Neutrophil extracellular traps promote intestinal barrier dysfunction by regulating macrophage polarization during trauma/hemorrhagic shock via the TGF-ß signaling pathway.

The mechanism by which neutrophil extracellular traps (NETs) may cause intestinal barrier dysfunction in response to trauma/hemorrhagic shock (T/HS) remains unclear. In this study, the roles and mechanisms of NETs in macrophage polarization were examined to determine whether this process plays a role in tissue damage associated with T/HS. Rat models of T/HS and macrophage polarization were developed and the levels of NETs formation in the intestinal tissue of T/HS rats were assessed. NET formation was inhibited in models of T/HS to examine the effect on intestinal inflammation and barrier injury. The proportions of pro-inflammatory and anti-inflammatory macrophages in the damaged intestinal tissues were measured. Finally, high-throughput sequencing was performed to investigate the underlying mechanisms involved in this process. The study revealed that the level of NETs formation was increased and that inhibition of NETs formation alleviated the intestinal inflammation and barrier injury. Moreover, the number of pro-inflammatory macrophages increased and the number of anti-inflammatory macrophages decreased. RNA sequencing analysis indicated that NETs formation decreased the expression of transforming growth factor-beta receptor 2 (TGFBR2), bioinformatic analyses revealed that TGFBR2 was significantly enriched in the transforming growth factor-beta (TGF-ß) signaling pathway. Verification experiments showed that NETs impeded macrophage differentiation into the anti-inflammatory/M2 phenotype and inhibited TGFBR2 and TGF-ß expression in macrophages. However, treatment with DNase I and overexpression of TGFBR2, and inhibition of TGF-ß promoted and prevented this process, respectively. NETs may regulate the macrophage polarization process by promoting intestinal barrier dysfunction in T/HS rats through the TGFBR2-mediated TGF-ß signaling pathway.

Initial suction drainage decreases severe postoperative complications after pancreatic trauma: A cohort study.

BACKGROUND: Few studies have addressed the question of which drain types are more beneficial for patients with pancreatic trauma (PT). AIM: To investigate whether sustained low negative pressure irrigation (NPI) suction drainage is superior to closed passive gravity (PG) drainage in PT patients. METHODS: PT patients who underwent pancreatic surgery were enrolled consecutively at a referral trauma center from January 2009 to October 2021. The primary outcome was defined as the occurrence of severe complications (Clavien-Dindo grade ≥ Ⅲb). Multivariable logistic regression was used to model the primary outcome, and propensity score matching (PSM) was included in the regression-based sensitivity analysis. RESULTS: In this study, 146 patients underwent initial PG drainage, and 50 underwent initial NPI suction drainage. In the entire cohort, a multivariable logistic regression model showed that the adjusted risk for severe complications was decreased with NPI suction drainage [14/50 (28.0%) vs 66/146 (45.2%); odds ratio (OR), 0.437; 95% confidence interval (CI): 0.203-0.940]. After 1:1 PSM, 44 matched pairs were identified. The proportion of each operative procedure performed for pancreatic injury-related and other intra-abdominal organ injury-related cases was comparable in the matched cohort. NPI suction drainage still showed a lower risk for severe complications [11/44 (25.0%) vs 21/44 (47.7%); OR, 0.365; 95%CI: 0.148-0.901]. A forest plot revealed that NPI suction drainage was associated with a lower risk of Clavien-Dindo severity in most subgroups. CONCLUSION: This study, based on one of the largest PT populations in a single high-volume center, revealed that initial NPI suction drainage could be recommended as a safe and effective alternative for managing complex PT patients.

Sequential changes in body composition and metabolic response after pancreatic trauma.

OBJECTIVES: Pancreatic trauma and subsequent pancreatic operation result in early pathophysiologic alterations. Understanding changes in energy expenditure and body composition is essential for optimal management. This study aims to observe changes in energy expenditure and body composition in patients during the early postoperative days (PODs) after pancreatic trauma. METHODS: This is a retrospective review of patients who underwent surgery for blunt pancreatic trauma in a single trauma center. Data of body composition by bioimpedance spectroscopy and energy expenditure by indirect calorimetry were collected and analyzed in patients during the early PODs. The association of body composition parameters with major complications was analyzed. RESULTS: Forty-one patients were included. Compared with POD-3, the total body water, extracellular water, fat-free mass, and skeletal muscle mass on POD-7 and -14 decreased significantly (all P < 0.05). The phase angle (PhA) increased significantly from POD-3 to -14 (P < 0.05). Resting energy expenditure was significantly higher than predicted and remained high throughout the study period. Over the 14-d study period, delivered energy was escalated to the level of resting energy expenditure. The PhA was significantly lower in patients with severe morbidity than in those without (3.6 [3.3-4.2] versus 4.5 [4.2-5.0]; P < 0.001). A multivariate analysis found that PhA was the independent variable for severe complications, with an odds ratio of 0.069 (95% CI, 0.011-0.427; P = 0.004). The predictive ability of PhA revealed an area under the receiver operating characteristic curve of 0.837, with an optimal threshold of 4.23. CONCLUSIONS: Changes in body composition and hypermetabolism state were observed from POD-3 to -14 after pancreatic trauma. A postoperative value of PhA < 4.23 is associated with severe complications.

Hesperetin attenuates sepsis-induced intestinal barrier injury by regulating neutrophil extracellular trap formation via the ROS/autophagy signaling pathway.

Background: Hesperetin (HES), one of the major flavonoids that has various biological activities, such as anti-inflammatory and antioxidant activities, may preserve the intestinal barrier during sepsis. However, the detailed mechanism remains unclear. Our previous studies confirmed that neutrophil extracellular traps (NETs) may jeopardize the intestinal barrier via a reactive oxygen species (ROS)-dependent pathway during sepsis. Therefore, we hypothesized that HES may inhibit NET formation and protect the intestinal barrier function during sepsis. Methods: Mice were pretreated with HES (50 mg kg-1) intraperitoneally for one week, and sepsis models were then induced using lipopolysaccharides (LPS) (10 mg kg-1). The mice were randomly divided into three groups: (1) sham group; (2) LPS group; and (3) HES + LPS group. Twenty-four hours after LPS injection, the serum and terminal ileum specimens were collected for subsequent studies. To detect ROS production and NET formation in vitro, human neutrophils were collected and incubated with phorbol-12-myristate-13-acetate (PMA) and various concentrations of HES. The level of autophagy was measured by an immunofluorescence assay and western blot analysis. TUNEL staining was utilized to analyze cell apoptosis. Results: The outcomes demonstrated that HES decreased inflammatory cytokine and myeloperoxidase (MPO) levels in serum and attenuated distant organ dysfunction in LPS-induced septic mice. Meanwhile, HES treatment reversed intestinal histopathological damage in septic mice, improving intestinal permeability and enhancing tight junction expression. Moreover, we found that neutrophil infiltration and NET formation in the intestine were suppressed during sepsis after HES pretreatment. In vitro, HES treatment reduced PMA-induced ROS production and NET formation, which were reversed by hydrogen peroxide (H2O2) administration. Notably, HES also inhibited NET formation by reducing the microtubule-associated protein light chain 3 (LC3)-II/LC3-I ratio (an indicator of autophagy) in PMA-induced neutrophils, which was reversed by rapamycin. Moreover, when autophagy was suppressed by chloroquine or induced by rapamycin, apoptosis in cells will be switched with autophagy. Conclusion: Taken together, these findings suggest that HES may inhibit NET formation in a ROS/autophagy-dependent manner and switch neutrophil death from NETosis to apoptosis, which reduced NETs-related intestinal barrier damage, providing a novel protective role in intestinal barrier dysfunction during sepsis.

Persistent fibrinolysis shutdown is associated with increased mortality in traumatic pancreatic injury.

PURPOSE: The features of fibrinolytic system modifications and their relationship with prognosis are still unknown in traumatic pancreatic injury. The object of this prospective cohort research was to identify fibrinolytic characteristics in patients with pancreatic trauma and to identify the correlation to mortality. METHOD: A prospective screening of traumatic pancreatic injury patients was done for five years. The fibrinolytic status of patients was determined by thromboelastography (TEG). The percentage reduction in clot strength 30 min (LY30) after the time of maximal clot strength was utilized to distinguish the fibrinolytic phenotype of individuals, including fibrinolytic shutdown (SD), physiologic fibrinolysis (PHYS) and hyperfibrinolysis (HF). Two cohorts, transient fibrinolytic shutdown (TSD) and persistent fibrinolytic shutdown (PSD), were divided according to whether fibrinolytic shutdown persisted within one week. Demographics, injury severity, characteristics of pancreatic injury, treatment, and outcomes were compared. RESULT: A total of 180 cases enrolled, aged 42(interquartile range 32-51) years, 88% males, 97% were blunt trauma. The median ISS was 19(IQR 10-25), and 76% were AAST grade III to V (high-grade). At admission, there were 159 cases of SD (88%), 15 cases of PHYS (8%) while 6 cases of HF (3%). Of these, the TSD cohort included 54 patients (34%), while the PSD cohort included 105 patients (66%). Compared with the TSD cohort, the PSD cohort had more severe injury (ISS 21[IQR 12-27] vs 16[IQR 9-22], p = 0.006) and a higher proportion of AAST high-grade (83% vs 67%, p = 0.035). Persistent fibrinolytic shutdown was associated with operative treatment (odds ratio [OR] 3.111; 95%CI 1.146-8.447; p = 0.026), associated intra-abdominal injury (OR 8.331; 95% CI 1.301-53.336; p = 0.025) and admission LY30 (OR 0.016; 95% CI 0.002 - 0.120; p < 0.001). It was an independent predictor of mortality (adjusted odds ratio [AOR] 4.674; 95% CI 1.03 to 21.14; p = 0.045). CONCLUSION: Fibrinolytic shutdown especially persistence of this phenotype is more common in traumatic pancreatic injury than PHYS and HF, which related with mortality. Risk factors including LY30 at admission, intra-abdominal injury and operative treatment were associated with the persistent fibrinolytic shutdown. Sheltered the patients from these risk factors seems to be beneficial, which need to be confirmed by further large-scale studies.

Multiple portions enteral nutrition and chyme reinfusion of a blunt bowel injury patient with hyperbilirubinemia undergoing open abdomen: A case report.

Blunt bowel injury (BBI) is relatively rare but life-threatening when delayed in surgical repair or anastomosis. Providing enteral nutrition (EN) in BBI patients with open abdomen after damage control surgery is challenging, especially for those with discontinuity of the bowel. Here, we report a 47-year-old male driver who was involved in a motor vehicle collision and developed ascites on post-trauma day 3. Emergency exploratory laparotomy at a local hospital revealed a complete rupture of the jejunum and then primary anastomosis was performed. Postoperatively, the patient was transferred to our trauma center for septic shock and hyperbilirubinemia. Following salvage resuscitation, damage control laparotomy with open abdomen was performed for abdominal sepsis, and a temporary double enterostomy (TDE) was created where the anastomosis was ruptured. Given the TDE and high risk of malnutrition, multiple portions EN were performed, including a proximal portion EN support through a nasogastric tube and a distal portion EN via a jejunal feeding tube. Besides, chyme delivered from the proximal portion of TDE was injected into the distal portion of TDE via a jejunal feeding tube. Hyperbilirubinemia was alleviated with the increase in chyme reinfusion. After 6 months of home EN and chyme reinfusion, the patient finally underwent TDE reversal and abdominal wall reconstruction and was discharged with a regular diet. For BBI patients with postoperative hyperbilirubinemia who underwent open abdomen, the combination of multiple portions EN and chyme reinfusion may be a feasible and safe option.

Postoperative hemorrhage following pancreatic injury: Risk factors and clinical outcomes.

BACKGROUND: Postoperative hemorrhage (POH) is a severe adverse event following pancreatic injury. The present study aimed to investigate the risk factors and outcomes of POH after pancreatic injury. METHODS: All patients with a confirmed diagnosis of pancreatic injury who underwent surgical intervention between January 2010 and December 2018 were identified and extracted from the trauma database. Logistic regression was performed to identify the risk factors for POH and specific outcomes. RESULTS: A total of 88 cases that underwent surgical intervention were analyzed, and POH occurred in 31 (35.23%) patients. After multivariable analysis, independent predictors of POH were intra-abdominal abscess (IAA) (p = .002), intestinal fistula (p = .008), shock on admission (p = .003), absence of abdominal suction drainage (p = .005), and higher body mass index (BMI) (p = .005). In addition, patients with POH after pancreatic injury also showed more complications, prolonged hospital and ICU durations, and a significantly higher mortality rate (p = .004). CONCLUSIONS: Patients with IAA, intestinal fistula, shock on admission, absence of abdominal suction drainage, and higher BMI score were associated with POH after pancreatic injury. Moreover, POH was associated with a poor prognosis. CLINICAL TRIAL REGISTER: The study was registered on ClinicalTrials.gov (Unique identifier: NCT03681041).