Early prevention of trauma-related infection/sepsis

Ma, Xiaoyuan; Tian, Lixing; Liang, Huaping

doi:10.1186/s40779-016-0104-3

Cited by 28 publications

(32 citation statements)

References 69 publications

(86 reference statements)

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“…In addition, the inability to have sufficient resolution from SIRS or CARS can lead to the development of PICS. The consequences of these altered immune phenotypes can lead to impaired wound healing, late onset sepsis, MODS, and acute respiratory distress syndrome (ARDS) [5, 6].…”

Section: Late Complications Of Altered Immune Function After Injurymentioning

confidence: 99%

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Late immune consequences of combat trauma: a review of trauma-related immune dysfunction and potential therapies

2019

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With improvements in personnel and vehicular body armor, robust casualty evacuation capabilities, and damage control resuscitation strategies, more combat casualties are surviving to reach higher levels of care throughout the casualty evacuation system. As such, medical centers are becoming more accustomed to managing the deleterious late consequences of combat trauma related to the dysregulation of the immune system. In this review, we aim to highlight these late consequences and identify areas for future research and therapeutic strategies. Trauma leads to the dysregulation of both the innate and adaptive immune responses, which places the injured at risk for several late consequences, including delayed wound healing, late onset sepsis and infection, multi-organ dysfunction syndrome, and acute respiratory distress syndrome, which are significant for their association with the increased morbidity and mortality of wounded personnel. The mechanisms by which these consequences develop are complex but include an imbalance of the immune system leading to robust inflammatory responses, triggered by the presence of damage-associated molecules and other immune-modifying agents following trauma. Treatment strategies to improve outcomes have been difficult to develop as the immunophenotype of injured personnel following trauma is variable, fluid and difficult to determine. As more information regarding the triggers that lead to immune dysfunction following trauma is elucidated, it may be possible to identify the immunophenotype of injured personnel and provide targeted treatments to reduce the late consequences of trauma, which are known to lead to significant morbidity and mortality.

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Section: Late Complications Of Altered Immune Function After Injurymentioning

confidence: 99%

“…The associated morbidity and mortality is multifactorial, among which dysregulation of the immune system is an important contributing factor. Immune dysregulation leads to an increased risk for late onset sepsis and infection, acute respiratory distress syndrome, and delayed wound healing in addition to late MODS [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Late immune consequences of combat trauma: a review of trauma-related immune dysfunction and potential therapies

2019

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“…Septicemia is a pressing medical issue due to the emergence of antibiotic-resistance and rising longevity of patients suffering from chronic diseases 40 . Moreover, high mortality rates due to septicemia still remain a medical challenge following trauma in the battlefield, highlighting the need for novel prevention strategies 41 .…”

Section: Resultsmentioning

confidence: 99%

Synthetic immunomodulation with a CRISPR super-repressor in vivo

et al. 2020

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Transient modulation of genes involved in immunity, without exerting a permanent change in the DNA code, can be an effective strategy to modulate the course of many inflammatory conditions. CRISPR-Cas9 technology represents a promising platform for achieving this goal. Truncation of guide RNA (gRNA) from 5’ end, enables the application of a nuclease competent Cas9 protein for transcriptional modulation of genes, allowing multi-functionality of CRISPR. Here, we introduce an enhanced CRISPR-based transcriptional repressor to reprogram immune homeostasis in vivo . In this repressor system, two transcriptional repressors heterochromatin protein 1 (HP1a) and Krüppel associated box (KRAB) are fused to MS2 coat protein and subsequently recruited by gRNA aptamer binding to a nuclease competent CRISPR complex containing truncated gRNAs. With the enhanced repressor, we demonstrate transcriptional repression of the Myeloid differentiation primary response 88 ( Myd88 ) gene in vitro and in vivo. We demonstrate that this strategy can efficiently downregulate Myd88 expression in lung, blood and bone marrow of Cas9 transgenic mice, which receive systemic injection of adeno-associated virus- (AAV)2/1 carrying truncated gRNAs targeting Myd88 and MS2-Hp1aKRAB cassette. This downregulation is accompanied by changes in downstream signaling elements such as TNF-α and ICAM-1. Myd88 repression leads to decrease in immunoglobulin G (IgG) production against AAV2/1 and AAV2/9 and the strategy modulates IgG response against AAV cargos. It improves the efficiency of a subsequent AAV9/CRISPR treatment for repression of Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), a gene when repressed can lower blood cholesterol levels. We also demonstrate that CRISPR-mediated Myd88 repression can act as a prophylactic measure against septicemia in both Cas9 transgenic and C57BL/6J mice. When delivered by nanoparticles, this repressor can serve as a therapeutic modality to influence the course of septicemia. Collectively, we report that CRISPR-mediated repression of endogenous Myd88 can effectively modulate host immune response against AAV-mediated gene therapy and influence the course of septicemia. The ability to control Myd88 transcript levels using a CRISPR-based synthetic repressor can be an effective strategy for AAV-based CRISPR therapies, as this pathway serves as a key node in induction of humoral immunity against AAV serotypes.

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“…This results in late, unfavorable, and inadequate initial interventions. As a result, chronic soft tissue and bone infections and nosocomial resistant bacterial infections can lead to sepsis, multiorgan failure, and death in these patients (10).…”

Section: Introductionmentioning

confidence: 99%

“…This factor plays a major role in the development of acute respiratory distress syndrome in patients. The existence of both sepsis and acute respiratory distress syndrome in the same case complicates the condition of the patient and makes treatment difficult (10,11).…”

Section: Introductionmentioning

confidence: 99%

Treatment of sepsis secondary to blast injuries

2021

jsurgarts

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Blast injuries are an important cause of morbidity and mortality due to ongoing conflicts, especially among young patients. Due to the adversities of warfare, the first interventions for these patients are performed in unsuitable environments. Patients generally do not receive further treatment in their own country, but in other countries as wounded war refugees. Local and systemic infections in patients with associated polytrauma, soft tissue damage, and blast effects cause mortality and morbidity. All of the patients were injured during the Libyan civil war and the first intervention was performed in hospitals in their own country or in Tunisia. The patients were transferred to our clinic by ambulance plane. All patients presented bone-soft tissue infection and sepsis. Bone-soft tissue and blood cultures were obtained from the patients. The first interventions for the patients were performed multidisciplinarily in orthopedics, general surgery, infection, and intensive care clinics. The patients were followed in our clinic for one year including inten-sive care, service, and outpatient monitoring. Sixteen patients with a mean age of 28.8 years were included in the study. All patients were wounded by explosives or missiles. The patients were admitted to our clinic at a mean of approximately 24.4 days after these events. The patients were followed in the intensive care unit for an average of 7.9 days. The mean follow-up was 4 months. After the service follow-up, each patient continued outpatient follow-up for a total of 12 months. Antibiotics were given according to the causative infectious agent during the intensive care and service follow-up. Three patients had lung infections. Colistin-induced renal failure or hepatotoxicity developed due to resistant infections in 4 patients. After colistin was ceased, this situation resolved. Two of the 16 patients died. The sepsis and bone-soft tissue infections were controlled in all other patients. Four patients had femoral nonu-nion and one patient had short femoral healing. While 2 patients were able to walk without support and 11 patients could walk using support and one patient who was Quadriplegic was unable to walk. The treatment of bone-soft tissue infections accompanied by sepsis should be multidisciplinary. This should be kept in mind for patients with systemic injuries due to explosion effects. The infectious agents in these patients are often drug-resistant and there may be complications secondary to the antibiotics used during treatment.

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Early prevention of trauma-related infection/sepsis

Cited by 28 publications

References 69 publications

Late immune consequences of combat trauma: a review of trauma-related immune dysfunction and potential therapies

Late immune consequences of combat trauma: a review of trauma-related immune dysfunction and potential therapies

Synthetic immunomodulation with a CRISPR super-repressor in vivo

Treatment of sepsis secondary to blast injuries

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