UNASSIGNED: Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or septic shock have a high mortality rate of 30-50%. Therefore, novel strategies to treat sepsis are urgently needed.
UNASSIGNED: Andrographolide (AD), the main active ingredient of Andrographis paniculata, reportedly exerts beneficial effects on mice with sepsis. However, its exact mechanism of action in attenuating inflammation due to intra-abdominal sepsis remains unclear to date. Hence, this study aimed to examine the therapeutic effects of AD on cecal ligation and puncture (CLP)-induced sepsis and elucidate the underlying mechanisms.
UNASSIGNED: Results showed that AD therapy could significantly improve the 7-day survival rate and alleviate pathological organ injury in mice with CLP. In addition, AD treatment decreased the levels of proinflammatory factors, such as tumor necrosis factor-α and interleukin (IL)-6 in the peritoneal cavity fluid and blood and increased the level of anti-inflammatory factor IL-10 in the peritoneal cavity fluid of mice with CLP. Moreover, bacterial counts in the blood and peritoneal lavage fluid were lower in the mice treated with AD than in those untreated. Mechanistically, AD treatment increased the percentage and phagocytic activity of macrophages in the peritoneal cavity.
UNASSIGNED: These data showed that AD can improve the survival of mice with intra-abdominal sepsis by enhancing bacterial clearance, as evidenced by the increased percentages and phagocytic activity of macrophages in the peritoneal cavity. This study is the first to demonstrate the protective effects of AD against intra-abdominal sepsis.

To deal with intra-abdominal sepsis, one of the major global causes of death in hospitalized patients, efficient abscess drainage is crucial. Despite decades of advances, traditional catheters have demonstrated poor drainage and absorption properties due to their simple tubular structures and their dense nonporous surface. Herein, inspired by porous sponges and fractal roots, a multifaceted hydrogel catheter with effective drainage, absorptive, and robust properties, is presented. Its unique fractal structures provide extensive internal branching and a high specific surface area for effective drainage, while the hierarchical porous structures provide a wide range of absorption capabilities. Additionally, its distinctive multi-interpenetration network maintains robust and appropriate mechanical properties, even after absorption multiple times of liquid and mechanical disturbance, allowing for intact removal from the abdominal cavity without harm to the animal in vivo. Besides, the loaded antimicrobial peptides are capable of being released in situ to inhibit the potential for infections. In vivo experiments have demonstrated that this hydrogel catheter efficiently removes lethal abscesses and improves survival. It is believed that this innovative and practical catheter will create a future precedent for hydrogel drainage devices for more effective management of intra-abdominal sepsis.

BACKGROUND: Studies on prognostic factors for older patients with intra-abdominal sepsis are scarce, and the association between skeletal muscle mass and prognosis among such patients remains unclear.
OBJECTIVE: To develop a nomogram to predict in-hospital mortality among older patients with intra-abdominal sepsis.
METHODS: Older patients with intra-abdominal sepsis were prospectively recruited. Their demographics, clinical features, laboratory results, abdominal computed tomography-derived muscle mass, and in-hospital mortality were recorded. The predictors of mortality were selected via least absolute shrinkage and selection operator and multivariable logistic regression analyses, and a nomogram was developed. The nomogram was assessed and compared with Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, and Simplified Acute Physiology Score II.
RESULTS: In total, 464 patients were included, of whom 104 (22.4%) died. Six independent risk factors (skeletal muscle index, cognitive impairment, frailty, heart rate, red blood cell distribution width, and blood urea nitrogen) were incorporated into the nomogram. The Hosmer-Lemeshow goodness-of-fit test and calibration plot revealed a good consistency between the predicted and observed probabilities. The area under the receiver operating characteristic curve was 0.875 (95% confidence interval = 0.838-0.912), which was significantly higher than those of commonly used scoring systems. The decision curve analysis indicated the nomogram had good predictive performance.
CONCLUSIONS: Our nomogram, which is predictive of in-hospital mortality among older patients with intra-abdominal sepsis, incorporates muscle mass, a factor that warrants consideration by clinicians. The model has a high prognostic ability and might be applied in clinical practice after external validation.

Inflammatory cytokine interleukin-6 (IL-6) plays a pivotal role in skeletal muscle degradation after intra-abdominal sepsis (IAS), with mechanism remained to be elucidated. Indoleamine 2,3-dioxygenase 1 (IDO-1), a key enzyme in converting tryptophan into kynurenine, could be activated by IL-6, and kynurenine has been shown to be involved in muscle degradation. We hypothesized that IL-6 could promote muscle degradation via tryptophan-IDO-1-kynurenine pathway in IAS patients.
Serum and rectus abdominis (RA) were obtained from IAS or non-IAS patients. Mouse model of IAS-induced muscle wasting was generated by caecal ligation and puncture (CLP) and lipopolysaccharide (LPS) injection. IL-6 signalling was blocked by anti-mouse IL-6 antibody (IL-6-AB), and the IDO-1 pathway was blocked by navoximod. To elucidate the role of kynurenine in muscle mass and physiology, kynurenine was administered to IAS mice treated with IL-6-AB.
Compared to non-IAS patients, kynurenine levels in serum (+2.30-fold vs. non-IAS, P < 0.001) and RA (+3.11-fold vs. non-IAS, P < 0.001) were elevated, whereas tryptophan levels in serum (-53.65% vs. non-IAS, P < 0.01) and RA (-61.39% vs. non-IAS, P < 0.01) were decreased. Serum IL-6 level of the IAS group was significantly higher compared to non-IAS patients (+5.82-fold vs. non-IAS, P = 0.01), and muscle cross-sectional area (MCSA) was markedly reduced compared to non-IAS patients (-27.73% vs. non-IAS, P < 0.01). In animal experiments, IDO-1 expression was up-regulated in the small intestine, colon and blood for CLP or LPS-treated mice, and there was correlation (R2  = 0.66, P < 0.01) between serum and muscle kynurenine concentrations. Navoximod significantly mitigated IAS-induced skeletal muscle loss according to MCSA analysis (+22.94% vs. CLP, P < 0.05; +23.71% vs. LPS, P < 0.01) and increased the phosphorylated AKT (+2.15-fold vs. CLP, P < 0.01; +3.44-fold vs. LPS, P < 0.01) and myosin heavy chain (+3.64-fold vs. CLP, P < 0.01; +2.13-fold vs. LPS, P < 0.01) protein expression in myocytes. In the presence of anti-IL-6 antibody, a significantly decreased IDO-1 expression was observed in the small intestine, colon and blood in CLP or LPS mice (all P < 0.01), whereas the decrease of MCSA was alleviated (+37.43% vs. CLP + IgG, P < 0.001; +30.72% vs. LPS + IgG, P < 0.001). In contrast, additional supplementation of kynurenine decreased the MCSA in septic mice treated with IL-6-AB (both P < 0.01).
This study provided novel insights into the tryptophan-IDO-1-kynurenine-dependent mechanisms that underlie inflammatory cytokine-induced skeletal muscle catabolism during intra-abdominal sepsis.

Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent. An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database.
All consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality.
Predictive systems with an area under-the-receiving-operating characteristic (AUC) curve > 0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score ≥ 2 (78.4%), followed by the WSESSSS score ≥ 8 (73.1%), SOFA ≥ 3 (75.2%), and APACHE II ≥ 14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS ≥ 8 increased detection to 80%. Including CPIRO score ≥ 3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA ≥ 4 and WSESSSS ≥ 8 with or without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality).
No one scoring system behaves perfectly, and all are largely dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to offer the widest \"inclusion-criteria\" to recognize patients with a high chance of mortality and ICU admission.
https://clinicaltrials.gov/ct2/show/NCT03163095; Registered on May 22, 2017.