Sepsis is a life-threatening disease with limited treatment options, and the inflammatory process represents an important factor affecting its progression. Many studies have demonstrated the critical roles of signal transducer and activator of transcription 3 (STAT3) in sepsis pathophysiology and pro-inflammatory responses. Inhibition of STAT3 activity may therefore represent a promising treatment option for sepsis. We here used a mouse model to demonstrate that (E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP) treatment prevented the liver sepsis-related mortality induced by 30 mg/kg lipopolysaccharide (LPS) treatment and reduced LPS-induced increase in alanine transaminase, aspartate transaminase, and lactate dehydrogenase levels, all of which are markers of liver sepsis progression. These recovery effects were associated with decreased LPS-induced STAT3, p65, and JAK1 phosphorylation and proinflammatory cytokine (interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha) level; expression of cyclooxygenase-2 and induced nitric oxide synthase were also reduced by MMPP. In an in vitro study using the normal liver cell line THLE-2, MMPP treatment prevented the LPS-induced increase of STAT3, p65, and JAK1 phosphorylation and inflammatory protein expression in a dose-dependent manner, and this effect was enhanced by combination treatment with MMPP and STAT3 inhibitor. The results clearly indicate that MMPP treatment prevents LPS-induced mortality by inhibiting the inflammatory response via STAT3 activity inhibition. Thus, MMPP represents a novel agent for alleviating LPS-induced liver sepsis.

Penetrating abdominal injury is a major cause of death in trauma. Sodium alginate hydrogel, a hemostatic agent, offers a platform for targeting both mechanical and biological injuries. The current study assessed the effect of Very Low Viscosity (high) G (VLVG) alginate following abdominal trauma in a swine model of penetrating abdominal injury. Seven anesthetized pigs were instrumented with invasive monitoring catheters and abdominal trauma was introduced by laparoscopic hepatectomy. Ten minutes after the induction of hypovolemic shock, three animals were intra-abdominally administered with VLVG alginate (study group) and four animals with saline (control group). During 8 h of continuous monitoring, various hemodynamic and biochemical variables were measured and liver biopsies for histological evaluation were taken. Hemodynamically, VLVG alginate-treated animals were more stable than controls, as reflected by their lower heart rate and higher blood pressure (p < 0.05 for both). They also had lower levels of liver enzymes and lactate, and less histopathological damage. We show that VLVG alginate might be a promising new agent for reducing penetrating intra-abdominal injury, with hemostatic and biocompatibility efficiency, and tissue preserving properties. Future effort of integrating it with a dispersal device may turn it into a valuable pre-hospital emergency tool to improve survival of trauma casualties.

Two randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach.

The International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries.

The invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval.

In this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction.

Patients with traumatic acute subdural hematoma (ASDH) often require surgical treatment. Among patients who primarily underwent craniotomy for the removal of hematoma, some consequently developed aggressive intracranial hypertension and brain edema, and required secondary decompressive craniectomy (DC). To avoid reoperation, we investigated factors which predict the requirement of DC by comparing groups of ASDH patients who did and did not require DC after craniotomy.

The 129 patients with ASDH who underwent craniotomy from September 2007 to September 2017 were reviewed. Among these patients, 19 patients who needed additional DC (group A) and 105 patients who underwent primary craniotomy only without reoperation (group B) were evaluated. A total of 17 preoperative and intraoperative factors were analyzed and compared statistically. Univariate and multivariate analyses were used to compare these factors.

Five factors showed significant differences between the two groups. They were the length of midline shifting to maximal subdural hematoma thickness ratio (magnetization transfer [MT] ratio) greater than 1 (p<0.001), coexistence of intraventricular hemorrhage (IVH) (p<0.001), traumatic intracerebral hemorrhage (TICH) (p=0.001), intraoperative findings showing intracranial hypertension combined with brain edema (p<0.001), and bleeding tendency (p=0.02). An average value of 2.74±1.52 was obtained for these factors for group A, which was significantly different from that for group B (p<0.001).

An MT ratio >1, IVH, and TICH on preoperative brain computed tomography images, intraoperative signs of intracranial hypertension, brain edema, and bleeding tendency were identified as factors indicating that DC would be required. The necessity for preemptive DC must be carefully considered in patients with such risk factors.

Sepsis is a systemic inflammatory response to infection eliciting high mortality rate which is a serious health problem. Despite numerous studies seeking for therapeutic alternatives, the mechanisms involved in this disease remain elusive. In this study we evaluated the influence of cholesteryl ester transfer protein (CETP), a glycoprotein that promotes the transfer of lipids between lipoproteins, on the inflammatory response in mice. Human CETP transgenic mice were compared to control mice (wild type, WT) after polymicrobial sepsis induced by cecal ligation and puncture (CLP), aiming at investigating their survival rate and inflammatory profiles. Macrophages from the peritoneal cavity were stimulated with LPS in the presence or absence of recombinant CETP for phenotypic and functional studies. In comparison to WT mice, CETP mice showed higher survival rate, lower IL-6 plasma concentration, and decreased liver toll-like receptor 4 (TLR4) and acyloxyacyl hydrolase (AOAH) protein. Moreover, macrophages from WT mice to which recombinant human CETP was added decreased LPS uptake, TLR4 expression, NF-κB activation and IL-6 secretion. This raises the possibility for new therapeutic tools in sepsis while suggesting that lowering CETP by pharmacological inhibitors should be inconvenient in the context of sepsis and infectious diseases.

The risk factors of predicting the need for postoperative decompressive craniectomy due to intracranial hypertension after primary craniotomy remain unclear. This study aimed to investigate the value of intraoperative intracranial pressure (ICP) monitoring in predicting re-operation using salvage decompressive craniectomy (SDC).

From January 2008 to October 2014, we retrospectively reviewed 284 patients with severe traumatic brain injury (STBI) who underwent craniotomy for mass lesion evacuation without intraoperative brain swelling. Intraoperative ICP was documented at the time of initial craniotomy and then again after the dura was sutured. SDC was used when postoperative ICP was continually higher than 25 mmHg for 1 h without a downward trend. Univariate and multivariate analyses were applied to both initial demographic and radiographic features to identify risk factors of SDC requirement.

Of 284, 41 (14.4%) patients who underwent SDC had a higher Initial ICP than those who didn't (38.1 ± 9.2 vs. 29.3 ± 8.1 mmHg, P < 0.001), but there was no difference in ICP after the dura was sutured. The factors which have significant effects on SDC are higher initial ICP [odds ratio (OR): 1.100, 95% confidence interval (CI): 1.052-1.151, P < 0.001], older age (OR: 1.039, 95% CI: 1.002-1.077, P = 0.039), combined lesions (OR: 3.329, 95% CI: 1.199-9.244, P = 0.021) and early hypotension (OR: 2.524, 95% CI: 1.107-5.756, P = 0.028). The area under the curve of multivariate regression model was 0.771.

The incidence of re-operation using SDC after craniotomy was 14.4%. The independent risk factors of SDC requirement are initial ICP, age, early hypotension and combined lesions.

To investigate whether the heat shock protein 70-2 (HSP70-2) polymorphism is associated with enterocutaneous fistulas in a Chinese population.

This study included 131 patients with enterocutaneous/enteroatmospheric fistulas. Patients with inflammatory bowel disease or other autoimmune diseases were excluded from this study. All patients with enterocutaneous/enteroatmospheric fistulas were followed up for three months to observe disease recurrence. In addition, a total of 140 healthy controls were also recruited from the Jinling Hospital, matched according to the sex and age of the patient population. Genomic DNA was extracted from peripheral blood from each participant. The HSP70-2 restriction fragment length polymorphism related to the polymorphic PstI site at position 1267 was characterized by polymerase chain reaction (PCR). First PCR amplification was carried out, and then PCR products were digested with PstI restriction enzyme. The DNA lacking the polymorphic PstI site within HSP70-2 generates a product of 1117 bp in size (allele A), whereas the HSP70-2 PstI polymorphism produces two fragments of 936 bp and 181 bp in size (allele B).

The frequency of the HSP70-2 PstI polymorphism did not differ between patients and controls; however, the A allele was more predominant in patients with enterocutaneous fistulas than in controls (60.7% vs 51.4%, P = 0.038, OR = 1.425, 95%CI: 1.019-1.994). Sixty-one patients were cured by a definitive operation, drainage operation, or percutaneous drainage while 52 patients were cured by nonsurgical treatment. There was no significant difference in the frequency of the HSP70-2 PstI polymorphism between the patients who had surgery compared to those who did not (P = 0.437, OR = 1.237, 95%CI: 0.723-2.117). Moreover, 11 patients refused any treatment for economic reasons or tumor burden, and 7 patients with enterocutaneous fistulas (5.8%) died during the follow-up period. However, there was no significant difference in the frequency of the HSP70-2 PstI polymorphism between the patients who survived compared to those who died (P = 0.403, OR = 0.604, 95%CI: 0.184-1.986).

The A allele of the HSP70-2 PstI polymorphism was associated with enterocutaneous fistulas in this Chinese population.