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Background: Anastomotic leakage (AL) is a dreaded complication following colorectal cancer surgery, impacting patient outcome and leads to increasing healthcare consumption as well as economic burden. Bowel perfusion is a significant modifiable factor for anastomotic healing and thus crucial for reducing AL. Aims: The study aimed to calculate a cut-off value for quantified laser speckle perfusion units (LSPUs) in order to differentiate between ischemic and well-perfused tissue and to assess inter-observer reliability. Methods: LSCI was performed using a porcine ischemic small bowel loop model with the PerfusiX-Imaging® system. An ischemic area, a well-perfused area, and watershed areas, were selected based on the LSCI colormap. Subsequently, local capillary lactate (LCL) levels were measured. A logarithmic curve estimation tested the correlation between LSPU and LCL levels. A cut-off value for LSPU and lactate was calculated, based on anatomically ischemic and well-perfused tissue. Inter-observer variability analysis was performed with 10 observers. Results: Directly after ligation of the mesenteric arteries, differences in LSPU values between ischemic and well-perfused tissue were significant (p < 0.001) and increased significantly throughout all following measurements. LCL levels were significantly different (p < 0.001) at both 60 and 120 min. Logarithmic curve estimation showed an R2 value of 0.56 between LSPU and LCL values. A LSPU cut-off value was determined at 69, with a sensitivity of 0.94 and specificity of 0.87. A LCL cut-off value of 3.8 mmol/L was found, with a sensitivity and specificity of 0.97 and 1.0, respectively. There was no difference in assessment between experienced and unexperienced observers. Cohen's Kappa values were moderate to good (0.52–0.66). Conclusion: Real-time quantification of LSPUs may be a feasible intraoperative method to assess tissue perfusion and a cut-off value could be determined with high sensitivity and specificity. Inter-observer variability was moderate to good, irrespective of prior experience with the technique. [ABSTRACT FROM AUTHOR]

Background: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45–50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol — a xanthine oxidase inhibitor — reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. Methods/design: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. Results: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and."will be stratified for the two treatment groups. Discussion: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. Trial registration: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017. [ABSTRACT FROM AUTHOR]

This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0–2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort. [ABSTRACT FROM AUTHOR]

Background: Intraoperative near-infrared fluorescence imaging (NIRF) with preoperative optical dye administration is a promising technique for quick and easy intraoperative visualization of the ureter and for an improved, real-time assessment of intestinal perfusion. During colorectal surgery, there is a need for simultaneous non-invasive ureteral imaging and bowel perfusion assessment, using one single camera system. The purpose of this study is to investigate the feasibility of simultaneous intestinal perfusion and ureteral imaging using a single commercially available NIRF imaging system. Methods: Six Landrace pigs underwent laparotomy under general anesthesia in this experiment. An intravenous (IV) dose of 0.2 mg/kg indocyanine green (ICG) was given to assess bowel perfusion. Two pairs received a methylene blue (MB) iv injection of 0.75, 0.50 or 0.25 mg/kg respectively to investigate ureteral visualization. Quest Spectrum Fluorescence Camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging. Results: Ureter visualization and bowel perfusion under NIRF imaging was achieved in all animals. All ureters were visible after five to ten minutes and remained clearly visible until the end of every experiment (120–420 min). A mixed model analysis did not show any significant differences neither between the three groups nor over time. Importantly, we demonstrated that bowel perfusion could be visualized with methylene blue (MB) as well. We observed no interference between ICG and MB and a faster washout of MB. Conclusion: We successfully demonstrated simultaneous fluorescence angiography with ICG and ureteral imaging with MB in the same surgical procedure, with the same commercially available NIRF imaging equipment. More importantly, we showed that the use MB is adequate for bowel perfusion assessment and ureter visualization with this NIRF imaging system. Besides, MB showed an earlier washout time, which can be clinical beneficial as a repeated dye injection may be necessary during a surgical procedure. [ABSTRACT FROM AUTHOR]

Patients with locally extensive high-grade extremity soft tissue sarcomas (eSTS) are often presented in multidisciplinary teams to decide between ablative surgery (amputation) or limb-salvage surgery supplemented with either neo-adjuvant radiotherapy (RT) or induction isolated limb perfusion (ILP). In The Netherlands, ILP typically aims to reduce the size of tumors that would otherwise be considered irresectable, whereas neo-adjuvant RT aims mainly at improving local control and reducing morbidity of required marginal margins. This study presents a 15-year nationwide cohort to describe the oncological outcomes of both pre-operative treatment strategies. All consecutive patients with locally extensive primary high-grade eSTS surgically treated between 2000 and 2015 at five tertiary sarcoma centers that received neo-adjuvant ILP or RT were included. 169 patients met the inclusion criteria (89 ILP, 80 RT). Median follow-up was 7.3 years. Limb salvage was achieved in 84% of cases in the ILP group (80% for patients with amputation indication) and 96% of cases in the RT group. 5-Year overall survival was 47% in the ILP group, 69% in the RT group. 5-Year local recurrence rate was 14% in the ILP group, 10% in the RT group. Distant metastasis rate was 55% in the ILP group, 36% in the RT group. We find oncological outcomes and limb salvage rates in line with existing literature for both treatment modalities. Whether the tumor was locally advanced with an indication for induction therapy to prevent amputation or morbid surgery appeared to be the main determinant in choosing between neo-adjuvant ILP or RT. [ABSTRACT FROM AUTHOR]

• It is feasible to create a fully perfused human specimen model with circulating arterial and venous flow via a single arterial inflow cannula. • This perfused human flow model can be used in trauma scenario training for realistic training of advanced bleeding control techniques. • The use of AnubiFiX embalmed human specimen has the advantage of reusability while preserving color, flexibility, and suppleness of the tissues. • Regional arteriovenous flow can be used to reduce the development of tissue edema and increase the durability of the flow model. Prompt and effective hemorrhage control is paramount to improve survival in patients with catastrophic bleeding. In the ever-expanding field of bleeding control techniques, there is a need for a realistic training model to practice these life-saving skills. This study aimed to create a realistic perfused post-mortem human specimen (PMHS) flow model that is suitable for training various bleeding control techniques. This laboratory study was conducted in the SkillsLab & Simulation Center of Erasmus MC, University Medical Center Rotterdam, the Netherlands. One fresh frozen and five AnubiFiX® embalmed PMHS were used for the development of the model. Subsequent improvements in the exact preparation and design of the flow model were made based on model performance and challenges that occurred during this study and are described. Circulating arteriovenous flow with hypertonic saline was established throughout the entire body via inflow and outflow cannulas in the carotid artery and jugular vein of embalmed PMHS. We observed full circulation and major hemorrhage could be mimicked. Effective bleeding control was achieved by placing a resuscitative endovascular balloon occlusion of the aorta (REBOA) catheter in the model. Regional perfusion significantly reduced the development of tissue edema. Our perfused PMHS model with circulating arterial and venous flow appears to be a feasible method for the training of multiple bleeding control techniques. Regional arteriovenous flow successfully reduces tissue edema and increases the durability of the model. Further research should focus on reducing edema and enhancing the durability of the model. [ABSTRACT FROM AUTHOR]

Purpose: Perfusion imaging generates multimaps of ischemic tissues and is a proven decision-making tool in patients with acute ischemic stroke. However, the reliability of perfusion post-processing outcomes has been debated, given disparate results of various software applications, especially for patients with small ischemic core volume. This study was undertaken to compare ischemic volume estimates determined by imSTROKE (a software with new imaging protocol) and RAPID computer applications, respectively. Methods: A total of 611 patients qualified for study, each having met inclusion and exclusion criteria of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN trial). Subjects were examined by computed tomography perfusion (CTP) imaging (n = 349) or perfusion-weighted (PWI) and diffusion-weighted (DWI) imaging (n = 262). Ischemic volumes estimated by imSTROKE and RAPID applications were then compared. We used Bland-Altman analysis and intraclass correlation coefficients (ICCs) to ascertain agreement between applications. Accuracies of estimated core infarct and penumbra volumes were tested at specific thresholds (core: 25 mL, 50 mL, and 70 mL; penumbra: 45 mL, 90 mL, and 125 mL). Results: Median core infarct volumes by imSTROKE and RAPID were 29.18 mL and 29.53 mL, respectively (ICC = 0.9880, 95% confidence interval [CI]: 0.9860–0.9898). Median penumbra volumes by imSTROKE and RAPID were 68.20 mL and 68.55 mL, respectively (ICC = 0.9885, 95% CI: 0.9865–0.9902). Conclusion: In estimating core infarct and penumbra volumes, imSTROKE and RAPID applications showed high-level agreement. For patients with small ischemic core volume, compared with RAPID, imSTROKE may have better sensitivity. [ABSTRACT FROM AUTHOR]

This study investigated if current predictive values for increased lactate formation: VCO2i > 60 ml min−1 m−2, respiratory quotient (RQ) > 0.90, and DO2/VCO2 < 5.0, are valid under normothermic conditions. CO2 derived parameters were analyzed in 91 patients undergoing normothermic CABG and related to increase of blood lactate concentrations during bypass. In this study population, 85 patients (93%) had a median VCO2i above 60 ml min−1 m−2 and 53 patients (58%) had a DO2/VCO2 ⩽ 5.0. Eighteen patients (20%) had a median RQ ⩾ 0.90, but RQ remained with a maximum value of 0.94 below the biological threshold of 1.0. Increase of lactate concentrations remained without clinical significance and showed weak correlations with VCO2i (rs = 0.277, p = 0.008) and RQ (rs = 0.346, p = 0.001). The cohort was separated for the different CO2 variables by their median value to compare increase in lactate concentration. Patients with a high VCO2i (⩾70 ml min−1 m−2) and a high RQ (⩾0.82) showed significant higher increase in lactate concentration compared to patients with VCO2i < 70 ml min−1 m−2 (p = 0.004), and a RQ < 0.82 (p = 0.012). Groups separated by a median DO2/VCO2 of 4.8 did not show a difference in increase of lactate concentration in blood. In summary, specific CO2 derived threshold values for the prediction of lactate formation, which have been reported in other studies, cannot be confirmed with our findings. However, a CO2 production ⩾70 ml min−1 m−2 and a RQ ⩾ 0.82 in this study population were correlated with increased lactate formation. Because CO2 production during bypass depends on patient temperature, a different cutoff value, that may take into account the influence of demographic variables, should be determined during normothermic CPB. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate whether the addition of brain CT imaging data to a model incorporating clinical risk factors improves prediction of ischemic stroke recurrence over 5 years of follow-up. Methods: A total of 638 patients with ischemic stroke from three centers were selected from the Dutch acute stroke study (DUST). CT-derived candidate predictors included findings on non-contrast CT, CT perfusion, and CT angiography. Five-year follow-up data were extracted from medical records. We developed a multivariable Cox regression model containing clinical predictors and an extended model including CT-derived predictors by applying backward elimination. We calculated net reclassification improvement and integrated discrimination improvement indices. Discrimination was evaluated with the optimism-corrected c-statistic and calibration with a calibration plot. Results: During 5 years of follow-up, 56 patients (9%) had a recurrence. The c-statistic of the clinical model, which contained male sex, history of hyperlipidemia, and history of stroke or transient ischemic attack, was 0.61. Compared with the clinical model, the extended model, which contained previous cerebral infarcts on non-contrast CT and Alberta Stroke Program Early CT score greater than 7 on mean transit time maps derived from CT perfusion, had higher discriminative performance (c-statistic 0.65, P = 0.01). Inclusion of these CT variables led to a significant improvement in reclassification measures, by using the net reclassification improvement and integrated discrimination improvement indices. Conclusion: Data from CT imaging significantly improved the discriminatory performance and reclassification in predicting ischemic stroke recurrence beyond a model incorporating clinical risk factors only. [ABSTRACT FROM AUTHOR]

Background and Purpose: In the setting of an extended time window for endovascular treatment (EVT) for acute stroke patients, computed tomography perfusion (CTP) has become a major tool in patient selection. However, there are some data suggesting that the initial ischemic core may be overestimated by CTP depending on stroke onset time. This study aims to evaluate possible predictors of overestimation of infarct core by CTP.Methods: We studied all consecutive stroke patients undergoing EVT during 1 year who underwent CTP at admission and had a successful recanalization. Admission infarct core was measured on cerebral blood volume maps generated using the Intellispace Portal (Philips Healthcare, Best, the Netherlands) and final infarct was measured on noncontrast follow-up computed tomography at 24 hours. We defined overestimation of the infarct core as initial core minus final infarct >10 mL.Results: Out of 107 patients undergoing EVT in the study period, 60 were anterior circulation and had CTP done at our institute, and of them 31 were compatible with the inclusion criteria (known time of onset, no hemorrhagic conversion, and good recanalization). Median National Institute of Health Stroke Scale on admission was 13. Median time from symptoms to CTP was 148 minutes. Seventeen patients were found to have overestimation of the infarct core. Logistic regression analyses showed time from symptom onset to CTP to be inversely related to overestimation with a cutoff of 170 minutes (sensitivity 94% and specificity 43%).Conclusion: Over estimation of the infarct core by CTP in patients undergoing EVT is time dependent and so CTP results among early arrivers should be interpreted cautiously. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cognitive impairment is a frequent problem among older patients attending the Emergency Department (ED) and can be the result of pre-existing cognitive impairment, delirium, or neurologic disorders. Another cause can also be acute disturbance of brain perfusion and oxygenation, which may be reversed by optimal resuscitation. This study aimed to assess the relationship between vital signs, as a measure of acute hemodynamic changes, and cognitive impairment in older ED patients. Design: Prospective cohort study Setting: ED’s of two tertiary care and two secondary care hospitals in the Netherlands. Participants: 2629 patients aged 70-years and older Measurements: Vital signs were measured at the moment of ED arrival as part of routine clinical care. Cognition was measured using the Six-Item Cognitive Impairment Test (6-CIT). Results: The median age of patients was 78 years (IQR 74–84). Cognitive impairment was present in 738 patients (28.1%). When comparing lowest with highest quartiles, a systolic blood pressure of <129 mmHg (OR 1.30, 95% confidence interval (95%CI) 0.98–1.73)was associated with increased risk of cognitive impairment. A higher respiratory rate (>21/min) was associated with increased risk of impaired cognition (OR 2.16, 95% CI 1.58–2.95) as well as oxygen saturation of <95% (OR 1.64, 95%CI 1.24–2.19). Conclusion: Abnormal vital signs associated with decreased brain perfusion and oxygenation are also associated with cognitive impairment in older ED patients. This may partially be explained by the association between disease severity and delirium, but also by acute disturbance of brain perfusion and oxygenation. Future studies should establish whether normalization of vital signs will also acutely improve cognition. [ABSTRACT FROM AUTHOR]

View large Download slide View large Download slide OBJECTIVES Despite progress in lung transplantation (LTx) techniques, a shortage of donor lungs persists worldwide. Ex vivo lung perfusion (EVLP) is a technique that evaluates, optimizes and enables transplantation of the lungs that would otherwise have been discarded. Herein, we present our centre's first EVLP experiences between July 2012 and June 2016, when we performed 149 LTxs. METHODS It was a single-centre, retrospective analysis of a prospectively collected database. The EVLP group (n  = 9) consisted of recipients who initially received discarded donor lungs that were reconditioned using EVLP. The non-EVLP (N-EVLP) group (n  = 18) consisted of data-matched patients receiving conventional quality lungs in the conventional way. Both groups were compared on primary graft dysfunction (PGD) grades 0–3, pulmonary function, chronic lung allograft dysfunction and survival. RESULTS In the EVLP group, 33% (3/9) developed PGD1 at 72 h post-LTx. In the N-EVLP group, 11% (2/18) developed PGD1, 6% (1/18) PGD2 and 11% (2/18) PGD3 at 72 h post-LTx. At 3 and 24 months post-LTx, forced expiratory volume in 1 s as percentage of predicted was similar in the EVLP (78% and 92%) and N-EVLP groups (69% and 89%). Forced vital capacity as a percentage of predicted was comparable in the EVLP (77% and 93%) and N-EVLP groups (68% and 101%). Chronic lung allograft dysfunction was diagnosed in 1 N-EVLP patient at 2 years post-LTx. Three-year survival was 78% (7/9) (the EVLP group) vs 83% (15/18) (the N-EVLP group). CONCLUSIONS These results are in line with the existing literature suggesting that transplantation of the previously discarded lungs recovered by EVLP leads to equal outcomes compared to conventional LTx methods. [ABSTRACT FROM AUTHOR]

Background: Arterial elastance (Ea) represents the total afterload imposed on the left ventricle, and it is largely influenced by systemic vascular resistance (SVR). Although one can expect that Ea is influenced by peripheral endothelial function, no data are available to support it in patients. The aim of this study was to investigate the relationship between Ea, SVR, and microvascular perfusion in critically ill patients undergoing the fluid challenge (FC).Methods: A prospective study in patients receiving a fluid challenge. A pulse wave analysis system (MostCare, Vygon, France) was used to estimate Ea and an incident dark field (IDF) handheld device (Braedius Medical BV, The Netherlands) to evaluate the sublingual microcirculation. Microvascular perfusion was assessed using the proportion of small-perfused vessels (PPV). Relative changes in each variable were calculated before and after FC; fluid responsiveness was defined as an increase in the cardiac index by at least 10% from baseline.Results: We studied 20 patients requiring a fluid challenge (n=10 for hypotension; n=5 for oliguria; n=3 for lactate values greater than 2 mmol/l; n=2 for tachycardia), including 12 fluid responders. There was a strong correlation between Ea and SVR (r2 = 0.75; p < 0.001) and only a weak correlation between Ea and PPV at baseline (r2 = 0.22; p=0.04). Ea decreased from 1.4 [1.2-1.6] to 1.2 [1.1-1.4] mmHg/mL (p=0.01), SVR from 1207 [1006-1373] to 1073 [997-1202] dyn ∗ s/cm5 (p=0.06), and PPV from 56 [51-64] % to 59 [47-73] % (p=0.25) after fluid challenge. Changes in Ea were significantly correlated with changes in SVR, but not with changes in PPV.Conclusions: The correlation between Ea and indexes of microvascular perfusion in the sublingual region is weak. The impact of microcirculatory perfusion on the arterial load is probably limited. [ABSTRACT FROM AUTHOR]

Objectives. The aim of the study was to examine the effect of bosentan on blood flow in the hand in a subset of patients who had reduced blood flow relative to healthy subjects. Additionally, the relationship between blood flow in the hands of SSc patients and the presence of digital ulcers (DUs) was assessed.Methods. SSc patients with a recent history of DUs and healthy subjects were included. Patients were classified into four subgroups: no current DUs or pitting scars, pitting scars only, new DUs or persistent DUs. The hand was categorized into three regions of interest (ROIs) and blood flow was measured by laser Doppler perfusion imaging at baseline, 4 and 12 weeks. Patients who had a reduction in blood flow of >50% relative to healthy control subjects in ROI 1 on baseline were treated with bosentan for 12 weeks.Results. Fifty-two SSc patients and 51 healthy subjects were included in the analysis. There was no significant difference in blood flow in the hand across the patient subgroups at baseline. Sixteen SSc patients had a reduction of blood flow of ≥50% vs healthy subjects and received bosentan. Bosentan significantly (P < 0.05) increased blood flow in the whole hand after 12 weeks compared with baseline.Conclusion. No relationship was found between blood flow in the hands and the presence of DUs. After 12 weeks of bosentan treatment, blood flow had increased in the SSc patients but had not normalized to that of healthy subjects.Trial registration: https://www.clinicaltrialsregister.eu/ (EudraCT number 2010-023908-27). [ABSTRACT FROM PUBLISHER]

Background: Early accurate assessment of burn depth is important to determine the optimal treatment of burns. The method most used to determine burn depth is clinical assessment, which is the least expensive, but not the most accurate. Laser Doppler imaging (LDI) is a technique with which a more accurate (>95%) estimate of burn depth can be made by measuring the dermal perfusion. The actual effect on therapeutic decisions, clinical outcomes and the costs of the introduction of this device, however, are unknown. Before we decide to implement LDI in Dutch burn care, a study on the effectiveness and cost-effectiveness of LDI is necessary. Methods/design: A multicenter randomised controlled trial will be conducted in the Dutch burn centres: Beverwijk, Groningen and Rotterdam. All patients treated as outpatient or admitted to a burn centre within 5 days post burn, with burns of indeterminate depth (burns not obviously superficial or full thickness) and a total body surface area burned of = 20% are eligible. A total of 200 patients will be included. Burn depth will be diagnosed by both clinical assessment and laser Doppler imaging between 2-5 days post burn in all patients. Subsequently, patients are randomly divided in two groups: 'new diagnostic strategy' versus 'current diagnostic strategy'. The results of the LDI-scan will only be provided to the treating clinician in the 'new diagnostic strategy' group. The main endpoint is the effect of LDI on wound healing time. In addition we measure: a) the effect of LDI on other patient outcomes (quality of life, scar quality), b) the effect of LDI on diagnostic and therapeutic decisions, and c) the effect of LDI on total (medical and non-medical) costs and cost-effectiveness. Discussion: This trial will contribute to our current knowledge on the use of LDI in burn care and will provide evidence on its cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background: Cardiopulmonary bypass procedures remain complex, involving many potential risks. Therefore, a nationwide retrospective study was conducted to gain insight into the number of incidents and accidents in Dutch adult perfusion practice. Methods: An anonymous postal survey (85 questions about hardware, disposables, fluids and medication, air emboli, anticoagulation, practice, and safety measures) was sent to all Dutch perfusionists involved in adult cardiovascular perfusion during 2006 and 2007. To guarantee complete anonymity, respondents were asked to return the survey to a notary who discarded personal information. Results: The net response rate was 72% and covered 23,500 perfusions. Individual respondents performed 240 ± 103 perfusions during the 2-year study period and had 13.8 ± 8.7 years of practical experience. The incident rate was 1 per 15.6 perfusions and the adverse event rate was 1 per 1,236 perfusions. The three most reported incidents were: (1) persistent inability to raise the activated coagulation time above 400s during perfusion (184 incidents); (2) an allergic or anaphylactic reaction to drugs, fluids, or blood products (114 incidents); and (3) clotting formation in the extracorporeal circuit (74 incidents). Furthermore, pre-bypass safety measures showed no statistically significant association with the reported incidents. Conclusions: In comparison with data from the recent literature, the reported number of incidents is high. Nevertheless, the adverse outcome rate is well matched to other published surveys. The relatively high response rate conveys the impression that the Dutch perfusionist is vigilant and willing to report incidents. Hence, a web-based Dutch perfusion incident registration system is recommended. [ABSTRACT FROM AUTHOR]

Background: Open abdomen treatment (OAT) is considered a lifesaving procedure in patients with abdominal compartment syndrome (ACS) after endovascular or open intervention for ruptured abdominal aortic aneurysms (RAAA). Standardized treatment methods and algorithms for its use are still lacking. The high, published mortality rates may reflect difficulties in detecting and treating ACS, especially in patients treated by emergency endovascular aneurysm repair (eEVAR). Presented are standardized algorithms for OAT, including a new technique using the vacuum-assisted closure (VAC) system developed during 10 years of experience with eEVAR for RAAA. Methods: We retrospectively analyzed 102 patients with RAAA treated by eEVAR from January 1998 to April 2008. Abdominal decompression was done when intravesical pressure >20 mm Hg or when abdominal perfusion pressure was <50 to 60 mm Hg and concomitant organ deterioration occurred. OAT was initially done with a subcutaneously sutured plastic bag or with a nonsutured zipper drape combined with a VAC device (VAC/ETHIZIP; KCI International Inc, Amstelveen, The Netherlands; Ethicon, Somerville, NJ). All patients were switched to VAC/ETHIZIP as soon as possible. Dressings were generally changed every 3 to 5 days. Intra-abdominal pressure was monitored until stability was observed after delayed direct abdominal closure. Results: Overall 30-day mortality for eEVAR was 13% (13 of 102); 8% (7 of 82) for patients without ACS and 30% (6 of 20) for those with ACS. Decompression for ACS was needed in 20 patients (20%) primarily during the intervention (n = 14) or secondarily in the intensive care unit (n = 6). Six of 20 (30%) patients requiring OAT died ≤30 days (4 primary, 2 secondary). A mean of 3.6 (range, 1-12) planned second-look interventions were done per patient at an interval of 3 to 5 days. No bowel lesions were observed. Four patients required antibiotic therapy for abdominal infection, and all infections resolved. Delayed abdominal wall closure (direct closure, 11; closure with polypropylene mesh, 3; bilateral anterior rectus abdominis sheath turnover flap, 1) was achieved after a median of 6 days (range, 1-47 days). Conclusion: The use of standardized novel techniques and a treatment protocol and algorithm for OAT after eEVAR for RAAA were feasible and safe. It decreased the workload of the medical and nursing staff, enhanced patient comfort because the need for dressing changes was minimized, and likely contributed to lower overall mortality in RAAA patients. Delayed direct fascial closure was possible in most patients. [Copyright &y& Elsevier]

Highlights the annual congress of the European Association of Nuclear Medicine in Amsterdam, Netherlands. Focus of the event on the quality in nuclear medicine; Discussion about detection of the sentinel node in the field of oncology; Abstracts received in the field of perfusion studies.

FOR MANY YEARS, TREATMENT OF ACUTE MI WITH ST SEGMENT elevation (STEMI) has been fibrinolytic therapy or percutaneous intervention (PCI), with the primary objective to engage patients as soon as possible after the onset of chest pain in efforts to remove or decrease thrombus burden. In spite of many efforts, very little progress has been made to improve the proportion of patients successfully reperfused with preservation of myocardial tissue and/or a decrease in infarct size. Attempts to directly remove the infarct clot itself have been made, but results are inconclusive. The adverse effects of STEMI include, in part, microvascular embolization of plaque or thrombus material downstream from the infarct site, resulting in microvascular obstruction and inadequate or suboptimal reperfusion, both with thrombolytic agents, as well as PCI. This study sought to evaluate the efficacy of direct aspiration of the thrombus mass causing the infarct in an effort to improve myocardial perfusion, as well as the clinical course of the MI. The TAPAS trial is from University Medical Center in Groningen, The Netherlands, is a prospective, randomized, and open study with blinded evaluation of end points. The primary purpose of the study was to see whether direct aspiration of the STEMI artery, in addition to PCI, would improve myocardial function, decrease LV muscle loss, and improve clinical outcomes. Approximately 1000 patients were enrolled between January 2005 and December 2006. Admission to the study was dependent on ischemic symptoms lasting greater than 30 minutes, with symptom onset less than 12 hours and ST segment elevation in two or more leads. Patients were randomly assigned to undergo thrombus aspiration during PCI or conventional PCI alone. All subjects had a floppy PCI guide wire passed through the target thrombus. In the aspiration cohort, a six-french aspiration catheter was placed in the target coronary segment, resulting in continuous manual aspiration. Balloon dilation was performed before stenting in appropriate patients; intracoronary nitrates were given to maximize epicardial vasodilatation. Only bare metal stents were utilized. Aspirin, heparin, and clopidogrel were administered, as well as a platelet glycoprotein IIb/IIIa inhibitor. The primary end point of TAPAS was the post procedure myocardial blush grade of 0 or 1 (no perfusion). Secondary end points included TIMI flow grade of 3, complete or no evidence of persistent ST segment deviation, target vessel revascularization, reinfarction, death, and the combination of major adverse events at 30 days. Coronary angiography was performed before and after PCI. Myocardial blush flow grades were assessed as follows: 0 = no myocardial blush; 1 = minimal myocardial blush or contrast density; 2 = moderate myocardial blush or contrast density, but less than that obtained during angiography of a contralateral or ipsilateral non-infarctrelated coronary artery; and 3 = normal myocardial blush or contrast density. Twelve lead EKGs were obtained at presentation and 30-60 minutes after PCI, and ST segments were evaluated for the degree of ST segment resolution. ST deviation was assessed by the degree of ST resolution, including complete (> 70%), partial (30-70%), or none (less than 30%). Aspirated material was examined with H and E and immunostaining, with attention to visualization of smooth muscle and macrophage cells. Aspiration was defined as effective, or not by the presence of atherothrombotic material in the aspirate. Thrombi were defined as containing only platelets, having an RBC component, or thrombus with plaque; length of thrombus was also measured. Followup at 30 days was obtained. Target vessel revascularization (TVR), with PCI or CABG, was assessed. Major adverse events included death, reinfarction, or TVR.… [ABSTRACT FROM AUTHOR]

Background The role of subtle disturbances of brain perfusion in the risk of transient ischemic attack ( TIA) or ischemic stroke remains unknown. We examined the association between global brain perfusion and risk of TIA and ischemic stroke in the general population. Methods and Results Between 2005 and 2015, 5289 stroke-free participants (mean age, 64.3 years; 55.6% women) from the Rotterdam Study underwent phase-contrast brain magnetic resonance imaging at baseline to assess global brain perfusion. These participants were followed for incident TIA or ischemic stroke until January 1, 2016. We investigated associations between global brain perfusion (mL of blood flow/100 mL of brain/min) and risk of TIA and ischemic stroke using Cox regression models with adjustment for age, sex, and cardiovascular risk factors. Additionally, we investigated whether associations were modified by retinal vessel calibers, small and large vessel disease, blood pressure, and heart rate. During a median follow-up of 7.2 years (36 103 person-years), 137 participants suffered a TIA and another 108 an ischemic stroke. We found that lower global brain perfusion was associated with a higher risk of TIA , but not with the risk of ischemic stroke (adjusted hazard ratio, 95% CI, per standard deviation decrease of global brain perfusion: 1.29, 1.07-1.55 for TIA and adjusted hazard ratio of 1.06, 0.87-1.30 for ischemic stroke). Across strata of wider arteriolar retinal calibers, lower brain perfusion was more prominently associated with TIA , but not with ischemic stroke. Conclusions In a community-dwelling population, impaired global brain perfusion increased the risk of TIA , but not of ischemic stroke.

The article focuses on a study conducted on 2593 patient with cardiac arrest to examine the efficacy of mechanical cardiopulmonary resuscitation in comparison of conventional pulmonary resuscitation (CPR). Topics discussed include exclusion of patients whose body was not fit for chest compression, preparation of mechanical algorithm using LUCAS Chest Compression System and survival of patients with good neurological outcome. Also mentioned is the return of spontaneous circulation in patients.

Background: Prediction of clinical outcome in the acute stage of ischaemic stroke can be difficult when based on patient characteristics, clinical findings and on non-contrast CT. CT perfusion and CT angiography may provide additional prognostic information and guide treatment in the early stage. We present the study protocol of the Dutch acute Stroke Trial (DUST). The DUST aims to assess the prognostic value of CT perfusion and CT angiography in predicting stroke outcome, in addition to patient characteristics and non-contrast CT. For this purpose, individualised prediction models for clinical outcome after stroke based on the best predictors from patient characteristics and CT imaging will be developed and validated.Methods/design: The DUST is a prospective multi-centre cohort study in 1500 patients with suspected acute ischaemic stroke. All patients undergo non-contrast CT, CT perfusion and CT angiography within 9 hours after onset of the neurological deficits, and, if possible, follow-up imaging after 3 days. The primary outcome is a dichotomised score on the modified Rankin Scale, assessed at 90 days. A score of 0-2 represents good outcome, and a score of 3-6 represents poor outcome. Three logistic regression models will be developed, including patient characteristics and non-contrast CT (model A), with addition of CT angiography (model B), and CT perfusion parameters (model C). Model derivation will be performed in 60% of the study population, and model validation in the remaining 40% of the patients. Additional prognostic value of the models will be determined with the area under the curve (AUC) from the receiver operating characteristic (ROC) curve, calibration plots, assessment of goodness-of-fit, and likelihood ratio tests.Discussion: This study will provide insight in the added prognostic value of CTP and CTA parameters in outcome prediction of acute stroke patients. The prediction models that will be developed in this study may help guide future treatment decisions in the acute stage of ischaemic stroke. [ABSTRACT FROM AUTHOR]

Aims: Cardiac resynchronization therapy (CRT) improves hemodynamic parameters, exercise capacity, symptoms, functional status, and prognosis among patients with chronic heart failure (CHF). The role of the vascular endothelium in these improvements is largely unknown. In this study, we aimed to investigate whether the endothelium-dependent reactivity of the peripheral microcirculation improves in CHF patients during the first 2 months of CRT. Methods: We used local heating and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to measure endothelial function and smooth muscle function in the cutaneous microvasculature of 11 CHF patients before and 2 months after CRT. Results: We found that the perfusion response in the skin to local heating was increased 2 months post-CRT compared with baseline, both in terms of maximum perfusion (baseline: 113 [90-137] vs 2-months post-CRT: 137 [98-175], P = 0.037) and area under curve (baseline: 1,601 [935-2,268] vs 2-months CRT: 2,205 [1,654-2,757], P = 0.047). Also, the perfusion response to iontophoresis of ACh was improved (Emax: 23.9 [20.6-26.2] vs at 2-months CRT: 31.2 [29.3-33.4], P = 0.005). No difference was found between the responses to SNP before and after CRT. Conclusion: These results show that CRT improves endothelium-dependent vasodilatory capacity in the peripheral microcirculation within 2 months of therapy. The improvement in functional capacity that is seen in patients treated with CRT may, therefore, be in part mediated by an improvement of endothelium-dependent vasodilatory capacity. [ABSTRACT FROM AUTHOR]

Changes in endothelial glycocalyx are one of the earliest changes in development of cardiovascular disease. The endothelial glycocalyx is both an important biological modifier of interactions between flowing blood and the vessel wall, and a determinant of organ perfusion. We hypothesize that deeper penetration of erythrocytes into the glycocalyx is associated with reduced microvascular perfusion. The population-based prospective cohort study (the Netherlands Epidemiology of Obesity [NEO] study) includes 6,673 middle-aged individuals (oversampling of overweight and obese individuals). Within this cohort, we have imaged the sublingual microvasculature of 915 participants using sidestream darkfield (SDF) imaging together with a recently developed automated acquisition and analysis approach. Presence of RBC (as a marker of microvascular perfusion) and perfused boundary region (PBR), a marker for endothelial glycocalyx barrier properties for RBC accessibility, were assessed in vessels between 5 and 25 µm RBC column width. A wide range of variability in PBR measurements, with a mean PBR of 2.14 µm (range: 1.43-2.86 µm), was observed. Linear regression analysis showed a marked association between PBR and microvascular perfusion, reflected by RBC filling percentage (regression coefficient β: -0.034; 95% confidence interval: -0.037 to -0.031). We conclude that microvascular beds with a thick ("healthy") glycocalyx (low PBR), reflects efficient perfusion of the microvascular bed. In contrast, a thin ("risk") glycocalyx (high PBR) is associated with a less efficient and defective microvascular perfusion.

Purpose: The aims of this study are to determine the general relationship of perfused vessel density (PVD) to mortality and organ dysfunctions and to explore if patients in the lowest quartile of distribution for this parameter present a higher risk of bad outcome and to identify systemic hemodynamic and perfusion variables that enhances the probability of finding a severe underlying microvascular dysfunction., Materials and Methods: This is a retrospective multicenter study including 122 septic shock patients participating in 7 prospective clinical trials on which at least 1 sublingual microcirculatory assessment was performed during early resuscitation., Results: Perfused vessel density was significantly related to organ dysfunctions and mortality, but this effect was largely explained by patients in the lowest quartile of distribution for PVD (P = .037 [odds ratio {OR}, 8.7; 95% confidence interval {CI}, 1.14-66.78] for mortality). Hyperlactatemia (P < .026 [OR, 1.23; 95% CI, 1.03-1.47]) and high norepinephrine requirements (P < .019 [OR, 7.04; 95% CI, 1.38-35.89]) increased the odds of finding a severe microvascular dysfunction., Conclusions: Perfused vessel density is significantly related to organ dysfunctions and mortality in septic shock patients, particularly in patients exhibiting more severe abnormalities as represented by the lowest quartile of distribution for this parameter. The presence of hyperlactatemia and high norepinephrine requirements increases the odds of finding a severe underlying microvascular dysfunction during a sublingual microcirculatory assessment., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: We retrospectively analyzed the hospital mortality and neurologic outcome after surgery on the thoracic aorta with the aid of antegrade selective cerebral perfusion to determine a predictive risk model., Methods: Between October 1995 and May 2002, 462 patients (mean age 62.7 +/- 11.7 years) underwent surgery on the thoracic aorta using antegrade selective cerebral perfusion. The indication for surgery was acute type A dissection in 132 patients (28.6%), degenerative aneurysm in 258 (55.8%), and post-dissection aneurysm in 72 (15.6%). One hundred and forty-one patients (30.5%) were operated on urgently; concomitant procedures were performed in 190 patients (41.1%). The mean cerebral perfusion time was 63 +/- 39 min. Predictors of hospital mortality and neurologic outcome were identified by univariate and multivariate analysis of the preoperative and intraoperative variables., Results: The hospital mortality rate was 10.2%. Stepwise logistic regression identified an urgency status (odds ratio--OR 5.2, p = 0.001), a history of a central neurologic event (OR 4.1, p = 0.007) and coronary artery bypass graft (OR 3.2, p = 0.039) as being independent determinants for hospital mortality. The transient neurologic dysfunction rate was 6.2%. An urgency status (OR 3.4, p = 0.003) and a history of a central neurologic event (OR 5.1, p = 0.002) were independent determinants of transient neurologic dysfunction. An urgency status (OR 6.0, p = 0.011) was the only independent determinant for permanent neurologic dysfunction (3.8%). A cerebral perfusion time > 90 min was not associated with an increased risk of hospital mortality and permanent or transient neurologic dysfunction., Conclusions: Antegrade selective cerebral perfusion proved to be a safe method of brain protection allowing complex aortic repair to be performed with encouraging results in terms of hospital mortality and neurologic outcome.

In 1996 the Dutch Melanoma Working Party, in co-operation with the National Organization for Quality Assurance in Hospitals in the Netherlands and the Dutch Association of Comprehensive Cancer Centres, organized the third consensus conference on the management of melanoma of the skin. The following guidelines were approved. The recommended margin for diagnostic excision is 2 mm of macroscopically normal skin around the lesion; the margins for therapeutic excision are 1 cm of normal skin for a Breslow thickness of < or = 2 mm and 2 cm for a Breslow thickness of > 2 and < or = 4 mm. A margin of at least 2 cm also appears to be justified for thicker melanomas. Elective lymph node dissection is not recommended. Sentinel node biopsy appears to be a promising method to detect occult metastases in the regional lymph nodes. If regional lymph node metastases are present, therapeutic regional lymph node dissection must be conducted. Isolated regional perfusion is indicated for inoperable tumour growth in an extremity. Radiotherapy can be applied curatively (for example, if surgery is not possible), palliatively (if desired in combination with hyperthermia) or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy for melanoma patients is still experimental. Atypical (dysplastic) naevi and congenital naevi are major risk factors for melanoma. No consensus has been reached about the prophylactic excision of all congenital naevi. A follow-up period of 5 years is sufficient for patients with a melanoma of < or = 1.5 mm Breslow thickness (provided there are no histological signs of regression) and of 10 years when the Breslow thickness is > 1.5 mm. The patient should be actively involved in the follow-up (inspection, palpation). Regular routine blood tests, radiological examination and ultrasound scanning are not considered to be worthwhile. There is no evidence that the growth of micro-metastases is stimulated by hormonal changes during pregnancy or contraceptive pill use. Excessive exposure to ultraviolet radiation should be discouraged. Regular population screening for melanoma is not considered to be worthwhile, owing to the relatively low frequency and the predominantly favourable stage at the time of diagnosis, particularly in young people.