A Systematic Review and Meta-Analysis on Perioperative Cerebral and Hemodynamic Monitoring Methods during Carotid Endarterectomy.

BACKGROUND: To compare outcomes between different strategies of perioperative cerebral and hemodynamic monitoring during carotid endarterectomy. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL databases were searched. METHODS: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and prospectively registered in the international prospective register of systematic reviews (CRD42021241891). The Grading of Recommendations, Assessment, Development and Evaluation approach was used to describe the methodological quality of the studies and certainty of the evidence. The primary outcome was 30-day stroke rate. Secondary outcomes measures are 30-day ipsilateral stroke, 30-day mortality, shunt rate, and complication rates. RESULTS: The search identified 3,460 articles. Seventeen randomized controlled trials (RCTs), three prospective observational studies and seven registries were included, reporting on 236,983 patients. The overall pooled 30-day stroke rate is 1.8% (95% CI 1.4-2.2%), ranging from 0 to 12.6%. In RCT's the pooled 30-day stroke rate is 2.7% (95% CI 1.6-3.7%) compared to 1.3% (95% CI 0.8-1.8%) in the registries. The overall stroke risk decreased from 3.7% before the year 2000 to 1.6% after 2000. No significant differences could be identified between different monitoring and shunting strategies, although a trend to higher stroke rates in routine no shunting arms of RCTs was observed. Overall, 30-day mortality, myocardial infarction and nerve injury rates are 0.6% (95% CI 0.4-0.8), 0.8% (95% CI 0.6-1.0) and 1.3% (95% CI 0.4-2.2), respectively. CONCLUSIONS: No significant differences between the compared shunting and monitoring strategies are found. However, routine no shunting is not recommended. The available data are too limited to prefer 1 method of neuromonitoring over another method when selective shunting is applied.

The Use of the Oxygenated AirdriveTM Machine Perfusion System in Kidney Graft Preservation: A Clinical Pilot Study.

BACKGROUND: The shortage of donor kidneys has led to the use of marginal donors, e.g., those whose kidneys are donated after circulatory death. Preservation of the graft by hypothermic machine perfusion (HMP) provides a viable solution to reduce warm ischemic damage. This pilot study was undertaken to assess the feasibility and patient safety of the AirdriveTM HMP system in clinical kidney transplantation. METHODS: Five deceased-donor kidneys were preserved using the oxygenated Airdrive HMP system between arrival at the recipient center (Amsterdam UMC) and implantation in the patient. The main study end-points were adverse effects due to the use of Airdrive HMP. Secondary end-points were clinical outcomes and perfusion parameters. All events occurring during the transplantation procedure or within 1 month of follow-up were monitored. RESULTS: Five patients were included in this pilot study. No technical failures were observed during the preservation period using the Airdrive HMP. Mean perfusion parameters were: duration 8.5 h (3-15 h), pressure 25 mm Hg (18-25 mm Hg), flow 49.77 mL/min (19-58 mL/min), resistance 0.57 mm Hg/min/mL (0.34-1.3 mm Hg/min/mL), and temperature 8.2 °C (2-13°C). Mean cold ischemia time (CIT) was 20.2 h (11-29.5 h). No adverse events or technical failures were observed during preservation and transplantation or during the 1-month follow-up. CONCLUSIONS: This pilot study showed the feasibility of the use of the Airdrive HMP system with no adverse events in clinical kidney transplantation.

Systematic Review and Meta-Analysis on the Management of Open Abdominal Aortic Graft Infections.

OBJECTIVE: Aortic graft infection (AGI) is a disastrous complication with an incidence of 0.2-6% in operated patients. With little or no high quality evidence, the best treatment option remains unclear. Therefore, the literature on the management of open abdominal AGI was systematically reviewed to determine optimal treatment. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review and meta-analysis was conducted for AGI. MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched. Methodological quality was assessed using the Methodological Index for Non-randomised Studies (MINORS) score. Primary outcomes were 30 day mortality and one year survival. Secondary outcomes were survival, infection recurrence, limb salvage, and graft patency. RESULTS: Of 1574 studies identified, 32 papers were included in the study. The overall quality of the studies was moderate, with an average MINORS score of 11.9. Pooled overall 30 day mortality and one year survival were 13.5% (95% CI 10.5-16.4) and 73.6% (95% CI 68.8-78.4), respectively. The lowest 30 day mortality and highest one year survival were found for in situ repair compared with extra-anatomic repair and for prosthetic grafts compared with venous grafts or arterial allografts. The infection recurrence rate was highest for prosthetic grafts. CONCLUSIONS: There is a lack of well designed, qualitative comparative studies making conclusive recommendations impossible. The current best available data suggests that partial graft removal should be avoided and the lowest 30 day mortality and best one year survival are achieved with in situ repair using prosthetic grafts. Initiatives such as the MAGIC database to collaboratively collect prospective data are an important step forward in obtaining more solid answers on this topic.

Spontaneous aortoenteric fistula involving the sigmoid: A case report and review of literature.

INTRODUCTION: Primary aortoenteric fistula (PAEF) is a pathological communication between the aorta and any portion of the gastrointestinal tract. The pathology is very rare and easily overlooked during the diagnostic process. PRESENTATION OF CASE: We report the exceptional case of an 86-year-old man with episodes of abdominal pain and rectal bleeding of unknown cause over a period of 1,5 months due to a PAEF to the sigmoid. A sigmoidectomy was performed and a rifampicin-soaked aortic graft was placed. The patient had an uneventful post-operative recovery. The duration of symptoms, the anatomic location of the fistula and the outcome after surgery makes this case unique. DISCUSSION: With an incidence of 0.04-0.07% in all patients with aortic aneurysms a PAEF is very rare. Only 2% of PAEF's involves the sigmoid. The most common cause is an atherosclerotic aortic aneurysm. Patients with PAEF can present with a triad of symptoms including gastrointestinal bleeding, abdominal pain and a pulsating mass. A contrast-enhanced computer-tomography scan (CTa) is the most accurate tool to demonstrate a PAEF. Without a strong clinical suspicion, diagnosing a PAEF is hard and frequently delayed. The overall PAEF-related mortality is high (61-100%) and decreases after surgery (30-40%). CONCLUSION: A primary aortoenteric fistula involving the sigmoid is very rare. Clinical presentation can vary, diagnosis can be difficult and surgical options may differ. Even with low suspicion of PAEF, we recommend performing a CTa. With a high overall mortality of more than 60% due to exsanguinating, surgical treatment is always indicated.

The complicated Allen-Masters syndrome: small bowel herniation through a broad ligament defect.

Small bowel obstruction through a broad ligament defect is a very rare condition. We present 2 cases, one without any associated abdominal trauma. Rapid diagnosis and treatment of this rare condition is of paramount importance.

Endothelial cell preservation at hypothermic to normothermic conditions using clinical and experimental organ preservation solutions.

INTRODUCTION: Endothelial barrier function is pivotal for the outcome of organ transplantation. Since hypothermic preservation (gold standard) is associated with cold-induced endothelial damage, endothelial barrier function may benefit from organ preservation at warmer temperatures. We therefore assessed endothelial barrier integrity and viability as function of preservation temperature and perfusion solution, and hypothesized that endothelial cell preservation at subnormothermic conditions using metabolism-supporting solutions constitute optimal preservation conditions. METHODS: Human umbilical vein endothelial cells (HUVEC) were preserved at 4-37°C for up to 20 h using Ringer's lactate, histidine-tryptophan-ketoglutarate solution, University of Wisconsin (UW) solution, Polysol, or endothelial cell growth medium (ECGM). Following preservation, the monolayer integrity, metabolic capacity, and ATP content were determined as positive parameters of endothelial cell viability. As negative parameters, apoptosis, necrosis, and cell activation were assayed. A viability index was devised on the basis of these parameters. RESULTS: HUVEC viability and barrier integrity was compromised at 4°C regardless of the preservation solution. At temperatures above 20°C, the cells' metabolic demands outweighed the preservation solutions' supporting capacity. Only UW maintained HUVEC viability up to 20°C. Despite high intracellular ATP content, none of the solutions were capable of sufficiently preserving HUVEC above 20°C except for ECGM. CONCLUSION: Optimal HUVEC preservation is achieved with UW up to 20°C. Only ECGM maintains HUVEC viability at temperatures above 20°C.

Efficacy of liver graft washout as a function of the perfusate, pressure, and temperature.

Donor graft washout can be impaired by colloids in organ preservation solutions that increase the viscosity and agglutinative propensity of red blood cells (RBCs) and potentially decrease organ function. The colloid-induced agglutinative effects on RBCs and RBC retention after liver washout with Ringer's lactate (RL), histidine tryptophan ketoglutarate solution, University of Wisconsin solution, and Polysol were determined as a function of the washout pressure (15 or 100 mm Hg) and temperature (4 or 37°C) in a rat liver washout model with (99m) Tc-pertechnetate-labeled RBCs. Colloids (polyethylene glycol in Polysol and hydroxyethyl starch in University of Wisconsin) induced RBC agglutination, regardless of the solution's composition. RL was associated with the lowest degree of (99m) Tc-pertechnetate-labeled RBC retention after simultaneous arterial and portal washout at 37°C and 100 mm Hg. RL washout was also associated with the shortest washout time. A single portal washout with any of the solutions did not result in differences in the degree of RBC retention, regardless of the temperature or pressure. In conclusion, no differences were found in portal washout efficacy between colloidal solutions, histidine tryptophan ketoglutarate, and RL. Simultaneous arterial and portal washout with RL at 37°C and 100 mm Hg resulted in the least RBC retention and the shortest washout time.

A novel oxygenated machine perfusion system for preservation of the liver.

Machine perfusion (MP) is a potential method to increase the donor pool for organ transplantation. However, MP systems for liver grafts remain difficult to use because of organ-specific demands. Our aim was to test a novel, portable MP system for hypothermic preservation of the liver. A portable, pressure-regulated, oxygenated MP system designed for kidney preservation was adapted to perfuse liver grafts via the portal vein (PV). Three porcine livers underwent 20 h of hypothermic perfusion using Belzer MP solution. The MP system was assessed for perfusate flow, temperature, venous pressure, and pO2 /pCO2 during the preservation period. Biochemical and histological parameters were analyzed to determine postpreservation organ damage. Perfusate flow through the PV increased over time from 157 ± 25 mL/min at start to 177 ± 25 mL/min after 20 h. PV pressure remained stable at 13 ± 1 mm Hg. Perfusate temperature increased from 9.7 ± 0.6°C at the start to 11.0 ± 0.0°C after 20 h. Aspartate aminotransferase and lactate dehydrogenase increased from 281 ± 158 and 308 ± 171 U/L after 1 h to 524 ± 163 and 537 ± 168 U/L after 20 h, respectively. Blood gas analysis showed a stable pO2 of 338 ± 20 mm Hg before perfusion of the liver and 125 ± 14 mm Hg after 1 h perfusion. The pCO2 increased from 15 ± 5 mm Hg after 1 h to 53 ± 4 mm Hg after 20 h. No histological changes were found after 20 h of MP. This study demonstrated the feasibility of a portable MP system for preservation of the liver and showed that continuous perfusion via the PV can be maintained with an oxygen-driven pump system without notable preservation damage of the organ.

Laser speckle contrast imaging for assessment of liver microcirculation.

OBJECTIVE: Laser speckle contrast imaging (LSCI) is a novel technique for microcirculation imaging not previously used in the liver. The aim of the present experimental study was to evaluate the use of LSCI for assessing liver microcirculation. MATERIALS AND METHODS: In six male Wistar rats, the median liver lobe was exposed through a midline laparotomy. Liver blood perfusion was measured simultaneously with LSCI and sidestream dark-field (SDF) imaging at baseline and during sequential temporary occlusions of the portal vein, hepatic artery, and total blood inflow occlusion. Both the inter-individual variability associated with perfusion sampling area and comparisons in perfusion measurements between both imaging techniques were investigated and validated for the application of LSCI in the liver. RESULTS: Occlusion of the hepatic artery, portal vein, and total inflow occlusion resulted in a significant decrease in LSCI signal to 74.7±6.4%, 15.0±2.3%, and 10.4±0.5% respectively (p<0.005 vs. baseline). The LSCI perfusion units correlated with sinusoidal blood flow velocity as measured with SDF imaging (Pearson's r=0.94, p<0.001). In a 10 mm diameter region of interest, as measured with LSCI, baseline inter-individual variability measured by the coefficient of variability was 13%. CONCLUSION: Alterations in LSCI signal during sequential inflow occlusions were in accordance with previously published results on hepatic hemodynamics in the rat and correlated well with our SDF imaging-derived sinusoidal blood flow velocity measurements. We found that LSCI was able to produce reproducible real-time blood perfusion measurements of hepatic microcirculation. Compared to established techniques for liver blood perfusion measurements LSCI holds the advantages of non-contact measurements over large surfaces with a high speed of data acquisition.

Antibiotic prophylaxis in (sub)normothermic organ preservation: in vitro efficacy and toxicity of cephalosporins.

BACKGROUND: Bacterial contamination during cold organ preservation occurs without major complications. However, with organ preservation steering toward (sub)normothermic temperatures, bacterial contamination may be detrimental with limited evidence to support the choice of antibiotic. METHODS: This study aimed to determine the effective antibiotic prophylaxis for (sub)normothermic preservation by investigating whether Staphylococcus epidermidis was capable of growing in a subnormothermia-compatible preservation solution Polysol (PS) and in solutions designed for cold preservation (University of Wisconsin solution, histidine-tryptophan-ketoglutarate solution, and Belzer-machine perfusion solution). Various S. epidermidis and Staphylococcus aureus strains were exposed to ceftriaxone and cefazolin at concentrations from 0 to 1000 µg/mL under subnormothermic and normothermic conditions in PS. To mimic procedural conditions, the effect of cefazolin was determined after exposure of bacteria to 20-hr incubation at 28°C in the presence of cefazolin and subsequent incubation at 37°C in the absence of cefazolin. The toxicity of cefazolin was assessed by cell viability and caspase activation assays in porcine kidney endothelial cells. RESULTS: Without antibiotics, PS sustained bacterial growth under sub(normothermic) conditions, whereas growth was absent in cold preservation solutions. Cefazolin exhibited greater bactericidal effect on S. epidermidis than ceftriaxone. However, after inoculating PS with 10 colony-forming units/mL, only a cefazolin concentration of 1000 µg/mL was able to exert a complete bactericidal effect on S. epidermidis and S. aureus strains and maintain sterility after removal of cefazolin. Finally, 1000 µg/mL cefazolin showed no adverse effects on porcine kidney endothelial cells. CONCLUSIONS: Based on these findings, we recommend that high-dose cefazolin be used for prophylaxis in (sub)normothermic organ preservation with PS.

Characterization and quantification of porcine circulating endothelial cells.

BACKGROUND: Endothelial damage is a critical step in the development of (xeno) transplantation-related and cardiovascular pathology. In humans, the amount of circulating endothelial cells (CEC) correlates to disease intensity and functions as a valuable damage marker. While (xeno) transplantation and cardiovascular research is regularly performed in porcine models, the paucity of antibodies against porcine endothelium epitopes hinders the use of CEC as damage marker. OBJECTIVE: This study aimed to develop a method for porcine CEC detection using anti-human antibodies against porcine endothelium epitopes. METHODS: Human umbilical vein endothelial cells (HUVEC, control) and their swine equivalent (SUVEC) were used to assess the cross-species immunoreactivity of fluorescently labeled anti-human CD31/CD51/CD54/CD62E/CD105/CD106/CD144/CD146/PAL-E/lectin-1/vWF antibodies by isotype-controlled fluorescence-activated cell sorting (FACS) and confocal microscopy. Next, reactivity was ascertained with mature porcine kidney-derived endothelial cells (PKEC), and a FACS-based whole blood CEC quantification method was employed using osmotic erythrolysis and CD105 and CD146 double staining after CD45 exclusion. RESULTS: Of the 21 assayed antibodies, the MEM-229 clone of CD105 and P1H12 clone of CD146 showed immunoreactivity with SUVEC and PKEC. Double staining showed baseline porcine CEC count of 673.1 ± 551.4 CEC/ml, while the first 7.5 ml of drawn blood (representative of vascular damage) contained 1118 ± 661.4 CEC/ml (n = 14, P = 0.04). A second experiment (n = 5) including CD45 exclusion identified only 14.5 ± 10.8% double-positive CD105-146 events per ml blood. CONCLUSION: Porcine endothelium can be specifically labeled using anti-human CD146 and CD105 antibodies. These antibodies can therefore be used for the identification and quantification of CEC in porcine whole blood by FACS after osmotic erythrolysis.

Optimal flow and pressure management in machine perfusion systems for organ preservation.

Intra-organ flow is the most critical parameter in machine-perfused organ preservation systems (MPS). Ultrasonic flow sensors (UFS) are commonly employed in MPS. However, UFS are sensitive to changes in fluid composition and temperature and require recalibration. Novel Coriolis-type mass flow sensors (CFS) may be more suitable for MPS because the measurement technique is not amenable to these factors. The effect of viscosity, colloids, temperature, pressure, and preservation solution on flow measurement accuracy of UFS and CFS was therefore investigated. A CFS-based MPS was built and validated for setpoint stability using porcine kidneys and the ability to reproduce different pressure and flow waveforms. The UFS exhibited a temperature- and preservation solution-dependent overestimation of flow rate compared to the CFS. The CFS deviated minimally from the actual flow rate and did not require recalibration. The CFS-based MPS conformed to the preprogrammed temperature, flow, pressure, and vascular resistance settings during 6-h kidney preservation. The system was also able to accurately reproduce different pressure and flow waveforms. Conclusively, CFS-based MPS are more suitable for organ preservation than UFS-based MPS. Our CFS-based MPS provides a versatile yet robust experimental platform for testing and validating different types of clinical and experimental MPS.

Appraisal of the porcine kidney autotransplantation model.

Animal models are extensively used for transplantation related research, especially kidney transplantation. Porcine autotransplantation models are considered to be favorable regarding translatability to the human setting. The key determinants for translatability of the model are discussed, comprising animal age, development, anatomy, anesthesia and surgical protocols, and perioperative care. With the detailed discussion of these determinants and the pitfalls in diagnosing animal discomfort, an attempt is made to provide a uniform porcine kidney autotransplantation model with tools to improve currently used models.

[A 73-year-old man with a Merkel cell carcinoma]. / Een 73-jarige man met een merkelcel-carcinoom.

A 73-year-old man had a firm node on his right upper arm, which was caused by a Merkel cell carcinoma (MCC). The diagnosis was made on the basis of characteristic histopathological findings and a surgical excision with wide margins followed. Twenty months later a considerable swelling manifested in the right armpit due to a metastasis. During a CT scan of the thorax and abdomen, 2 suspicious abnormalities were seen in the mesenterial adipose tissue of the left lower abdomen and left perirenal adipose tissue. A tissue sample of the last abnormality taken under CT guidance confirmed this to be a metastasis of the MCC. The patient was irradiated but chose not to have chemotherapy. He died 2 years after the diagnosis. Merkel cell carcinoma is a rare and aggressive malignant skin neoplasm. Early recognition facilitates cure of the disease. Treatment is multidisciplinary, but surgery, either alone or in combination with radiotherapy, forms the basis of treating both the localised and regionalized forms of the disease. Chemotherapy may be used in case of disseminated disease and has a reasonable, albeit temporary, effect. The 10-year survival rate varies from 20-70%, dependent on the stage of the disease.

Real-time assessment of renal cortical microvascular perfusion heterogeneities using near-infrared laser speckle imaging.

Laser speckle imaging (LSI) is able to provide full-field perfusion maps of the renal cortex and allows quantification of the average LSI perfusion within an arbitrarily set region of interest and the recovery of LSI perfusion histograms within this region. The aim of the present study was to evaluate the use of LSI for mapping renal cortical microvascular perfusion and to demonstrate the capability of LSI to assess renal perfusion heterogeneities. The main findings were that: 1) full-field LSI measurements of renal microvascular perfusion were highly correlated to single-point LDV measurements; 2) LSI is able to detect differences in reperfusion dynamics following different durations of ischemia; and 3) renal microvascular perfusion heterogeneities can be quantitatively assessed by recovering LSI perfusion histograms.