Management and outcome of bronchial trauma due to blunt versus penetrating injuries.

BACKGROUND: The number of patients with bronchial trauma (BT) who survived to hospital admission has increased with the improvement of prehospital care; early diagnosis and treatment should be considered, especially among blunt trauma patients, whose diagnosis is frequently delayed. AIM: To describe the early recognition and surgical management considerations of blunt and penetrating BTs, and to elaborate the differences between them. METHODS: All patients with BTs during the past 15 years were reviewed, and data were retrospectively analyzed regarding the mechanism of injury, diagnostic and therapeutic procedures, and outcomes. According to the injury mechanisms, the patients were divided into two groups: Blunt BT (BBT) group and penetrating BT (PBT) group. The injury severity, treatment procedures, and prognoses of the two groups were compared. RESULTS: A total of 73 patients with BT were admitted during the study period. The proportion of BTs among the entire cohort with chest trauma was 2.4% (73/3018), and all 73 underwent thoracotomy. Polytrauma patients accounted for 81.6% in the BBT group and 22.9% in the PBT group, and the mean Injury Severity Score was 38.22 ± 8.13 and 21.33 ± 6.12, respectively. Preoperative three-dimensional spiral computed tomography (CT) and/or fiberoptic bronchoscopy (FB) were performed in 92.1% of cases in the BBT group (n = 38) and 34.3% in the PBT group (n = 35). In the BBT group, a delay in diagnosis for over 48 h occurred in 55.3% of patients. In the PBT group, 31 patients underwent emergency thoracotomy due to massive hemothorax, and BT was confirmed during the operation. Among them, 22 underwent pulmo-tractotomy for hemostasis, avoiding partial pneumonectomy. In this series, the overall mortality rate was 6.9% (5/73), and it was 7.9% (3/38) and 5.7% (2/35) in the BBT group and PBT group, respectively (P > 0.05). All 68 survivors were followed for 6 to 42 (23 ± 6.4) mo, and CT, FB, and pulmonary function examinations were performed as planned. All patients exhibited normal lung function and healthy conditions except three who required reoperations. CONCLUSION: The difference between blunt and penetrating BTs is obvious. In BBT, patients generally have no vessel injury, and the diagnosis is easily missed, leading to delayed treatment. The main cause of death is ventilation disturbance due to tension pneumothorax early and refractory atelectasis with pneumonia late. However, in PBT, most patients require emergency thoracotomy because of simultaneous vessel trauma and massive hemothorax, and delays in diagnosis are infrequent. The leading cause of death is hemorrhagic shock.

The Chinese consensus for surgical treatment of traumatic rib fractures 2021 (C-STTRF 2021).

Rib fracture is the most common injury in chest trauma. Most of patients with rib fractures were treated conservatively, but up to 50% of patients, especially those with combined injury such as flail chest, presented chronic pain or chest wall deformities, and more than 30% had long-term disabilities, unable to retain a full-time job. In the past two decades, surgery for rib fractures has achieving good outcomes. However, in clinic, there are still some problems including inconsistency in surgical indications and quality control in medical services. Before the year of 2018, there were 3 guidelines on the management of regional traumatic rib fractures were published at home and abroad, focusing on the guidance of the overall treatment decisions and plans; another clinical guideline about the surgical treatment of rib fractures lacks recent related progress in surgical treatment of rib fractures. The Chinese Society of Traumatology, Chinese Medical Association, and the Chinese College of Trauma Surgeons, Chinese Medical Doctor Association organized experts from cardiothoracic surgery, trauma surgery, acute care surgery, orthopedics and other disciplines to participate together, following the principle of evidence-based medicine and in line with the scientific nature and practicality, formulated the Chinese consensus for surgical treatment of traumatic rib fractures (STTRF 2021). This expert consensus put forward some clear, applicable, and graded recommendations from seven aspects: preoperative imaging evaluation, surgical indications, timing of surgery, surgical methods, rib fracture sites for surgical fixation, internal fixation method and material selection, treatment of combined injuries in rib fractures, in order to provide guidance and reference for surgical treatment of traumatic rib fractures.

Blunt Cardiac Injury: A Single-Center 15-Year Experience.

In recent years, the incidence of blunt cardiac injury (BCI) has increased rapidly and is an important cause of death in trauma patients. This study aimed to explore early diagnosis and therapy to increase survival. All patients with BCI during the past 15 years were analyzed retrospectively regarding the mechanism of injury, diagnostic and therapeutic methods, and outcome. The patients were divided into two groups according to the needs of their condition-nonoperative (Group A) and operative (Group B). Comparisons of the groups were performed. A total of 348 patients with BCI accounted for 18.3 per cent of 1903 patients with blunt thoracic injury. The main cause of injury was traffic accidents, with an incidence of 48.3 per cent. In Group A (n = 305), most patients sustained myocardial contusion, and the mortality was 6.9 per cent. In Group B (n = 43), including those with cardiac rupture and pericardial hernia, the mortality was 32.6 per cent. Comparisons of the groups regarding the shock rate and mortality were significant (P < 0.01). Deaths directly resulting from BCI in Group B were greater than those in Group A (P < 0.05). In all 348 patients, the mortality rate was 10.1 per cent. When facing a patient with blunt thoracic injury, a high index of suspicion for BCI must be maintained. To manage myocardial contusion, it is necessary to protect the heart, alleviate edema of the myocardium, and control arrhythmia with drugs. To deal with those requiring operation, early recognition and expeditious thoracotomy are essential.

Emergency Surgery for Blunt Cardiac Injury: Experience in 43 Cases.

BACKGROUND: Blunt cardiac injury (BCI) increases with traffic accidents and is an important cause of death in trauma patients. In particular, for patients who need surgical treatment, the mortality rate is extremely high unless the patient is promptly operated on. This study aimed to explore early recognition and expeditious surgical intervention to increase survival. METHODS: All patients with BCIs during the past 15 years were reviewed, and those who underwent operative treatment were analyzed retrospectively regarding the mechanism of injury, diagnostic and therapeutic methods, and outcome. RESULTS: A total of 348 patients with BCIs accounted for 18.3% of 1903 patients with blunt thoracic injury (BTI). Of 348 patients, 43 underwent operative treatment. The main cause of injury was traffic accidents, with an incidence of 48.8%. Of them, steering wheel injuries occurred in 15 patients. In 26 patients, a preoperative diagnosis was obtained by echocardiography, CT scanning, etc. In the remaining 17, who had to undergo urgent thoracotomy without any preoperative imaging, a definitive diagnosis of BCI was proven during the operation. The volume of preoperative infusion or crystalloid was <1000 ml in 31 cases. Preoperative pericardiocentesis was not used in anyone. In 12 patients, the operation commenced within 1 h. Overall mortality was 32.6%. The death was caused by BCI in 9. CONCLUSIONS: Facing a patient with BTI, a high index of suspicion for BCI must be maintained. To manage those requiring operations, early recognition and expeditious thoracotomy are essential. Preoperatively, limited fluid resuscitation is emphasized. We do not advocate preoperative pericardiocentesis.

Clinical relevance of single nucleotide polymorphisms in the CXCL1 and CXCL12 genes in patients with major trauma.

BACKGROUND: Genetic backgrounds have been recognized as significant determinants of susceptibility to sepsis. CXC chemokines play a significant role in innate immunity against infectious diseases. Genetic polymorphisms of CXC chemokine genes have been widely studied in inflammatory and infectious diseases but not in sepsis. Thus, we aimed to investigate the clinical relevance of CXC chemokine gene polymorphisms and susceptibility to sepsis in a traumatically injured population. METHODS: Thirteen tag single nucleotide polymorphisms were selected from CXC chemokine genes using a multimarker tagging algorithm in the Tagger software. Three independent cohorts of injured patients (n = 1700) were prospectively recruited. Selected single nucleotide polymorphisms were genotyped using an improved multiplex ligation detection reaction method. Cytokine production in lipopolysaccharide-stimulated whole blood was measured using an enzyme-linked immunosorbent assay. RESULTS: Among the 13 tag single nucleotide polymorphisms, four single nucleotide polymorphisms (rs1429638, rs266087, rs2297630, and rs2839693) were significantly associated with the susceptibility to sepsis, and three (rs3117604, rs1429638, and rs4074) were significantly associated with an increased multiple organ dysfunction score in the derivation cohort. However, only the clinical relevance of rs1429638 and rs266087 was confirmed in the validation cohorts. In addition, rs2297630 was significantly associated with interleukin 6 production. CONCLUSION: The rs1429638 polymorphism in the CXCL1 gene and the rs2297630 polymorphism in the CXCL12 gene were associated with altered susceptibility to sepsis and might be used as important genetic markers to assess the risks of sepsis in trauma patients. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level II.

China Medical Team: Medical rescue for "4.25" Nepal earthquake.

In recent years, global natural disasters have been frequent and resulted in great casualties and property loss. Since Wenchuan earthquake, the disaster emergency rescue system of China has obtained considerable development in various aspects including team construction, task scheduling, personnel training, facilities and equipments, logistics, etc. On April 25, 2015, an earthquake that measured 8.1 on the Richter scale attacked Nepal. Chinese government firstly organized a medical team, named China Medical Team, and sent it to the attacked region in Nepal to implement medical rescue. The medical team completed the rescue mission successfully and creatively based on their experiences.

Identification of Haplotype Tag Single-Nucleotide Polymorphisms within the PPAR Family Genes and Their Clinical Relevance in Patients with Major Trauma.

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) play important roles in the development of inflammatory diseases and sepsis. Recently, genetic variants of PPARs genes have been widely studied in some inflammatory diseases. However, the association between PPAR family of genes polymorphisms and sepsis risk in trauma patients was little known. METHODS: SNPs were selected from the PPARs genes through constructing haplotype blocks and genotyped by the improved multiplex ligation detection reaction (iMLDR) method. The association between the selected SNPs and the risk of sepsis and multiple organ dysfunction (MOD) scores was evaluated in 734 trauma patients. In addition, tumor necrosis factor α (TNFα) production of peripheral blood leukocytes was also analyzed after lipopolysaccharide (LPS) stimulation. RESULTS: Our results revealed that there were significant associations between the rs10865710 polymorphism and the risk of sepsis and MOD scores in Chinese Han trauma patients. Further, we found that the level of TNFα production was higher in patients with the rs10865710 G allele compared to those with the variant C allele. CONCLUSIONS: The rs10865710 polymorphism in the PPARγ gene might be used to assess the risk of sepsis and multiple organ dysfunction syndrome (MODS) in trauma patients.

Mobile emergency (surgical) hospital: Development and application in medical relief of "4.20" Lushan earthquake in Sichuan Province, China.

In the 21st century, natural disasters and emergencies occur frequently worldwide, which leads to the loss of hundreds of thousands of lives as well as the direct and indirect economic losses. China has a vast territory frequently struck by natural disasters. However, the reality is not optimistic. Poor organization and management during the rescue actions, the lack of large-scale, systematic medical rescue equipment were all great barriers to the outcomes. Mobile hospitals are expected to provide better health care. We were inspired by the concept of mobile hospital. Chongqing Emergency Medical Center, has set up trauma care system since 1988, in which prehospital care, intensive care, and in-hospital treatment is fully integrated. As a major advantage, such a system provided assurance of "golden hour" rescue treatment. Providing mobile intensive care and prehospital surgical service for severe trauma patients could reduce mortality significantly. Based on the civilian experiences in Chongqing Emergency Medical Center, the mobile emergency (surgical) hospital was developed.

Traumatic diaphragmatic rupture with combined thoracoabdominal injuries: Difference between penetrating and blunt injuries.

PURPOSE: Traumatic diaphragmatic rupture (TDR) needs early diagnosis and operation. However, the early diagnosis is usually difficult, especially in the patients without diaphragmatic hernia. The objective of this study was to explore the early diagnosis and treatment of TDR. METHODS: Data of 256 patients with TDR treated in our department between 1994 and 2013 were analyzed retrospectively regarding to the diagnostic methods, percentage of preoperative judgment, incidence of diaphragmatic hernia, surgical procedures and outcome, etc. Two groups were set up according to the mechanism of injury (blunt or penetrating). RESULTS: Of 256 patients with a mean age of 32.4 years (9-84), 218 were male. The average ISS was 26.9 (13-66); and shock rate was 62.9%. There were 104 blunt injuries and 152 penetrating injuries. Preoperatively diagnostic rate was 90.4% in blunt injuries and 80.3% in penetrating, respectively, P < 0.05. The incidence of diaphragmatic hernia was 94.2% in blunt and 15.1% in penetrating respectively, P < 0.005. Thoracotomy was performed in 62 cases, laparotomy in 153, thoracotomy plus laparotomy in 29, and combined thoraco-laparotomy in 12. Overall mortality rate was 12.5% with the average ISS of 41.8; and it was 21.2% in blunt injuries and 6.6% in penetrating, respectively, P < 0.005. The main causes of death were hemorrhage and sepsis. CONCLUSIONS: Diagnosis of blunt TDR can be easily obtained by radiograph or helical CT scan signs of diaphragmatic hernia. For penetrating TDR without hernia, "offside sign" is helpful as initial assessment. CT scan with coronal/sagittal reconstruction is an accurate technique for diagnosis. All TDR require operation. Penetrating injury has a relatively better prognosis.

Multi-slice computed tomography for diagnosis of combined thoracoabdominal injury.

PURPOSE: To investigate the diagnostic value of multi-slice computed tomography (MSCT) for combined thoracoabdominal injury. METHODS: A retrospective study was conducted to analyze the clinical data and MSCT images of 68 patients who sustained a combined thoracoabdominal injury associated with diaphragm rupture, and 18 patients without diaphragm rupture. All the patients were admitted and treated in the Chongqing Emergency Medical Center (a level I trauma center) between July 2005 and February 2014. There were 71 males and 15 females with a mean age of 39.1 years (range 13e88 years). Among the 86 patients, 40 patients suffered a penetrating injury, 46 suffered a blunt injury as a result of road traffic accident in 21 cases, fall from a height in 16, and crushing injury in 9. The MSCT images were retrospectively reviewed by two radiologists. The results of CT diagnosis were compared with surgical findings and/or follow-up results. RESULTS: Among the 86 cases, diaphragm discontinuity was found in 29 cases, segmental nonrecognition of the diaphragm in 14, diaphragmatic hernia in 21, collar sign in 14, dependent viscera sign in 18, elevated abdominal organs in 21, bowel wall thickening and/or hematoma in 6, and pneumoperitoneum in 8. CT diagnostic accuracy for diaphragm rupture was 88.4% in the right side and 90.7% in the left side. CT diagnostic accuracy for hemopneumothorax, pulmonary contusion, mediastinal hemorrhage, kidney and adrenal gland injuries was 100%, while for liver, spleen and pancreas injuries was 96.5%, 96.5%, 94.2% respectively. CONCLUSION: To reach an early diagnosis of combined thoracoabdominal injury, surgeons and radiologists should be familiar with all kinds of images which might show signs of diaphragm rupture, such as diaphragm discontinuity, segmental nonrecognition of the diaphragm, dangling diaphragm sign, diaphragm herniation, collar sign, dependent viscera sign, and elevated abdominal organs.

Identification of haplotype tag single nucleotide polymorphisms within the nuclear factor-κB family genes and their clinical relevance in patients with major trauma.

INTRODUCTION: Nuclear factor-κB (NF-κB) family plays an important role in the development of sepsis in critically ill patients. Although several single nucleotide polymorphisms (SNPs) have been identified in the NF-κB family genes, only a few SNPs have been studied. METHODS: A total of 753 patients with major blunt trauma were included in this study. Tag SNPs (tSNPs) were selected from the NF-κB family genes (NFKB1, NFKB2, RELA, RELB and REL) through construction of haplotype blocks. The SNPs selected from genes within the canonical NF-κB pathway (including NFKB1, RELA and REL), which played a critical role in innate immune responses were genotyped using pyrosequencing method and analyzed in relation to the risk of development of sepsis and multiple organ dysfunction (MOD) syndrome. Moreover, the rs842647 polymorphism was analyzed in relation to tumor necrosis factor α (TNF-α) production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. RESULTS: Eight SNPs (rs28362491, rs3774932, rs4648068, rs7119750, rs4803789, rs12609547, rs1560725 and rs842647) were selected from the NF-κB family genes. All of them were shown to be high-frequency SNPs in this study cohort. Four SNPs (rs28362491, rs4648068, rs7119750 and rs842647) within the canonical NF-κB pathway were genotyped, and rs842647 was associated with sepsis morbidity rate and MOD scores. An association was also observed between the rs842647 A allele and lower TNF-α production. CONCLUSIONS: rs842647 polymorphism might be used as relevant risk estimate for the development of sepsis and MOD syndrome in patients with major trauma.

Genetic variants of microRNA sequences and susceptibility to sepsis in patients with major blunt trauma.

OBJECTIVE: The objective of this study was to conduct a systematic survey of common precursor microRNA (pre-miRNA) single nucleotide polymorphisms (SNPs) and evaluate their clinical relevance in patients with major blunt trauma. BACKGROUND: Recent evidence indicates that small noncoding RNA molecules known as miRNAs can function as important negative gene regulators and are implicated in the pathogenesis of various diseases. METHODS: We conducted a 2-stage study to examine the impact of 9 selected SNPs with potential functional significance on the susceptibility to sepsis of 1268 trauma patients (1 screening cohort, n = 666) and 2 independent validated cohorts (n = 286 and n = 316, respectively) in China. RESULTS: Among the 9 selected SNPs with potential functional significance, only 1 (miR-608 rs4919510) was found to be strongly associated with a higher risk of developing sepsis and multiple organ dysfunction in all 3 independent study cohorts. An even stronger association was observed for the rs4919510 polymorphism when combining these 3 study cohorts together. In addition, the rs4919510 polymorphism showed a significant correlation with a higher production of proinflammatory cytokines and a lower production of anti-inflammatory cytokines. In vitro experiments further indicated that the G→C variant of this polymorphism could significantly increase the expression of mature miR-608. CONCLUSIONS: Our results indicate that the rs4919510G/C SNP in hsa-mir-608 may be a prognostic biomarker for sepsis in patients with major trauma. Further characterization of miRNA SNPs may open new avenues for studying sepsis and developing novel therapeutic approaches.

Plasma levels of high mobility group box 1 increase in patients with posttraumatic stress disorder after severe blunt chest trauma: a prospective cohort study.

BACKGROUND: High-mobility group box 1 (HMGB1), a key late mediator of systemic inflammation, is a potentially useful biomarker for predicting outcome in patients with severe blunt chest trauma. The purpose of this study was to define the relationship between plasma levels of HMGB1 and posttraumatic stress disorder (PTSD) in patients with severe blunt chest trauma. METHODS: All patients with severe blunt chest trauma (abbreviated injury score ≥3) who were admitted to traumatic surgery department and ultimately survived to follow-up at 6 mo were eligible for the study. HMGB1 was sampled every other day from day 1-day 7 after admission, and plasma concentrations of HMGB1 were measured by a quantitative enzyme-linked immunosorbent assay test. Multivariate regression analysis was used to define the independent contribution of possible risk factors selected by univariate analysis. RESULTS: PTSD was identified in 43 patients including acute PTSD (n = 21), chronic PTSD (n = 18), and delayed-onset PTSD (n = 4) after 6-mo follow-up, in whom significant higher plasma levels of HMGB1 on days three, five, and seven after blunt chest trauma were noted compared with those seen in patients without PTSD (n = 10). Multivariate logistic analysis showed that transfusion, injury severity score, and HMGB1 levels at day 7 were the valuable risk factors for PTSD. CONCLUSIONS: In blunt chest trauma, plasma HMGB1 levels were significantly higher in patients with PTSD compared with patients with non-PTSD. Our data indicate that patients with high plasma levels of HMGB1 may be more prone to develop PTSD including acute and chronic PTSD.

Brachiocephalic trunk and left brachiocephalic vein injuries following penetrating right sternoclavicular junction trauma: a case report.

A 46-year-old male sustained severe pe- netrating injury by a sharp instrument to his right upper sternoclavicular junction. The wound tract was from suprasternal notch to mediastinum. Exploratory operation via median sternotomy under general anesthesia found a large mediastinal septum hematoncus, as well as brachiocephalic trunk and left brachiocephalic vein injuries. The perforating vascular wounds were repaired with 5-0 prolene suture. He was recovered uneventfully and discharged 9 days after operation. There was no sequel found during 7 years follow-up.

[Risk factors of mortality in severe chest trauma patients].

OBJECTIVE: To investigate the risk factors of mortality in patients with severe chest trauma (SCT). METHODS: The clinical data of 777 SCT [abbreviated injury scale (AIS) ≥3] patients who were treated in the Chongqing Emergency Medical Center from January 2006 to April 2009 were retrospectively reviewed. Stepwise logistic regression analysis was used to explore 15 possible mortality-related risk factors. RESULTS: Seven factors were found to be correlated with the mortality of SCT: age, hemorrhagic shock, multiple organ dysfunction syndrome (MODS), pulmonary infection, abdominal organ injury, Glasgow coma scale (GCS) score, and thorax AIS score. Among them five factors were the independent factors that might increase the mortality of SCT: hemorrhagic shock (B=1.710, OR=1.291, P=0.001), MODS (B=3.453, OR=1.028, P<0.001), pulmonary infection (B=2.396, OR=10.941, P<0.001), abdominal organ injury (B=1.542, OR=1.210, P=0.005), and thorax AIS score ≥4 (B=0.487, OR=1.622, P<0.001). Two factors showed protective effects: age ≤60 years (B=-0.035, OR=0.962, P=0.01) and GCS score ≥12 (B=-0.635, OR=0.320, P<0.001). CONCLUSIONS: Age, disease severity, and complications (hemorrhagic shock, MODS, and pulmonary infection) are independent risk factors of the mortality of SCT. Effective treatment programs targeting these risk factors may improve the outcomes of SCT patients.

Identification of haplotype tag single nucleotide polymorphisms within the receptor for advanced glycation end products gene and their clinical relevance in patients with major trauma.

INTRODUCTION: The receptor for advanced glycation end products (RAGE) has been considered as one of the major pattern recognition receptors and plays an important role in the development of sepsis and multiple organ dysfunction in critical illnesses. Although genetic variants of the RAGE gene have been shown to be well associated with susceptibility to some inflammatory diseases, little is known about their clinical relevance in the development of sepsis in critical ill patients. METHODS: Four genetic variants were selected from the entire RAGE gene and genotyped using pyrosequencing and polymerase chain reaction-length polymorphism methods. Association studies were performed in two independent Chinese Han populations. RESULTS: Among the four genetic variants, only the rs1800625 polymorphism was significantly associated with sepsis morbidity rate and multiple organ dysfunction (MOD) scores in patients with major trauma both in Chongqing (n = 496) and Zhejiang (n = 232) districts, respectively. Results from ex vivo responsiveness of peripheral blood leukocytes indicated that the rs1800625 polymorphism was well associated with decreased production of TNFα. In addition, the rs1800625 polymorphism could significantly inhibit the promoter activities of the RAGE gene. CONCLUSIONS: The rs1800625 polymorphism is a functional variant, which might be used as a relevant risk estimate for the development of sepsis and multiple organ dysfunction syndrome in patients with major trauma.

Endothelialization and in-stent restenosis on the surface of glycoprotein IIIa monoclonal antibody eluting stent.

Since the percutaneous transtuminal coronary angioplasty was introduced into China in 1984, this procedure has become widely accepted as an important step in coronary revascularization. This study shows the effect of the monoclonal antibody (mAb) on the platelet glycoprotein IIIa receptor during endothelialization and in-stent restenosis by implanting the mAb-eluting stents into iliac arteries of rabbits. The hard tissue cross sections of the stent-implanted arterial segments were made by polymethylmethacrylate embedding. Arterial intima proliferation was observed and analyzed. The endothelialization of the stent surface was observed using scanning electron microscope, whereas the ultrastructure of the neointima was observed using transmission electron microscope. After one month of stent implantation, the surfaces of both groups were covered by intact endothelial layers, but the neointimal areas and the ratio of stenosis were significantly lesser in the mAb-eluting stent group (p < 0.01). After 3 months, the ratio of stenosis in the mAb-eluting stent group was 14.67 ± 0.79, whereas that of the bare stent group was 21.58 ± 1.76 (p < 0.01). Therefore, the mAb eluting from the stent surface has the potential to accelerate endothelialization, prevent thrombosis formation due to the interaction of stent with blood, and decrease the stenosis ratio by inhibiting neointima proliferation.

Identification of haplotype tag SNPs within the whole myeloid differentiation 2 gene and their clinical relevance in patients with major trauma.

Myeloid differentiation 2 (MD-2) plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire MD-2 gene and to investigate their clinical relevance in patients with major trauma. A total of 726 patients with major trauma were prospectively recruited and composed of two different geographic populations (Chongqing in southwestern China and Zhejiang in eastern China). The htSNPs of the MD-2 gene were determined using HapMap database and linkage disequilibrium analysis. The htSNPs were genotyped using pyrosequencing method. The whole peripheral blood samples obtained immediately after admission were stimulated with bacterial lipopolysaccharide and then determined for production of tumor necrosis factor α. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were accessed. Three SNPs (rs7843858, rs11465996, and rs2114169) were identified as htSNPs for the MD-2 gene. All of them were shown to be high-frequent SNPs in this study cohort. However, only the rs11465996 polymorphism was shown to be significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma in both Chongqing and Zhejiang districts. In addition, the rs11465996 polymorphism was significantly associated with tumor necrosis factor α production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Among the three htSNPs of the entire MD-2 gene, only the rs11465996 might be used as relevant risk estimate for the development of sepsis and MOD syndrome in patients with major trauma.

A functional variant of lipopolysaccharide binding protein predisposes to sepsis and organ dysfunction in patients with major trauma.

OBJECTIVE: To determine the hypothesis that genetic variations of the lipopolysaccharide-binding protein (LBP) gene influence risk for the development of sepsis and multiple organ dysfunction (MOD) in patients with major trauma. BACKGROUND: Lipopolysaccharide-binding protein plays a central role in innate immune response as the first line of defense and directing the microbial-induced activation of the inflammatory host response. Although a total of 112 single nucleotide polymorphisms (SNPs) have been identified so far within the entire LBP gene, only a few SNPs have been studied. METHODS: Nine haplotype tagging SNPs (htSNPs) were selected from 51 SNPs with a minor allele frequency of ≥5% using the HapMap database for the Chinese Han population. Two independent cohorts of major trauma patients were recruited. The 9 htSNPs were genotyped using pyrosequencing method and analyzed in relation to the risk of development of sepsis and MOD, LBP production, and lipopolysaccharide (LPS)-induced activation of peripheral blood leukocytes. Moreover, the functionality of the rs2232618 polymorphism was assessed by the observation of its effects on the binding and activation of LPS and the LBP-CD14 interaction. RESULTS: Among the 9 htSNPs, only the rs2232618 was significantly associated with higher susceptibility to sepsis and MOD in the 2 independent cohorts of major trauma patients recruited from southwest and eastern China. This SNP was also significantly associated with LPS-induced activation of peripheral blood leukocytes. In addition, the rs2232618 polymorphism could enhance LBP protein activities, showing significant increases in LPS binding to macrophages, LPS-induced cellular activation, and LBP-CD14 interaction at the presence of the variant LBP protein. CONCLUSIONS: The rs2232618 polymorphism is a functional SNP and confers host susceptibility to sepsis and multiple organ dysfunction in patients with major trauma.

Clinical relevance of single nucleotide polymorphisms of the high mobility group box 1 protein gene in patients with major trauma in southwest China.

BACKGROUND: High-mobility group box protein 1 (HMGB1) is a pivotal late mediator involved in the development of sepsis and multiple organ dysfunction syndrome (MODS) in critically ill patients. While several single nucleotide polymorphisms (SNPs) have been demonstrated to be critical determinants for outcome of critically ill patients, little is known about the clinical relevance of SNPs of the HMGB1 gene up to date. METHODS: A total of 3 tag SNPs of the HMGB1 gene were selected using HapMap database and linkage disequilibrium analysis. The tag SNPs were genotyped using a pyrosequencing methodology in 556 unrelated patients with major trauma. Peripheral whole blood samples obtained immediately after admission were determined for HMGB1 production in response to ex vivo lipopolysaccharide (LPS) stimulation. RESULTS: The rs2249825 SNP and the haplotype TCG were significantly associated with LPS-induced HMGB1 production by peripheral blood leukocytes. There were also significant differences in sepsis morbidity rate and MOD scores among patients with different genotypes of the rs2249825. In addition, the patients with the wild-type haplotype TCG had a lesser sepsis morbidity rate and MOD scores than those without the TCG haplotype. CONCLUSION: A total of 3 SNPs might act as tag SNPs for the entire HMGB1 gene. The rs2249825 and the haplotype TCG might be used as relevant risk estimate for the development of sepsis and MODS in patients with major trauma.