serum IFN-γ (>2 pg/ml) levels was observed in the response group, but not in the no-response group. Furthermore, an increase in IL-10 levels and the Treg/Th17 ratio and a reduction in IL-6 levels appeared 2-3 weeks after the transient IFN-γ increase. CONCLUSIONS: Allogeneic MSCT is safe and feasible, and we propose high serum IFN-γ levels as a potent biomarker for predicting MSCT response. Trial registration chictr.org, ChiCTR-ONC-16008770. Registered 3 July 2016, http://www.chictr.org.cn/showproj.aspx?proj=14820.
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Artrite Reumatoide/sangue , Artrite Reumatoide/terapia , Interferon gama/sangue , Transplante de Células-Tronco Mesenquimais , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Microambiente Celular , Humanos , Inflamação/sangue , Inflamação/patologiaRESUMO
PURPOSE: To evaluate the effect of retention sutures on abdominal pressure and postoperative prognosis in abdominal surgery patients. METHODS: This prospective cohort study included patients who were admitted to Daping Hospital from May 15, 2014 to October 11, 2014. A total of 57 patients were enrolled, including 18 patients in the "U" type retention suture group, 17 patients in the intermittent retention suture group, and 22 patients in non-retention suture group. The demographic data, clinical data and risk factors for abdominal wound dehiscence were recorded. The bladder pressure (IVP) was monitored preoperatively, intraoperatively, and four days postoperatively. Additionally, the incidence of abdominal wound dehiscence and infection 14 days after the operation was recorded. RESULTS: During the operation, the IVP decreased and then increased; it was at its lowest 1 h after the start of the operation (5.3 mmHg ± 3.2 mmHg) and peaked after tension-reducing (8.8 mmHg ± 4.0 mmHg). The IVP values in the "U" type retention suture group and intermittent retention suture group were higher than in the non-retention suture group 4 days after operation (p < 0.005). The Visual Analogue Scale (VAS) pain scores were 3.9 ± 2.2, 3.8 ± 2.0, and 3.0 ± 1.0 in the retention suture group, intermittent retention suture group and non-retention suture group, respectively. The VAS pain scores in the "U" type tension-reducing group and intermittent tension-reducing group were higher than in the non-tension-reducing group (p < 0.005). CONCLUSION: Although retention sutures may reduce the incidence of postoperative wound dehiscence in abdominal surgery patients, they can increase the IVP and postoperative pain.
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Abdome/cirurgia , Suturas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Complicações Pós-Operatórias/prevenção & controle , PressãoRESUMO
To identify the epidemiology, treatments, outcomes, and risk factors for patients with early- or late-onset invasive candidiasis (EOIC or LOIC) in intensive care units in China.Patients were classified as EOIC (≤10 days) or LOIC (>10 days) according to the time from hospital admission to IC onset to identify distinct clinical characteristics.There were 105 EOIC cases and 201 LOIC cases in this study. EOIC was related to more severe clinical conditions at ICU admission or prior to IC. Significantly, more cases of Candida parapsilosis infection were found in patients with LOIC than in those with EOIC. The mortality of EOIC was significantly lower than that for LOIC. Sequential Organ Failure Assessment (SOFA) score at ICI diagnosis in the EOIC group and the interval from ICU admission to ICI occurrence in the LOIC group were identified as risk factors for mortality. Susceptibility to the first-line agent was associated with a lower risk of mortality in the LOIC group.The mortality rate was significantly lower in the EOIC group, and there were more cases of non-albicans infection in the LOIC group. Susceptibility to the first-line agent was an important predictor of mortality in the LOIC group. SOFA score at ICI diagnosis in the EOIC group and interval from ICU admission to ICI occurrence in the LOIC group were identified as risk factors for mortality.
Assuntos
Candida , Candidíase Invasiva/mortalidade , Infecção Hospitalar/mortalidade , Mortalidade Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Adulto , Idoso , Candidíase Invasiva/microbiologia , Candidíase Invasiva/patologia , China/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Fatores de Risco , Fatores de TempoRESUMO
Traumatic brain injury-induced acute lung injury (TBI-ALI) is a serious complication after brain injury for which predictive factors are lacking. In this study, we found significantly elevated blood glutamate concentrations in patients with TBI or multiple peripheral trauma (MPT), and patients with more severe injuries showed higher blood glutamate concentrations and longer durations of elevated levels. Although the increase in amplitude was similar between the two groups, the duration was longer in the patients with TBI. There were no significant differences in blood glutamate concentrations in the patients with MPT with regard to ALI status, but the blood glutamate levels were significantly higher in the patients with TBI-ALI than in those without ALI. Moreover, compared to patients without ALI, patients with TBI showed a clearly enhanced inflammatory response that was closely correlated with the blood glutamate levels. The blood glutamate concentration was also found to be a risk factor (adjusted odds ratio, 2.229; 95% CI, 1.082-2.634) and was a better predictor of TBI-ALI than the Glasgow Coma Scale (GCS) score. These results indicated that dramatically increased blood glutamate concentrations were closely related to the occurrence of TBI-ALI and could be used as a predictive marker for "at-risk" patients.