REBOA Use in a Medicalized Prehospital Setting Proposal for a First Protocol Based on the Delphi Method.

BACKGROUND: The resuscitative endovascular balloon occlusion of the aorta (REBOA) technique controls abdominal, pelvic, junctional, and postpartum hemorrhage via aortic endoclamping. There are no protocols or clear indications guiding REBOA use in a two-tiered prehospital emergency medical system, as found in France. We conducted a Delphi study to clarify the indications and contraindications for REBOA application in such a system. METHODS: We performed a Delphi study in three rounds with an international group of doctors with REBOA expertise and clinical experience (members of the EndoVascular and Trauma Management Society). Based on the consensus answers, complemented by existing data in the literature, we developed a protocol for REBOA use in a medicalized prehospital setting. RESULTS: We identified 10 questions that were not answered in the literature and submitted them to 21 experts. Over three rounds, consensus was reached on these 10 questions. The most important ones were "In your opinion, in a hemorrhagic patient, vascularly well-filled and whose hemodynamics remain unstable with 3mg/h of norepinephrine, should we inflate a REBOA to prevent the patients death and get them to the operating room alive?" and "In the case of REBOA placement (zone I) in the prehospital setting, would you agree that the maximum occlusion duration is approximately 30 minutes, with a partial or intermittent occlusion when possible?" CONCLUSION: We propose a protocol for REBOA use in a medicalized prehospital setting. This protocol clarifies that hemorrhagic shock, despite a noradrenaline (also known as norepinephrine) dose of 0.6µg/kg/min, is considered too serious for the patient to be transported to the trauma center without REBOA. Moreover, it clarifies that a zone 1 REBOA should be inflated for maximum 30 minutes and with a partial occlusion strategy, if possible. This protocol should be updated based on feedback following the establishment of prehospital REBOA and large randomized studies.

Intestinal Fatty Acid-Binding Protein as a Potential Biomarker for Gastrointestinal Complications after Complex Endovascular Aortic Surgery.

BACKGROUND: This study aimed to investigate the association between intestinal fatty acid-binding protein (I-FABP), acute gastrointestinal injury (AGI) grade, and gastrointestinal (GI) complications after fenestrated or branched endovascular aortic aneurysm repair. METHODS: A total of 17 patients undergoing endovascular aortic repair for thoracoabdominal, juxtarenal, suprarenal, or pararenal aneurysm between May 2017 and September 2018 were enrolled. Blood samples were collected preoperatively and during postoperative intensive care. The blood samples were analyzed for I-FABP with enzyme-linked immunosorbent assay. Gastrointestinal function was assessed according to the AGI grade every day during postoperative intensive care. RESULTS: Higher concentrations of I-FABP at 24 hr and 48 hr correlated to higher AGI grade on postoperative days 1, 2, and 3 (P = 0.032 and P = 0.048, P = 0.040 and P = 0.018, and P = 0.012 and P = 0.016, respectively). Patients who developed a GI complication within 90 days postoperatively had a higher overall AGI grade than those who did not develop a GI complication (P < 0.001), as well as higher concentrations of I-FABP at 48 hrs (P = 0.019). Patients developing GI dysfunction (AGI grade ≥2) had a higher frequency of complications (P = 0.009) and longer length of stay in the intensive care unit (P = 0.008). CONCLUSIONS: In patients undergoing endovascular aortic repair for complex aneurysm increased postoperative plasma I-FABP concentrations and postoperative GI dysfunction, evaluated using the AGI grade, were associated with GI complications, indicating that these measures may be useful in the postoperative management of these patients.

The effect of an endovascular Heaney maneuver to achieve total hepatic isolation on survival, hemodynamic stability, retrohepatic bleeding, and collateral flow in a porcine model.

PURPOSE: Combining resuscitative endovascular balloon occlusion of the aorta (REBOA) and the inferior vena cava (REBOVC) with open surgery is a new hybrid approach for treating retrohepatic vena caval injuries. We compared endovascular total hepatic isolation with supraceliac REBOA ± suprahepatic REBOVC and no occlusion in experimental retrohepatic vena cava bleeding regarding survival, bleeding volume, hemodynamic stability, and arterial collateral blood flow. METHODS: Twenty-five anesthetized pigs (n = 6-7/group) were randomized to REBOA; REBOA + REBOVC; REBOA + infra and suprahepatic REBOVC + portal vein occlusion (endovascular Heaney maneuver, four-balloon-occlusion, 4BO) or no occlusion. After balloon inflation, free bleeding was initiated from an open sheath in the retrohepatic vena cava. Bleeding volume, right internal thoracic artery (RITA) blood flow, hemodynamics, and arterial blood variables were measured until death or up to 90 min. RESULTS: The REBOA group had a longer median survival time (63 min) compared with the 4BO (24 min, P = 0.02) and no occlusion (30 min, P = 0.02) groups, not versus the REBOA + REBOVC group (49 min, P > 0.05). The first 15 min accumulated bleeding was comparable in all groups (P > 0.05); Thereafter, bleeding volume was higher in the REBOA group versus the 4BO group (P < 0.05), not versus the other groups. RITA blood flow and MAP were higher in the REBOA group versus the other groups after 10 min of bleeding (P < 0.05). CONCLUSIONS: Endovascular Heaney maneuver was not beneficial for survival or hemodynamic stability in this porcine model, whereas supraceliac REBOA was. Anatomical differences in thoracoabdominal collaterals between pigs and humans must be considered when interpreting these results.

Consensus on resuscitative endovascular balloon occlusion of the aorta in civilian (prehospital) trauma care: A Delphi study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) could prevent lethal exsanguination and support cardiopulmonary resuscitation. In prehospital trauma and medical emergency settings, a small population with high mortality rates could potentially benefit from early REBOA deployment. However, its use in these situations remains highly disputed. Since publication of the first Delphi study on REBOA, in which consensus was not reached on all addressed topics, new literature has emerged. The aim of this study was to establish consensus on the use and implementation of REBOA in civilian prehospital settings for noncompressible truncal hemorrhage and out-of-hospital cardiac arrest as well as for various in-hospital settings. METHODS: A Delphi study consisting of three rounds of questionnaires was conducted based on a review of recent literature. REBOA experts with different medical specialties, backgrounds, and work environments were invited for the international panel. Consensus was reached when a minimum of 75% of panelists responded to a question and at least 75% (positive) or less than 25% (negative) of these respondents agreed on the questioned subject. RESULTS: Panel members reached consensus on potential (contra)indications, physiological thresholds for patient selection, the use of ultrasound and practical, and technical aspects for early femoral artery access and prehospital REBOA. CONCLUSION: The international expert panel agreed that REBOA can be used in civilian prehospital settings for temporary control of noncompressible truncal hemorrhage, provided that personnel are properly trained and protocols are established. For prehospital REBOA and early femoral artery access, consensus was reached on (contra)indications, physiological thresholds and practical aspects. The panel recommends the initiation of a randomized clinical trial investigating the use of prehospital REBOA for noncompressible truncal hemorrhage. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.

Critical systolic blood pressure threshold for endovascular aortic occlusion-A multinational analysis to determine when to place a REBOA.

BACKGROUND: Systolic blood pressure (SBP) is a potential indicator that could guide when to use a resuscitative endovascular balloon occlusion of the aorta (REBOA) in trauma patients with life-threatening injuries. This study aims to determine the optimal SBP threshold for REBOA placement by analyzing the association between SBP pre-REBOA and 24-hour mortality in severely injured hemodynamically unstable trauma patients. METHODS: We performed a pooled analysis of the aortic balloon occlusion (ABO) trauma and AORTA registries. These databases record the details related to the use of REBOA and include data from 14 countries worldwide. We included patients who had suffered penetrating and/or blunt trauma. Patients who arrived at the hospital with a SBP pre-REBOA of 0 mm Hg and remained at 0 mm Hg after balloon inflation were excluded. We evaluated the impact that SBP pre-REBOA had on the probability of death in the first 24 hours. RESULTS: A total of 1,107 patients underwent endovascular aortic occlusion, of these, 848 met inclusion criteria. The median age was 44 years (interquartile range [IQR], 27-59 years) and 643 (76%) were male. The median injury severity score was 34 (IQR, 25-45). The median SBP pre-REBOA was 65 mm Hg (IQR, 49-88 mm Hg). Mortality at 24 hours was reported in 279 (32%) patients. Math modeling shows that predicted probabilities of the primary outcome increased steadily in SBP pre-REBOA below 100 mm Hg. Multivariable mixed-effects analysis shows that when SBP pre-REBOA was lower than 60 mm Hg, the risk of death was more than 50% (relative risk, 1.5; 95% confidence interval, 1.17-1.92; p = 0.001). DISCUSSION: In patients who do not respond to initial resuscitation, the use of REBOA in SBPs between 60 mm Hg and 80 mm Hg may be a useful tool in resuscitation efforts before further decompensation or complete cardiovascular collapse. The findings from our study are clinically important as a first step in identifying candidates for REBOA. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

International registry on aortic balloon occlusion in major trauma: Partial inflation does not improve outcomes in abdominal trauma.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a method for temporary hemorrhage control used in haemodynamically unwell patients with severe bleeding. In haemodynamically unwell abdominal trauma patients, laparotomy remains the initial procedure of choice. Using REBOA in patients as a bridge to laparotomy is a novel option whose feasibility and efficacy remain unclear. We aimed to assess the clinical outcome in patients with abdominal injury who underwent both REBOA placement and laparotomy. METHODS: This is a retrospective study, including trauma patients with an isolated abdominal injury who underwent both REBOA placement and laparotomy, during the period 2011-2019. All data were collected via the Aortic Balloon Occlusion Trauma Registry database. RESULTS: One hundred and three patients were included in this study. The main mechanism of trauma was blunt injury (62.1%) and the median injury severity score (ISS) was 33 (14-74). Renal failure and multi-organ dysfunction syndrome (MODS) occurred in 15.5% and 35% of patients, respectively. Overall, 30-day mortality was 50.5%. Post balloon inflation systolic blood pressure (SBP) >80 mmHg was associated with lower 24-h mortality (p = 0.007). No differences in mortality were found among patients who underwent partial occlusion vs. total occlusion of the aorta. CONCLUSIONS: Our results support the feasibility of REBOA use in patients with isolated abdominal injury, with survival rates similar to previous reports for haemodynamically unstable abdominal trauma patients. Post-balloon inflation SBP >80 mmHg was associated with a significant reduction in 24-h mortality rates, but not 30-day mortality. Total aortic occlusion was not associated with increased mortality, MODS, and complication rates compared with partial occlusion.

An International Expert-Based CONsensus on Indications and Techniques for aoRtic balloOn occLusion in the Management of Ruptured Abdominal Aortic Aneurysms (CONTROL-RAAA).

OBJECTIVE: To report on the recommendations of an expert-based consensus on the indications, timing, and techniques of aortic balloon occlusion (ABO) in the management of ruptured abdominal aortic aneurysms (rAAA). METHODS: Eleven facilitators created appropriate statements regarding the study issues that were voted on using a 4-point Likert scale with open-comment fields, by a selected panel of international experts (vascular surgeons and interventional radiologists) using a 3-round modified Delphi consensus procedure (study period: January-April 2023). Based on the experts' responses, only the statements reaching grade A (full agreement ≥75%) or B (overall agreement ≥80% and full disagreement <5%) were included in the final study report. The consistency of each round's answers was also graded using Cohen's kappa, the intraclass correlation coefficient, and, in case of double resubmission, Fleiss kappa. RESULTS: Sixty-three experts were included in the final analysis and voted on 25 statements related to indication and timing (n=6), and techniques (n=19) of ABO in the setting of rAAA. Femoral sheath or ABO should be preferably placed in the operating room, via a percutaneous transfemoral access, on a stiff wire (grade B, consistency I), ABO placement should be suprarenal and last less than 30 minutes (grade B, consistency II), postoperative peripheral vascular status (grade A, consistency II) and laboratory testing every 6 to 12 hours (grade B, consistency) should be assessed to detect complications. Formal training for ABO should be implemented (grade B, consistency I). Most of the statements in this international expert-based Delphi consensus study might guide current choices for indications, timing, and techniques of ABO in the management of rAAA. Clinical practice guidelines should incorporate dedicated statements that can guide clinicians in decision-making. CONCLUSIONS: At arrival and during both open or endovascular procedures for rAAA, selective use of intra-aortic balloon occlusion is recommended, and it should be performed preferably by the treating physician in aortic pathology. CLINICAL IMPACT: This is the first consensus study of international vascular experts aimed at defining the indications, timing, and techniques of optimal use of ABO in the clinical setting of rAAA. Aortic occlusion by endovascular means (or ABO) is a quick procedure in properly trained hands that may play an important role as a temporizing measure until the definitive aortic repair is achieved, whether by endovascular or open means. Since data on its use in hemodynamically unstable patients are limited in the literature, owing to practical challenges in the performance of well-conducted prospective studies, understanding real-world use by experts is of importance in addressing critical issues and identifying main gaps in knowledge.

A 12-year experience of endovascular repair for ruptured abdominal aortic aneurysms in all patients.

OBJECTIVE: Endovascular aneurysm repair (EVAR) has been increasingly performed for ruptured abdominal aortic aneurysms (rAAAs). However, multiple randomized trials have failed to demonstrate a survival benefit compared with open aortic surgery. During a 12-year period, 100% of patients without a history of aneurysm surgery had undergone EVAR for a rAAA at Örebro University Hospital, with no emergent open aortic surgery performed. In the present study, we evaluated the mortality and technical success during this "EVAR-only" period. METHODS: A single-center, retrospective observational study was conducted. We identified all patients who had presented to Örebro University Hospital with a rAAA between October 2009 and September 2021. Patients with isolated iliac artery, thoracic, and thoracoabdominal aortic ruptures were not included. Patients who had received previous aortic interventions (open or endovascular) and patients who had received palliative treatment instead of surgical intervention were also excluded. The patient characteristics, perioperative and postoperative data, and mortality rate were investigated. RESULTS: EVAR had been performed in 100 patients. Preoperative hemodynamic instability had been present in 54 patients (54%), and 18 (18%) had undergone aortic balloon occlusion. The aneurysm location was infrarenal in 89 patients (89%). Bifurcated stent grafts had been used in 97 patients (97%), and adjunct endovascular techniques had been used for 27 patients (27%). Of 98 patients, EVAR had been performed with the patient under local anesthesia for 62 patients (63%). Peri- and postoperative complications at 30 days had occurred in 20 of 100 patients (20%) and 22 of 79 patients (28%), respectively. The overall mortality at 30 days was 27% (27 of 100 patients), and the mortality for those with an isolated infrarenal rAAA was 24% (21 of 89 patients). The overall mortality at 1 year was 39% (39 of 100 patients) and for those with an isolated infrarenal rAAA was 37% (33 of 89 patients). The presence of preoperative hemodynamic instability and the use of ABO were statistically significantly and independently associated with increased 30-day mortality on multivariate logistic regression analysis. CONCLUSIONS: All 100 patients who had undergone surgery for a rAAA had been treated using EVAR and endovascular adjuncts, with a relatively low mortality rate, thus continuing the "EVAR-only" approach. A low proportion of rAAA patients were considered surgically unsuitable. These findings support the applicability of EVAR for the treatment of all rAAAs at suitable centers.

Emergent vessel embolization for major traumatic and non-traumatic hemorrhage: Indications, tools and outcomes.

Endovascular embolization of bleeding vessels in trauma and non-trauma patients is frequently used and is an important tool for bleeding control. It is included in the EVTM (endovascular resuscitation and trauma management) concept and its use in patients with hemodynamic instability is increasing. When the correct embolization tool is chosen, a dedicated multidisciplinary team can rapidly and effectively achieve bleeding control. In this article, we will describe the current use and possibilities for embolization of major hemorrhage (traumatic and non-traumatic) and the published data supporting these techniques as part of the EVTM concept.

A porcine study of ultrasound-guided versus fluoroscopy-guided placement of endovascular balloons in the inferior vena cava (REBOVC) and the aorta (REBOA).

Objectives: In fluoroscopy-free settings, alternative safe and quick methods for placing resuscitative endovascular balloon occlusion of the aorta (REBOA) and resuscitative endovascular balloon occlusion of the inferior vena cava (REBOVC) are needed. Ultrasound is being increasingly used to guide the placement of REBOA in the absence of fluoroscopy. Our hypothesis was that ultrasound could be used to adequately visualize the suprahepatic vena cava and guide REBOVC positioning, without significant time-delay, when compared with fluoroscopic guidance, and compared with the corresponding REBOA placement. Methods: Nine anesthetized pigs were used to compare ultrasound-guided placement of supraceliac REBOA and suprahepatic REBOVC with corresponding fluoroscopic guidance, in terms of correct placement and speed. Accuracy was controlled by fluoroscopy. Four intervention groups: (1) fluoroscopy REBOA, (2) fluoroscopy REBOVC, (3) ultrasound REBOA and (4) ultrasound REBOVC. The aim was to carry out the four interventions in all animals. Randomization was performed to either fluoroscopic or ultrasound guidance being used first. The time required to position the balloons in the supraceliac aorta or in the suprahepatic inferior vena cava was recorded and compared between the four intervention groups. Results: Ultrasound-guided REBOA and REBOVC placement was completed in eight animals, respectively. All eight had correctly positioned REBOA and REBOVC on fluoroscopic verification. Fluoroscopy-guided REBOA placement was slightly faster (median 14 s, IQR 13-17 s) than ultrasound-guided REBOA (median 22 s, IQR 21-25 s, p=0.024). The corresponding comparisons of the REBOVC groups were not statistically significant, with fluoroscopy-guided REBOVC taking 19 s, median (IQR 11-22 s) and ultrasound-guided REBOVC taking 28 s, median (IQR 20-34 s, p=0.19). Conclusion: Ultrasound adequately and quickly guide the placement of supraceliac REBOA and suprahepatic REBOVC in a porcine laboratory model, however, safety issues must be considered before use in trauma patients. Level of evidence: Prospective, experimental, animal study. Basic science study.

A randomized porcine study of hemorrhagic shock comparing end-tidal carbon dioxide targeted and proximal systolic blood pressure targeted partial resuscitative endovascular balloon occlusion of the aorta in the mitigation of metabolic injury.

BACKGROUND: The definition of partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) is not yet determined and clinical markers of the degree of occlusion, metabolic effects and end-organ injury that are clinically monitored in real time are lacking. The aim of the study was to test the hypothesis that end-tidal carbon dioxide (ETCO2) targeted pREBOA causes less metabolic disturbance compared to proximal systolic blood pressure (SBP) targeted pREBOA in a porcine model of hemorrhagic shock. MATERIALS AND METHODS: Twenty anesthetized pigs (26-35 kg) were randomized to 45 min of either ETCO2 targeted pREBOA (pREBOAETCO2, ETCO2 90-110% of values before start of occlusion, n = 10) or proximal SBP targeted pREBOA (pREBOASBP, SBP 80-100 mmHg, n = 10), during controlled grade IV hemorrhagic shock. Autotransfusion and reperfusion over 3 h followed. Hemodynamic and respiratory parameters, blood samples and jejunal specimens were analyzed. RESULTS: ETCO2 was significantly higher in the pREBOAETCO2 group during the occlusion compared to the pREBOASBP group, whereas SBP, femoral arterial mean pressure and abdominal aortic blood flow were similar. During reperfusion, arterial and mesenteric lactate, plasma creatinine and plasma troponin concentrations were higher in the pREBOASBP group. CONCLUSIONS: In a porcine model of hemorrhagic shock, ETCO2 targeted pREBOA caused less metabolic disturbance and end-organ damage compared to proximal SBP targeted pREBOA, with no disadvantageous hemodynamic impact. End-tidal CO2 should be investigated in clinical studies as a complementary clinical tool for mitigating ischemic-reperfusion injury when using pREBOA.

Intra-aortic and Intra-caval Balloon Pump Devices in Experimental Non-traumatic Cardiac Arrest and Cardiopulmonary Resuscitation.

Intra-aortic balloon pump (IABP) use during CPR has been scarcely studied. Intra-caval balloon pump (ICBP) may decrease backward venous flow during CPR. Mechanical chest compressions (MCC) were initiated after 10 min of cardiac arrest in anesthetized pigs. After 5 min of MCC, IABP (n = 6) or ICBP (n = 6) was initiated. The MCC device and the IABP/ICBP had slightly different frequencies, inducing a progressive peak pressure phase shift. IABP inflation 0.15 s before MCC significantly increased mean arterial pressure (MAP) and carotid blood flow (CBF) compared to inflation 0.10 s after MCC and to MCC only. Coronary perfusion pressure significantly increased with IABP inflation 0.25 s before MCC compared to inflation at MCC. ICBP inflation before MCC significantly increased MAP and CBF compared to inflation after MCC but not compared to MCC only. This shows the potential of IABP in CPR when optimally synchronized with MCC. The effect of timing of intra-aortic balloon pump (IABP) inflation during mechanical chest compressions (MCC) on hemodynamics. Data from12 anesthetized pigs.

NO-Donation Increases Visceral Circulation in a Porcine Model of Abdominal Hypertension.

Intraabdominal hypertension (IAH) is negative for outcome after intensive care. Little research has focused on medical intervention to improve visceral circulation during IAH. A nitric oxide (NO)-donor was compared with placebo in 25 pigs; each pig was randomized into three groups: PDNO (NO-donor), Control (placebo), or Sham. IAH was induced by CO2 insufflation to 30 mmHg. Sham group had surgical preparation only. Blood gases, invasive venous and arterial blood pressure, intestinal microcirculation and superior mesenteric blood flow were measured. The PDNO group had significantly increased intestinal microcirculation compared with Controls during IAH (last hour, P = 0.009). The mean arterial pressure and abdominal perfusion pressures (APP) were decreased, and the cardiac index were increased in the PDNO group. Also, systemic and pulmonary vascular resistances were lower in the PDNO group compared with Controls. These experimental findings indicate that NO should be further explored with potential application to improve intestinal microcirculation in IAH patients.

Fully covered self-expandable metal stent placed over a stapled colon anastomosis in an animal model: A pilot study of colon metabolism over the stent.

Background and Aim: Anastomotic leakage (AL) in colorectal resection and primary anastomosis is a common and feared complication. Fully covered self-expandable metal stents (FCSEMSs) have been used for the treatment of AL. It is still unknown whether FCSEMSs affect anastomosis healing negatively by causing ischemia. In an animal study, we investigated the metabolic effects over a FCSEMS covering a stapled colon anastomosis. Methods: Seven pigs were investigated using microdialysis after laparotomy, colon resection, and anastomosis with stent placement. Measurements were done at the proximal and distal ends of the anastomosis and at a reference catheter placed at the small intestine. Measurements of glucose, pyruvate, lactate, glycerol, and the lactate/pyruvate ratio (L/P) were carried out. Results: Lactate and L/P were significantly higher at the oral part of the anastomosis, while glucose showed a small declining tendency. At the distal part of the anastomosis, glucose decreased significantly after the resection but did not reach zero. Lactate increased significantly whereas L/P increased only slightly. Glycerol levels were stable. Conclusion: Colon resection caused initially hypermetabolism in the intestinal ends next to the resection site. This hypermetabolism neither deteriorated nor turned into ischemia during the initial postoperative course, but the start of hypoxemia could not be excluded during the study and after the placement of an FCSEMS.

A Reliable Approach for Revealing Molecular Targets in Secondary Ion Mass Spectrometry.

Nano secondary ion mass spectrometry (nanoSIMS) imaging is a rapidly growing field in biological sciences, which enables investigators to describe the chemical composition of cells and tissues with high resolution. One of the major challenges of nanoSIMS is to identify specific molecules or organelles, as these are not immediately recognizable in nanoSIMS and need to be revealed by SIMS-compatible probes. Few laboratories have generated such probes, and none are commercially available. To address this, we performed a systematic study of probes initially developed for electron microscopy. Relying on nanoscale SIMS, we found that antibodies coupled to 6 nm gold particles are surprisingly efficient in terms of labeling specificity while offering a reliable detection threshold. These tools enabled accurate visualization and sample analysis and were easily employed in correlating SIMS with other imaging approaches, such as fluorescence microscopy. We conclude that antibodies conjugated to moderately sized gold particles are promising tools for SIMS imaging.

Altered mRNA Expression Due to Rectal Perforation in a Porcine Model - A Pilot Study.

BACKGROUND: Anastomotic leakage is the most serious and unwelcome complication in rectal surgery. It has a great impact on postoperative morbidity and mortality. In this pilot study, changes of mRNA expression in blood were analyzed in an animal model designed to imitate anastomotic leakage. MATERIALS AND METHODS: Twelve pigs were randomized into two groups: A sham-operated control group and an experimental group in which iatrogenic rectal perforation was performed. The changes in the mRNA expression at 4 hours after creating the perforation were studied. Microarray analysis was performed using Gene Chip whole porcine genome array. mRNA expression of 19,124 genes was investigated. RESULTS: Significantly increased levels of genes with a fold change greater than 2 were found, including 276 coding for unknown proteins and 48 coding for known proteins. Eleven of those which coded for known proteins were up-regulated with a fold change >4. CONCLUSION: Eleven known genes were highly up-regulated after rectal perforation. These genes were mainly involved in inflammatory response, intracellular signaling and cell membrane regulation. Their corresponding proteins might potentially be clinical biomarkers of anastomotic leakage and should be evaluated in further clinical studies.

Extracellular Matrix Recycling as a Novel Plasticity Mechanism With a Potential Role in Disease.

The extracellular matrix (ECM) stabilizes neural circuits and synapses in the healthy brain, while also retaining the ability to be remodeled, to allow synapses to be plastic. A well-described mechanism for ECM remodeling is through the regulated secretion of proteolytic enzymes at the synapse, together with the synthesis of new ECM molecules. The importance of this process is evidenced by the large number of brain disorders that are associated with a dysregulation of ECM-cleaving protease activity. While most of the brain ECM molecules are indeed stable for remarkable time periods, evidence in other cell types, as cancer cells, suggests that at least a proportion of the ECM molecules may be endocytosed regularly, and could even be recycled back to the ECM. In this review, we discuss the involvement of such a mechanism in the brain, under physiological activity conditions and in relation to synapse and brain disease.

The Synaptic Extracellular Matrix: Long-Lived, Stable, and Still Remarkably Dynamic.

In the adult brain, synapses are tightly enwrapped by lattices of the extracellular matrix that consist of extremely long-lived molecules. These lattices are deemed to stabilize synapses, restrict the reorganization of their transmission machinery, and prevent them from undergoing structural or morphological changes. At the same time, they are expected to retain some degree of flexibility to permit occasional events of synaptic plasticity. The recent understanding that structural changes to synapses are significantly more frequent than previously assumed (occurring even on a timescale of minutes) has called for a mechanism that allows continual and energy-efficient remodeling of the extracellular matrix (ECM) at synapses. Here, we review recent evidence for such a process based on the constitutive recycling of synaptic ECM molecules. We discuss the key characteristics of this mechanism, focusing on its roles in mediating synaptic transmission and plasticity, and speculate on additional potential functions in neuronal signaling.

Use of REBOA in the universe of magical realism: a real-world review / Uso de REBOA en el universo del realismo mágico: revisión de vida real

Abstract While reading the novella "Chronicle of a Death Foretold" by the Colombian Nobel Laureate Gabriel García-Marquez, we were surprised to realize that the injuries sustained by the main character could have been successfully treated had he received modern trauma care in which REBOA may have been considered. This is a discussion of Mr. Nasar's murder to explore whether he could have been saved by deploying REBOA as a surgical adjunct to bleeding control and resuscitation. In reading García-Marquez's novel we noted the events that unfolded at the time of Santiago Nasar's murder. To contextualize the claim that Mr. Nasar could have survived, had his injuries been treated with REBOA, we explored and illustrated what could have done differently and why. On the day of his death, Mr. Nasar sustained multiple penetrating stab wounds. Although he received multiple stab wounds to his torso, the book describes seven potentially fatal injuries, resulting in hollow viscus, solid viscus, and major vascular injuries. We provided a practical description of the clinical and surgical management algorithm we would have followed in Mr. Nasar's case. This algorithm included the REBOA deployment for hemorrhage control and resuscitation. The use of REBOA as part of the surgical procedures performed could have saved Mr. Nasar's life. Based on our current knowledge about REBOA in trauma surgery, we claim that its use, coupled with appropriate surgical care for hemorrhage control, could have saved Santiago Nasar's life, and thus prevent a death foretold.

Resumen Leyendo la novela "Crónica de una muerte anunciada" del Nobel de Literatura Gabriel García Márquez, nos sorprendió reconocer que las heridas provocadas al personaje principal se habrían podido tratar exitosamente en un centro de trauma moderno donde hubieran optado por REBOA. Hacemos referencia al asesinato del señor Nasar para explorar la posibilidad de que se hubiera podido salvar de haberse utilizado REBOA como adyuvante de la cirugía para reanimación y control de la hemorragia. En la lectura de la novela de García Márquez tomamos nota de los sucesos que tuvieron lugar en el momento del asesinato de Santiago Nasar. Para contextualizar la afirmación de que Nasar habría podido sobrevivir si le hubieran manejado sus heridas con REBOA, exploramos e ilustramos lo que habría podido hacerse de otra manera y porqué. El día en que murió, el señor Nasar sufrió múltiples heridas por arma blanca y si bien muchas de ellas fueron en el torso, el libro describe siete heridas mortales que comprometieron los órganos sólidos, además de lesiones vasculares mayores. Presentamos una descripción práctica del algoritmo para el manejo clínico y quirúrgico que habríamos seguido en el caso del señor Nasar. Este algoritmo incluye el uso de REBOA para el control de la hemorragia y la reanimación, el cual, como parte de los procedimientos quirúrgicos realizados, habría podido salvarle la vida a la víctima. Basados en nuestro conocimiento actual acerca del uso de REBOA en la cirugía de trauma, planteamos que, junto con la atención quirúrgica apropiada para controlar la hemorragia, este procedimiento habría podido salvarle la vida a Santiago Nasar y, por tanto, evitar una muerte anunciada.