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OBJECTIVE: Aim: To determine the effect of the developed complex treatment of patients with peritonitis on the dynamics of humoral factors of nonspecific reactivity in the course of the disease. PATIENTS AND METHODS: Materials and Methods: The study included 124 patients with toxic and terminal stages of peritonitis, who were divided into 3 groups. Group I (main) included 39 patients whose complex treatment included cytochrome C. Group II (main) included 41 patients whose complex treatment included cytochrome C and a solution containing levocarnitine and arginine hydrochloride. The comparison group comprised 44 patients who did not receive the specified drugs. The patients underwent determination of the levels of fibronectin, ceruloplasmin, and procalcitonin in the serum during the course of the disease. RESULTS: Results: In patients of the I and II main groups, the use of the proposed treatment contributed to the optimization of the production of acute phase proteins: a decrease in procalcitonin production during the study, optimization of ceruloplasmin and fibronectin production, especially in the II main group. In patients of the comparison group, decompensation in the production of humoral inflammatory factors was determined, associated with a significant increase in fibronectin production, a decrease in ceruloplasmin content, and an increase in procalcitonin throughout the entire period. CONCLUSION: Conclusions: The use of cytochrome C and a solution containing levocarnitine and arginine hydrochloride in the complex treatment of patients with disseminated peritonitis helps to optimize the production of acute phase proteins, which leads to a decrease in inflammation and the preservation of factors of nonspecific humoral activity at a subcompensated level.

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We present a case of a 34-year-old patient with abdominal sepsis caused by an infrequent species: Chimaeribacter arupi. Genomic analysis confirmed the identification which is difficult to achieve by other methods so far. To our knowledge, this represents the first case of infection by this species reported in Argentina.

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BACKGROUND: Sepsis is an uncontrolled systemic inflammatory response to an infection that can result in acute failure of the function of the lung called acute respiratory distress syndrome. Leukocyte recruitment is an important hallmark of acute lung failure in patients with sepsis. Endothelial cells (EC) participate in this process by facilitating tethering, rolling, adhesion, and transmigration of leukocytes via adhesion molecules on their cell surface. In in vivo studies, endothelial nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 and mitogen-activated protein kinase (MAPK) c-Jun intracellular signal transduction pathways were reported to regulate the expression of adhesion molecules. METHODS: Mice underwent cecal ligation and puncture (CLP) to induce polymicrobial sepsis and were sacrificed at different time points up to 72 h after sepsis onset. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses were used to determine the kinetics of nuclear localization of p65 and c-Jun in EC, expression and location of adhesion molecules E-selectin and vascular cell adhesion molecule 1 (VCAM-1). Furthermore, the extent and location of leukocyte recruitment were assessed based on Ly6G staining of neutrophils, cluster determinant (CD) 3 staining of T lymphocytes, and CD68 staining of macrophages. RESULTS: In all pulmonary microvascular beds, we identified p65 and c-Jun nuclear accumulation in a subset of endothelial cells within the first 24 h after CLP-sepsis initiation. E-selectin protein was expressed in a subset of microvessels at 4 and 7 h after sepsis initiation, while VCAM-1 was expressed in a scattered pattern in alveolar tissue and microvessels, without discernible changes during sepsis development. CLP-induced sepsis predominantly promoted the accumulation of neutrophils and T lymphocytes 4 and 7 h after disease onset. Neutrophil accumulation occurred in all pulmonary microvascular beds, while T lymphocytes were present in alveolar tissue and postcapillary venules. Taken together, nuclear localization of p65 and c-Jun in EC and neutrophil recruitment could be associated with induced E-selectin expression in the pulmonary microvessels in CLP-septic mice at the early stage of the disease. In alveolar capillaries, on the other hand, activation of these molecular pathways and leukocyte accumulation occurred in the absence of E-selectin or VCAM-1. CONCLUSIONS: Endothelial activation and leukocyte recruitment in sepsis-induced lung injury are regulated by multiple, heterogeneously controlled mechanisms, which vary depending on the type of microvascular bed involved.

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A perforated peptic ulcer (PPU) is a surgical emergency with a high mortality rate. PPUs cause secondary peritonitis due to bacterial and fungal peritoneal contamination. Surgery is the main treatment modality and patient's comorbidites impacts perioperative morbidity and surgical outcomes. Even after surgery, resuscitation efforts should continue. While empiric antibiotics are recommended, the role of empiric anti-fungal treatment is unclear due to a lack of scientific evidence. This literature review demonstrated a paucity of studies evaluating the role of empiric anti-fungals in PPUs, and with conflicting results. Studies were heterogeneous in terms of patient demographics and underlying surgical pathology (PPUs vs. any gastrointestinal perforation), type of anti-fungal agent, timing of administration and duration of use. Other considerations include the need to differentiate between fungal colonization vs. invasive fungal infection. Despite positive fungal isolates from fluid culture, it is important for clinical judgement to identify the right group of patients for anti-fungal administration. Biochemistry investigations including new fungal biomarkers may help to guide management. Multidisciplinary discussions may help in decision making for this conundrum. Moving forward, further research may be conducted to select the right group of patients who may benefit from empiric anti-fungal use.

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BACKGROUND: Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity, that negatively affect the patients' quality of life. Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation. Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features. Despite the advances in experimental protocols and techniques, designing a high-quality study is still challenging for the investigators as there is a plethora of different models used. AIM: To review current state of the art for experimental protocols in high-risk anastomosis in rats. METHODS: This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. To identify eligible studies, a comprehensive literature search was performed in the electronic databases PubMed (MEDLINE) and Scopus, covering the period from conception until 18 October 2023. RESULTS: From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis. Methods of assessing anastomotic healing were extracted and were individually appraised. CONCLUSION: Anastomotic healing studies have evolved over the last decades, but the findings are yet to be translated into human studies. There is a need for high-quality, well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.

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Sepsis is a dysregulated systemic inflammatory response to an infection, which can lead to multiple organ dysfunction syndrome that includes the kidney. Leukocyte recruitment is an important process of the host immune defense in response to sepsis. Endothelial cells (EC) actively regulate leukocyte recruitment by expressing adhesion molecules following the activation of dedicated intracellular signal transduction pathways. Previous studies reported that the expression of adhesion molecules was associated with the activation of endothelial NF-κB p65 and MAPK c-Jun pathways in vitro in response to conditions that mimic processes that occur in inflammation. This study aimed to investigate the spatiotemporal patterns of leukocyte recruitment, expression of adhesion molecules, and endothelial nuclear p65 and c-Jun localization in renal microvascular beds of septic mice. Here, we used a cecal ligation and puncture (CLP) sepsis mouse model and RT-qPCR and immunohistochemical staining. We showed that neutrophils, macrophages, and T lymphocytes were all present in the kidney, yet only neutrophils accumulated in a spatiotemporally discernible pattern, mainly in glomeruli at 4 hours after CLP-sepsis initiation. E-selectin, not VCAM-1, was expressed in glomeruli at the same time point. In a subset of mice at 72 hours after CLP-sepsis started, VCAM-1 expression was prominent in glomerular EC, which was not related to changes in mmu-microRNA(miR)-126a-3p levels, a short noncoding microRNA previously shown to inhibit the translation of VCAM-1 mRNA into protein. Nuclear localization of p65 and c-Jun occurred in EC of all microvascular segments at 4 and 7 hours after CLP-sepsis initiation. In summary, sepsis-induced recruitment of neutrophils, E-selectin expression, and NF-κB p65 and MAPK c-Jun pathway activation coincided in glomeruli at the early stage of the disease. In the other microvascular beds, sepsis led to NF-κB p65 and MAPK c-Jun pathway activation with limited expression of E-selectin and no association with VCAM-1 expression or leukocyte recruitment.

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INTRODUCTION: A dysregulated immune system is a major driver of the mortality and long-term morbidity from sepsis. With respect to macrophages, it has been shown that phenotypic changes are critical to effector function in response to acute infections, including intra-abdominal sepsis. Invariant natural killer T cells (iNKT cells) have emerged as potential central regulators of the immune response to a variety of infectious insults. Specifically, various iNKT cell:macrophage interactions have been noted across a spectrum of diseases, including acute events such as sepsis. However, the potential for iNKT cells to affect peritoneal macrophages during an abdominal septic event is as yet unknown. METHODS: Cecal ligation and puncture (CLP) was performed in both wild type (WT) and invariant natural killer T cell knockout (iNKT-/-) mice. 24 h following CLP or sham operation, peritoneal macrophages were collected for analysis. Analysis of macrophage phenotype and function was undertaken to include analysis of bactericidal activity and cytokine or superoxide production. RESULTS: Within iNKT-/- mice, a greater degree of intraperitoneal macrophages in response to the sepsis was noted. Compared to WT mice, within iNKT-/- mice, CLP did induce an increase in CD86+ and CD206+, but no difference in CD11b+. Unlike WT mice, intra-abdominal sepsis within iNKT-/- mice induced an increase in Ly6C-int (5.2% versus 14.9%; P < 0.05) and a decrease in Ly6C-high on peritoneal macrophages. Unlike phagocytosis, iNKT cells did not affect macrophage bactericidal activity. Although iNKT cells did not affect interleukin-6 production, iNKT cells did affect IL-10 production and both nitrite and superoxide production from peritoneal macrophages. CONCLUSIONS: The observations indicate that iNKT cells affect specific phenotypic and functional aspects of peritoneal macrophages during polymicrobial sepsis. Given that pharmacologic agents that affect iNKT cell functioning are currently in clinical trial, these findings may have the potential for translation to critically ill surgical patients with abdominal sepsis.

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This case involves a 53-year-old male who was diagnosed with stenotic ascending colon cancer and peritoneal metastatic deposits. He was initially planned for cytoreductive surgery and heated intraperitoneal chemotherapy (CRS and HIPEC), along with resection of the primary tumor in the form of right hemicolectomy. Intraoperatively, the disease was found to be more extensive than anticipated. Consequently, the plan was modified to include debulking right hemicolectomy with hand-sewn ileocolic anastomosis and extensive peritoneal procedures. Postoperatively, he experienced an anastomotic leak, leading to another laparotomy. However, due to anatomical challenges, creating a stoma was considered unsafe. Therefore, innovative interventions were performed, including controlling the anastomotic defect with a 30Fr Foley catheter without disrupting the anastomosis. A collaborative effort from various medical teams facilitated the patient's discharge home after an extended stay in the critical care unit (CCU).

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This comprehensive review aims to provide a practical guide for intensivists, focusing on enhancing patient care associated with nosocomial peritonitis (NP). It explores the epidemiology, diagnosis, and management of NP, a significant contributor to the mortality of surgical patients worldwide. NP is, per definition, a hospital-acquired condition and a consequence of gastrointestinal surgery or a complication of other diseases. NP, one of the most prevalent causes of sepsis in surgical Intensive Care Units (ICUs), is often associated with multi-drug resistant (MDR) bacteria and high mortality rates. Early clinical suspicion and the utilization of various diagnostic tools like biomarkers and imaging are of great importance. Microbiology is often complex, with antimicrobial resistance escalating in many parts of the world. Fungal peritonitis and its risk factors, diagnostic hurdles, and effective management approaches are particularly relevant in patients with NP. Contemporary antimicrobial strategies for treating NP are discussed, including drug resistance challenges and empirical antibiotic regimens. The importance of source control in intra-abdominal infection management, including surgical and non-surgical interventions, is also emphasized. A deeper exploration into the role of open abdomen treatment as a potential option for selected patients is proposed, indicating an area for further investigation. This review underscores the need for more research to advance the best treatment strategies for NP.

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INTRODUCTION: The use of tissue adhesives has been proposed as an anastomosis reinforcement; however, their efficacy has not been evaluated in a contaminated environment. The objective of this study was to determine if the use of sutures reinforced with ethyl-2-cyanoacrylate for colonic anastomoses in the presence of fecal peritonitis, in a murine animal model, decreases the frequency of dehiscence. METHODS: Wistar rats were used. Fecal peritonitis was established until reaching 18 hours of evolution. Then, resection and anastomosis of the colon were performed with only polydioxanone (PDS) sutures in the control group and reinforcement with ethyl-2-cyanoacrylate in the experimental group. The dehiscence frequency and burst pressure were evaluated six days after the anastomosis was performed. RESULTS: We included 30 Wistar rats, all males, with a median age of five months and an average weight of 350.43 g. Anastomotic dehiscence was observed in 53.33% of the control group, in contrast with 13.33% of the experimental group (p = 0.020). There was no significant difference in burst pressure between the two groups. CONCLUSION: The use of ethyl-2-cyanoacrylate, in an experimental murine animal model, as reinforcement in colonic anastomoses in the presence of fecal peritonitis decreases the frequency of anastomotic dehiscence, although it does not increase resistance to burst pressure.

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Adrenal hemorrhage is a rare, but important, diagnosis to recognize, in particular when there is involvement of both adrenal glands. Bilateral adrenal hemorrhage can in fact lead to adrenal insufficiency, with dramatic consequences if not promptly recognized and treated. It is normally caused by systemic conditions that lead to the vasoconstriction and thrombosis of the adrenal vein. Oftentimes, the clinical diagnosis of this condition can be very challenging, as its signs and symptoms are generalized and nonspecific (abdominal pain, nausea, and fatigue). Here, we present the cases of two patients admitted to the Emergency Department in 2016 and 2022 with acute abdominal pain, having recently undergone surgery and subsequently prescribed low-molecular-weight heparin. In both cases, laboratory results revealed neutrophilic leukocytosis and an unexplained anemia. Due to the persistence of abdominal pain despite medication, a CT scan was performed, showing an enlargement of both adrenal glands suggestive of bilateral adrenal hemorrhage. Adrenal function was tested that correlated with a diagnosis of adrenal insufficiency, and both patients were promptly treated with parenteral hydrocortisone as a result. On 5 years' follow-up from the acute event, the second patient's adrenal function had returned to normal, and he has not needed further adrenal replacement therapy; the first patient however demonstrated persistence of adrenal failure requiring replacement therapy. In this paper, through our experience and a literature analysis, we will aim to outline some clues to identify patients at potential risk of bilateral adrenal hemorrhage.

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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.

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Sepsis and colorectal cancer (CRC) exhibit a complex relationship that warrants further exploration. This review delves into the interplay of factors between sepsis and CRC, uncovering shared pathophysiological traits and potential bacterial associations. Understanding these connections could pave the way for earlier diagnosis, improved management, and enhanced outcomes in CRC patients. The role of immune system dysfunction, hypoalbuminemia, and specific microbial imbalances, such as Streptococcus bovis and Clostridium septicum, are discussed. Recognizing sepsis in CRC patients is crucial for timely intervention, and tailored approaches encompassing antibiotic therapy, source control measures, and cancer treatment are essential for comprehensive care. Monitoring biomarkers and ratios can provide valuable insights into complications and overall health outcomes. A multidisciplinary approach involving various specialists is necessary to address the global burden of CRC and its association with sepsis while exploring novel interventions, such as fecal microbiota transplantation and personalized care. We conducted a thorough search using reputable databases such as PubMed, Scopus, and Google Scholar to investigate the connection between sepsis and CRC. We refined our search terms, utilized sidebar filters, and examined references in selected articles. This meticulous process helped us create a comprehensive literature review and gain valuable insights into this relationship.

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Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

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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. AIMS: 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. DISCUSSION: 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.

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Introduction: In emergency surgeries, open abdomen or laparostomy, especially with perforated viscus, has been used primarily to prevent delayed ventral hernia, burst abdomen, and abdominal compartment syndrome. In the present study, the clinical and resuscitative factors that are linked with open abdomen morbidity are evaluated. Material and Methods: A retrospective analysis was done for all the subjects who were admitted at the tertiary care center between May 2020 and May 2022 for the open abdomen surgeries. These patients were examined to see whether they needed more postoperative care than usual, including the need for resuscitative treatments and other critical clinical indicators. Patients were evaluated if they had any complications. The data that were collected were analysed for any variance using analysis of variance considering P <.05 as significant. Results: A total of 100 subjects were analysed in this study. Forty nine patients had intra-abdominal sepsis of the 100 cases examined from historical case records and 1 had entero-cutaneous fistulas. These patients did not necessitate additional actions for intensive care unit care, resuscitation, an chest infection, extended hospital stay, or any disabilities compared to those who did not undergo laparotomy during the same period. In this group of patients with open abdomens, the immediate postoperative period was not linked to an increase in resuscitation efforts or a load on clinical staff. Once patients are stabilized, early definitive abdominal closure is advised to prevent problems associated to laparostomies. Conclusion: The quantity of initial fluid revival and the coagulation factors at the time of admission are not related to intra-abdominal sepsis and enteric fistula following laparostomy after significant abdominal injuries.

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In recent decades, multiple efforts have been made to identify targets and therapeutic measures in the host response to infection. Haemoadsorption, under the attractive theoretical premise of inflammatory response modulation through the adsorption of soluble inflammatory mediators, could have a place as an adjuvant therapy in septic patients. The development of new devices and the recent COVID-19 pandemic has renewed interest in this therapy. The aim of this report is to describe our experience in patients with abdominal sepsis for whom haemoadsorption with a neutral microporous resin column was added to conventional treatment and to describe its performance through patient cases in the absence of large randomised trials with this device. We present five patients with abdominal sepsis admitted to a Spanish intensive care unit in which haemoadsorption was used as adjuvant treatment. The key practical aspects of the treatment protocol have been used as a guide for conducting a multicentric study. Based on the experience gathered in these five cases, the potential benefit of haemoadsorption as adjuvant therapy in patients with abdominal sepsis with multiple organ failure after control of the source of infection and adequate treatment should be investigated. Likewise, it must be defined which patients can benefit from the therapy, the most appropriate biomarkers to guide the therapy, the ideal time of initiation and discontinuation, its potential side effects, and the interaction with other therapies, especially how such treatment affects the antibiotics levels.

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BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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BACKGROUND: Intra-abdominal infections are the second most common cause of sepsis in the intensive care unit. Intestinal epithelial injury due to abdominal sepsis results in a variety of pathological changes, such as intestinal bacteria and toxins entering the blood, leading to persistent systemic inflammation and multiple organ dysfunction. The increased apoptosis of intestinal epithelial cells induced by sepsis further exacerbates the progression of sepsis. Although several studies have revealed that circRNAs are involved in intestinal epithelial injury in sepsis, few studies have identified the roles of circRNAs in intestinal epithelial apoptosis. METHODS: We used laser capture microdissection to obtain purified epithelial cells located in intestinal crypts from four patients with abdominal sepsis induced by intestinal perforation and four samples from age and sex-matched non-septic patients. Microarray analysis of circRNAs was conducted to assess differentially expressed circRNAs between patients with and without sepsis. Lastly, in vitro and in vivo assays were performed to study the mechanism of circFLNA in intestinal epithelial apoptosis during sepsis. RESULTS: circFLNA was upregulated in the intestinal epithelium after abdominal sepsis induced by intestinal perforation. Inhibition of miR-766-3p impaired si-circFLNA-mediated inhibition of apoptosis and inflammation factor levels in lipopolysaccharide (LPS)-treated HIEC-6 cells. circFLNA aggravated apoptosis and inflammation through the Fas-mediated apoptosis pathway in both LPS-treated HIEC-6 cells and a mouse cecal ligation and puncture model. CONCLUSION: Our findings showed that circFLNA promotes intestinal injury in abdominal sepsis through the Fas-mediated apoptosis pathway by sponging miR-766-3p. The circFLNA/miR-766-3p/Fas axis has potential as a novel therapeutic target for treating intestinal injury in sepsis.

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PURPOSE: Herein, we identified whether the clinical outcomes differ according to secondary culture results in postoperative sepsis patients and determined the predictors of culture-negative sepsis after abdominal surgery based on the secondary culture results. METHODS: Patients who admitted to the intensive care unit(ICU) after surgery due to abdominal infection and diagnosed with postoperative sepsis were included. Culture tests were obtained from body fluids and drains. Primary culture test was performed immediately after surgery, and secondary culture test was performed within 48 h to 7days after surgery. The participants were divided into the culture-positive sepsis(CPSS) and the culture-negative sepsis group(CNSS) according to culture positivity, and the clinical outcomes were compared. The predisposing factors of secondary CNSS were determined using multiple logistic regression analysis. RESULTS: Among 83 participants, 51 patients (61.4%) showed secondary culture-positivity(2'CPSS) and 32 patients (38.6%) showed secondary culture-negativity(2'CNSS). ICU mortality and in-hospital mortality were not different between two groups, but the length of ICU and hospital stay were significantly longer in 2'CPSS. In multivariate analysis, non-bowel surgery [odds ratio(OR) = 6.934, 95% confidence interval(CI):1.609-29.884, p=0.009], no diabetes (OR = 4.027,95%CI:1.161-13.973, p=0.028), and the prolonged administration of preoperative antibiotics (OR = 1.187,95%CI:1.023-1.377, p=0.024) were revealed as significant predisposing factors of 2'CNSS. CONCLUSION: Mortality showed no difference according to secondary culture positivity in postoperative sepsis patients after abdominal surgery. If a patient underwent non-bowel surgery or had no diabetes or administered preoperative antibiotics for more than 3 days, the physician should pay more attention to clinical deterioration, even if the seconday culture results are negative.

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