-
European Journal of Trauma and... Feb 2024Recently, retrospective registry-based studies have reported the decreasing incidence and increasing mortality of postinjury multiple organ failure (MOF). We aimed to...
BACKGROUND
Recently, retrospective registry-based studies have reported the decreasing incidence and increasing mortality of postinjury multiple organ failure (MOF). We aimed to describe the current epidemiology of MOF following the introduction of haemostatic resuscitation.
METHODS
A 10-year prospective cohort study was undertaken at a Level-1 Trauma Centre-based ending in December 2015. Inclusion criteria age ≥ 16 years, Injury Severity Score (ISS) > 15, Abbreviated Injury Scale (AIS) Head < 3 and survived > 48 h. Demographics, physiological and shock resuscitation parameters were collected. The primary outcome was MOF defined by a Denver Score > 3.
SECONDARY OUTCOMES
intensive care unit length of stay (ICU LOS), ventilation days and mortality.
RESULTS
Three hundred and forty-seven patients met inclusion criteria (age 48 ± 20; ISS 30 ± 11, 248 (71%) were males and 23 (6.6%) patients died. The 74 (21%) MOF patients (maximum Denver Score: 5.5 ± 1.8; Duration; 5.6 ± 5.8 days) had higher ISS (32 ± 11 versus 29 ± 11) and were older (54 ± 19 versus 46 ± 20 years) than non-MOF patients. Mean daily Denver scores adjusted for age, sex, MOF and ISS did not change over time. Crystalloid usage decreased over the 10-year period (p value < 0.01) and PRBC increased (p value < 0.01). Baseline cumulative incidence of MOF at 28 days was 9% and competing risk analyses showed that incidence of MOF increased over time (subdistribution hazard ratio 1.14, 95% CI 1.04 to 1.23, p value < 0.01). Mortality risk showed no temporal change. ICU LOS increased over time (subdistribution hazard ratio 0.95, 95% CI 0.92 to 0.98, p value < 0.01). Ventilator days increased over time (subdistribution hazard ratio 0.94, 95% CI 0.9 to 0.97, p value < 0.01).
CONCLUSION
The epidemiology of MOF continues to evolve. Our prospective cohort suggests an ageing population with increasing incidence of MOF, particularly in males, with little changes in injury or shock parameters, who are being resuscitated with less crystalloids, stay longer on ICU without improvement in survival.
Topics: Male; Humans; Adolescent; Adult; Middle Aged; Aged; Female; Prospective Studies; Retrospective Studies; Multiple Organ Failure; Crystalloid Solutions; Multiple Trauma; Injury Severity Score
PubMed: 36598541
DOI: 10.1007/s00068-022-02202-8 -
Journal of Clinical Immunology Nov 2023Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a very rare autoinflammatory disease related to STING1 mutation. SAVI is...
Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a very rare autoinflammatory disease related to STING1 mutation. SAVI is mainly characterized by fever attacks and skin and respiratory manifestations such as interstitial lung disease or alveolar hemorrhage. Respiratory involvement occurs in 80% of cases and might progress to severe lung fibrosis and require lung transplantation (LT). Three patients with SAVI who underwent LT have been reported to date. Two of the three patients died months or years after LT due to multiple organ failure or sepsis. However, the diagnosis of SAVI was made after LT, thus preventing the use of targeted therapy, such as the Janus kinase 1 and 2 inhibitor (JAK1/2i) ruxolitinib, which might be beneficial for the respiratory status of these patients. We aimed to report our experience in managing three patients who were followed in three large lung transplantation centers in France and who benefited from ruxolitinib before undergoing LT. We describe posttransplant complications that occurred as well as outcomes.
Topics: Humans; Janus Kinase Inhibitors; Lung Transplantation; Syndrome; Pyrazoles; Rare Diseases
PubMed: 37814086
DOI: 10.1007/s10875-023-01595-4 -
International Journal of Molecular... Dec 2023Sepsis is a systemic inflammatory syndrome that results in multiple-organ failure caused by a dysregulated host immune response to microbial infection. Astragali...
Sepsis is a systemic inflammatory syndrome that results in multiple-organ failure caused by a dysregulated host immune response to microbial infection. Astragali complanati semen extract (ACSE) exhibits pharmacological activities, including antioxidant, anticancer, antiaging, and anti-diabetes effects. It is widely used in traditional medicine to treat liver and kidney diseases; however, the protective effect of ACSE on sepsis and its mechanisms are unknown. In the present study, we investigated the anti-inflammatory effects and potential mechanisms of the action of ACSE on sepsis. We show that ACSE improved survival rates in mouse models of acute sepsis induced by CLP (cecal ligation and puncture) and LPS stimulation. ACSE administration decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in sepsis-induced mice. Furthermore, ACSE reduced the levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the serum of septic mice. ACSE treatment inhibited the expression of these proinflammatory genes in LPS-stimulated J774 macrophages. Moreover, ACSE inhibited the phosphorylation of the IκB kinase (IKK) and the nuclear translocation of p65 NF-κB by LPS stimulation in macrophages. These results reveal the mechanism underlying the protective effect of ACSE against sepsis by inhibiting NF-κB activation and suggest that ACSE could be a potential therapeutic candidate to treat acute inflammatory diseases.
Topics: Animals; Mice; Shock, Septic; Lipopolysaccharides; NF-kappa B; Sepsis; Astragalus Plant; Ethanol; Anti-Inflammatory Agents
PubMed: 38203555
DOI: 10.3390/ijms25010384 -
Aging Aug 2023The respiratory and cardiovascular systems are often the most severely impacted by the rapid onset of sepsis, which can lead to multiple organ failure. The mortality has...
The respiratory and cardiovascular systems are often the most severely impacted by the rapid onset of sepsis, which can lead to multiple organ failure. The mortality has ranged from 10 to 40% when it has evolved into septic shock. This study sought to demonstrate the potential and role of Hmgcs2 in safeguarding against cardiovascular harm in septic mouse models. The cecal ligament and puncture (CLP) model was used to induce sepsis in C57BL/6 mice, with Hmgcs2 expression in the myocardium of the mice being heightened and inflammatory factors being augmented. Subsequently, we utilized ASOs to silence the hmgcs2 gene, and found that silencing accelerated septic myocardial injury and cardiac dysfunction in CLP mice models. In contrast, hmgcs2 attenuated inflammation and apoptosis and protected against septic cardiomyopathy in murine septicemia models. Src production, spurred on by Hmgcs2, triggered the PI3K/Akt pathway and augmented M2 macrophage polarization. Moreover, the inhibition of M2 polarization by an Src antagonist significantly contributed to apoptosis of cardiomyocytes. Our research revealed that Hmgcs2 inhibited the activation of pro-inflammatory macrophages and, through Src-dependent activation of PI3K/Akt pathway, promoted the anti-inflammatory phenotype, thus safeguarding myocardial damage from sepsis. This offers a novel theoretical basis for prevention and treatment of infectious complications.
Topics: Mice; Animals; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Mice, Inbred C57BL; Macrophages; Myocytes, Cardiac; Heart Injuries; Sepsis
PubMed: 37561521
DOI: 10.18632/aging.204944 -
Critical Care Explorations Oct 2023Acute kidney injury (AKI) requiring continuous kidney replacement therapy is a significant complication in ICU patients with mortality rates exceeding 50%. A... (Review)
Review
Safety Summary of the Selective Cytopheretic Device: A Review of Safety Data Across Multiple Clinical Trials in ICU Patients With Acute Kidney Injury and Multiple Organ Failure.
OBJECTIVES
Acute kidney injury (AKI) requiring continuous kidney replacement therapy is a significant complication in ICU patients with mortality rates exceeding 50%. A dysregulated immune response can lead to systemic inflammation caused by hyperactivity of pro-inflammatory neutrophils and monocytes leading to tissue damage. The selective cytopheretic device (SCD) is an investigational medical device in a new class of cell-directed extracorporeal therapies distinct from cytokine adsorbers or filters, as it targets activated leukocytes. These leukocytes are the cellular sources driving this hyperinflammatory process. The objective of this report is to summarize the safety experience from clinical studies of the SCD in ICU patients with AKI or acute respiratory distress syndrome (ARDS) and multiple organ dysfunction (MOD).
DATA SOURCES AND STUDY SELECTION
The studies included in this report represent all relevant trials of the SCD conducted in patients with AKI or ARDS and MOD. Adverse event data, clinical laboratory data and mortality rates were described and summarized in this report.
DATA EXTRACTION AND DATA SYNTHESIS
Five clinical studies were included in this report, including four adult studies of AKI and/or ARDS and one pediatric AKI study, which involved 151 patients treated with the SCD in an ICU setting. Over 800 SCD sessions were deployed with an estimated 19,000 exposure hours with no device-related infections or attributable serious adverse events. Furthermore, there were no safety signals of leukopenia, thrombocytopenia, or other indications of immunodepletion or immunosuppression.
CONCLUSIONS
The SCD has shown to be a promising extracorporeal therapy with promising clinical results and a favorable safety profile. These studies support that the SCD can be added as a therapeutic intervention in critically ill AKI patient populations with multiple organ failure without adding additional safety risks.
PubMed: 37868028
DOI: 10.1097/CCE.0000000000000995 -
World Journal of Clinical Cases Jun 2024Following the withdrawal of paraquat, diquat (DQ) has emerged as the predominant herbicide. When people come into contact with or ingest DQ, may lead to poisoning and...
Following the withdrawal of paraquat, diquat (DQ) has emerged as the predominant herbicide. When people come into contact with or ingest DQ, may lead to poisoning and potentially fatal outcomes. Reports suggest that the mortality of DQ poisoning can be as high as 50%. DQ poisoning can be categorized as mild, moderate to severe or fulminant. In cases of fulminant poisoning, victims often succumb to multiple organ failure within 48 h. This presents a significant challenge in the clinical management. Scholars have discovered that oxidative stress, inflammatory injury, and cell apoptosis play crucial roles in the DQ poisoning. However, the underlying connection of the extensive organ damage remains unknown. The abnormal function and activity of endothelial cells (EC) should play a crucial role in tissue damage caused by DQ due to rich microcirculation and high sensitivity to perfusion in the vulnerable organs. However, reports on DQ-induced EC injury is rare. We made a preliminary discovery-the presence of severe vascular endothelial damage in the kidneys and lungs affected by DQ. Therefore, we hypothesize that DQ poisoning may be attributed to EC damage, ultimately resulting in multiple organ failure.
PubMed: 38898842
DOI: 10.12998/wjcc.v12.i17.2917 -
Thrombosis Research Nov 2023Heat-related illness is becoming more problematic due to ongoing global warming. Heat-related injury causes systemic inflammation and coagulopathy, due to leukocyte,... (Review)
Review
Heat-related illness is becoming more problematic due to ongoing global warming. Heat-related injury causes systemic inflammation and coagulopathy, due to leukocyte, platelet, and vascular endothelial cell activation and injury. Hyperthermia directly modulates platelet function and can induce cellular damage. Meanwhile, heat also affects platelet function via activated coagulation, excess inflammation, production of cytokines, and heat shock proteins. Aberrant hyperthermia-induced interactions between leukocytes and endothelial cells are also involved in platelet regulation. Heat-induced coagulopathy commonly progresses to disseminated intravascular coagulation (DIC), leading to multiple organ failure and in some cases enhanced bleeding. Consequently, platelet count, prothrombin time, and DIC score are useful for evaluating the severity of heat-related illness in addition to other organ damage markers such as Glasgow Coma Scale, creatinine, and bilirubin. Despite the increasing risk, therapeutic modalities targeting platelets are limited and no established therapy exists. In this review, we summarize the current knowledge about the role of platelets in the pathogenesis, diagnosis, and management of heat-related illness.
Topics: Humans; Disseminated Intravascular Coagulation; Endothelial Cells; Blood Coagulation Disorders; Hemostasis; Inflammation
PubMed: 35989192
DOI: 10.1016/j.thromres.2022.08.009 -
Science Bulletin Dec 2023The spread of hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) is a global health concern. Here, we report the intrahospital colonization and spread of...
The spread of hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) is a global health concern. Here, we report the intrahospital colonization and spread of Hv-CRKP isolates in a tertiary hospital from 2017 to 2022. Analyses of 90 nonredundant CRKP isolates from 72 patients indicated that Hv-CRKP transferability relies on the dominant ST11-K64 clone. Whole-genome sequencing of 11 representative isolates gave 31 complete plasmid sequences, including 12 KPC-2 resistance carriers and 10 RmpA virulence vehicles. Apart from the binary vehicles, we detected two types of fusion plasmids, favoring the cotransfer of RmpA virulence and KPC-2 resistance. The detection of ancestry/relic plasmids enabled us to establish genetic mechanisms by which rare fusion plasmids form. Unexpectedly, we found a total of five rmpA promoter variants (P-P) exhibiting distinct activities and varying markedly in their geographic distributions. CRISPR/Cas9 manipulation confirmed that an active P-rmpA regulator is a biomarker for the "high-risk" ST11-K64/CRKP clone. These findings suggest clonal spread and clinical evolution of the prevalent ST11-K64/Hv-CRKP clones. Apart from improved public awareness of Hv-CRKP convergence, our findings might benefit the development of surveillance (and/or intervention) strategies for the dominant ST11-K64 lineage of the Hv-CRKP population in healthcare sectors.
Topics: Humans; Klebsiella pneumoniae; Multilocus Sequence Typing; Klebsiella Infections; Plasmids; Carbapenem-Resistant Enterobacteriaceae; Carbapenems
PubMed: 37949739
DOI: 10.1016/j.scib.2023.10.038 -
Journal of Intensive Care Medicine May 2024Intensive care physicians may assume the primary care of patients with transplant-associated thrombotic microangiopathy (TA-TMA), an uncommon but potentially critical... (Review)
Review
Intensive care physicians may assume the primary care of patients with transplant-associated thrombotic microangiopathy (TA-TMA), an uncommon but potentially critical complication of hematopoietic stem cell transplants (HSCTs) and solid organ transplants. TA-TMA can have a dramatic presentation with multiple organ dysfunction syndrome (MODS) associated with high morbidity and mortality. The typical presenting clinical features are hemolytic anemia, thrombocytopenia, refractory hypertension, proteinuria and worsening renal failure. Intestinal involvement, with abdominal pain, nausea and vomiting, gastrointestinal bleeding, and ascites are also common. Cardiopulmonary involvement may develop from various causes including pulmonary arteriolar hypertension, pleural and pericardial effusions, and diffuse alveolar hemorrhage. Due to other often concurrent complications after HSCT, early diagnosis and effective management of TA-TMA may be challenging. Close collaboration between ICU and transplant physicians, along with other relevant specialists, is needed to best manage these patients. There are currently no approved therapies for the treatment of TA-TMA. Plasma exchange and rituximab are not recommended unless circulating factor H (CFH) antibodies or thrombotic thrombocytopenic purpura (TTP; ADAMTS activity < 10%) are diagnosed or highly suspected. The role of the complement pathway activation in the pathophysiology of TA-TMA has led to the successful use of targeted complement inhibitors, such as eculizumab. However, the relatively larger studies using eculizumab have been mostly conducted in the pediatric population with limited data on the adult population. This review is focused on the role of intensive care physicians to emphasize the clinical approach to patients with suspected TA-TMA and to discuss diagnosis and treatment strategies.
Topics: Adult; Humans; Child; Thrombotic Microangiopathies; Hypertension; Multiple Organ Failure; Organ Transplantation; Hematopoietic Stem Cells; Hematopoietic Stem Cell Transplantation
PubMed: 37990516
DOI: 10.1177/08850666231200193 -
Critical Care (London, England) Oct 2023Restoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Restoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral L-citrulline administration reduced organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score and affected selected immune parameters in mechanically ventilated medical intensive care unit (ICU) patients.
METHODS
A randomized, double-blind, multicenter clinical trial of enteral administration of L-citrulline versus placebo for critically ill adult patients under invasive mechanical ventilation without sepsis or septic shock was conducted in four ICUs in France between September 2016 and February 2019. Patients were randomly assigned to receive enteral L-citrulline (5 g) every 12 h for 5 days or isonitrogenous, isocaloric placebo. The primary outcome was the SOFA score on day 7. Secondary outcomes included SOFA score improvement (defined as a decrease in total SOFA score by 2 points or more between day 1 and day 7), secondary infection acquisition, ICU length of stay, plasma amino acid levels, and immune biomarkers on day 3 and day 7 (HLA-DR expression on monocytes and interleukin-6).
RESULTS
Of 120 randomized patients (mean age, 60 ± 17 years; 44 [36.7%] women; ICU stay 10 days [IQR, 7-16]; incidence of secondary infections 25 patients (20.8%)), 60 were allocated to L-citrulline and 60 were allocated to placebo. Overall, there was no significant difference in organ dysfunction as assessed by the SOFA score on day 7 after enrollment (4 [IQR, 2-6] in the L-citrulline group vs. 4 [IQR, 2-7] in the placebo group; Mann‒Whitney U test, p = 0.9). Plasma arginine was significantly increased on day 3 in the treatment group, while immune parameters remained unaffected.
CONCLUSION
Among mechanically ventilated ICU patients without sepsis or septic shock, enteral L-citrulline administration did not result in a significant difference in SOFA score on day 7 compared to placebo.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016).
Topics: Adult; Humans; Female; Middle Aged; Aged; Male; Organ Dysfunction Scores; Shock, Septic; Citrulline; Multiple Organ Failure; Critical Illness; Respiration, Artificial; Sepsis; Intensive Care Units; Dietary Supplements; Arginine
PubMed: 37784110
DOI: 10.1186/s13054-023-04651-y