Mesenteric Ischemia Research Articles

Navigating the intussusception scoring system: A journey beyond boundaries

Bowel resection is usually performed in the operative management of pediatric intussusception patients when the strangulation process lasts for a long time, causing intestinal ischemia and necrosis. A combined scoring system of biological markers and clinical conditions of pediatric patients with intussusception can be a tool to help make decisions to perform appropriate and rapid intestinal resection to reduce patient morbidity and mortality. This was a retrospective cross-sectional study of pediatric intussusception patients undergoing laparotomy surgery at Dr. Soetomo Hospital in 2019 – 2024. The data were collected from electronic medical records, with 69 patients meeting the inclusion criteria, multivariate analysis was performed to obtain markers and ratios of inflammatory markers associated with the occurrence of intestinal necrosis in pediatric patients with intussusception. Of the total 69 subjects, 49 (58%) underwent bowel resection and the rest (29 [42%]) resolves without bowel resection, 49 (58%) was male and dominated by age group of < 12 months old (51 [73,9%]), the most common clinical symptoms was abdominal pain (68 of 69 [98,6%]). Using the Backward Stepwise method, 2 clinical factors were obtained in the form of significant vomiting and abdominal mass (p < 0.05) and a biological marker in the form of CAR cut off (p < 0.05). Conclusion: A scoring system could not be created in this study, but several variables could be used as components of a scoring system in the future study.

Concurrent Emphysematous Gastritis and Small Bowel Ischemia Induced by Methamphetamine Abuse

Methamphetamine abuse poses significant health risks, including cardiovascular and cerebrovascular events. Herein is presented a young woman with chronic amphetamine abuse having developed severe abdominal pain and vomiting. Investigations revealed emphysematous gastritis and small bowel ischemia, leading to rapid deterioration and death despite aggressive intervention. This unique case underscores the need for early recognition and intervention to prevent the life-threatening consequences of methamphetamine abuse. The concurrent occurrence of emphysematous gastritis and small bowel ischemia has not been, to our knowledge, previously documented in methamphetamine users, highlighting the importance of clinician vigilance as abuse rates rise.

REEVALUATING MEAN ARTERIAL PRESSURE TARGETS IN SEPSIS AND SEPTIC SHOCK: INSIGHTS FROM A SYSTEMATIC REVIEW AND META-ANALYSISREEVALUATING MEAN ARTERIAL PRESSURE TARGETS IN SEPSIS AND SEPTIC SHOCK: INSIGHTS FROM A SYSTEMATIC REVIEW AND META-ANALYSIS

The conflicting evidence on the clinical impact of higher versus lower mean arterial pressure (MAP) targets in sepsis and septic shock underscores the urgent need to redefine optimal MAP thresholds to improve outcomes in these critical illnesses. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A data search was conducted on July 1, 2024, for randomized controlled trials and observational studies published from January 2004 to December 2023, assessing patient outcomes based on MAP goal parameters. The primary outcomes were all-cause mortality and overall adverse events. Patients with elevated MAP targets exhibited significantly higher odds of all-cause mortality (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.00–1.22), atrial fibrillation (OR: 2.52, 95% CI: 1.25–5.07), and supraventricular arrhythmia (OR: 1.81, 95% CI: 1.07–3.04) compared to those with lower MAP targets (all p≤0.05). In contrast, higher MAP patients with chronic hypertension and sepsis had significantly lower odds of requiring renal replacement therapy (RRT) (OR: 0.77, 95% CI: 0.62–0.97; p=0.03). No significant differences were observed in overall adverse events, acute myocardial infarction, intensive care unit length of stay, major bleeding, mesenteric ischemia, RRT, 28-day survival, or ventricular tachycardia between the groups. This study highlights that targeting higher MAP in sepsis patients may elevate the risk of cardiac complications, such as atrial fibrillation and supraventricular arrhythmia, without having substantial benefits in reducing mortality or adverse events. The conflicting evidence on the clinical impact of higher versus lower mean arterial pressure (MAP) targets in sepsis and septic shock underscores the urgent need to redefine optimal MAP thresholds to improve outcomes in these critical illnesses. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A data search was conducted on July 1, 2024, for randomized controlled trials and observational studies published from January 2004 to December 2023, assessing patient outcomes based on MAP goal parameters. The primary outcomes were all-cause mortality and overall adverse events. Patients with elevated MAP targets exhibited significantly higher odds of all-cause mortality (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.00–1.22), atrial fibrillation (OR: 2.52, 95% CI: 1.25–5.07), and supraventricular arrhythmia (OR: 1.81, 95% CI: 1.07–3.04) compared to those with lower MAP targets (all p≤0.05). In contrast, higher MAP patients with chronic hypertension and sepsis had significantly lower odds of requiring renal replacement therapy (RRT) (OR: 0.77, 95% CI: 0.62–0.97; p=0.03). No significant differences were observed in overall adverse events, acute myocardial infarction, intensive care unit length of stay, major bleeding, mesenteric ischemia, RRT, 28-day survival, or ventricular tachycardia between the groups. This study highlights that targeting higher MAP in sepsis patients may elevate the risk of cardiac complications, such as atrial fibrillation and supraventricular arrhythmia, without having substantial benefits in reducing mortality or adverse events.

Computed Tomography Imaging of Acute Mesenteric Ischemia for Interventional Radiology

Computed Tomography Imaging of Acute Mesenteric Ischemia for Interventional Radiology

Interventional Radiology in Treating Acute Mesenteric Arterial Occlusion: A Narrative Review

Interventional Radiology in Treating Acute Mesenteric Arterial Occlusion: A Narrative Review

Combined PD-1 and IL-10 blockade reinvigorates mucosal CD8+T exhaustion and relieves liver damage after intestinal ischemia reperfusion attack

Currently, impairments in gut mucosal immunity following intestinal ischemia reperfusion (IR) remain unclear. Mucosal CD8+T cells are critical for host defense against bacterial translocation from the gut lumen, and exhausted T cells lose robust effector functions. The present study was designed to verify the hypothesis that intestinal IR leads to mucosal CD8+T cell exhaustion, and that reinvigoration of exhausted CD8+T cell attenuates IR-induced bacterial translocation and liver damage. The intestinal IR model was performed through clamping the superior mesenteric artery in mice. The percent of exhausted CD8+T cells and the effector function of CD8+T cells were examined to determine the occurrence of intestinal mucosal CD8+T cell exhaustion. Subsequently, PD-1 blockade or combined PD-1 and IL-10 blockade was respectively used to reinvigorate exhausted CD8+T cells. Serum biomarkers, bacterial RNA and colonies, and inflammatory factors were examined to determine bacterial translocation and liver damage. The results indicated that intestinal IR induced CD8+T cell exhaustion in mucosal tissues, as evidenced by increased PD-1+ and PD-1+LAG-3+CD8+T cells and decreased IL-2 and TNF-α expression in CD8+T cells. Combined PD-1 and IL-10 blockade, but not PD-1 blockade alone, reinvigorated CD8+T cell exhaustion, as evidenced by increased generation of exhausted CD8+T cells with cytotoxicity and effector function, and elevated production of IFN-γ. Moreover, combined blockade significantly reduced the translocation of gut bacteria and injury to the liver after IR. In conclusion, intestinal IR leads to mucosal CD8+T cell exhaustion. Combined PD-1 and IL-10 blockade reinvigorates exhausted CD8+T cells, and ameliorates bacterial translocation and liver damage following IR.

Zinc pretreatment for protection against intestinal ischemia-reperfusion injury.

Intestinal ischemia-reperfusion (I/R) injury (II/RI) is a critical condition that results in oxidative stress, inflammation, and damage to multiple organs. Zinc, an essential trace element, offers protective benefits in several tissues during I/R injury, but its effects on intestinal II/RI remain unclear. To investigate the effects of zinc pretreatment on II/RI and associated multiorgan damage. C57BL/6 mice were pretreated with zinc sulfate (ZnSO4, 10 mg/kg) daily for three days before I/R injury was induced via superior mesenteric artery occlusion (SMAO) and abdominal aortic occlusion (AAO) models. Tissue and serum samples were collected to evaluate intestinal, liver, and kidney damage using Chiu's score, Suzuki score, and histopathological analysis. Caco-2 cells and intestinal organoids were used for in vitro hypoxia-reoxygenation injury models to measure reactive oxygen species (ROS) and superoxide dismutase (SOD) levels. Zinc pretreatment significantly reduced intestinal damage in the SMAO and AAO models (P < 0.001). The serum levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase) and kidney markers (creatinine and urea) were lower in the zinc-treated mice than in the control mice, indicating reduced hepatic and renal injury. In vitro, zinc decreased ROS levels and increased SOD activity in Caco-2 cells subject to hypoxia-reoxygenation injury. Intestinal organoids pretreated with zinc exhibited enhanced resilience to hypoxic injury compared to controls. Zinc pretreatment mitigates II/RI and reduces associated multiorgan damage. These findings suggest that zinc has potential clinical applications in protecting against I/R injuries.

Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury.

The gastrointestinal tract can be deranged by ailments including sepsis, trauma and haemorrhage. Ischaemic injury provokes a common constellation of microscopic and macroscopic changes that, together with the paradoxical exacerbation of cellular dysfunction and death following restoration of blood flow, are collectively known as ischaemia-reperfusion injury (IRI). Although much of the gastrointestinal tract is normally hypoxemic, intestinal IRI results when there is inadequate oxygen availability due to poor supply (pathological hypoxia) or abnormal tissue oxygen use and metabolism (dysoxia). Intestinal oxygen uptake usually remains constant over a wide range of blood flows and pressures, with cellular function being substantively compromised when ischaemia leads to a>50% decline in intestinal oxygen consumption. Restoration of perfusion and oxygenation provokes additional injury, resulting in mucosal damage and disruption of intestinal barrier function. The primary cellular mechanism for sensing hypoxia and for activating a cascade of cellular responses to mitigate the injury is a family of heterodimer proteins called hypoxia-inducible factors (HIFs). The HIF system is connected to numerous biochemical and immunologic pathways induced by IRI and the concentration of those proteins increases during hypoxia and dysoxia. Activation of the HIF system leads to augmented transcription of specific genes in various types of affected cells, but may also augment apoptotic and inflammatory processes, thus aggravating gut injury. KEY POINTS: During intestinal ischaemia, mitochondrial oxygen uptake is reduced when cellular oxygen partial pressure decreases to below the threshold required to maintain normal oxidative metabolism. Upon reperfusion, intestinal hypoxia may persist because microcirculatory flow remains impaired and/or because available oxygen is consumed by enzymes, intestinal cells and neutrophils.

Characteristics and outcomes of portal vein thrombosis in patients with inflammatory bowel disease in Korea.

Portal vein thrombosis (PVT) frequently occurs in patients with inflammatory bowel disease (IBD), particularly when influenced by factors such as abdominal infections, IBD flare-ups, or surgical procedures. The implications of PVT range from immediate issues such as intestinal ischemia to long-term concerns including portal hypertension and its complications. However, there is a notable gap in comprehensive studies on PVT in IBD, especially with the increasing incidence of IBD in Asia. This research aimed to evaluate the clinical features and outcomes of PVT in patients with IBD at a leading hospital in South Korea. This retrospective analysis reviewed adult patients diagnosed with both IBD and PVT from 1989 to 2021 at a renowned South Korean medical center. The study focused on patient characteristics, specifics of PVT, administered treatments, and outcomes, all confirmed through enhanced CT scans. A total of 78 patients met the study's criteria. Notably, only 20.5% (16/78) were treated with oral anticoagulants; however, a vast majority (96.2%; 75/78) achieved complete radiographic resolution (CRR). When comparing patients receiving anticoagulants to those who did not, a significant preference for anticoagulant use was observed in cases where the main portal vein was affected, as opposed to just the left or right veins (p = 0.006). However, multivariable analysis indicated that neither anticoagulant use nor previous surgeries significantly impacted CRR. Patients with IBD and PVT generally had favorable outcomes, regardless of anticoagulant use.

AGA Clinical Practice Update on Management of Portal Vein Thrombosis in Patients With Cirrhosis: Expert Review.

Portal vein thromboses (PVTs) are common in patients with cirrhosis and are associated with advanced portal hypertension and mortality. The treatment of PVTs remains a clinical challenge due to limited evidence and competing risks of PVT-associated complications vs bleeding risk of anticoagulation. Significant heterogeneity in PVT phenotype based on anatomic, host, and disease characteristics, and an emerging spectrum of therapeutic options further complicate PVT management. This Clinical Practice Update (CPU) aims to provide best practice advice for the evaluation and management of PVT in cirrhosis, including the role of direct oral anticoagulants and endovascular interventions. This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Asymptomatic patients with compensated cirrhosis do not require routine screening for PVT. BEST PRACTICE ADVICE 2: Patients with cirrhosis with PVTs identified on Doppler ultrasound should undergo cross-sectional imaging with computed tomography or magnetic resonance imaging to confirm the diagnosis, evaluate for malignancy, and document the degree of lumen occlusion, clot extent, and chronicity. BEST PRACTICE ADVICE 3: Patients with cirrhosis and PVT do not require a hypercoagulable workup in the absence of additional thromboemboli or laboratory abnormalities or family history suggestive of thrombophilia. BEST PRACTICE ADVICE 4: Patients with cirrhosis and PVT with evidence of intestinal ischemia require urgent anticoagulation to minimize ischemic injury. If available, these patients should be managed by a multidisciplinary team, including gastroenterology and hepatology, interventional radiology, hematology, and surgery. BEST PRACTICE ADVICE 5: Consider observation, with repeat imaging every 3 months until clot regression, in patients with cirrhosis without intestinal ischemia and recent (<6 months) thrombosis involving the intrahepatic portal vein branches or when there is <50% occlusion of the main portal vein, splenic vein, or mesenteric veins. BEST PRACTICE ADVICE 6: Anticoagulation should be considered in patients with cirrhosis without intestinal ischemia who develop recent (<6 months) PVT that is >50% occlusive or involves the main portal vein or mesenteric vessels. Patients who have increased benefit of recanalization include those with involvement of more than 1 vascular bed, those with thrombus progression, potential liver transplantation candidates, and those with inherited thrombophilia. BEST PRACTICE ADVICE 7: Anticoagulation is not advised for patients with cirrhosis with chronic (>6 months) PVT with complete occlusion with collateralization (cavernous transformation). BEST PRACTICE ADVICE 8: Patients with cirrhosis and PVT warrant endoscopic variceal screening if they are not already on nonselective beta-blocker therapy for bleeding prophylaxis. Avoid delays in the initiation of anticoagulation for PVT, as this decreases the odds of portal vein recanalization. BEST PRACTICE ADVICE 9: Vitamin K antagonists, low-molecular-weight heparin, and direct oral anticoagulants are all reasonable anticoagulant options for patients with cirrhosis and PVT. Decision making should be individualized and informed by patient preference and Child-Turcotte-Pugh class. Direct oral anticoagulants may be considered in patients with compensated Child-Turcotte-Pugh class A and Child-Turcotte-Pugh class B cirrhosis and offer convenience as their dosages are independent of international normalized ratio monitoring. BEST PRACTICE ADVICE 10: Patients with cirrhosis on anticoagulation for PVT should have cross-sectional imaging every 3 months to assess response to treatment. If clot regresses, anticoagulation should be continued until transplantation or at least clot resolution in nontransplantation patients. BEST PRACTICE ADVICE 11: Portal vein revascularization with transjugular intrahepatic portosystemic shunting may be considered for selected patients with cirrhosis and PVT who have additional indications for transjugular intrahepatic portosystemic shunting, such as those with refractory ascites or variceal bleeding. Portal vein revascularization with transjugular intrahepatic portosystemic shunting may also be considered for transplantation candidates if recanalization can facilitate the technical feasibility of transplantation.

Preventable diagnostic errors of lower gastrointestinal perforation: a secondary analysis of a large-scale multicenter retrospective study

BackgroundLower gastrointestinal perforation (LGP) is an acute abdominal condition associated with a high mortality rate. Timely and accurate diagnosis is crucial. Nevertheless, a diagnostic delay has been estimated to occur in approximately one-third of the cases, and the factors contributing to this delay are yet to be clearly understood. This study aimed to evaluate the diagnostic process for appropriate clinical reasoning and availability of image interpretation in cases of delayed diagnosis of LGP.MethodsA secondary data analysis of a large multicenter retrospective study was conducted. This descriptive study analyzed data from a multicenter, observational study conducted across nine hospitals in Japan from January 2015 to December 2019. Out of 439 LGP cases, we included 138 cases of delayed diagnosis, excluding patients with traumatic or iatrogenic perforations, or those secondary to mesenteric ischemia, appendicitis, or diverticulitis. Clinical history and computed tomography (CT) imaging information were collected for 138 cases. Additionally, information on the clinical course of 50 cases, which were incorrectly diagnosed as gastroenteritis, constipation, or small bowel obstruction, was also collected.ResultsIn 42 (30.4%) cases of delayed diagnosis of LGP, CT imaging was performed before diagnosis, indicating a missed opportunity for timely diagnosis. Moreover, 33 of the 50 patients initially diagnosed with gastroenteritis, constipation, or small bowel obstruction at the time of initial examination had atypical findings that were not consistent with the initial diagnosis. Of the 138 cases with delayed diagnosis in our study, 67 cases (48.6%) showed problems with either the interpretation of CT scans or with the process of clinical reasoning.ConclusionOur retrospective study results indicate that approximately half of the cases with delayed diagnosis of LGP were due to problems in interpreting CT images or in clinical reasoning. This finding suggests that clinical reasoning and image interpretation by radiologists are important in improving the diagnostic process for LGP.

Intraoperative evaluation of the intestinal wall viability

An analysis of data from national and foreign literature was carried out in terms of intraoperative determination of the intestinal viability in cases of developing the diseases in the abdominal cavity organs, associated with impaired intestinal blood supply. The basis of this work is the analysis of the modern literature on the methods of intraoperative evaluation of mesenteric ischemia. Impaired mesenteric blood supply is often the consequence of a number of reasons of developing critical conditions (mesenteric thrombosis, acute adhesive intestinal obstruction, incarcerated hernia etc.), also representing a high risk factor for lethal outcomes. Special attention is paid to the occlusion-related pathogenetic mechanism of developing mesenteric ischemia, which is accompanied by rapid development of irreversible morphological changes in the tissues and by significant disorders in the homeostasis systems of the organism. The generally available method for visual evaluation of the intestine viability is not always valid in terms of determining the degree of intensity of the ischemic changes in the intestinal wall. The algorithm of determining the intestine viability includes the determination of the intestine color, the peristaltic motions, the pulsation and the blood filling of mesenteric vessels with dynamic evaluation of these signs after the injecting the local anesthetic drug solution into the mesenterium and after “warming” the intestine with towels soaked in warm sodium chloride solution. In the current surgical conditions, a more precise method is required for intraoperative determination of the tissue viability. For the purpose of the objective evaluation of the intestinal blood supply, the recommendations include using intraoperative ultrasonic and laser Doppler flowmetry, as well as the regional transillumination angiotensometry of the intramural vessels in the small intestine. At the same time, a number of optical spectroscopy and visualization methods show high sensitivity to changes in blood microcirculation without using exogenous contrasting, which can also be successfully used when evaluating the intestinal circulation. According to data from modern literature, there is still controversy on the efficiency of various methods for intraoperative evaluation of disorders of the regional blood microcirculation and the intestine viability, which justifies the conduct of further research works.

Longitudinal analysis of serum intestinal fatty acid-binding protein in a patient with non-occlusive mesenteric ischemia following brachial plexus block-induced hypotension: a case study.

Intestinal fatty acid-binding protein (I-FABP) is a promising biomarker for small-bowel ischemia including non-occlusive mesenteric ischemia (NOMI). A 75-year-old woman with diabetic nephropathy sustained a distal radius fracture. Two days later, she underwent a brachial plexus block to facilitate orthopedic surgery, which resulted in hypotension. Despite prompt fluid resuscitation and ephedrine administration, the patient developed abdominal pain. Contrast-enhanced computed tomography revealed hepatic portal venous gas, but no direct evidence of small-bowel ischemia. The gastrointestinal surgery team opted for cautious in-hospital observation overnight. Unfortunately, the patient's condition significantly worsened the following day, prompting an urgent laparotomy. Surgery confirmed ileal segment necrosis, macroscopically characterized by a distinctive geographic pattern. Retrospective analysis of stored serum samples using a human enzyme-linked immunosorbent assay demonstrated that I-FABP levels were moderately elevated (7.2ng/mL) at the initial outpatient visit for the fracture, peaked (17.9ng/mL) at the clinical onset of NOMI, and returned to normal (0.7ng/mL) by postoperative day 2. Serum I-FABP levels correlated with the progression of NOMI, showing potential as an early detection marker. However, the longitudinal analysis of serum I-FABP also highlighted significant challenges of this biomarker, including the influence of renal function and the importance of sampling timing.

What about a strangulated broad ligament hernia? Case experience.

Little known, herniation of the broad ligament of the uterus is a rare entity of internal hernias which poses a real diagnostic dilemma for clinicians. These clinical and radiological findings are often nonspecific and the entity is generally discovered incidentally intraoperatively during urgent surgery for occlusive syndrome. Although such a scenario is not a usual condition, a high index of suspicion is required in time to avoid progression to intestinal ischemia. Until a few years ago, conventional surgery was the approach systematically used in the therapeutic management of the pathology. With advances in minimally invasive techniques, more and more clinical reports have attested to the value of laparoscopy in the diagnostic and therapeutic adequacy of the condition. However, the experience remains remarkable and the literature reported is rare to date. To this end, we present the case of a patient diagnosed with acute intestinal obstruction without radiological confirmation of the etiological conjecture. Emergency laparoscopy finally revealed the incarceration of the small intestine through a herniation of the broad ligament and also allowed therapeutic success. This report aims to highlight the diagnostic difficulties of the pathology and the potential advantages of its laparoscopic management.

Modern Open Surgery for Coral Reef Aorta with Visceral Artery Involvement.

Coral reef atherosclerosis of the visceral aorta (CRA) is associated with renovascular hypertension (RVH), chronic mesenteric ischaemia (CMI), and malperfusion of the lower limbs (PAD). The outcomes of open surgery for this rare disease are described in this paper. This retrospective study included all patients who underwent open surgical repair of CRA at a single high volume referral centre between January 2009 and June 2023. The operation was preceded by pre-operative computerised tomography angiography (CTA). Follow up was carried out to assess clinical improvement regarding walking, blood pressure control, visceral and renal ischaemia. Post-operative survival and patency of the aorta and revascularised visceral arteries were evaluated by the Kaplan-Meier method. Thirty eight patients, with a mean age of 65 years and predominantly women (57.9%), were included in the study. The surgical indication was RVH in 40.6%, CMI in 25%, and PAD in 71.9% of patients. All procedures were performed by left lumbotomy, with re-implantation or visceral/renal artery bypass in 15 patients (39.5%) and 17 (44.7%) cases of simultaneous infrarenal aortic revascularisation. One death (2.6%) secondary to acute mesenteric ischaemia occurred post-operatively. Three patients (7.9%) presented with myocardial infarction and 11 (28.9%) with post-operative acute kidney failure without haemodialysis. Median follow up was 32.5 months. Post-operatively, all patients with CMI and claudication became asymptomatic, and 17 (56.7%) showed improved hypertension. Six patients needed repeat visceral artery revascularisation. No death related to CRA occurred during follow up. Survival rates were 91.9% and 61.6% at one and five years, respectively. Visceral aortic endarterectomy by left sided lumbotomy, preceded by multiplanar reconstruction CTA is a safe and effective procedure for CRA, with low operative mortality and acceptable morbidity rates. Long term clinical monitoring by colour duplex scan or CTA is recommended due to a risk of restenosis of endarterectomised visceral arteries.

Bifidobacterium longum Metabolite Indole-3-Carboxaldehyde Blocks HDAC3 and Inhibits Macrophage NLRP3 Inflammasome Activation in Intestinal Ischemia/Reperfusion Injury.

Indole-3-carboxaldehyde (3-IAld), a tryptophan metabolite derived from gut microbiota, has been reported to protect the intestine against radiation injury. This study aimed to clarify the role of Bifidobacterium longum (B. longum) and its metabolite indole-3-carboxaldehyde (3-IAld) in the pathophysiology of intestinal ischemia/reperfusion (II/R) injury. Superior mesenteric artery occlusion and reperfusion were performed to establish II/R mice, and pathological injury in II/R mice was evaluated. II/R mice showed impaired gut microbiota diversity and reduced abundance of B. longum in the intestines. Transplantation of B. longum mitigated II/R injury by protecting the integrity of the intestinal barrier and reducing inflammatory response. The 3-IAld level increased after transplantation of B. longum, and 3-IAld treatment inhibited the inflammatory response of bone marrow-derived macrophages (BMDM). Histone deacetylase 3 (HDAC3) was a target of 3-IAld, and HDAC3 was translocated to mitochondria to promote mitochondrial fatty acid oxidation (FAO) during macrophage inflammasome formation. HDAC3 overexpression promoted the formation of macrophage inflammasomes in intestinal tissues. Overall, this study confirmed the beneficial effects of B. longum in combating II/R injury through HDAC3-mediated control of mitochondrial FAO and macrophage inflammasome formation via 3-IAld.

Shock Patients and Enteral Nutrition?

Shock is a life-threatening condition characterized by microcirculatory disturbances and inadequate tissue perfusion. In hemodynamically unstable individuals, arterial pressure is maintained with vasoactive agents. Enteral nutrition (EN) is crucial for the intensive treatment of critically ill patients, facilitating intestinal recovery and improving clinical outcomes such as reducing infections, shortening hospital stays, and lowering costs. The impact of vasoactive agents on gastrointestinal blood flow varies, depending on the drug, dose, body size, and individual sensitivity. EN is categorized into early and delayed, and multiple guidelines recommend delayed EN due to the risks in the early stage, which may lead to EFI, non-obstructive mesenteric ischemia and necrosis. Guidelines for early EN in shock patients are still evolving, exploring the optimal timing and safety thresholds. Studies have shown that early EN can be safely implemented in hemodynamically stable patients maintaining a mean arterial pressure of 70 mmHg with stable doses of antihypertensives. This review summarizes the optimal and safe timing of initiating EN in shock patients to guide clinical practice. The pathophysiology of shock, EN selection, considerations, nutritional regimens, effects of antihypertensive agents, and feeding regimens are further discussed.

Early and concomitant administration of norepinephrine and ilomedin improves microcirculatory perfusion without impairing macrocirculation in an intestinal ischemia-reperfusion injury swine model : a randomized experimental trial.

Intestinal ischemia-reperfusion injury is associated with both macrocirculatory and microcirculatory failure. Association of a vasoconstrictor in combination with a vasodilator such as ilomedin may improve macrocirculation parameters, microcirculation perfusion and reduce endothelial dysfunction. The primary objective was to demonstrate a difference in mean arterial pressure (MAP) after intestinal reperfusion with the concomitant administration of norepinephrine and ilomedin during ischemia compared with traditional hemodynamic treatment strategies (fluid resuscitation and vasopressors only). Secondary objectives were to demonstrate an improvement in peripheral and intestinal microcirculatory perfusion and endothelial dysfunction after intestinal reperfusion using this association. We conducted a randomized preclinical trial in twenty-one large white pigs, in which a 2-hour small bowel ischemia was performed using a segmental mesenteric occlusion model, followed by a 2-hour reperfusion. Pigs were randomized into 3 groups: goal directed fluid therapy, early administration of norepinephrine before reperfusion and early administration of ilomedin and norepinephrine before reperfusion. Macrocirculatory (MAP and Cardiac Index (CI)), microcirculatory (Sublingual with SideStream Dark Field system and intestinal hemoglobin oxygen saturation with hyperspectral imaging (HSI)) measurements and biological analysis (biomarkers of endothelial dysfunction) were performed. There were no significant differences in the MAP (p = 0.499) and the CI (p = 0.659) between the 3 groups. Perfused Vessel Density (PVD) in sublingual microcirculation was significantly higher immediately after reperfusion and 2 hours after reperfusion in the early administration of ilomedin and norepinephrine group compared with the other 2 groups (p < 0.05). Hemoglobin oxygen saturation measured at the intestinal level was significantly higher immediately after reperfusion in the early administration of ilomedin and norepinephrine group compared with the other 2 groups (p < 0.01). There were no significant differences in biomarkers of endothelial dysfunction between the 3 groups. Creatinine, AST and alkaline phosphatases increased significantly 2 hours after reperfusion in the early administration of ilomedin and norepinephrine group compared with baseline (p < 0.05). Early administration of norepinephrine and ilomedin during ischemia improved short-term post-reperfusion sublingual and intestinal microcirculation without worsening macrocirculatory parameters in an intestinal ischemia-reperfusion injury model. However, use of this strategy seemed to worsen both liver and kidney function.

Radiological assessment of pulmonary vascular changes and gastrointestinal changes in patients with COVID-19 referred to a tertiary health care center in Chennai, India: a prospective cross-sectional study

BACKGROUND: The coronavirus disease pandemic (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has led to significant morbidity and mortality worldwide since its emergence in 2019. Although primarily a respiratory illness, COVID-19 can also affect other organ systems, including the vascular and gastrointestinal systems. COVID-19 is linked to both venous and arterial thrombosis, and numerous studies have indicated a heightened risk of pulmonary embolism. Autopsies have revealed pulmonary vasculature thrombosis and bowel ischemia in patients with COVID-19. AIM: To assess radiological pulmonary vascular changes, specifically pulmonary embolism, and gastrointestinal changes in patients with COVID-19 referred to a tertiary healthcare center in Chennai, India. MATERIALS AND METHODS: Computed tomography pulmonary angiography and contrast-enhanced computed tomography of the abdomen were conducted in 100 patients with COVID-19 who met the selection criteria. A radiologist with 5 years of experience evaluated pulmonary vascular and bowel changes. Subsequently, statistical analysis was performed to determine the significance of the relationship between patients with COVID-19 and the occurrence of pulmonary vascular and bowel changes. RESULTS: In this study, 11 patients exhibited pulmonary thromboembolism, and 7 showed significant bowel changes such as bowel wall thickening, mesenteric ischemia, and omental infarction, indicative of potential gastrointestinal involvement of patients with COVID-19. A positive correlation was found between pulmonary embolism prevalence in patients with COVID-19. Pulmonary embolism was diagnosed at a mean of 11 days from disease onset. Of the 24 patients with severe acute respiratory illness, 7 showed pulmonary embolism, detected by computed tomography pulmonary angiography. In addition, of the 10 patients on mechanical ventilation, pulmonary embolism was found in 7. Among the seven patients with bowel changes, four had pulmonary embolism, as detected by computed tomography pulmonary angiography, indicating a significant association between the two concomitant complications. The observed bowel changes were attributed to intravascular thrombosis. CONCLUSIONS: Based on our findings, pulmonary emboli and bowel changes often occur in patients with COVID-19. Multivariate analyses also revealed a connection between invasive mechanical ventilation and pulmonary embolism. The results indicate that patients with severe COVID-19 may also experience concurrent acute pulmonary embolism. Thus, for these patients, the use of contrast-enhanced computed tomography instead of standard non-contrast computed tomography may aid in treatment decision-making.

Large animal models enhance the study of crypt-mediated epithelial recovery from prolonged intestinal ischemia reperfusion injury.

Intestinal ischemia and reperfusion injury (IRI) is a deadly and common condition. Death is associated with sepsis due to insufficient epithelial repair, requiring stem cell-driven regeneration, typically beginning 48 h after injury. Animal models are critical to advancing this field. To effectively study epithelial healing, models must survive clinically relevant intestinal ischemic injury extending to the crypt. Although mouse models are indispensable to intestinal research, their application for studying epithelial repair following severe IRI may be limited. Ischemic injury was induced in mouse and porcine jejunum for up to 3 h, with up to 72 h of reperfusion. Histologic damage was scored by Chiu-Park grade, and animal survival was assessed. Findings were compared between species. A mouse IRI literature review was performed to evaluate the purported degree of injury, duration of recovery, and reported survival rates. In mice and pigs, 3 h of ischemia induced severe, reliable injury extending into the crypt. However, at 48 h, mouse survival was only 23.5% compared with 100% survival in pigs. In literature, ischemia was induced for >1 h in only 4 of 102 mouse studies and none to 3 h. Recovery was attempted for 48 h in only six reports. Forty-seven studies reported intestinal crypt injury. Of those that featured histologic intestinal crypt damage, survival rates at 48 h ranged from 10 to 50% (median 30%). Mouse models are not ideal for studying intestinal stem cell-mediated recovery from severe IRI. Alternative large animal models, like pigs, are recommended.NEW & NOTEWORTHY Additional research is needed to improve recovery from severe intestinal ischemia. The selection of the ideal animal model is critical to facilitating this work. Based on our experimentation and literature review, porcine models, with increased translatability and an improved ability to survive both prolonged ischemia and the recovery period, appear to be the most appropriate choice for future studies.