EFFECT OF MIR-21-3P ON INTESTINAL INJURY IN RATS WITH TRAUMATIC HEMORRHAGIC SHOCK RESUSCITATED WITH THE SODIUM BICARBONATE RINGER'S SOLUTION.

ABSTRACT: Background : This study aims to determine the impact and mechanism of miR-21-3p on intestinal injury and intestinal glycocalyx during fluid resuscitation in traumatic hemorrhagic shock (THS), and the different impacts of sodium lactate Ringer's solution (LRS) and sodium bicarbonate Ringer's solution (BRS) for resuscitation on intestinal damage. Methods : A rat model of THS was induced by hemorrhage from the left femur fracture. The pathological changes of intestinal tissues and glycocalyx structure were observed by hematoxylin-eosin staining and transmission electron microscope. MiR-21-3p expression in intestinal tissues was detected by real-time quantitative polymerase chain reaction. The expression of glycocalyx-, cell junction-, and PI3K/Akt/NF-κB signaling pathway-related proteins was analyzed by western blot. Results : MiR-21-3p expression was increased in THS rats, which was suppressed by resuscitation with BRS. BRS or LRS aggravated the intestinal injury and damaged intestinal glycocalyx in THS rats. The expression of SDC-1, HPA, ß-catenin, MMP2, and MMP9 was upregulated, the expression of E-cad was downregulated, and the PI3K/Akt/NF-κB signaling pathway was activated in THS rats, which were further aggravated by BRS or LRS. The adverse effect of LRS was more serious than BRS. MiR-21-3p overexpression deteriorated the injury of intestinal tissues and intestinal glycocalyx; increased the expression of SDC-1, HPA, ß-catenin, MMP2, and MMP9 while decreasing E-cad expression; and activated the PI3K/Akt/NF-κB signaling pathway in BRS-resuscitated THS rats. Conclusion : MiR-21-3p aggravated intestinal tissue injury and intestinal glycocalyx damage through activating PI3K/Akt/NF-κB signaling pathway in rats with THS resuscitated with BRS.

Abdominal computed tomography scoring systems and experienced radiologists in the radiological diagnosis of small bowel and mesenteric injury.

PURPOSE: Blunt bowel and/or mesenteric injury requiring surgery presents a diagnostic challenge. Although computed tomography (CT) imaging is standard following blunt trauma, findings can be nonspecific. Most studies have focused on the diagnostic value of CT findings in identifying significant bowel and/or mesenteric injury (sBMI). Some studies have described scoring systems to assist with diagnosis. Little attention, has been given to radiologist interpretation of CT scans. This study compared the discriminative ability of scoring systems (BIPS and RAPTOR) with radiologist interpretation in identifying sBMI. METHODS: We conducted a retrospective chart review of trauma patients with suspected sBMI. CT images were reviewed in a blinded fashion to calculate BIPS and RAPTOR scores. Sensitivity and specificity were compared between BIPS, RAPTOR, and the admission CT report with respect to identifying sBMI. RESULTS: One hundred sixty-two patients were identified, 72 (44%) underwent laparotomy and 43 (26.5%) had sBMI. Sensitivity and specificity were: BIPS 49% and 87%, AUC 0.75 (0.67-0.81), P < 0.001; RAPTOR 46% and 82%, AUC 0.72 (0.64-0.79), P < 0.001; radiologist impression 81% and 71%, AUC 0.82(0.75-0.87), P < 0.001. The discriminative ability of the radiologist impression was higher than RAPTOR (P = 0.04) but not BIPS (P = 0.13). There was not a difference between RAPTOR vs. BIPS (P = 0.55). CONCLUSION: Radiologist interpretation of the admission CT scan was discriminative of sBMI. Although surgical vigilance, including evaluation of the CT images and patient, remains fundamental to early diagnosis, the radiologist's impression of the CT scan can be used in clinical practice to simplify the approach to patients with abdominal trauma.

PRMT6-FOXO3A ATTENUATES APOPTOSIS BY UPREGULATING PARKIN EXPRESSION IN INTESTINAL ISCHEMIA-REPERFUSION INJURY.

ABSTRACT: Intestinal ischemia-reperfusion injury (IIRI) is a serious disease with high morbidity and mortality. This study aims to investigate the potential regulatory mechanisms involving protein arginine methyltransferase 6 (PRMT6), Forkhead box O3a (FoxO3a), and Parkin in IIRI and elucidate their roles in mediating cell apoptosis. The IIRI animal model was established and confirmed using hematoxylin and eosin staining. Oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established to mimic ischemic injury in vitro . Transient transfection was used to overexpress or knock down genes. Cell death or apoptosis was assessed by propidium iodide staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and flow cytometry. The expression of proteins was detected by western blot. The histopathology observed by hematoxylin and eosin staining suggested that the IIRI animal model was successfully established. Our findings revealed that IIRI resulted in increased Bax and decreased Bcl-2 levels. In vitro experiments showed that overexpression of Parkin decreased OGD/R injury and suppressed elevation of Bax/Bcl-2. PRMT6 regulated the methylation level of FoxO3a. Moreover, FoxO3a directly binds to Parkin, and FoxO3a overexpression reduced OGD/R-induced cell death and regulation of Parkin. Overexpression of PRMT6 can attenuate the downregulation of Parkin and elevation of Bax/Bcl-2 caused by OGD/R. Knockdown of PRMT6 promoted apoptosis in intestinal epithelial cells of OGD/R group, while PRMT6 overexpression exhibited the opposite effect. Notably, the levels of PRMT6, FoxO3a, and Parkin were decreased in IIRI mouse intestinal tissue. Knocking out PRMT6 causes a significant decrease in the lifespan of mice. Altogether, our results demonstrated that PRMT6 upregulated the expression of Parkin by regulating FoxO3a methylation level, attenuating the apoptosis induced by IIRI.

Performance of three predictive scores to avoid delayed diagnosis of significant blunt bowel and mesenteric injury: A 12-year retrospective cohort study.

BACKGROUND: Avoiding missed diagnosis and therapeutic delay for significant blunt bowel and mesenteric injuries (sBBMIs) after trauma is still challenging despite the widespread use of computed tomography (CT). Several scoring tools aiming at reducing this risk have been published. The purpose of the present work was to assess the incidence of delayed (>24 hours) diagnosis for sBBMI patients and to compare the predictive performance of three previously published scores using clinical, radiological, and laboratory findings: the Bowel Injury Prediction Score (BIPS) and the scores developed by Raharimanantsoa Score (RS) and by Faget Score (FS). METHODS: A population-based retrospective observational cohort study was conducted; it included adult trauma patients after road traffic crashes admitted to Lausanne University Hospital, Switzerland, between 2008 and 2019 (n = 1,258) with reliable information about sBBMI status (n = 1,164) and for whom all items for score calculation were available (n = 917). The three scores were retrospectively applied on all patients to assess their predictive performance. RESULTS: The incidence of sBBMI after road traffic crash was 3.3% (38 of 1,164), and in 18% (7 of 38), there was a diagnostic and treatment delay of more than 24 hours. The diagnostic performances of the FS, the RS, and the BIPS to predict sBBMI, expressed as the area under the receiver operating characteristic curve, were 95.3% (95% confidence interval [CI], 92.7-97.9%), 89.2% (95% CI, 83.2-95.3%), and 87.6% (95% CI, 81.8-93.3%) respectively. CONCLUSION: The present study confirms that diagnostic delays for sBBMI still occur despite the widespread use of abdominal CT. When CT findings during the initial assessment are negative or equivocal for sBBMI, using a score may be helpful to select patients for early diagnostic laparoscopy. The FS had the best individual diagnostic performance. However, the BIPS or the RS, relying on clinical and laboratory variables, may be helpful to select patients for early diagnostic laparoscopy when there are unspecific CT signs of bowel or mesenteric injury. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Targeting sting to reduce sepsis-induced acute intestinal injury.

BACKGROUND: Sepsis is a dysregulated host response to infection syndrome leading to life-threatening organ dysfunction. Sepsis-induced intestinal dysfunction is a key element in the progression to multisystem organ failure. The stimulator of interferon genes is an intracellular protein implicated in intestinal injury in sepsis. H151, a small molecule inhibitor of stimulator of interferon genes, has not yet been studied as a potential therapeutic in sepsis. We hypothesize that H151 therapeutically reduces sepsis-induced acute intestinal injury. METHODS: Male mice underwent cecal ligation and puncture and were treated with intraperitoneal H151 (10 mg/kg body weight) or vehicle. Intestines and serum were collected for analysis 20 hours after cecal ligation and puncture. Oral gavage of mice with FITC-dextran was performed 15 hours after cecal ligation and puncture. Five hours after gavage, serum was collected, and intestinal permeability was assessed. Mice were monitored for 10 days after cecal ligation and puncture to assess survival. RESULTS: Zonula occludens 1 tight junctional protein expression was reduced after cecal ligation and puncture and recovered with H151 treatment. This was associated with a 62.3% reduction in intestinal permeability as assessed by fluorimetry. After cecal ligation and puncture, treatment with H151 was associated with a 58.7% reduction in intestinal histopathologic injury (P < .05) and a 56.6% reduction in intestinal apoptosis (P < .05). Intestinal myeloperoxidase activity was decreased by 70.8% after H151 treatment (P < .05). Finally, H151 improved 10-day survival from 33% to 80% after cecal ligation and puncture (P = .011). CONCLUSION: H151, a novel stimulator of interferon genes inhibitor, reduces intestinal injury, inflammation, and permeability when administered as a treatment for cecal ligation and puncture-induced sepsis. Thus, targeting stimulator of interferon genes shows promise as a therapeutic strategy to ameliorate sepsis-induced acute intestinal injury.

Complete transection of the descending colon following blunt abdominal trauma.

We present the case of a man in his 30s who was crushed between two vehicles sustaining blunt trauma to his lower limbs and torso. The patient was in shock on arrival to the emergency department, and immediate resuscitation was given with massive transfusion protocol activation. Once the patient's haemodynamic status was stabilised, a CT scan revealed a complete colon transection. The patient was taken to the operating theatre where a midline laparotomy was performed, and the transected descending colon was managed with a segmental resection and handsewn anastomosis. The patient followed an unremarkable postoperative course, with bowels opening on day 8 postoperatively. Colon injuries are rare following blunt abdominal trauma, and a delay in diagnosis may lead to increased morbidity and mortality. As such, a low threshold for surgical intervention is recommended.

Anastomotic leak rates after repair of mesenteric bucket-handle injuries: A multi-center retrospective cohort study.

BACKGROUND: Primary aim was to assess the relative risk (RR) of anastomotic leak (AL) in intestinal bucket-handle (BH) compared to non-BH injury. METHODS: Multi-center study comparing AL in BH from blunt trauma 2010-2021 compared to non-BH intestinal injuries. RR was calculated for small bowel and colonic injury using R. RESULTS: AL occurred in 20/385 (5.2%) of BH vs. 4/225 (1.8%) of non-BH small intestine injury. AL was diagnosed 11.6 ± 5.6 days from index operation in small intestine BH and 9.7 ± 4.3 days in colonic BH. Adjusted RR for AL was 2.32 [0.77-6.95] for small intestinal and 4.83 [1.47-15.89] for colonic injuries. AL increased infections, ventilator days, ICU & total length of stay, reoperation, and readmission rates, although mortality was unchanged. CONCLUSION: BH carries a significantly higher risk of AL, particularly in the colon, than other blunt intestinal injuries.

Oral Microalgae-Nano Integrated System against Radiation-Induced Injury.

The increasing applications of ionizing radiation in society raise the risk of radiation-induced intestinal and whole-body injury. Astaxanthin is a powerful antioxidant to reduce the reactive oxygen generated from radiation and the subsequent damage. However, the oral administration of astaxanthin remains challenging owing to its low solubility and poor bioavailability. Herein, we facilely construct an orally used microalgae-nano integrated system (SP@ASXnano) against radiation-induced intestinal and whole-body injury, combining natural microalgae Spirulina platensis (SP) with astaxanthin nanoparticles (ASXnano). SP and ASXnano show complementation in drug delivery to improve distribution in the intestine and blood. SP displays limited gastric drug loss, prolonged intestinal retention, constant ASXnano release, and progressive degradation. ASXnano improves drug solubility, gastric stability, cell uptake, and intestinal absorption. SP and ASXnano have synergy in many aspects such as anti-inflammation, microbiota protection, and fecal short-chain fatty acid up-regulation. In addition, the system is ensured with biosafety for long-term administration. The system organically combines the properties of microalgae and nanoparticles, which was expected to expand the medical application of SP as a versatile drug delivery platform.

Actualización de biomarcadores para la detección precoz de isquemia intestinal / Update on biomarkers for early detection of intestinal ischemia

La isquemia intestinal asocia una elevada mortalidad debida principalmente a un retraso en el diagnóstico. Sibien el angio tC es una herramienta sensible y específica, suele transcurrir demasiado tiempo hasta su realizacióndebido a una presentación clínica poco específica. en este tiempo la isquemia intestinal puede progresar a estadiosirreversibles con afectación sistémica. La obtención de biomarcadores precisos y de elevación precoz acortaría eltiempo diagnóstico de esta patología, lo que disminuiría su mortalidad asociada. Se sabe que las moléculas usadastradicionalmente, entre ellas el lactato, no tienen buena capacidad diagnóstica. no obstante, se ha observado unaelevada sensibilidad con el uso del esteroisómero D del lactato y la procalcitonina para detectar colitis isquémicatras cirugía de aorta, al tiempo que se recomienda valorar los niveles de dímero D para descartar isquemia mesen-térica aguda en pacientes con dolor abdominal. Otras moléculas con un potencial rendimiento diagnóstico sonla proteína ligadora de ácidos grasos intestinales (I-FaBp) y el péptido similar al glucagón de tipo 1 (GLp-1), aúnen investigación.(AU)

Intestinal ischemia associates high mortality rates, mainly due to a delay in diagnosis. although computed tomog-raphy angiography (Cta) remains a sensitive and specifi c tool, it usually takes quite long until it is done, due to anunspecific clinical presentation. In this time lapse, intestinal ischemia may progress to an irreversible stage withsigns of systemic failure. the acquisition of precise and early detection biomarkers for the disease would shortenthe time to diagnosis and hence its associated mortality. It is acknowledged that those molecules which have beenclassically used-lactate amongst them-do not have a proper diagnostic capacity. nevertheless, the D stereoisomerof lactate and procalcitonin have shown high sensitivity for detection of ischemic colitis after open aortic surgery,while D-dimer measurement is recommended to rule out acute mesenteric ischemia in patients with abdominalpain. Other molecules with a potential for diagnostic yield are intestinal fatty acid binding protein (i-FaBp) andglucagon-like peptide-1 (GLp-1), still under investigation.(AU)

Intra-Abdominal Abscess of Unusual Origin.

This article describes the case of a woman who unknowingly swallowed several fishbones, one of which perforated the intestinal wall and subsequently formed an intra-abdominal abscess due to the foreign body reaction.

Intestinal injury in cardiac arrest is associated with multiple organ dysfunction: A prospective cohort study.

BACKGROUND: The impact of intestinal injury in cardiac arrest is not established. The first aim of this study was to assess associations between clinical characteristics in out-of-hospital cardiac arrest (OHCA) and a biomarker for intestinal injury, Intestinal Fatty Acid Binding Protein (IFABP). The second aim was to assess associations between IFABP and multiple organ dysfunction and 30-day mortality. METHODS: We measured plasma IFABP in 50 patients at admission to intensive care unit (ICU) after OHCA. Demographic and clinical variables were analysed by stratifying patients on median IFABP, and by linear regression. We compared Sequential Organ Failure Assessment (SOFA) score, haemodynamic variables, and clinical-chemistry tests at day two between the "high" and "low" IFABP groups. Logistic regression was applied to assess factors associated with 30-day mortality. RESULTS: Several markers of whole body ischaemia correlated with intestinal injury. Duration of arrest and lactate serum concentrations contributed to elevated IFABP in a multivariable model (p < 0.01 and p = 0.04, respectively). At day two, all seven patients who had died were in the "high" IFABP group, and all six patients who had been transferred to ward were in the "low" group. Of patients still treated in the ICU, the "high" group had higher total, renal and respiratory SOFA score (p < 0.01) and included all patients receiving inotropic drugs. IFABP predicted mortality (OR 16.9 per standard deviation increase, p = 0.04). CONCLUSION: Cardiac arrest duration and lactate serum concentrations were risk factors for intestinal injury. High levels of IFABP at admission were associated with multiple organ dysfunction and mortality. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02648061.

Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair.

BACKGROUND: The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. RESULTS: We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. CONCLUSION: Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstract.

CT-based diagnostic algorithm to identify bowel and/or mesenteric injury in patients with blunt abdominal trauma.

OBJECTIVES: To develop a CT-based algorithm and evaluate its performance for the diagnosis of blunt bowel and/or mesenteric injury (BBMI) in patients with blunt abdominal trauma. METHODS: This retrospective study included a training cohort of 79 patients (29 with BBMI and 50 patients with blunt abdominal trauma without BBMI) and a validation cohort of 37 patients (13 patients with BBMI and 24 patients with blunt abdominal trauma without BBMI). CT examinations were blindly analyzed by two independent radiologists. For each CT sign, the kappa value, sensitivity, specificity, and accuracy were calculated. A diagnostic algorithm was built using a recursive partitioning model on the training cohort, and its performances were assessed on the validation cohort. RESULTS: CT signs with kappa value > 0.6 were extraluminal gas, hemoperitoneum, no or moderate bowel wall enhancement, and solid organ injury. CT signs yielding best accuracies in the training cohort were extraluminal gas (98%; 95% CI: 91-100), bowel wall defect (97%; 95% CI: 91-100), irregularity of mesenteric vessels (97%; 95% CI: 90-99), and mesenteric vessel extravasation (97%; 95% CI: 90-99). Using a recursive partitioning model, a decision tree algorithm including extraluminal gas and no/moderate bowel wall enhancement was built, achieving 86% sensitivity (95% CI: 74-99) and 96% specificity (95% CI: 91-100) in the training cohort and 92% sensitivity (95% CI: 78-97) and 88% specificity (95% CI: 74-100) in the validation cohort for the diagnosis of BBMI. CONCLUSIONS: An effective diagnostic algorithm was built to identify BBMI in patients with blunt abdominal trauma using only extraluminal gas and no/moderate bowel wall enhancement on CT examination. KEY POINTS: • A CT diagnostic algorithm that included extraluminal gas and no/moderate bowel wall enhancement was built for the diagnosis of surgical blunt bowel and/or mesenteric injury. • A decision tree combining only two reproducible CT signs has high diagnostic performance for the diagnosis of surgical blunt bowel and/or mesenteric injury.

Con E de enfermera Consulta de manejo intestinal / With E for nurse Bowel management consultation

En el 2020, el Hospital Universitario La Fe, ubicado en Valencia, puso en marcha una consulta enfermera especializada en manejo intestinal. Eva García es su responsable, nos atiende para hablar del día a día de este servicio, de su labor y de la importancia de la Educación para la Salud para los pacientes con disfunción intestinal.(AU)

Pneumoperitoneum needle vs. introducer needle: Comparison of complications and short-term outcomes in percutaneously inserted peritoneal dialysis catheters in naïve abdomens.

Percutaneous peritoneal dialysis catheter (PDC) insertion for continuous ambulatory peritoneal dialysis (CAPD) entails a higher risk of complications such as bowel injury, vascular injury, and catheter migration compared to the surgical insertions. We conducted a comparative analysis of two techniques of peritoneal entry for PDC insertion by Seldinger technique. We performed a retrospective review of 426 percutaneously inserted PDCs in nonobese naïve abdomens for CAPD at two tertiary care teaching hospitals in India over 6 years. Comparison of various mechanical complications, and short-term catheter survival was done between use of introducer needle (Group "I") and spring-loaded pneumoperitoneum (Veress) needle (Group "V"). Group "I" to "V" patient ratio was 277:149. Group "I" had heavier patients (p = 0.03) whereas "V" group had a dominance of diabetes (p = 0.009) and prior hemodialysis patients (p = 0.03). At 3 months, the odds of mechanical complications (OR = 0.27, p = 0.004), PDC migration (OR = 0.18, p = 0.02), and omental wrapping (OR = 0.13, p = 0.04) were less in "V" group. No bowel injury occurred with Veress needle use. At 6 months, "V" group had higher odds of event-free sustained PDC tip position (OR = 0.39, p = 0.003), and catheter survival (p = 0.03), and the cumulative events were lesser too (p = 0.002). Refractory peritonitis and deaths with functioning catheter were comparable between both the groups. In this first-of-its-kind study, spring-loaded Veress pneumoperitoneum needle use was safer, entrusted sustained PDC tip position in pelvis, and had a better catheter survival compared to use of introducer needle for peritoneal entry in percutaneously inserted PDCs. These findings should be confirmed by a randomized controlled study.

Surgical Complications Requiring Intervention in Open versus Minimally Invasive Radical Prostatectomy.

INTRODUCTION: Injuries to surrounding structures during radical prostatectomy (RP) are rare but serious complications. However, it remains unknown if injuries to intestines, rectum, or vascular structures occur at different rates depending on the surgical approach. METHODS: We compared the frequency of these outcomes in open RP (ORP) and minimally invasive RP (MIS-RP) using the national American College of Surgeons National Surgical Quality Improvement Program database (2012-2017). Along with important metrics of clinical and surgical outcomes, patients were identified as undergoing surgical repair of small or large bowel, vascular structures, or hernias based on Current Procedural Terminology codes. RESULTS: In our propensity matched analysis, a total of 13,044 patients were captured. Bowel injury occurred more frequently in ORP than in MIS-RP (0.89 vs. 0.26%, p < 0.01). By intestinal segment, rectal and large bowel injuries were more common in ORP than MIS-RP (0.41 vs. 0.11% and 0.31 vs. 0.05%, both p < 0.01). However, there was no statistically significant difference between the groups for small bowel injury (0.17 vs. 0.11%, p = 0.39). Vascular injury was more common in MIS-RP (0.18 vs. 0.08%, p = 0.08). Hernias requiring repair were only identified in the MIS-RP group (0.12%). CONCLUSION: When considering surgical approach, rectal and large bowel injuries were more common in ORP, while vascular injuries and hernia repair were more common in MIS-RP. Our findings can be used in counseling patients and identifying risk factors and strategies to reduce these complications.