Burn Sepsis Research Articles

Selenoprotein P as a prognostic biomarker of burn sepsis: A prospective cohort study

IntroductionSeverely burned patients exhibit increased nutritional requirements and are at high risk of developing sepsis. Selenium is an essential trace element supporting antioxidant and anti-inflammatory pathways, mediated by incorporation into selenoproteins. The selenium status may affect sepsis risk in burn injury. MethodsThis prospective cohort study included 90 adult patients admitted to Zurich Burn Center, Switzerland. All patients received a continuous intravenous infusion of 1000μg sodium selenite per day during the first week as part of local standard of care. Three complementary biomarkers of serum selenium status were determined at nine time-points up to six months postburn, namely total selenium, selenoprotein P, and glutathione peroxidase 3. The resulting data were correlated to clinical parameters and outcomes, with sepsis as primary end point. ResultsA high fraction of the patients displayed selenium deficiency already at admission, and developed sepsis during hospitalization (n = 55; 61%). Selenium status at admission was inversely related to burn severity. Low baseline selenoprotein P was associated with sepsis incidence, irrespective of trauma severity (adjusted HR, 1.94; 95% CI, 1.05–3.63; p = 0.035). Burn severity and baseline concentrations of selenoprotein P and white blood cells corporately predicted sepsis with an area under the curve of 0.84 (95% CI, 0.75–0.93; p < 0.0001). Supplemental selenium was associated with a transient normalization of selenium status. ConclusionConsidering its rapid decline following severe burn injury, the assessment of serum selenoprotein P upon admission may contribute to an early prediction of sepsis risk.

Evaluation of Serum Procalcitonin as a Diagnostic and Prognostic Biomarker for Sepsis in Major Burn Patients: A Prospective Study

Abstract Background Sepsis in burns worsens the patient’s prognosis and increases the risk of organ failure and death. Multiple organ dysfunction syndrome (MODS), which is a direct response to sepsis is the main reason for death in burn patients. Identifying early sepsis is very important, given that every 6 h delay in the diagnosis of sepsis reduces survival by 10%. Complexity in diagnosing sepsis in the burn is due to the systemic response to the burn itself clinically simulating sepsis. Aim of the Work The aim of this study is: To investigate the diagnostic validity of PCT in burn sepsis as an early diagnostic tool and to identify its prognostic value in major burn patients with sepsis. Patients and Methods The study was a prospective study carried out in the Burn Intensive Care Unit (ICU) of Ain Shams University Hospitals on 30 patients that were admitted from October 2021 to April 2022 with major burn (more than 20% of TBSA) were included and the Local Ethics Committee approved the study, and informed consent was obtained from all participants or their guardians. Results It had been revealed that the first 3 samples have no significant increase in PCT levels in relation to sepsis. However, the following 2 samples which had been withdrawn on day 5 show a significant increase in PCT levels, and these on day 7 on admission are highly significant with a median (IQR) range of 9 ng/dl and median (IQR) range of 13.2 ng/dl respectively. Moreover, it had been noted that the PCT level on admission was significant for the prognosis of death with a median (IQR) range of 1.65 ng/dl while in survivor patients the median was 0.45 ng/dl. Conclusion Our study demonstrated that PCT level in major burn patients is a promising diagnostic biomarker in detecting sepsis that could facilitate ideal management and initiate proper antimicrobial therapy and good prognostic value as an early predictor of mortality.

Study of the Influencing Factors and their Predictive Value of Skin Graft Take in Early Excision and Grafting in Severe Burns: A Prospective Study

Abstract Background Burn injury is one of the most life-threatening traumas worldwide especially in developing countries. After severe burns, the patients suffer from loss of multiple functions of skin, such as fluid loss, and high infection rate with burn sepsis and septic shock. Objective To investigate the various factors that affect the survival rate of skin grafts in early excision and grafting procedures (from 3rd to 7th day after burn) in patients with severe burns. Patients and Methods This Prospective cohort study was done in Ain Shams University Burn Center attached to Plastic, burn and maxillofacial department during the period from May 2021 to May 2022. Results Analysis was performed on 75 individuals who had early burnt skin excised and early skin graft coverage. Two patient groups were analyzed, in the form of good skin graft take &amp;gt;70% in 45 patients, and poor skin graft take &amp;lt; 70% in 30 cases, based on the survival rate of the skin graft post operatively. Conclusion The univariate analysis and repeated measurement showed that burn intensity, the post-operative sepsis, the neutrophil lymphocytic ratio on day 3 (NLR3) in the poor skin graft take group were significantly higher than those in the good skin graft take group, while the estimated albumin levels in perioperative period and the estimated pre-albumin levels in perioperative period were higher in the good skin graft take group. Receiver operating characteristic curve showed that NLR3, the estimated albumin levels and pre-albumin levels in perioperative period had a good predictive value for the survival of skin grafts. The estimated albumin levels ≤3.18 gm/dl, estimated pre-albumin ≤23.9 mg/dl, and NLR3 ≥ 12 were independent risk factors for graft take in perioperative period.

Glutamine sustains energy metabolism and alleviates liver injury in burn sepsis by promoting the assembly of mitochondrial HSP60-HSP10 complex via SIRT4 dependent protein deacetylation

ABSTRACT Burns and burn sepsis, characterized by persistent and profound hypercatabolism, cause energy metabolism dysfunction that worsens organ injury and systemic disorders. Glutamine (Gln) is a key nutrient that remarkably replenishes energy metabolism in burn and sepsis patients, but its exact roles beyond substrate supply is unclear. In this study, we demonstrated that Gln alleviated liver injury by sustaining energy supply and restoring redox balance. Meanwhile, Gln also rescued the dysfunctional mitochondrial electron transport chain (ETC) complexes, improved ATP production, reduced oxidative stress, and protected hepatocytes from burn sepsis injury. Mechanistically, we revealed that Gln could activate SIRT4 by upregulating its protein synthesis and increasing the level of Nicotinamide adenine dinucleotide (NAD+), a co-enzyme that sustains the activity of SIRT4. This, in turn, reduced the acetylation of shock protein (HSP) 60 to facilitate the assembly of the HSP60-HSP10 complex, which maintains the activity of ETC complex II and III and thus sustain ATP generation and reduce reactive oxygen species release. Overall, our study uncovers a previously unknown pharmacological mechanism involving the regulation of HSP60-HSP10 assembly by which Gln recovers mitochondrial complex activity, sustains cellular energy metabolism and exerts a hepato-protective role in burn sepsis.

Adenosine diphosphate ribosylation factor 6 inhibition protects burn sepsis induced lung injury through preserving vascular integrity and suppressing ASC inflammasome transmission

BackgroundSevere burns are devastating injuries with significant immune dysfunction and result in substantial mortality and morbidity due to sepsis induced organ failure. Acute lung injury is the most common type of organ injury in sepsis, however, the mechanisms of which are poorly understood and effective therapeutic measures are limited. This study is aimed to investigate the effect of a small Guanosine triphosphatase (GTPase), Adenosine diphosphate ribosylation factor 6 (ARF6), on burn sepsis induced lung injury, and discuss the possible mechanisms. MethodsBurn sepsis was established in male C57BL/6 mice. Mice were anesthetised by intramuscular injection of ketamine and xylazine hydrochloride, then 30% TBSA full thickness burn followed by sub-eschar injection of lipopolysaccharide. Animals were treated with intraperitoneal injection of a small molecule inhibitor of ARF6: NAV-2729, or vehicle, right after the burn and sepsis stimuli were inflicted. Lung tissues were harvested for histopathological observation and the acute lung injury scores were calculated. Organ permeability, Vascular Endothelial Cadherin (VE-cadherin) expression, inflammatory cytokine levels and myeloperoxidase activity in lung tissues were detected. Rat pulmonary microvascular endothelial cells (PMVECs) were stimulated by burn sepsis serum with or without 10 μM NAV-2729. The ARF6 activation, VE-cadherin expression, inflammasome activity, adapter protein apoptosis speck-like protein containing a caspase recruiting domain (ASC) specks and cytokines secretion were determined. Student’s t test was used for comparison between two groups. Multiple comparisons among groups were performed by using analysis of variance, with Tukey’s test for the post hoc test. ResultsNAV-2729 treatment attenuated burn sepsis induced lung injury and promoted survival of burn septic mice by preserving VE-cadherin expression in endothelial cell adherent junction and limited vascular hyperpermeability in lung tissues. Moreover, inflammatory cytokine expression and inflammatory injury in lung tissues were alleviated. Mechanistically, NAV-2729 enhanced vascular integrity by inhibiting ARF6 activation and restoring VE-cadherin expression in PMVECs. In addition, NAV-2729 inhibited ARF6-dependent phagocytosis of ASC specks, thus preventing inflammation propagation mediated by cell-to-cell transmission of ASC specks. ConclusionsARF6 inhibition preserved vascular integrity by restoring expression of VE-cadherin and suppressed the spread of inflammation by affecting phagocytosis of ASC specks, thus protected against sepsis induced lung injury and improve survival of burn septic animals. The findings of this study implied potential therapeutics by which ARF6 inhibition can protect lung function from septic induced lung injury and improve outcomes in burn sepsis.

Sepsis in surgical patients: Burn sepsis

Patients with large burn injuries remain a challenge. The loss of skin barrier integrity and induced immunosuppression after injury increases their vulnerability to infection. Sepsis remains the primary cause of death for burn-injured patients who survive their acute injury and resuscitation. The objective of this work is to describe the current understanding and management of sepsis in the burn-injured patient and newer strategies to approach its management. Current understanding of the systemic inflammatory response to burn injury and sepsis, preventative strategies, and novel research will be discussed. Understanding the origin of burn sepsis from wounds themselves is key to understanding current paradigms. Infection control and management begins from the time of injury and continues throughout the patient’s hospital course. The use of personal protective equipment, burn unit design considerations, and optimization of prevention protocols and catheter care all play a role in burn sepsis prevention and management. The emergence of drug-resistant pathogens poses a particular challenge for burn patients due to the chronicity with which their wounds are sometimes open. The difficulty of systemic antibiotics to reach wounds has underscored the need to anticipate resistant organisms moving forward. Antibiotic strategies and newer approaches, such as phage therapy, will be discussed. Multi-omics approaches to understanding burn sepsis have developed in hopes of identifying patients more susceptible or at risk of developing burn sepsis. As with many aspects of burn care, a multidisciplinary, proactive approach to the management of burn sepsis is key to minimizing the morbidity and mortality associated with this complication.

Immune Diagnostics and Immunotherapy of Burn Sepsis

The paper analyzes the literature data and authors proper experience in the study of immunopathogenesis and immunodiagnosis of burn sepsis. It argues the issues of effective use of immunocorrection in the complex treatment of severely burned patients.Diagnosis of sepsis after severe burn injury is challenging due to the overlap of signs and clinical manifestations of the hypermetabolic reaction of thermal injury and sepsis. The systemic inflammatory response caused by burns can mimic manifestations of sepsis and complicate its early diagnosis. Considering this, modern immunodiagnostics can serve as an effective tool in identifying damaged key immune markers in burns, determining the severity of immune status disorders in burn disease and the risk of developing septic complications for timely immunocorrection and providing appropriate complex therapy for patients with extensive burns.However, the problem of immunocorrective therapy in severely burned patients remains extremely relevant, debatable and not fully resolved. It is a personalized approach based on immune analysis and clinical recommendations for the complex treatment of burn injury that should be applied in the immunotherapy of burn sepsis to improve the clinical outcomes and, possibly, prevent the development of sepsis in patients with severe burn injury.

USEFULNESS OF PROCALCITONIN AS A BIOMARKER IN BURN PATIENTS PLASTIC SURGERYDEPARTMENT, MOHAMMED VI UNIVERSITYHOSPITAL, MARRAKECH, MOROCCO

Infection is the most common complication and cause of death in patients suffering burnsinjuries.These patients are susceptible to infection and burn wound sepsis secondary to the alterations in their physiology .Procalcitonin is an inflammatory biomarkers , the serum concentration of which increases specifically during bacterial infections. For a burn patient, its sometimes difficult to differentiate, on the basis of the clinical examination , those who suffer from an acute inflammatory syndrome from those who show the first signs of a severe bacterial infection. However, a correct diagnosis is essential for the prompt initiation of appropriate treatment . Many markers associated with an infectious state have recently been investigated. Among them , serum pro calcitonin has the best sensitivity and specificity for sepsis or other severe bacterial infections. The aim of this work is to evaluate the impact of the implementation of procalcitonin (PCT) on the management of infected patients in the burns resuscitation department of the plastic surgery department at CHU Med VI.Our study is retrospective , observational, and conducted over a period of 6 months, extending from July 1, 2022, to December 31, 2022, for 24burned patients hospitalized in the intensive care unit of the plastic surgery department .The average age of the patients was 38 years they were predominantly male with a sex ratio of about 1.5 . The average burned skin surface was 27.75% 40.3% had a deepening with signsof skin infection all patients CRP was high 60% had a fever higher than 38.5 13.3% had a stay in the surgical resuscitation department and were discharged a PCT returned positive in 16.6% of patientsthe determination was repeated in 4 patients after 24h returned Negatif 26.6% had a positive bacteriological examination and 40% of patients received antibiotic therapy .PCT maybe used as a useful bio marker for the early diagnosis of burn sepsis in adults, and maybe combined with other diagnostic indexes to further improve the sensitivity and specificity. Thus, even throughout study provides us with the knowledge that the PCT maybe a helpful sepsis biomarker in burned patients, the findings should be viewd with caution.

Meta-analysis of the diagnostic value of serum procalcitonin for burn sepsis in adults.

Serum procalcitonin (PCT) reflects the infection status of the organism and the severity of the infection. The purpose of this study was to systematically evaluate the diagnostic value of serum PCT for burn sepsis in adults and to provide a factual basis for future clinical diagnosis and decision-making. On August 16, 2022, six databases were searched in this study and a total of 856 studies were found. The retrieved literature was comprehensively evaluated according to the inclusion and exclusion criteria, and the valid data were extracted and included for analysis. The number of true positives, false positives, true negatives and false negatives were used as indicators to evaluate the diagnostic value of serum PCT for burn sepsis in adults. In total, 15 studies met the inclusion criteria. Meta-analysis showed a combined sensitivity of 0.78 (95% CI: 0.69-0.84), a combined specificity of 0.85 (95% CI: 0.77-0.91), a combined positive likelihood ratio of 5.17 (95% CI: 3.25-8.25), a combined negative likelihood ratio of 0.26 (95% CI: 0.19-0.37), and a combined diagnostic ratio of 19.63 (95% CI: 10.17-37.90). The AUC was 0.88 (95% CI: 0.85-0.90). Serum PCT provides good early diagnostic benefits for burn sepsis in adults. More high-quality studies are required to clarify its specific early diagnostic value.

An Observational Study on Levels of Serum Fibrin Degradation Product (FDP), D-Dimer and Procalcitonin in Burn Sepsis

Background: Despite improvements in burn management, infection is still the biggest challenge in major burn cases globally. Burn causes extensive tissue destruction, immune dysfunction, increases the risk of infection and septicemia with high morbidity and mortality. The aim of this study was to observe the levels of serum fibrin degradation product (FDP), D-dimer and procalcitonin in patients with burn sepsis treated in intensive care unit (ICU). Materials &amp; Methods: This observational study was carried out in Department of Burn and Plastic Surgery, Dhaka Medical College Hospital, Dhaka from February 2018 to January 2019. Forty (40) patients with major burns, from (15% to 50% total body surface area burn) with burn sepsis, were recruited for the study. In all cases, plasma level of fibrin degradation product (FDP), D-dimer and procalcitonin were measured and recorded. Result: Male predominance (57.5%) was observed in our study. Eighty five percent (85%) patients had total body surface area burn (TBSA) 20% to 50%. Sixteen patients (40%) suffered from flame burn, 13 (32.5%) patients from scalds and 11 (27.5%) patients had high voltage electric burn. The value of FDP was raised in 62.5% patients, D- dimer in 67.5% patients. Serum procalcitonin level was high (&gt; 2ng/ml), indicating burn sepsis in 47.5% cases but it was not significant (2 sample t – test reveals no significant relationship between rise of serum level of procalcitonin and presence of burn sepsis) Conclusion: Fibrin degradation product (FDP) and D- dimer were raised in two-thirds of burn cases while procalcitonin in two-fifths cases. Measurement of serum level of FDP, Ddimer and procalcitonin may give an idea regarding early onset of bacterial infection and burn sepsis and can serve as an indicator for burn sepsis. J Bangladesh Coll Phys Surg 2023; 41: 193-197

713 Acute Change in qSOFA Score as a Prognostic Tool for Diagnosing Sepsis in Burn Patients

Abstract Introduction Sepsis is a diagnostic challenge in all critically ill patients, but particularly so in the burn patient population. The objective of this study was to evaluate if the modified sepsis-3 criteria defined as an acute change in SOFA score ≥2 was predictive of clinical infection. Methods The hospital database was reviewed between 2016 and 2019 to identify patients who received broad spectrum antibiotics within 2 days of sustaining their injury. Culture specimens taken at the time of antibiotic administration determined presence of a clinical infection. Results Between 2016 and 2019, a total of 98 patients were admitted to the burn unit within 2 days of their injury and received prophylactic meropenum and/or piperacillin/tazobactam for suspicion of clinical infection. When stratified based on an acute change in SOFA score within 48 hours prior to receiving antibiotics, 67 (72%) patients received antibiotics with an acute change in SOFA score ≤1, and 26 (27%) patients received antibiotics with an acute change in SOFA score ≥2. Of those patients with the acute change in SOFA score ≥2, 22 patients (85%) had positive cultures associated with the timing of prophylactic antibiotics, as compared to 60 patients (90%) with a change in SOFA score ≤1 (p value 0.05). Conclusions Our data suggests that the modified sepsis-3 criteria is not a reliable tool for diagnosing burn sepsis. Applicability of Research to Practice Improving our ability to accurately predict sepsis in burn patients can improve patient outcomes and decrease unnecessary administration of broad spectrum antibiotics.

Surviving Sepsis After Burn Campaign

IntroductionThe Surviving Sepsis Campaign was developed to improve outcomes for all patients with sepsis. Despite sepsis being the primary cause of death after thermal injury, burns have always been excluded from the Surviving Sepsis efforts. To improve sepsis outcomes in burn patients, an international group of burn experts developed the Surviving Sepsis After Burn Campaign (SSABC) as a testable guideline to improve burn sepsis outcomes. MethodsThe International Society for Burn Injuries (ISBI) reached out to regional or national burn organizations to recommend members to participate in the program. Two members of the ISBI developed specific “patient/population, intervention, comparison and outcome” (PICO) questions that paralleled the 2021 Surviving Sepsis Campaign [1]. SSABC participants were asked to search the current literature and rate its quality for each topic. At the Congress of the ISBI, in Guadalajara, Mexico, August 28, 2022, a majority of the participants met to create “statements” based on the literature. The “summary statements” were then sent to all members for comment with the hope of developing an 80% consensus. After four reviews, a consensus statement for each topic was created or “no consensus” was reported. ResultsThe committee developed sixty statements within fourteen topics that provide guidance for the early treatment of sepsis in burn patients. These statements should be used to improve the care of sepsis in burn patients. The statements should not be considered as “static” comments but should rather be used as guidelines for future testing of the best treatments for sepsis in burn patients. They should be updated on a regular basis. ConclusionMembers of the burn community from the around the world have developed the Surviving Sepsis After Burn Campaign guidelines with the goal of improving the outcome of sepsis in burn patients.

A comparative study of outcomes of burns across multiple levels of care

BackgroundBurn injuries are a significant contributor to the burden of diseases. The management of burns at specialised burn centres has been shown to improve survival. However, in low- and middle-income countries (LMICs) major burns are managed at non-specialised burn centres due to resource constraints. There is insufficient data on survival from treatment at non-specialised burn centres in LMICs. This study aimed to compare the outcomes of burns treatment between a specialised burn centre and five non-specialised centres. MethodsA prospective cohort study was conducted on patients aged 18 years or above from January 1, 2021 to September 30, 2021. Participants were selected from the admission register at the emergency department. All burns irrespective of the mechanism of injury or %TBSA were included. Data were entered into REDCap. Statistical analysis of outcomes such as positive blood culture, length of hospital stay (LOHS) and 90-day mortality between specialised burn versus non-specialised centres was performed. Furthermore, an analysis of risk factors for mortality was performed and survival data computed. ResultsOf the 488 study participants, 36% were admitted to a specialised burn centre compared to 64% admitted to non-specialised centres. The demographic characteristics were similar between centres. Patients at the specialised burn centre compared to non-specialised centres had a significantly higher inhalation injury of 30.9% vs 7.7% (p < 0.001), > 10%TBSA at 83.4% vs 45.7% (p < 0.001), > 20%TBSA at 46.9% vs 16.6% (p < 0.001), and a median (IQR) ABSI score of 6 (5−7) vs 5 (4−6) (p < 0.0001). Furthermore, patients from specialised burn vs non-specialised centres had a longer median (IQR) time from injury to first burn excision at 7 (4−11) vs 5 (2−10) days, higher rate of burn sepsis 69% vs 35%, increased LOHS 17 (11−27) vs 12 (6−22) days, and 90-day mortality rates at 19.4% vs 6.4%. After adjusting for cofounding variables, survival data showed no difference between specialised burn and non-specialised centres (HR 1.8 95% CI 1.0–3.2, p = 0.05). ConclusionAlthough it appears that the survival of burn patients managed at non-specialised centres in a middle-income country is comparable to those managed at specialised burn centres, there is uncounted bias in our survival data. Hence, a change in practice is not advocated. However, due to resource constraint specialised burn centres in addition to managing major burns should provide training and support to the non-specialised centres.

LncRNA NEAT1/miR-495-3p regulates angiogenesis in burn sepsis through the TGF-β1 and SMAD signaling pathways.

To investigate the role of the long-chain noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in the process of angiogenesis in human umbilical vein endothelial cells (HUVECs) and illustrate its potential role in burn sepsis (BS) pathogenesis. HUVECs were treated with BS patient serum or healthy control serum. NEAT1 shRNA, miR-495-3p mimics, and miR-495-3p inhibitor were transfected into HUVECs. NEAT1 and miR-495-3 levels in serum or HUVECs were detected using quantitative reverse transcription-polymerase chain reaction. Cell counting kit-8 and flow cytometry assays were used to explore the proliferation and apoptosis of HUVECs. The expression of vascular endothelial growth factor (VEGF) in the supernatant was detected using enzyme-linked immunosorbent assay. Tube formation of HUVECs was also analyzed. Western blot analysis was used to analyze signaling pathway proteins. In HUVECs stimulated with BS patient serum, NEAT1 expression was increased, while miR-495-3p expression was decreased. In addition, NEAT1 silencing by specific shRNA inhibited cell proliferation, VEGF production, and tube formation under burn patient serum treatment, which decreased the TGFβ1/SMAD signaling pathway activation. Moreover, miR-495-3p minics inhibited angiogenesis and the activation of signaling pathways induced by NEAT1 shRNA. Furthermore, miR-495-3p inhobitor promoted angiogenesis in HUVECs and activated the TGFβ1/SMAD signaling pathway. In patients with BS, NEAT1 expression was significantly increased and miR-495-3p expression was decreased compared to healthy controls, and NEAT1 and miR-495-3p expression was associated with the clinical features of patients. Our results indicate that lncRNA NEAT1 regulates angiogenesis and activates the TGFβ1/SMAD signaling pathway during the occurrence of BS.

Glutamine alleviates intestinal injury in a murine burn sepsis model by maintaining intestinal intraepithelial lymphocyte homeostasis

Intestinal intraepithelial lymphocytes (IELs) play a sentinel role in the mucosal immune system because of their unique anatomical location in the epithelial layer. The disruption of IEL homeostasis is implicated in driving the intestinal injury of many typical inflammatory disorders, such as inflammatory bowel disease (IBD) and sepsis. Therefore, it is meaningful to alleviate intestinal injury by restoring IEL homeostasis in disease conditions. This study explores the effects of glutamine on intestinal IEL homeostasis in a murine model of burn sepsis. We report that glutamine inhibits inflammatory response and reduces injury in the small intestine of burn septic mice. This effect is attributed to the maintaining of IEL homeostasis by suppressing apoptosis and restoring the disrupted subpopulation balance induced by burn sepsis. Mechanistically, we show that glutamine does not affect the IL-15 dependent mechanisms that drive the maintenance and differentiation of IELs. Instead, glutamine sustains IEL homeostasis by upregulate aryl hydrocarbon receptor (AHR) and interleukin (IL)-22 transcription and expression. Consistently, the protective roles of glutamine in burn septic mice were repressed by further supplement with an AHR antagonist CH-223191. Collectively, our study reveals a new role of glutamine to maintain IEL homeostasis by activating the AHR signaling pathway, which in turn ameliorates intestinal injury in burn sepsis.

Glutamine promotes O-GlcNAcylation of G6PD and inhibits AGR2 S-glutathionylation to maintain the intestinal mucus barrier in burned septic mice

Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. We found that anterior gradient-2 (AGR2) plays a key role in the posttranslational modification of MUC2. Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation.

Delayed management of paediatric burn sepsis resulting in limb loss

Primary health care centres, community health centres and district hospitals often have medical staff that have minimal exposure to paediatric patients. This may contribute to the challenge of recognising a critically ill paediatric patient. It is already a difficult task as many clinicians are not comfortable or well equipped to manage burn patients, even in regional or tertiary facilities. Identification of the systemic inflammatory response syndrome (SIRS) versus sepsis is difficult in burns owing to the clinical presentation. Identifying the clinical signs determines the need for immediate treatment (i.e., fluid resuscitation) no matter the cause. Investigations will follow to determine the cause, further management and response to treatment. These two cases illustrate the deficit in skill and knowledge in the identification of the sick burninjured child. Although telemedicine has made large advances in allowing access to expert advice in remote locations, its usefulness is dependent on the clinical signs being identified and adequately portrayed to the expert. The way forward is better undergraduate and postgraduate training in this area with an emphasis on clinical acumen.

MiR-181c, a potential mediator for acute kidney injury in a burn rat model with following sepsis.

The miRNA profile is changed after burn or sepsis and is involved in regulating inflammatory reactions. However, the function and molecular mechanism of miRNAs in regulating burn sepsis-induced acute kidney injury (AKI) are still unclear. In this study, animal and cell sepsis models were established after burned rats were injected with lipopolysaccharide (LPS) or NRK-52E cells treated with LPS, respectively. Cytokine expression, inflammatory cell infiltration, serum creatinine (Scr) and kidney injury molecule-1 (KIM-1) levels were analysed after the indicated treatments. Burn sepsis increased the expression of inflammatory factors (TNF-α and IL-1β) and chemokines (MIP-1α, MIP-2 and MCP-1). Moreover, burn sepsis promoted macrophage and neutrophil infiltration into the kidney and upregulated the levels of Scr and KIM-1 in the kidney and urine. Ectopic expression of miR-181c significantly reduced LPS-induced TLR4 protein expression, suppressed KIM-1 mRNA levels and subsequently inhibited the activation of inflammatory genes (TNF-α and IL-1β) and chemokine genes (MIP-1α, MIP-2 and MCP-1). Our results demonstrated that miR-181c could suppress TLR4 expression, reduce inflammatory factor and chemokine secretion, mitigate inflammatory cell infiltration into the kidney and downregulate KIM-1 expression, which might ultimately attenuate burn sepsis-induced AKI.

Acute Endotoxemia-Induced Respiratory and Intestinal Dysbiosis.

Systemic inflammatory response syndrome (SIRS) is a severe condition characterized by systemic inflammation, which may lead to multiple organ failure, shock and death. SIRS is common in burn patients, pancreatitis and sepsis. SIRS is often accompanied by intestinal dysbiosis. However, the mechanism, role and details of microbiome alterations during the early phase of acute SIRS are not completely understood. The current study aimed to characterize the dynamic alterations of both the intestinal and respiratory microbiome at two timepoints during the early phase of acute SIRS (4 and 8 h after LPS) and link these to the host response in a mouse model of a LPS-induced lethal SIRS. Acute SIRS had no effect on the microbiome in the large intestine but induced a rapid dysbiosis in the small intestine, which resembled the microbiome alterations commonly observed in SIRS patients. Later in the disease progression, a dysbiosis of the respiratory microbiome was observed, which was associated with the MMP9 expression in the lungs. Although similar bacteria were increased in both the lung and the small intestine, no evidence for a gut-lung translocation was observed. Gut dysbiosis is commonly observed in diseases involving inflammation in the gut. However, whether the inflammatory response associated with SIRS and sepsis can directly cause gut dysbiosis was still unclear. In the current study we provide evidence that a LPS-induced SIRS can directly cause dysbiosis of the small intestinal and respiratory microbiome.

A bibliometric analysis of publications on burn sepsis using VOSviewer.

BackgroundSepsis is one of the most common complications in burn patients and causes high morbidity, especially in those with severe burns. Nevertheless, there are no formal criteria for diagnosing and treating burn sepsis. Therefore, this bibliometric analysis is applied to reveal research trends in this field and predicts its possible hot spots.MethodsWe screened relevant literature on burn sepsis that met the inclusion criteria of the Web of Sciences (WOS) database and analyzed publication trends and research hot spots in related fields using VOSviewer software.ResultsFrom 1981 to 2022, we screened 2,486 documents that met the requirements and analyzed them bibliometrically. The American scholar Herndon DN had a much higher h-index [47] than other authors. Most published, cited, and h-indexed publications are from the USA (Np: 1193, Nc: 42154, H: 98). The second most publishing country is China, but the second most cited and h-indexed country is Germany. Burns also outperforms other journals in this field (Np: 376, Nc: 8019, H: 46). “Biomarkers” is a newly emerging keyword (cluster “clinical research,” APY was 2018.16), and clinically relevant research in burn sepsis maybe a future research trend.ConclusionsSepsis in burn patients has unique pathophysiological characteristics and the general diagnostic criteria for sepsis lack specificity. Consequently, we must establish a database and construct an intelligent predictive model to help achieve a more individualized and precise early diagnosis and treatment of burn sepsis. This may also be an important development direction for future research in this field.