Is the increased ozone dosage key factor for its anti-inflammatory effect in an experimental model of mesenteric ischemia?

BACKGROUND: Ischemia/reperfusion injury of the intestines is a severe surgical condition. This study aimed to reveal ozone therapy effects with relatively increased ozone dosage in a created ischemia/reperfusion injury model. METHODS: In this study, 24 albino Wistar rats were examined in three groups. Rats in the control group (CG, n=8) underwent only a laparotomy. In the sham group (SG, n=8) and ozone group (OG, n=8), the superior mesenteric artery (SMA) of the rats was occluded for 1 h. After deoccluding the SMA, the abdomen was closed, physiological saline was infused intraperitoneally in the SG, and an increased ozone/oxygen mixture dose (from 0.7 mg/kg to 1 mg/kg) was infused intraperitoneally in the OG. Small intestine samples were obtained at the 24th h for histopathological examination of intestinal mucosal injury and evaluated according to the Chiu score. In addition, Malondialdehyde and Myeloperoxidase levels were evaluated for oxidant levels, whereas, Glutathione (GSH) enzyme activity was measured to evaluate the tissue antioxidant system. RESULTS: Histopathologically, the Chiu score was the lowest in the CG. It was lower in the OG compared to the SG showing the ameliorating effect of ozone on the intestinal mucosa. Chiu score in the OG was higher compared to that in the CG, but not statistically significant. A significantly higher GSH level was observed in the OG compared to the SG, proving antioxidant activity. CONCLUSION: In this experimental model of ischemia/reperfusion in rats, treatment with an increased ozone level decreased the inflammatory process through antioxidant mechanisms and reduced intestinal mucosal damage. However, the effectiveness of ozone therapy depends on its dosages.

Low-dose sumatriptan improves the outcome of acute mesenteric ischemia in rats via downregulating kynurenine.

BACKGROUND: Mesenteric ischemia has remained without effective pharmacological management for many years. Sumatriptan, an abortive medication for migraine and cluster headaches, has potent anti-inflammatory properties and ameliorated organ ischemia in previous animal studies. Similarly, inhibition of the kynurenine pathway ameliorated renal and myocardial ischemia/reperfusion (I/R) in many preclinical studies. Herein, we assessed the effect of sumatriptan on experimental mesenteric I/R and investigated whether kynurenine pathway inhibition is a mechanism underlying its action. METHODS: Ischemia was induced by ligating the origin of the superior mesenteric artery (SMA) and its anastomosis with the inferior mesenteric artery (IMA) with bulldog clamps for 30 min. Ischemia was followed by 1 h of reperfusion. Sumatriptan (0.1, 0.3, and 1 mg/kg ip) was injected 5 min before the reperfusion phase, 1-methyltryptophan (1-MT) (100 mg/kg iv) was used to inhibit kynurenine production. At the end of the reperfusion phase, samples were collected from the jejunum of rats for H&E staining and molecular assessments. RESULTS: Sumatriptan improved the integrity of intestinal mucosa after I/R, and 0.1 mg/kg was the most effective dose of sumatriptan in this study. Sumatriptan decreased the increased levels of TNF-α, kynurenine, and p-ERK but did not change the decreased levels of NO. Furthermore, sumatriptan significantly increased the decreased ratio of Bcl2/Bax. Similarly, 1-MT significantly decreased TNF-α and kynurenine and protected against mucosal damage. CONCLUSIONS: This study demonstrated that sumatriptan has protective effects against mesenteric ischemia and the kynurenine inhibition is potentially involved in this process. Therefore, it can be assumed that sumatriptan has the potential to be repurposed as a treatment for acute mesenteric ischemia.

Trombosis de vena mesentérica superior como complicación de apendicitis aguda: una entidad poco frecuente / Superior mesenteric vein thrombosis as a complication of acute appendicitis: a rare entity

Las complicaciones de la apendicitis aguda ha sido ampliamente descrita en la literatura; la trombosis venosa mesenterica es una manifestación poco común de esta patologia correspondiento a menos del 1 % de frecuencia, esto puede desorientar al cirujano general al coexistir en el cuadro de apendicitis aguda. Presentamos el caso de un paciente masculino de 58 años, con dolor abdominal de 5 días de evolución, con sintomatologia poco especifica para el diagnóstico concreto de apendicitis. Se realizó una tomografía computarizada de abdomen con hallazgos de apendicitis aguda y trombososis venosa mesenterica con un coágulo de 11.5 cm. Se hizó también apendicectomia abierta y se inició anticoagulación al egreso hospitalario.

The complications of acute appendicitis have been widely described in the literature; Mesenteric venous thrombosis is a rare manifestation of this pathology corresponding to less than 1% frequency, this can confuse the general surgeon as it coexists with acute appendicitis. We present the case of a 58-year-old male patient, with abdominal pain of 5 days of evolution, with symptoms that are not very specific for the specific diagnosis of appendicitis. Computed tomography of the abdomen was performed with findings of acute appendicitis and mesenteric venous thrombosis with a clot of 11.5 cm. An open appendectomy was performed and anticoagulation was started on hospital discharge.

Non-occlusive mesenteric ischemia during bevacizumab treatment for glioblastoma: a case report.

Glioblastoma is one of the most aggressive brain tumors in adults. The standard treatment is radiotherapy and chemotherapy based on the Stupp regimen after maximal safe resection. One effective chemotherapeutic drug is bevacizumab, which can prolong progression-free survival in glioblastoma patients but not overall survival. Adverse events of bevacizumab include hypertension, proteinuria, delayed wound healing, bleeding of the nose and gums, and thromboembolism resulting in gastrointestinal perforation. Herein, we describe an autopsy case of a patient with glioblastoma who died from non-occlusive mesenteric ischemia that was presumably caused by bevacizumab.

Albendazole ameliorates inflammatory response in a rat model of acute mesenteric ischemia reperfusion injury.

BACKGROUND: Acute mesenteric ischemia is known as a life threatening condition. Re-establishment of blood flow in this condition can lead to mesenteric ischemia reperfusion (MIR) injury which is accompanied by inflammatory response. Still, clear blueprint of inflammatory mechanism underlying MIR injury has not been provided. Interestingly, Albendazole has exhibited notable effects on inflammation and cytokine production. In this study, we aimed to evaluate outcomes of MIR injury following pretreatment with Albendazole with respect to assessment of mesenteric inflammation and ischemia threshold. METHODS: Male rats were randomly divided into sham operated, vehicle treated, Albendazole 100 mg/kg and Albendazole 200 mg/kg groups. MIR injury was induced by occlusion of superior mesenteric artery for 30 min followed by 120 min of reperfusion. Samples were utilized for assessment of epithelial survival and villous height. Immunohistochemistry study revealed intestinal expression of TNF-α and HIF-1-α. Gene expression of NF-κB/TLR4/TNF-α/IL-6 was measured using RTPCR. Also protein levels of inflammatory cytokines in serum and intestine were assessed by ELISA method. RESULTS: Histopathological study demonstrated that pretreatment with Albendazole could ameliorate decline in villous height and epithelial survival following MIR injury. Also, systemic inflammation was suppressed after administration of Albendazole. Analysis of possible participating inflammatory pathway could demonstrate that intestinal expression of NF-κB/TLR4/TNF-α/IL-6 is significantly attenuated in treated groups. Eventually, IHC study illustrated concordant decline in mesenteric expression of HIF-1-α/TNF-α. CONCLUSION: Single dose pretreatment with Albendazole could ameliorate inflammatory response and enhance ischemia threshold following induction of MIR injury. More studies would clarify existing causality in this phenomenon.

Vasoactive agents in acute mesenteric ischaemia in critical care. A systematic review.

Background: Acute mesenteric ischaemia (AMI) is a surgical emergency which has an associated high mortality.  The mainstay of active treatment includes early surgical intervention, with resection of non-viable bowel, and revascularisation of the ischaemic bowel where possible. Due to the physiological insult of AMI however, perioperative care often involves critical care and the use of vasoactive agents to optimise end organ perfusion. A number of these vasoactive agents are currently available with varied mechanism of action and effects on splanchnic blood flow. However, specific guidance on which is the optimal vasoactive drug to use in these settings is limited. This systematic review aimed to evaluate the current evidence comparing vasoactive drugs in AMI. Methods: A systematic search of Ovid Medline, Ovid Embase, Cochrane CENTRAL and the Cochrane Database of Systematic Review was performed on the 5th of November 2020 to identify randomised clinical trials comparing different vasoactive agents in AMI on outcomes including mortality. The search was performed through the Royal College of Surgeons of England (RCSEng) search support library. Results were analysed using the Rayyan platform, and independently screened by four investigators. Results: 614 distinct papers were identified. After screening, there were no randomised clinical trials meeting the inclusion criteria. Conclusions: This review identifies a gap in literature, and therefore recommends an investigation into current practice and clinician preference in relation to vasoactive agents in AMI. Multicentre randomised controlled trials comparing these medications on clinical outcomes will therefore be required to address this question.

Our early experience with mesenteric ischemia in COVID-19 positive patients.

Literature has been published stating that thrombosis is occurring at higher rates in patients who are positive for COVID-19. This experience is more with limb ischemia. Reports of mesenteric ischemia are coming in from different parts of the globe. We share our early experience of managing two patients with acute mesenteric ischemia.

Antiphospholipid syndrome with mesenteric vein thrombosis and hepatic nodular regenerative hyperplasia in a child: A case report.

RATIONALE: Hepatic nodular regenerative hyperplasia (NRH), a nonspecific change in the liver parenchyma, is very rare in children. Hepatic microvascular changes may be the cause, as these vascular changes are uncommon in children. Antiphospholipid syndrome (APS), an autoimmune disease characterized by vascular thromboembolism, is extremely unusual in children. PATIENT CONCERNS: A 13-year-old girl who presented with abdominal pain and elevated liver enzymes was transferred to our hospital. Abdominal computed tomography and magnetic resonance imaging showed a massive mesenteric venous thrombus and a malignant mass with liver metastasis. DIAGNOSES: Her immunological profile was positive for antinuclear antibodies (ANA) at a titer of 1/160 (nucleolar pattern), anticardiolipin antibodies (aCL) immunoglobulin G, and anti-histone antibody. A liver biopsy revealed hepatic NRH. INTERVENTIONS: The patient was initially started on heparin upon hospitalization and switched to warfarin and a vitamin K antagonist and continued treatment with international normalized ratio monitoring. OUTCOMES: Her symptoms improved after 9 months of anticoagulation therapy. LESSONS: In the presence of hepatic NRH or vascular thrombosis in children, we recommend that APS be differentially diagnosed using lupus anticoagulant and aCL and appropriate management be implemented.

Protective Effects of Cinnamaldehyde against Mesenteric Ischemia-Reperfusion-Induced Lung and Liver Injuries in Rats.

The aim of this study was to characterize and reveal the protective effects of cinnamaldehyde (CA) against mesenteric ischemia-reperfusion- (I/R-) induced lung and liver injuries and the related mechanisms. Sprague-Dawley (SPD) rats were pretreated for three days with 10 or 40 mg/kg/d, ig of CA, and then induced with mesenteric ischemia for 1 h and reperfusion for 2 h. The results indicated that pretreatment with 10 or 40 mg/kg of CA attenuated morphological damage in both lung and liver tissues of mesenteric I/R-injured rats. CA pretreatment significantly restored the levels of aspartate transaminase (AST) and alanine transaminase (ALT) in mesenteric I/R-injured liver tissues, indicating the improvement of hepatic function. CA also significantly attenuated the inflammation via reducing myeloperoxidase (MOP) activity and downregulating the expression of inflammation-related proteins, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), cyclooxygenase-2 (Cox-2), and tumor necrosis factor receptor type-2 (TNFR-2) in both lung and liver tissues of mesenteric I/R-injured rats. Pretreatment with CA significantly downregulated nuclear factor kappa B- (NF-κB-) related protein expressions (NF-κB p65, NF-κB p50, I kappa B alpha (IK-α), and inhibitor of nuclear factor kappa-B kinase subunit beta (IKKß)) in both lung and liver tissues of mesenteric I/R-injured rats. CA also significantly downregulated the protein expression of p53 family members, including caspase-3, caspase-9, Bax, and p53, and restored Bcl-2 in both lung and liver tissues of mesenteric I/R-injured rats. CA pretreatment significantly reduced TUNEL-apoptotic cells and significantly inhibited p53 and NF-κB p65 nuclear translocation in both lung and liver tissues of mesenteric I/R-injured rats. CA neither induced pulmonary and hepatic histological alterations nor affected the parameters of inflammation and apoptosis in sham rats. We conclude that CA alleviated mesenteric I/R-induced pulmonary and hepatic injuries via attenuating apoptosis and inflammation through inhibition of NF-κB and p53 pathways in rats, suggesting the potential role of CA in remote organ ischemic injury protection.

Terlipressin relieves intestinal and renal injuries induced by acute mesenteric ischemia via PI3K/Akt pathway.

Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood. Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin. Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour. Immediately after unclamping, terlipressin or norepinephrine was intravenously administered for 2 hours. Meanwhile, in vitro, RAW264.7 cells were treated with lipopolysaccharide or lipopolysaccharide+terlipressin. In addition, wortmannin was used to determine the role of phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway in the potential impacts of terlipressin. Results: MI led to severe hypotension, caused notable intestinal and renal impairments and resulted in high mortality, which were markedly improved by terlipressin or norepinephrine. Terlipressin increased mean arterial pressure, decreased intestinal epithelial cell apoptosis, inhibited the generation of M1 macrophage in intestinal and renal tissues, and hindered the release of inflammatory cytokines after MI. Moreover, in cultured macrophages, terlipressin reduced the mRNA level of specific M1 markers and the release of inflammatory cytokines caused by lipopolysaccharide challenge. Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin. Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI. Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.

Effects of endothelin receptor blockade and COX inhibition on intestinal I/R injury in a rat model: Experimental research.

BACKGROUND: Intestinal ischemia is a highly morbid and mortal condition with no specific treatment. The present study aimed to investigate the effects of cyclooxygenase (COX) inhibition synchronized with nitric oxide (NO) release and endothelin (ET) receptor blockade on oxidative stress, inflammation, vasoconstriction, and bacterial translocation which occur during ischemia-reperfusion (I/R) injury in in-vivo rat intestinal I/R model. MATERIALS AND METHODS: 36 male Wistar rats were randomly divided into six groups (n = 6). Superior mesenteric artery blood flow (SMABF) was recorded; SMA was occluded for 30 min; SMABF was re-recorded at the beginning of the reperfusion phase. Rats were sacrificed after the reperfusion period of 60 min. Blood and tissue samples were obtained. Acetylsalicylic acid (ASA), NO-ASA, flurbiprofen (FLUR), and Tezosentan (TS) were administered 15 min after ischemia. Histopathological examination, bacterial translocation, and biochemical analysis were performed in plasma and tissue samples. RESULTS: SMABF difference, mean Chiu's score and bacterial translocation were increased in the I/R group and decreased in the treatment groups. Plasma LDH, transaminases, intestinal fatty acid-binding protein (I-FABP), TNF-α, ICAM-1, interferon-gamma (IFN-Ɣ) and proinflammatory cytokine panel; tissue lipid peroxidation, MPO, xanthine oxidase (XO), NO, NF-kB levels and the expression of TNF-α were significantly elevated in the I/R group and markedly decreased in the treatment groups. The tissue antioxidant status was decreased in the I/R group and increased in the treatment groups. CONCLUSION: It is suggested that NO-ASA, TS, and FLUR can be introduced as promising therapeutics to improve intestinal I/R injury. INSTITUTIONAL PROTOCOL NO: 2018-29-05 (Animal Experimentations Ethics Committee, Hacettepe University).

Management of superior mesenteric venous thrombus in cystic fibrosis related liver disease.

Abdominal pain is a common feature in patients with cystic fibrosis (CF) and CF related liver disease (CFLD). Superior mesenteric venous (SMV) thrombosis is an uncommon but important cause of abdominal pain. Management strategies are complicated by an underlying prothrombotic state and increased risk of bleeding from complications of CF and CFLD. This review addresses clinical presentation, detection and management options of an acute SMV thrombus in the context of CF.

Vasodilator Therapy and Mortality in Nonocclusive Mesenteric Ischemia: A Nationwide Observational Study.

OBJECTIVES: Previous studies have suggested that vasodilator therapy may be beneficial for patients with nonocclusive mesenteric ischemia. However, robust evidence supporting this contention is lacking. We examined the hypothesis that vasodilator therapy may be effective in patients diagnosed with nonocclusive mesenteric ischemia. DESIGN: Retrospective cohort study. SETTING: The Japanese Diagnosis Procedure Combination inpatient database. PATIENTS: A total of 1,837 patients with nonocclusive mesenteric ischemia from July 2010 to March 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared patients who received vasodilator therapy (vasodilator group; n = 161) and those who did not (control group; n = 1,676) using one-to-four propensity score matching. Vasodilator therapy was defined as papaverine and/or prostaglandin E1 administered via venous and/or arterial routes within 2 days of admission. Only patients who did not receive abdominal surgery within 2 days of admission were analyzed. The main outcomes were in-hospital mortality and abdominal surgery performed greater than or equal to 3 days after admission. After propensity score matching, in-hospital mortality was significantly lower in the vasodilator group (risk difference, -11.6%; p = 0.005). The proportion of patients who received abdominal surgery at greater than or equal to 3 days after admission was also significantly lower in the vasodilator group (risk difference, -10.2%; p = 0.002). CONCLUSIONS: Vasodilator therapy with papaverine and/or prostaglandin E1 is associated with lower in-hospital mortality and prevalence of abdominal surgery in patients with nonocclusive mesenteric ischemia.

Nonocclusive Mesenteric Ischemia and Interventional Local Vasodilatory Therapy: A Meta-Analysis and Systematic Review of the Literature.

BACKGROUND: Intensive care patients with nonocclusive mesenteric ischemia (NOMI) show mortality rates of 70% to 90%. Besides emergency surgery, different interventional local vasodilatory treatment (LVT) attempts have been described. We performed a systematic review and a meta-analysis to evaluate feasibility, efficacy, and tolerability of LVT in patients with life-threatening NOMI. METHODS: Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed until February 2019. Measured outcomes included immediate technical success rates (as indicated by mesenteric vasodilation on angiography or clinical improvement) and adverse events (AEs). Therapeutic efficacy was measured by the assessment of overall mortality. RESULTS: Twelve studies (335 patients, 245 received LVT) from 1977 to 2018 were included. All studies were retrospective (4 comparative and 8 noncomparative). Different intra-arterial vasodilators (4× papaverine, 6× prostaglandin E1, 1× tolazoline/heparin, 1× tolazoline + iloprost) were reported. Initial technical success rate was 75.9% (95% confidence interval [CI], 55.1%-89%, P = .017) with an AE rate of 2.9% (95% CI: 1.3%-6.6%; P = .983). Overall mortality in LVT patients was 40.3% (95% CI: 28.7%-53%, P = .134). In 4 studies, outcomes were compared between patients receiving LVT to those who received standard of care (odds ratio for death in LVT patients was 0.261 [95% CI: 0.095-0.712, P = .009]). CONCLUSIONS: Local vasodilatory treatment appears to be safe in patients with NOMI and might have the potential to at least partially reverse mesenteric vasoconstriction features in control angiographies. However, with no randomized and prospective studies available yet, the overall quality of published studies has to be considered as low; therefore, it is not possible to draw generalizable conclusions from the present data concerning clinical end points. Its application might hold promise as a rescue treatment strategy and deserves further evaluation in randomized controlled trials.

Percutaneous Pharmaco-Mechanical Thrombectomy of Acute Symptomatic Superior Mesenteric Vein Thrombosis.

PURPOSE: To evaluate the safety and the efficacy of percutaneous pharmaco-mechanical thrombectomy (PPMT) of acute superior mesenteric vein (SMV) thrombosis. METHODS: A database of patients treated between 2011 and 2018 with acute venous mesenteric ischemia (VMI) was reviewed. VMI was diagnosed in the presence of SMV thrombosis and CT evidence of jejunal thickening. All patients presented with mild to moderate peritonism, which allowed surgery to be postponed. Initial treatment consisted of heparinization. PPMT was indicated in case of worsening abdominal pain despite anticoagulation and was performed via a transjugular or transhepatic approach, using a rotational aspiration thrombectomy catheter, followed by transcatheter thrombolysis. Clinical success was defined as symptoms resolution. Technical success was defined as patency of > 50% of SMV at venography and resolution of jejunal thickening. Patients were discharged on lifelong oral anticoagulation (INR 2.5-3.5). Follow-ups were performed using CT and color Doppler ultrasound. RESULTS: Population consisted of eight males, aged 37-81 (mean 56.5 years). Causes for thrombosis were investigated. Urokinase infusion time ranged from 48 to 72 h (3,840,000-5,760,000 IU). Clinical and technical success was obtained in all cases. One patient experienced bleeding from the superior epigastric artery and was treated with embolization. One patient died of multi-organ failure after 35 days, despite resolution of SMV thrombosis. In no case was surgery required after PPMT; mean hospitalization was 14.1 days (9-24). Mean follow-up of remaining seven patients was 37.7 months (12-84 months). CONCLUSION: PPMT of acute SMV thrombosis seems safe and effective, with an 87.5% long-term survival rate and a 12.5% major complication rate.

Treatment of Superior Mesenteric Vein Thrombus by Catheter-Directed Thrombolysis.

Contrast-enhanced computed tomography (CT) greatly improves the diagnosis of superior mesenteric vein (SMV) thrombosis, which presents as the unspecific symptom of abdominal pain. Prothrombotic states or thrombophilia and local intra-abdominal infections are major causes of SMV thrombosis. A 37-year-old Chinese woman was diagnosed with SMV and portal vein thrombosis. The patient was initially given 40 mg of heparin sodium every 12 hr and 80,0000 U/day of urokinase using superior mesenteric artery angiography. The abdominal pain was not relieved after treatment. The patient then underwent open surgery, where an ileal branch of the SMV was punctured, a 4F sheath was introduced into the vein toward the portal vein, and a 20-cm Unifuse catheter was placed inside the thrombus for further thrombolysis. Both heparin sodium and urokinase were infused through catheter-directed thrombolysis. The patient's symptoms then gradually resolved.

Non-occlusive mesenteric ischaemia associated with anorexia nervosa.

Non-occlusive mesenteric ischaemia (NOMI) is a life-threatening condition that requires emergent intervention and anorexia nervosa is a chronic eating disorder that requires careful medical and nutritional management. A 54-year-old woman with a history of anorexia nervosa and undergoing chronic haemodialysis developed abdominal pain and called an ambulance. On arrival, she was in shock and abdominal examination was consistent with diffuse peritonitis. Computed tomography scan suggested ischaemia from the distal ileum to the ascending colon. Emergency laparotomy revealed NOMI from the distal ileum to the transverse colon. The treatment strategy included staged operations and careful medical management to optimise nutritional support and electrolyte management with survival of the patient. NOMI and anorexia nervosa are both difficult to manage. Meticulous interdisciplinary management can result in a good outcome.

Interleukin-6 Therapy Improves Intestinal Recovery Following Ischemia.

BACKGROUND: Interleukin-6 (IL6) has both proinflammatory and anti-inflammatory pathways, but its effects on intestinal recovery following ischemia are unknown. We hypothesized that administration of IL6 following intestinal ischemia would improve mesenteric perfusion and mucosal injury. METHODS: Adult male C57Bl6J mice were anesthetized, and a laparotomy was performed. Baseline intestinal perfusion was assessed by laser Doppler imaging. Intestinal ischemia was induced for 60 min by temporarily occluding the superior mesenteric artery. After ischemia, treatments were administered intraperitoneally before closure (Vehicle: 250 µL phosphate-buffered-saline, IL6 low dose (20 ng), IL6 medium dose (200 ng), or IL6 high dose (2 µg)). Animals were allowed to recover for 24 h, were reanesthetized, and their mesenteric perfusion was reassessed. Perfusion was expressed as percentage of baseline. Animals were then sacrificed, and the intestines were explanted for histological analysis. Separate frozen samples were homogenized and analyzed by ELISA for vascular endothelial growth factor (VEGF) and interferon gamma-induced protein 10. RESULTS: IL6 increased mesenteric perfusion in low dose groups only, whereas it improved postischemic mucosal injury scores in both low and medium dose groups. No differences in perfusion or histology were seen when high dose IL6 was utilized. Intestinal VEGF was higher in the low dose IL6 group compared to vehicle, whereas IP-10 levels were lower in low and medium dose groups compared to vehicle. No differences were noted compared to vehicle in intestinal VEGF and IP-10 with high dose IL6 therapy. CONCLUSIONS: Lower doses of IL6 may serve as effective therapy to decrease intestinal injury after ischemia. Further studies are needed to elucidate the downstream mechanisms before widespread clinical use.

Orthotopic Liver Transplant in a Patient Anticoagulated With Rivaroxaban: A Case Report.

Direct oral anticoagulants are approved for use in the United States and Europe and are increasingly used in chronic liver disease patients who have or are at risk of thrombotic events. While these drugs are clinically attractive because no monitoring is required, the risks and benefits in patients with hepatic or renal insufficiency who undergo surgery remain unclear. In this report, we describe the perioperative consequences, safety issues, and lessons learned from a patient undergoing an orthotopic liver transplant who was anticoagulated with rivaroxaban due to partial superior mesenteric vein thrombosis.

The role of PI3K/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion1.

PURPOSE: To investigate the role of PI3k/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion(I/R). METHODS: Male Sprague-Dawley rats were subjected to 45 min of ischemia by occluding the superior mesenteric artery and to 2h of reperfusion to establish the model of I/R. Twenty four rats were randomly divided into four groups: Sham, intestinal I/R (II/R), propofol (P), wortmannin (W). In groups P, W, propofol was injected intravenously and continuously at the onset of reperfusion via infusion pump. PI3K inhibitor (wortmannin) was administered intravenously in group W 25 min before ischemia. Intestinal tissues and lung tissues were obtained for determination of histologic injury, wet/dry weight ratio, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. Meanwhile, the expressions of caspase-3 and phosphorylated Akt (p-Akt) in intestines and lungs were detected by western blot. RESULTS: Propofol treatment alleviated intestinal and lung morphological changes which were observed in II/R group，Moreover, wet/dry weight ratio, the MDA level, MPO activity and expression of caspase-3 were significantly decreased whereas the SOD activity and p-Akt expression were significantly increased. Notably, the protections were significantly reversed by pretreatment of wortmannin. CONCLUSION: PI3K/Akt pathway activation play a critical role in the protective effects of propofol on intestinal and lung injury induced by ischemia/reperfusion.