Single-balloon Enteroscopy for Evaluation of Small Bowel Crohn Disease Strictures: Peripheral Blood Lymphocytes As a Risk Factor for Strictures.

BACKGROUND: Few reports have focused on single-balloon enteroscopy (SBE) for evaluation of small bowel Crohn disease (CD) strictures. The aim of this study was to analyze the relationships between peripheral blood inflammatory markers and small bowel CD strictures observed by SBE. MATERIALS AND METHODS: CD patients who underwent SBE between January 2016 and December 2020 were enrolled. The clinical characteristics and peripheral blood inflammatory markers were collected and analyzed to screen for predictive factors significantly associated with small bowel CD strictures. RESULTS: A total of 221 CD patients underwent SBE. The lymphocyte (LC) counts in peripheral blood were significantly lower in the active group (n=178) than in the inactive group (n=43) according to the simple endoscopic score for CD (SES-CD), P =0.011, and was correlated with the SES-CD ( r =-0.134, P =0.047). The LC levels were significantly lower in the stricture group (n=116) than in the nonstricture group (n=105) based on whether small bowel strictures developed, P =0.000, and LC was a risk factor for strictures in the multivariate analysis [hazard ratio (HR), 2.332; 95% CI, 1.102-4.937; P =0.027]. In the subgroup analysis, LC levels notably decreased after stricture aggravation ( P =0.000). Forty-seven patients who underwent small bowel resection underwent SBE at 6 to 12 months after surgery. The LC level was significantly lower in the postoperative patients with strictures ( P =0.025), and LC (HR, 4.444; 95% CI, 1.265-15.617; P =0.020) was a risk of postoperative strictures by univariate analysis, but the age at diagnosis (HR, 6.462; 95% CI, 1.272-22.560; P =0.022) was an independent risk factor by multivariate analysis. CONCLUSION: Peripheral blood LC levels were correlated with SES-CD and gradually decreased as the intestinal stricture increased in small bowel CD patients. The LC level was also significantly lower in the postoperative CD patients with strictures. The level of LC was a risk factor for small bowel strictures. These results suggest that peripheral blood LC could be a novel marker of small bowel CD strictures to guide CD diagnosis and therapy.

Acute Colonic Pseudo-Obstruction with Feeding Intolerance in Critically Ill Patients: A Study according to Gut Wall Analysis.

Objective. To compare the differences between acute colonic pseudo-obstruction (ACPO) with and without acute gut wall thickening. Methods. ACPO patients with feeding tolerance were divided into ACPO with no obvious gut wall thickening (ACPO-NT) group and ACPO with obvious acute gut wall thickening (ACPO-T) group according to computed tomography and abdominal radiographs. Patients' condition, responses to supportive measures, pharmacologic therapy, endoscopic decompression, and surgeries and outcomes were compared. Results. Patients in ACPO-T group had a significantly higher APACHE II (11.82 versus 8.25, p = 0.008) and SOFA scores (6.47 versus 3.54, p < 0.001) and a significantly higher 28-day mortality (17.78% versus 4.16%, p = 0.032) and longer intensive care unit stage (4 versus 16 d, p < 0.001). Patients in ACPO-NT group were more likely to be responsive to supportive treatment (62.50% versus 24.44%, p < 0.001), neostigmine (77.78% versus 17.64%, p < 0.001), and colonoscopic decompression (75% versus 42.86%, p = 0.318) than those in ACPO-T group. Of the patients who underwent ileostomy, 81.25% gained benefits. Conclusions. ACPO patients with gut wall thickening are more severe and are less likely to be responsive to nonsurgical treatment. Ileostomy may be a good option for ACPO patients with gut wall thickening who are irresponsive to nonsurgical treatment.

Estrogen Maintains Skeletal Muscle in Septic Rats Associated with Altering Hypothalamic Inflammation and Neuropeptides.

Muscle wasting is one of the main contributors to the worse outcomes in sepsis. Whether estrogen could alleviate muscle wasting induced by sepsis remains unclear. This study was designed to test the effect of estrogen on muscle wasting and its relationship with central alteration in sepsis. Thirty Sprague-Dawley rats were divided into 3 groups: control group, sepsis group, and estrogen treated sepsis group. Animals were intraperitoneally injected with lipopolysaccharide (10 mg/kg) or saline, followed by subcutaneous injection of 17ß-estradiol (1 mg/kg) or saline. Twenty-four hours later, all animals were killed and their hypothalamus and skeletal muscles were harvested for analysis. Muscle wasting markers, hypothalamic neuropeptides, and hypothalamic inflammatory markers were measured. As a result, lipopolysaccharide administration caused a significant increase in muscle wasting, hypothalamic inflammation, and anorexigenic neuropeptides (POMC and CART) gene expression, and a significant decrease in orexigenic neuropeptides (AgRP and NPY) gene expression. Administration of estrogen signifcantl attenuated lipopolysaccharide-induced muscle wasting (body weight and extensor digitorum longus loss [52 and 62 %], tyrosine and 3-methylhistidine release [17 and 22 %], muscle ring fnger 1 [MuRF-1; 65 %], and muscle atrophy F-box [MAFbx] gene expression), hypothalamic inflammation (Tumor necrosis factor-α and interlukin-1ß [69 and 70%]) as well as alteration of POMC, CART and AgRP (61, 37, and 1008 %) expression.In conclusion, estrogen could alleviate sepsis-induced muscle wasting and it was associated with reducing hypothalamic inflammation and alteration of hypothalamic neuropeptides.

The Addition of Dexmedetomidine to Analgesia for Patients After Abdominal Operations: A Prospective Randomized Clinical Trial.

BACKGROUND: Postoperative pain and anxiety are two common factors influencing patient's recovery. Benefits and safety in the use of sedative agents after abdominal operations to improve recovery are not well known. The present study is to evaluate the efficacy and safety of dexmedetomidine use in this population. METHODS: A prospective randomized controlled trial of 145 patients undergoing abdominal operations was conducted in the Surgical Intensive Care Unit of Jinling Hospital between October and December 2015. Thirty-two patients were excluded, and 113 were included and divided into the experimental group (59 patients) receiving dexmedetomidine and analgesics for 72 h after abdominal operations, and the control group (54 patients) receiving only analgesics. Postoperative pain, inflammatory response, recovery of gastrointestinal function, adverse events, and sedation level were analyzed. RESULTS: Pain scores, assessed by Prince Henry Pain Scale (PHPS), in the experimental group were significantly lower than in the control group on the first (1.53 vs. 2.07, p ≤ 0.01), second (1.07 vs. 1.63, p ≤ 0.01), and third day (1.08 vs. 1.82, p = 0.01). Time to defecation was 0.60 days shorter in the experimental group than the control group (2.51 vs. 3.11, p = 0.01). There was no significant difference between inflammatory responses in the two groups (p > 0.05). Both groups had similar blood pressure, heart rate, prevalence of bradycardia, and hypotension requiring interventions (p > 0.05). CONCLUSIONS: The addition of dexmedetomidine to analgesia after abdominal operations is safe and could enhance gastrointestinal function recovery and pain control when monitored carefully. The capacity of dexmedetomidine to attenuate inflammatory responses requires further investigation.

Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting.

Growing evidence suggests acute skeletal muscle wasting is a key factor affecting nutritional support and prognosis in critical patients. Previously, plenty of studies of muscle wasting focused on the peripheral pathway, little was known about the central role. We tested the hypothesis whether central inflammatory pathway and neuropeptides were involved in the process. In lipopolysaccharide (LPS) treated rats, hypothalamic NF-κB pathway and inflammation were highly activated, which was accompanied with severe muscle wasting. Central inhibition of nuclear factor kappa-B (NF-κB) pathway activation by infusion of an inhibitor (PS1145) can efficiently reduce muscle wasting as well as attenuate hypothalamic neuropeptides alteration. Furthermore, knockdown the expression of anorexigenic neuropeptide proopiomelanocortin (POMC) expression with a lentiviral vector containing shRNA can significantly alleviate LPS-induced muscle wasting, whereas hypothalamic inflammation or NF-κB pathway was barely affected. Taken together, these results suggest activation of hypothalamic POMC is pivotal for acute muscle wasting caused by endotoxemia. Neuropeptide POMC expression may have mediated the contribution of hypothalamic inflammation to peripheral muscle wasting. Pharmaceuticals with the ability of inhibiting hypothalamic NF-κB pathway or POMC activation may have a therapeutic potential for acute muscle wasting and nutritional therapy in septic patients.

The influence of extracorporeal membrane oxygenation therapy on intestinal mucosal barrier in a porcine model for post-traumatic acute respiratory distress syndrome.

BACKGROUND: It is unclear at present whether extracorporeal membrane oxygenation (ECMO) therapy can improve intestinal mucous barrier function through increased perfusion. The present study establishes an animal model for post-traumatic acute respiratory distress syndrome (ARDS) and evaluates the effect of v-vECMO treatment on the intestinal mucosal barrier. METHOD: Pulmonary contusion combined with ischemia-reperfusion injury was induced in 30 piglets. The animals were randomly divided into control, model, and ECMO groups. Serum I-FABP, D-lactate, and endotoxin were measured over a 24-h period. The jejunum and colon were collected post-mortem and evaluated histopathologically. The tissue was also examined using electron microscopy, and intestinal tight junction proteins (ZO-1 and occludin) were measured after 24 h of ECMO therapy. Mortality rate and cause of death were also recorded. RESULTS: The serum markers evaluating the intestinal mucosal barrier deteriorated in the model group compared to the control group (p < 0.05). At 2 h, serum I-FABP, D-lactate, and endotoxin were significantly increased in the ECMO group compared to the model group (p < 0.05). At 12 h, I-FABP and D-lactate in the ECMO group dropped to model group levels. Serum D-lactate was slightly lower in the ECMO group (p > 0.05) and serum I-FABP was significantly lower than in the model group (p < 0.05) at 24 h. Similarly, serum endotoxin was slightly lower in the ECMO group than in the model group (p > 0.05) at 24 h. After 24 h of ECMO therapy, the occludin and ZO-1 protein concentrations in jejunum and colon mucosa increased moderately compared to that in the model group (p < 0.05). Morphologic structure of the jejunum and colon did not improved significantly after ECMO therapy. Finally, we observed that ECMO therapy moderately decreased mortality (25% vs. 50%). CONCLUSION: Intestinal mucosal barrier continued to deteriorate in the model group. Although early ECMO therapy aggravates intestinal mucosal injury, the damage gradually improves later during therapy. The results show that ECMO therapy has a protective effect on the intestinal mucosal barrier in the later treatment stage.

Insulin alleviates the inflammatory response and oxidative stress injury in cerebral tissues in septic rats.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt central nervous system (CNS) infection. SAE is frequently encountered in critically ill patients in intensive care units and can be detected in up to 50-70% of septic patients. Previous studies have demonstrated that inflammatory cytokine release and oxidative stress injury are major pathophysiological mechanisms of SAE in critically ill patients. However, there are no effective strategies for the treatment of SAE. Insulin has important immunomodulatory effects and protective effects against oxidative stress injury in the peripheral organs of septic patients. However, very few studies of the possible effects of insulin in cerebral tissues of septic patients have been reported. Therefore, in this study, we aimed to explore whether insulin therapy can inhibit cytokine production (IL-1, IL-6, and TNF-a) and oxidative stress injury of the brain tissue in septic rats. We observed that the protein concentrations of IL-1, IL-6, and TNF-а, in addition to MDA and H2O2 were notably increased, inversely SOD, and GSH were sigificantly decreased in cortex, hippocampus, and hypothalamus of septic rats. Furthermore, the levels of S100 and NSE significantly increased. After 6 hours of insulin therapy, we found that the cytokine concentrations notably decreased and oxidative stress injuries in the cortex, hypothalamus, and hippocampus were alleviated in septic rats. In addition, the S100 and NSE levels significantly decreased. We concluded that insulin can inhibit the production of inflammatory cytokines and the oxidative stress response, thereby improving brain tissue damage.

Effects of continuous renal replacement therapy on intestinal mucosal barrier function during extracorporeal membrane oxygenation in a porcine model.

BACKGROUNDS: Extracorporeal membrane oxygenation (ECMO) has been recommended for treatment of acute, potentially reversible, life-threatening respiratory failure unresponsive to conventional therapy. Intestinal mucosal barrier dysfunction is one of the most critical pathophysiological disorders during ECMO. This study aimed to determine whether combination with CRRT could alleviate damage of intestinal mucosal barrier function during VV ECMO in a porcine model. METHODS: Twenty-four piglets were randomly divided into control(C), sham(S), ECMO(E) and ECMO + CRRT(EC) group. The animals were treated with ECMO or ECMO + CRRT for 24 hours. After the experiments, piglets were sacrificed. Jejunum, ileum and colon were harvested for morphologic examination of mucosal injury and ultrastructural distortion. Histological scoring was assessed according to Chiu's scoring standard. Blood samples were taken from the animals at -1, 2, 6, 12 and 24 h during experiment. Blood, liver, spleen, kidney and mesenteric lymphnode were collected for bacterial culture. Serum concentrations of diamine oxidase (DAO) and intestinal fatty acid binding protein (I-FABP) were tested as markers to assess intestinal epithelial function and permeability. DAO levels were determined by spectrophotometry and I-FABP levels by enzyme linked immunosorbent assay. RESULTS: Microscopy findings showed that ECMO-induced intestinal microvillus shedding and edema, morphological distortion of tight junction between intestinal mucous epithelium and loose cell-cell junctions were significantly improved with combination of CRRT. No significance was detected on positive rate of serum bacterial culture. The elevated colonies of bacterial culture in liver and mesenteric lymphnode in E group reduced significantly in EC group (p < 0.05). Compared with E group, EC group showed significantly decreased level of serum DAO and I-FABP (p < 0.05). CONCLUSIONS: CRRT can alleviate the intestinal mucosal dysfunction and bacterial translocation during VV ECMO, which may extenuate the ECMO-associated SIRS and raise the clinical effect and safety.

The effect of extracorporeal membrane oxygenation therapy on systemic oxidative stress injury in a porcine model.

Extracorporeal membrane oxygenation (ECMO) therapy can result in systemic immune inflammation and trigger a hemolytic response, both of which can lead to oxidative stress injury. However, currently, there are few studies about whether ECMO can lead to oxidative stress injury. The objective of this study was to determine the effect of ECMO therapy on systemic oxidative stress. Twelve pigs were randomly divided into control and ECMO treatment groups. Blood samples were collected at -1, 0, 2, 6, 12, and 24 h during ECMO therapy in order to measure the levels of various oxidative stress markers in plasma. All animals included in the study were euthanized after 24 h of ECMO treatment. Malondialdehyde (MDA) was used as a marker of oxidation, and superoxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (T-AOC) were used as indices for antioxidant activity. The plasma levels of each molecule were similar when measured at -1 and 0 h (P > 0.05). In the control group, MDA, SOD, GSH, and T-AOC remained relatively constant throughout the study period. However, when ECMO was administered for 2 h, plasma levels of MDA increased significantly; conversely, levels of SOD, GSH, and T-AOC decreased. Maximum MDA levels and minimal SOD, GSH, and T-AOC levels were observed after 6 h of ECMO treatment. MDA and SOD levels had returned to baseline at 24 h. At this time-point, levels of MDA and T-AOC in samples from the right frontal cortex and jejunum differed significantly between the control and ECMO treatment groups. These results show that early ECMO treatment can induce significant oxidative stress injury in plasma. However, in the latter stage of the treatment, the oxidative stress injury can be repaired gradually. ECMO treatment can also result in mild oxidative stress injury in the jejunum and brain tissue.

Continuous renal replacement therapy reduces the systemic and pulmonary inflammation induced by venovenous extracorporeal membrane oxygenation in a porcine model.

Pulmonary changes in veno-venous extracorporeal membrane oxygenation (VV-ECMO) are rarely determined. We compared the contribution of VV-ECMO and cannulation based on the observation of pulmonary inflammatory reaction and parenchymal construction in a porcine model of low tidal volume (VT ) ventilation. We also evaluated the effect of adding continuous renal replacement therapy (CRRT) to the ECMO circuit, because CRRT is known to reduce systemic cytokine release induced by VV-ECMO. A total of 18 pigs undergoing low-VT ventilation were randomly divided into three groups (group 1, cannulation; group 2, VV-ECMO; group 3, VV-ECMO + CRRT) and studied for 24 h. Hemodynamic and ventilation parameters were recorded. We assessed plasma and alveolar cytokines, expression of pulmonary inflammatory genes, histopathological grading, and ultrastructural changes of the lungs. During the process, inspiratory volume increased and PaO2 decreased in group 1. Systemic tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels increased at 2 h in group 2 and partly decreased in group 3. At 24 h, the levels of bronchoalveolar lavage fluid, TNF-α, and IL-6 in group 2 were remarkably higher than those in groups 1 and 3. Pulmonary mRNA expression of cytokines did not differ between the groups. We observed an increased score of pulmonary pathological findings in pro-inflammatory cell infiltration and interstitial thickening of the lungs in group 2. The epithelium of the blood-air barrier after VV-ECMO was swollen. In group 3, the pulmonary parenchyma and blood-air barrier were well preserved. We concluded that in a porcine model of low-VT ventilation, both VV-ECMO and VV-ECMO in combination with CRRT provided adequate oxygenation and carbon dioxide removal. Compared with VV-ECMO alone, VV-ECMO in combination with CRRT better preserved the lung parenchyma by eliminating systemic cytokines.

The effect of venovenous extra-corporeal membrane oxygenation (ECMO) therapy on immune inflammatory response of cerebral tissues in porcine model.

BACKGROUND: Extra-Corporeal Membrane Oxygenation (ECMO) therapy is associated with high risk of neurologic injury. But the mechanism of neurologic injury during and/or after ECMO therapy is still unclear. Recent animal experiments confirmed that ECMO treatment increases the immune inflammatory response. The aim of this study is to investigate the effect of VV- ECMO on immune inflammatory response of cerebral tissues and neurological impairment. METHODS: 18 porcine were randomly divided into control, sham and ECMO group (n = 6/group). ECMO was run 24 h in the ECMO group, and serum collected at 0, 2, 6, 12 and 24 h during ECMO treatment for the analysis of cytokine (IL-1ß, IL-6, IL-10, TNF-a) and cerebral injury specific biomarker S100B and NSE. After 24 h ECMO treatment, all animals were euthanized and cerebral tissues (hypothalamus, hippocampus and cortex) were collected for measure of mRNA and protein levels of cytokine (IL-1ß, IL-6, IL-10, TNF-a). RESULTS: The results during ECMO treatment showed that all the pro-inflammation cytokines were increased significantly after 2 h, and anti-inflammation IL-10 showed transient hoist in the first 2 h in serum. After 24 h ECMO therapy, the mRNA levels of pro-inflammation cytokines and anti-inflammation IL-10 were simultaneously up-regulated in cerebral tissues (hypothalamus, hippocampus and cortex). And protein concentrations also showed different increasing levels in cerebral tissues. However, during the ECMO treatment, S100B and NSE protein in serum did not change significantly. CONCLUSION: These findings suggest VV-ECMO treatment can not only lead to immune inflammatory response in blood, but can also produce immune and inflammatory response in cerebral tissues. However the extent of immune inflammation was not sufficient to cause significant neurological impairment in this study. But the correlation between cerebral inflammatory response and cerebral impairment need to further explore.

Effect of venovenous extracorporeal membrane oxygenation on the heart in a healthy piglet model.

BACKGROUND: Cardiac function is important for patients treated by venovenous extracorporeal membrane oxygenation (VV ECMO), but data about the effect of VV ECMO on the heart in nonneonates is absent. We studied the effect of VV ECMO on cardiac performance, cardiomyocyte and mitochondria in an animal model. METHODS: Twelve farm piglets were randomly assigned into two groups: control group and ECMO group. In the ECMO group, ECMO cannulaes were placed and ECMO was instituted. Hemodynamics was recorded at baseline, 1 hour after induction, and every 4 hours thereafter, to assess the cardiac performance. All animals were monitored for 24 hours and were euthanized and myocardium was harvested. Myocardial histology, ultrastructure of cardiomyocyte and mitochondria were observed, and activities of mitochondrial complexes I-V were measured, to assess the effect to cardiomyocyte and mitochondria. RESULTS: Hemodynamics were stable in each group of animals throughout the experiment. Interstitial edema, disorderd and dissolved of focal myofilament, morphological deformations of mitochondria were observed in the ECMO group. The activities of mitochondrial complexes were decreased in the ECMO group, and complex I and IV reached significance. CONCLUSIONS: VV ECMO therapy is associated with changes of ultrastructure and function of cardiomyocyte and mitochondria, inducing myocardium injury. However, the injury was mild and had no effect on the cardiac performance for healthy piglets.

Continuous renal replacement therapy (CRRT) attenuates myocardial inflammation and mitochondrial injury induced by venovenous extracorporeal membrane oxygenation (VV ECMO) in a healthy piglet model.

In this study, we investigated the myocardial inflammation and mitochondrial function during venovenous extracorporeal membrane oxygenation (VV ECMO) and further evaluated the effects of continuous renal replacement therapy (CRRT) on them. Eighteen piglets were assigned to the control group, ECMO group, and ECMO+CRRT group. Myocardial inflammation was assessed by the activity of myeloperoxidase (MPO), myocardial concentrations, and mRNA expression of TNF-α, IL-1ß, and IL-6; mitochondrial function was assessed by activities of mitochondrial complexes I-V. VV ECMO elicited a general activation of serum and myocardial inflammation and significantly decreased the activities of mitochondrial complexes I and IV. After being combined with CRRT, serum and myocardial concentrations of IL-1ß and IL-6, myocardial mRNA expression of IL-6, and the activity of MPO were decreased significantly; the activities of mitochondrial complexes were increased. We conclude that myocardial inflammation was activated during ECMO therapy, inducing mitochondrial injury; moreover, CRRT reduced myocardial inflammation and partially ameliorated mitochondrial function.