Emergence of immunosuppressive LOX-1+ PMN-MDSC in septic shock and severe COVID-19 patients with acute respiratory distress syndrome.
Ontology highlight
ABSTRACT:
SUBMITTER: Coudereau R
PROVIDER: S-EPMC8242532 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Any new pulmonary edema warrants an urgent rule out of acute cardiac dysfunction. Because sepsis protocols emphasize rapid stabilization and treatment over etiologic evaluation, some cases of endocarditis may be missed as sepsis with acute respiratory distress syndrome.
| S-EPMC7752453 | biostudies-literature
Project description:RationaleDegradation of the endothelial glycocalyx, a glycosaminoglycan (GAG)-rich layer lining the vascular lumen, is associated with the onset of kidney injury in animal models of critical illness. It is unclear if similar pathogenic degradation occurs in critically ill patients.ObjectivesTo determine if urinary indices of GAG fragmentation are associated with outcomes in patients with critical illnesses such as septic shock or acute respiratory distress syndrome (ARDS).MethodsWe prospectively collected urine from 30 patients within 24 hours of admission to the Denver Health Medical Intensive Care Unit (ICU) for septic shock. As a nonseptic ICU control, we collected urine from 25 surgical ICU patients admitted for trauma. As a medical ICU validation cohort, we obtained serially collected urine samples from 70 patients with ARDS. We performed mass spectrometry on urine samples to determine GAG (heparan sulfate, chondroitin sulfate, and hyaluronic acid) concentrations as well as patterns of heparan sulfate/chondroitin sulfate disaccharide sulfation. We compared these indices to measurements obtained using dimethylmethylene blue, an inexpensive, colorimetric urinary assay of sulfated GAGs.Measurements and main resultsIn septic shock, indices of GAG fragmentation correlated with both the development of renal dysfunction over the 72 hours after urine collection and with hospital mortality. This association remained after controlling for severity of illness and was similarly observed using the inexpensive dimethylmethylene blue assay. These predictive findings were corroborated using urine samples previously collected at three consecutive time points from patients with ARDS.ConclusionsEarly indices of urinary GAG fragmentation predict acute kidney injury and in-hospital mortality in patients with septic shock or ARDS. Clinical trial registered with www.clinicaltrials.gov (NCT01900275).
| S-EPMC5003330 | biostudies-literature
Project description:BackgroundAcute respiratory failure in septic patients contributes to higher in-hospital mortality. Intubation may improve outcome but there are no specific criteria for intubation. Intubation of septic patients with respiratory distress and hemodynamic compromise may result in clinical deterioration and precipitate cardiovascular failure. The decision to intubate is complex and multifactorial. The purpose of this study was to evaluate the impact of intubation in patients with respiratory distress and predominant hemodynamic instability within 24 h after ICU admission for septic shock.MethodsWe conducted a retrospective analysis of a prospective registry of adult patients with septic shock admitted to the medical ICU at Mayo Clinic, between April 30, 2014 and December 31, 2017. Septic shock was defined by persistent lactate > 4 mmol/L, mean arterial pressure < 65 mmHg, or vasopressor use after 30 mL/kg fluid boluses and suspected or confirmed infection. Patients who remained hospitalized in the ICU at 24 h were separated into intubated while in the ICU and non-intubated groups. The primary outcome was hospital mortality. The first analysis used linear regression models and the second analysis used time-dependent propensity score matching to match intubated to non-intubated patients.ResultsOverall, 358 (33%) ICU patients were eventually intubated after their ICU admission and 738 (67%) were not. Intubated patients were younger, transferred more often from an outside facility, more critically ill, had more lung infection, and achieved blood pressure goals more often, but lactate normalization within 6 h occurred less often. Among those who remained hospitalized in the ICU 24 h after sepsis diagnosis, the crude in-hospital mortality was higher in intubated than non-intubated patients, 89 (26%) vs. 82 (12%), p < 0.001, as was the ICU mortality and ICU and hospital length of stay. After adjustment, intubation showed no effect on hospital mortality but resulted in fewer hospital-free days through day 28. One-to-one propensity resulted in similar conclusion.ConclusionsIntubation within 24 h of sepsis was not associated with hospital mortality but resulted in fewer 28-day hospital-free days. Although intubation remains a high-risk procedure, we did not identify an increased risk in mortality among septic shock patients with predominant hemodynamic compromise.
| S-EPMC8543776 | biostudies-literature
Project description: Not available
| S-EPMC8409473 | biostudies-literature
Project description:Acute ischemic stroke (AIS) is common in patients with cancer, and mounting clinical evidence suggests that it may shorten the survival of cancer patients. But how stroke affects the progression of cancer remains unclear. We inoculated B16 tumor cells (2 × 105) subcutaneously before distal middle cerebral artery occlusion (dMCAO) or sham surgery in C57BL/6 mice and found that compared to sham operated mice, dMCAO mice developed significantly increased tumor volume and were accompanied by lower survival rate. To explore the underlying mechanism, we performed RNA-sequencing analysis of the tumor tissue from mice with or without stroke and found prominent upregulation of lipocalin 2 (LCN2) in the tumor from stroke mice compared to those from sham mice. Using quantitative reverse transcription-PCR, we confirmed increased mRNA expression of LCN2 as well as anti-inflammatory cytokines-Arg1, IL-10, and decreased mRNA level of pro-inflammatory cytokines-IL-6, IL-23 in the tumor of cancer-bearing stroke mice. Both immunofluorescence staining and flow cytometry analysis revealed that increased expression of LCN2 was mainly derived from the polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) in the tumor. We also found that stroke reduced the PMN-MDSCs in the peripheral blood, but increased PMN-MDSCs in the tumor of the cancer-bearing mice after stroke. In conclusion, cerebral ischemic stroke may exacerbate cancer progression by increasing LCN2 expression in PMN-MDSCs, which turns out to be a promising therapeutic target to suppress cancer progression after ischemic stroke.
| S-EPMC7050632 | biostudies-literature
Project description:BackgroundNo direct approach assessing pulmonary vascular permeability exists in the current therapeutic strategy for patients with acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution measures hemodynamic parameters such as pulmonary vascular permeability index and extravascular lung water, enabling clinicians to assess ARDS severity. The aim of this study is to explore a precise transpulmonary thermodilution-based criteria for quantifying the severity of lung injury using a clinically relevant septic-ARDS pig model.MethodsThirteen female pigs (weight: 31 ± 2 kg) were intubated, mechanically ventilated under anesthesia, and either assigned to septic shock-induced ARDS or control group. To confirm the development of ARDS, we performed computed tomography (CT) imaging in randomly selected animals. The pulmonary vascular permeability index, extravascular lung water, and other hemodynamic parameters were consecutively measured during the development of septic lung injury. Lung status was categorized as normal (partial pressure of oxygen/fraction of inspired oxygen ≥ 400), or injured at different degrees: pre-ARDS (300-400), mild-to-moderate ARDS (100-300), or severe ARDS (< 100). We also measured serum inflammatory cytokines and high mobility group box 1 levels during the experiment to explore the relationship of the pulmonary vascular permeability index with these inflammatory markers.ResultsUsing CT image, we verified that animals subjected to ARDS presented an extent of consolidation in bilateral gravitationally dependent gradient that expands over time, with diffuse ground-glass opacification. Further, the post-mortem histopathological analysis for lung tissue identified the key features of diffuse alveolar damage in all animals subjected to ARDS. Both pulmonary vascular permeability index and extravascular lung water increased significantly, according to disease severity. Receiver operating characteristic analysis demonstrated that a cut-off value of 3.9 for the permeability index provided optimal sensitivity and specificity for predicting severe ARDS (area under the curve: 0.99, 95% confidence interval, 0.98-1.00; sensitivity = 100%, and specificity = 92.5%). The pulmonary vascular permeability index was superior in its diagnostic value than extravascular lung water. Furthermore, the pulmonary vascular permeability index was significantly associated with multiple parameters reflecting clinicopathological changes in animals with ARDS.ConclusionThe pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.
| S-EPMC9789654 | biostudies-literature
Project description:BackgroundDengue can cause plasma leakage that may lead to dengue shock syndrome (DSS). In approximately 30% of DSS cases, recurrent episodes of shock occur. These patients have a higher risk of fluid overload, respiratory distress and poor outcomes. We investigated the association of echocardiographically-derived cardiac function and intravascular volume parameters plus lactate levels, with the outcomes of recurrent shock and respiratory distress in severe dengue.Methods/principle findingsWe performed a prospective observational study in Paediatric and adult ICU, at the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam. Patients with dengue were enrolled within 12 hours of admission to paediatric or adult ICU. A haemodynamic assessment and portable echocardiograms were carried out daily for 5 days from enrolment and all interventions recorded. 102 patients were enrolled; 22 patients did not develop DSS, 48 had a single episode of shock and 32 had recurrent shock. Patients with recurrent shock had a higher enrolment pulse than those with 1 episode or no shock (median: 114 vs. 100 vs. 100 b/min, P = 0.002), significantly lower Stroke Volume Index (SVI), (median: 21.6 vs. 22.8 vs. 26.8mls/m2, P<0.001) and higher lactate levels (4.2 vs. 2.9 vs. 2.2 mmol/l, P = 0.001). Higher SVI and worse left ventricular function (higher Left Myocardial Performance Index) on study days 3-5 was associated with the secondary endpoint of respiratory distress. There was an association between the total IV fluid administered during the ICU admission and respiratory distress (OR: 1.03, 95% CI 1.01-1.06, P = 0.001). Admission lactate levels predicted patients who subsequently developed recurrent shock (P = 0.004), and correlated positively with the total IV fluid volume received (rho: 0.323, P = 0.001) and also with admission ALT (rho: 0.764, P<0.001) and AST (rho: 0.773, P<0.001).Conclusions/significanceEcho-derived intravascular volume assessment and venous lactate levels can help identify dengue patients at high risk of recurrent shock and respiratory distress in ICU. These findings may serve to, not only assist in the management of DSS patients, but also these haemodynamic endpoints could be used in future dengue fluid intervention trials.
| S-EPMC5519203 | biostudies-literature
Project description:Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical care outcomes, has led to the development of clinical practice guidelines in a variety of areas related to infection and sepsis. The Surviving Sepsis Guidelines for Management of Severe Sepsis and Septic Shock were first published in 2004, revised in 2008, and recently revised again and published in 2013. The first part of this manuscript is a summary of the 2013 guidelines with some editorial comment. The second part of the manuscript characterizes hospital based sepsis performance improvement programs and highlights the sepsis bundles from the Surviving Sepsis Campaign as a key component of such a program.
| S-EPMC3916373 | biostudies-literature
Project description:Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by the damage of alveolar epithelial cells and pulmonary capillary endothelial cells. It is mainly manifested by non-cardiogenic pulmonary edema, resulting from intrapulmonary and extrapulmonary risk factors. ARDS is often accompanied by immune system disturbance, both locally in the lungs and systemically. As a common heterogeneous disease in critical care medicine, researchers are often faced with the failure of clinical trials. Latent class analysis had been used to compensate for poor outcomes and found that targeted treatment after subgrouping contribute to ARDS therapy. The subphenotype of ARDS caused by sepsis has garnered attention due to its refractory nature and detrimental consequences. Sepsis stands as the most predominant extrapulmonary cause of ARDS, accounting for approximately 32% of ARDS cases. Studies indicate that sepsis-induced ARDS tends to be more severe than ARDS caused by other factors, leading to poorer prognosis and higher mortality rate. This comprehensive review delves into the immunological mechanisms of sepsis-ARDS, the heterogeneity of ARDS and existing research on targeted treatments, aiming to providing mechanism understanding and exploring ideas for accurate treatment of ARDS or sepsis-ARDS.
| S-EPMC10682474 | biostudies-literature
Project description:An immunosuppressive tumor microenvironment is one of the major obstacles to the efficacy of standard chemotherapies, such as doxorubicin, used to treat triple negative breast cancer (TNBC). Combination therapy may be a potential way to overcome this barrier. A nitric oxide (NO) donor such as glyceryl trinitrate (GTN) has shown beneficial effects in combination with standard chemotherapy/radiotherapy in patients with cancer. In this study, we investigated the combination of doxorubicin/GTN in a mouse model of TNBC. The results indicated that GTN significantly improved the anti-tumor efficacy of doxorubicin in mouse models of BC. Flow cytometry and immunohistochemistry analysis revealed that the GTN/doxorubicin combination increases the intra-tumor recruitment and activation of CD8+ lymphocytes that is associated with the ability of doxorubicin and doxorubicin/GTN to recruit and dampen the immunosuppressive function of PMN-MDSCs PD-L1low. Mechanistically, in PMN-MDSC, doxorubicin/GTN combination reduced STAT5 phosphorylation, while GTN +/- doxorubicin induced a ROS-dependent cleavage of STAT5 associated with a decrease of FATP2. Our results identify a new combination enhancing the immune-mediated anticancer therapy in a TNBC mouse model through a ROS-dependent reprograming of PMN-MDSCs towards a less immunosuppressive phenotype. These findings open up a new therapeutic perspective by combining GTN to doxorubicin for patients with TNBC.
2023-04-30 | GSE223016 | GEO