Twelve years of circulatory extracorporeal life support at the University Medical Centre Utrecht.

INTRODUCTION: Circulatory extracorporeal life support (ECLS) has been performed at the University Medical Centre Utrecht for 12 years. During this time, case mix, indications, ECLS set-ups and outcomes seem to have substantially changed. We set out to describe these characteristics and their evolution over time. METHODS: All patients receiving circulatory ECLS between 2007 and 2018 were retrospectively identified and divided into six groups according to a 2-year period of time corresponding to the date of ECLS initiation. General characteristics plus data pertaining to comorbidities, indications and technical details of ECLS commencement as well as in-hospital, 30-day, 1­year and overall mortality were collected. Temporal trends in these characteristics were examined. RESULTS: A total of 347 circulatory ECLS runs were performed in 289 patients. The number of patients and ECLS runs increased from 8 till a maximum of 40 runs a year. The distribution of circulatory ECLS indications shifted from predominantly postcardiotomy to a wider set of indications. The proportion of peripheral insertions with or without application of left ventricular unloading techniques substantially increased, while in-hospital, 30-day, 1­year and overall mortality decreased over time. CONCLUSION: Circulatory ECLS was increasingly applied at the University Medical Centre Utrecht. Over time, indications as well as treatment goals broadened, and cannulation techniques shifted from central to mainly peripheral approaches. Meanwhile, weaning success increased and mortality rates diminished.

New diagnostic and treatment strategies in renal artery stenosis: a promising pursuit or disappointment foretold?

Clinical management of renal artery stenosis has seen a major shift, after randomised clinical trials have shown no group benefit of endovascular intervention relative to optimal medical control. However, the inclusion criteria of these trials have been criticised for focusing on a subset of patients with atherosclerotic renal artery stenosis where intervention was unlikely to be beneficial. Moreover, new imaging and computational techniques have become available, which have the potential to improve identification of patients that will respond to interventional treatment. This review addresses the challenges associated with clinical decision making in patients with renal artery stenosis. Opportunities for novel diagnostic techniques to improve patient selection are discussed, along with ongoing Dutch studies and network initiatives that investigate these strategies.

The role of AIP variants in pituitary adenomas and concomitant thyroid carcinomas in the Netherlands: a nationwide pathology registry (PALGA) study.

PURPOSE: Germline mutations in the aryl-hydrocarbon receptor interacting protein (AIP) have been identified often in the setting of familial isolated pituitary adenoma (FIPA). To date there is no strong evidence linking germline AIP mutations to other neoplasms apart from the pituitary. Our primary objective was to investigate the prevalence of AIP gene mutations and mutations in genes that have been associated with neuroendocrine tumors in series of tumors from patients presenting with both pituitary adenomas and differentiated thyroid carcinomas (DTCs). METHODS: Pathology samples were retrieved from all pituitary adenomas in patients with concomitant DTCs, including one with a known germline AIP variant. Subsequently, two additional patients with known germline AIP variants were included, of which one presented only with a follicular thyroid carcinoma (FTC). RESULTS: In total, 17 patients (14 DTCs and 15 pituitary adenomas) were investigated by targeted next generation sequencing (NGS). The pituitary tumor samples revealed no mutations, while among the thyroid tumor samples BRAF (6/14, 42.9%) was the most frequently mutated gene, followed by NRAS (3/11, 27.3%). In one AIP-mutated FIPA kindred, the AIP-variant c.853C>T; p.Q285* was confirmed in the FTC specimen, including evidence of loss of heterozygosity (LOH) at the AIP locus in the tumor DNA. CONCLUSION: Although most observed variants in pituitary adenomas and DTCs were similar to those of sporadic DTCs, we confirmed in one AIP mutation-positive case the AIP-variant and LOH at this locus in an FTC specimen, which raises the potential role of the AIP mutation as a rare initiating event.

How do farm models compare when estimating greenhouse gas emissions from dairy cattle production?

The European Union Effort Sharing Regulation (ESR) will require a 30% reduction in greenhouse gas (GHG) emissions by 2030 compared with 2005 from the sectors not included in the European Emissions Trading Scheme, including agriculture. This will require the estimation of current and future emissions from agriculture, including dairy cattle production systems. Using a farm-scale model as part of a Tier 3 method for farm to national scales provides a more holistic and informative approach than IPCC (2006) Tier 2 but requires independent quality control. Comparing the results of using models to simulate a range of scenarios that explore an appropriate range of biophysical and management situations can support this process by providing a framework for placing model results in context. To assess the variation between models and the process of understanding differences, estimates of GHG emissions from four farm-scale models (DairyWise, FarmAC, HolosNor and SFARMMOD) were calculated for eight dairy farming scenarios within a factorial design consisting of two climates (cool/dry and warm/wet)×two soil types (sandy and clayey)×two feeding systems (grass only and grass/maize). The milk yield per cow, follower:cow ratio, manure management system, nitrogen (N) fertilisation and land area were standardised for all scenarios in order to associate the differences in the results with the model structure and function. Potential yield and application of available N in fertiliser and manure were specified separately for grass and maize. Significant differences between models were found in GHG emissions at the farm-scale and for most contributory sources, although there was no difference in the ranking of source magnitudes. The farm-scale GHG emissions, averaged over the four models, was 10.6 t carbon dioxide equivalents (CO2e)/ha per year, with a range of 1.9 t CO2e/ha per year. Even though key production characteristics were specified in the scenarios, there were still significant differences between models in the annual milk production per ha and the amounts of N fertiliser and concentrate feed imported. This was because the models differed in their description of biophysical responses and feedback mechanisms, and in the extent to which management functions were internalised. We conclude that comparing the results of different farm-scale models when applied to a range of scenarios would build confidence in their use in achieving ESR targets, justifying further investment in the development of a wider range of scenarios and software tools.

Economic modelling of grazing management against gastrointestinal nematodes in dairy cattle.

Grazing management (GM) interventions, such as reducing the grazing time or mowing pasture before grazing, have been proposed to limit the exposure to gastrointestinal (GI) nematode infections in grazed livestock. However, the farm-level economic effects of these interventions have not yet been assessed. In this paper, the economic effects of three GM interventions in adult dairy cattle were modelled for a set of Flemish farms: later turnout on pasture (GM1), earlier housing near the end of the grazing season (GM2), and reducing the daily grazing time (GM3). Farm accountancy data were linked to Ostertagia ostertagi bulk tank milk ELISA results and GM data for 137 farms. The economic effects of the GM interventions were investigated through a combination of efficiency analysis and a whole-farm simulation model. Modelling of GM1, GM2 and GM3 resulted in a marginal economic effect of € 8.36, € -9.05 and € -53.37 per cow per year, respectively. The results suggest that the dairy farms can improve their economic performance by postponing the turnout date, but that advancing the housing date or reducing daily grazing time mostly leads to a lower net economic farm performance. Overall, the GM interventions resulted in a higher technical efficiency and milk production but these benefits were offset by increased feed costs as a result of higher maintenance and cultivation costs. Because the results differed highly between farms, GM interventions need to be evaluated at the individual level for appropriate decision support.

The selective 5-HT6 receptor antagonist SLV has putative cognitive- and social interaction enhancing properties in rodent models of cognitive impairment.

In the present study, our aim was to investigate whether the novel highly selective 5-hydroxytryptamine6 (5-HT6) receptor antagonist SLV can ameliorate impairments in cognition and social interaction with potential relevance for both schizophrenia and Alzheimer's disease (AD). SLV sub-chronically - treated Wistar rats reared in isolation showed significantly enhanced prepulse inhibition (PPI) and object recognition performance when compared to vehicle - treated rats. In the isolated rats, also a significant reduction in expression of hippocampal neural cell adhesion molecule polysialylation (NCAM-PSA) was found which was ameliorated following treatment with SLV (30mg/kg). The social engagement deficit in rats exposed in utero (on gestational day 12.5) to valproic acid (VPA) was reversed by treatment with SLV (30mg/kg). SLV (20 and 30mg/kg, p.o.) fully reversed MK-801 - induced deficits in the ORT and also scopolamine - induced deficits in both the Object Recognition Task (ORT) and Object Location Task (OLT) in Wistar rats. In addition, a combination of sub-optimal doses of SLV and donepezil attenuated scopolamine-induced ORT deficits. Furthermore, SLV (10mg/kg, p.o.) reversed spontaneous alternation deficits in the T-maze induced by MK-801 administration in Swiss mice and in aged C57Bl/6J mice. SLV additionally improved T-Maze spatial learning and passive avoidance learning in Sprague-Dawley rats with amyoid-beta (Aß) injections into the hippocampus. In contrast, no benefits were found with SLV or the tested reference compounds (donepezil and RVT-101) on cognitive performance of 12months old Tg2576 mice. Also, in the social recognition task, an absence of cognitive enhancing properties was observed with SLV on "normal forgetting" in Wistar rats. Finally, analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) frequency recorded from pyramidal cells revealed a reduction in the presence of 1µM of SLV. In conclusion, SLV was investigated in several rodent animal models and found to be effective at a least effective dose (LED) of 20mg/kg and 10mg/kg (p.o.) in the rat and the mouse, respectively.

Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry.

BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to efficacy, safety, predictors for success and long-term effects. To answer these important questions, we initiated a Dutch RDN registry aiming to collect data from all RDN procedures performed in the Netherlands. METHODS: The Dutch RDN registry is an ongoing investigator-initiated, prospective, multicentre cohort study. Twenty-six Dutch hospitals agreed to participate in this registry. All patients who undergo RDN, regardless of the clinical indication or device that is used, will be included. Data are currently being collected on eligibility and screening, treatment and follow-up. RESULTS: Procedures have been performed since August 2010. At present, data from 306 patients have been entered into the database. The main indication for RDN was hypertension (n = 302, 99%). Patients had a mean office blood pressure of 177/100 (±29/16) mmHg with a median use of three (range 0-8) blood pressure lowering drugs. Mean 24-hour blood pressure before RDN was 157/93 (±18/13) mmHg. RDN was performed with different devices, with the Simplicity™ catheter currently used most frequently. CONCLUSION: Here we report on the rationale and design of the Dutch RDN registry. Enrolment in this investigator-initiated study is ongoing. We present baseline characteristics of the first 306 participants.

The total cost of rearing a heifer on Dutch dairy farms: calculated versus perceived cost.

BACKGROUND: As farmers do not often keep a record of the expenditures for rearing, an economic tool that provides insight into the cost of rearing is useful. In the Netherlands, an economic tool (Jonkos) has been developed that can be used by farmers to obtain insight into the cost of rearing on their farm. The first objective of this study is to calculate the total cost of rearing young stock in Dutch dairy herds using Jonkos. The second objective is to compare the calculated total cost of rearing with the farmers' own estimation of the cost of rearing (the perceived cost). FINDINGS: Information was available for 75 herds that reared their own young stock and who had used the Jonkos tool. The perceived cost of rearing young stock was only available for 36 herds. In the 75 herds, the average herd size was 100 dairy cows. The average calculated total cost of rearing a heifer was €1,790. The average perceived total cost of rearing a heifer (including labour and housing costs) was €1,030. CONCLUSION: Most Dutch farmers in the study underestimated the total cost of rearing. The Jonkos economic tool has the advantage that herd-specific information can be entered as input values. The output of the tool can improve the awareness of farmers about the total costs of rearing. This awareness can lead to a higher priority of young stock rearing and consequently to an improved quality of young stock rearing.

Hemodynamic significance of collateral blood flow in chronic venous obstruction.

INTRODUCTION: Complaints related to the post-thrombotic syndrome do not always correlate well with the extent of post-thrombotic changes on diagnostic imaging. One explanation might be a difference in development of collateral blood flow. The aim of this study is to investigate the hemodynamic effect of collateralisation in deep venous obstruction. METHODOLOGY: Resting intravenous pressure of the common femoral vein was measured bilaterally in the supine position of patients with unilateral iliofemoral post-thrombotic obstruction. In addition, pressure in control limbs was also measured in the common femoral vein after sudden balloon occlusion in the external iliac vein. RESULTS: Fourteen patients (median age 42 years, 12 female) were tested. In eleven limbs post-thrombotic disease extended below the femoral confluence. Median common femoral vein pressure was 17.0 mmHg in diseased limbs compared to 12.8 mmHg in controls (p = 0.001) and 23.5 mmHg in controls after sudden balloon occlusion (p = 0.009). Results remained significant after correcting for non-occlusive post-thrombotic disease. CONCLUSION: This study shows that common femoral vein pressure is increased in post-thrombotic iliofemoral deep venous obstruction, though not as much as after sudden balloon occlusion. The latter difference could explain the importance of collateralisation in deep venous obstructive disease and the discrepancy between complaints and anatomical changes; notwithstanding, the presence of collaterals does not eliminate the need for treatment.

Strategies to prevent spinal cord ischemia in thoracoabdominal aortic aneurysm repair.

Spinal cord ischemia (SCI) after thoracic and thoracoabdominal aortic aneurysm repair is a devastating complication, which happens after both open and endovascular repair. Incidence of SCI varies widely in the literature. Many factors during preoperative, operative and postoperative phases influence this incidence. The purpose of this article was to provide an overview on all factors influencing SCI and to report on the evidence in the literature about how to prevent SCI.

Contemporary management of the demanding infra-renal neck in abdominal aortic aneurysm repair.

Proximal infrarenal neck anatomy is a crucial factor in determining outcome of abdominal aortic aneurysm (AAA) repair. Unfavorable or demanding infrarenal neck anatomy significantly increases the complexity of both standard endovascular and open repair resulting in increased rates of morbidity and mortality. While technological improvements and expanding institutional experience have resulted in an increased proportion of patients with an AAA with unfavorable infrarenal neck treated by (fenestrated) endovascular techniques, open repair has also remained a valid technique. The purpose of this manuscript was to describe the wide array of endovascular and open techniques in use to treat patients with an AAA with a demanding infrarenal neck and discuss their results and indications.

Septocutaneous tensor fasciae latae perforator flap for breast reconstruction: radiological considerations and clinical cases.

INTRODUCTION: The deep inferior epigastric artery perforator (DIEP) flap is the first choice in autologous breast reconstruction; in cases when it cannot be used, alternative flaps are available. A radiological study and clinical cases using septocutaneous tensor fasciae latae (sc-TFL) flap for breast reconstruction are presented. MATERIALS: Magnetic resonance angiographies (MRAs) of 55 patients were evaluated. The pedicle and the perforators of the TFL were studied. Five consecutive sc-TFL flaps for breast reconstruction were performed. RESULTS: Thirty-seven MRA scans were included. There was a mean of 1.5 septocutaneous perforators per thigh. The mean pedicle length was 8.3 cm. Every perforator originated from a branch of the lateral circumflex femoral artery (LCFA). The LCFA originated from the arteria femoralis profunda in 89.2% of cases. In the vertical plane, the mean distance of the perforator from the antero-superior iliac spine was 8.7 cm. There were no major complications in the five sc-TFL performed. CONCLUSION: On MRA, the septocutaneous pedicle of the TFL perforator flap was consistently present. MR angiographic assessment of the septocutaneous branches was very helpful in the preoperative evaluation of our patients. Dissection of the sc-TFL can be performed in a supine position simultaneously with mastectomy and/or dissection of the mammary vessels. Finally, the donor-site scar can be hidden by underwear, giving minimal deformity. We recommend the sc-TFL flap as a good alternative to the DIEP flap for autologous breast reconstruction. Preoperative imaging is mandatory for correct planning of the flap.

The current endovascular therapeutic spectrum for short neck and juxtarenal aneurysms.

Endovascular treatment of short neck infrarenal and juxtarenal abdominal aortic aneurysms (AAA) is feasible. Many different techniques have been used, including standard stent-grafts with or without adjuncts as endoanchors or chimney grafts, fenestrated stent-grafts or even newer concepts like the multilayer flow modulating stent. The purpose of this article was to describe the techniques, the indications and results of the various endovascular methods to treat short neck infrarenal and juxtarenal AAA.

CTA with fluoroscopy image fusion guidance in endovascular complex aortic aneurysm repair.

OBJECTIVES: To evaluate the effect of intraoperative guidance by means of live fluoroscopy image fusion with computed tomography angiography (CTA) on iodinated contrast material volume, procedure time, and fluoroscopy time in endovascular thoraco-abdominal aortic repair. METHODS: CTA with fluoroscopy image fusion road-mapping was prospectively evaluated in patients with complex aortic aneurysms who underwent fenestrated and/or branched endovascular repair (FEVAR/BEVAR). Total iodinated contrast material volume, overall procedure time, and fluoroscopy time were compared between the fusion group (n = 31) and case controls (n = 31). Reasons for potential fusion image inaccuracy were analyzed. RESULTS: Fusion imaging was feasible in all patients. Fusion image road-mapping was used for navigation and positioning of the devices and catheter guidance during access to target vessels. Iodinated contrast material volume and procedure time were significantly lower in the fusion group than in case controls (159 mL [95% CI 132-186 mL] vs. 199 mL [95% CI 170-229 mL], p = .037 and 5.2 hours [95% CI 4.5-5.9 hours] vs. 6.3 hours (95% CI 5.4-7.2 hours), p = .022). No significant differences in fluoroscopy time were observed (p = .38). Respiration-related vessel displacement, vessel elongation, and displacement by stiff devices as well as patient movement were identified as reasons for fusion image inaccuracy. CONCLUSION: Image fusion guidance provides added value in complex endovascular interventions. The technology significantly reduces iodinated contrast material dose and procedure time.

Coronary artery-bronchial artery fistulas: report of two Dutch cases with a review of the literature.

BACKGROUND: Coronary bronchial artery fistulas (CBFs) are rare anomalies, which may be isolated or associated with other disorders. MATERIALS AND METHODS: Two adult patients with CBFs are described and a PubMed search was performed using the keywords "coronary bronchial artery fistulas" in the period from 2008 to 2013. RESULTS: Twenty-seven reviewed subjects resulting in a total of 31 fistulas were collected. Asymptomatic presentation was reported in 5 subjects (19 %), chest pain (n = 17) was frequently present followed by haemoptysis (n = 7) and dyspnoea (n = 5). Concomitant disorders were bronchiectasis (44 %), diabetes (33 %) and hypertension (28 %). Multimodality and single-modality diagnostic strategies were applied in 56 % and 44 %, respectively. The origin of the CBFs was the left circumflex artery in 61 %, the right coronary artery in 36 % and the left anterior descending artery in 3 %. Management was conservative (22 %), surgical ligation (11 %), percutaneous transcatheter embolisation (30 %), awaiting lung transplantation (7 %) or not reported (30 %). CONCLUSIONS: CBFs may remain clinically silent, or present with chest pain or haemoptysis. CBFs are commonly associated with bronchiectasis and usually require a multimodality approach to be diagnosed. Several treatment strategies are available. This report presents two adult cases with CBFs and a review of the literature.

Time requirements and health effects of participation in colorectal cancer screening with colonoscopy or computed tomography colonography in a randomized controlled trial.

BACKGROUND AND STUDY AIMS: Time limitations and unwanted health effects may act as barriers to participation in colorectal cancer (CRC) screening. The aim of the study was to measure the time requirements and health effects of colonoscopy and computed tomography colonography (CTC) screening. PATIENTS AND METHODS: This was a prospective diary study in a consecutive sample within a randomized controlled CRC screening trial, comparing primary colonoscopy and CTC screening for average-risk individuals aged 50 - 74 years. The diary ended when all screening-related complaints had passed. RESULTS: The diary was returned by 75 % (241/322) of colonoscopy and 75 % (127/170) of CTC screenees. The median interval between leaving home and returning from the examination was longer for colonoscopy (4 hours and 18 minutes [4:18], interquartile range [IQR] 3:30 - 5:00) than for CTC (2:30 hours, IQR 2:06 - 3:00; P < 0.001). Similarly, the time to return to routine activities was longer after colonoscopy (3:54 hours, IQR 1:48 - 15:00) than after CTC (1:36 hours, IQR 0:54 - 4:42). The duration of screening-related symptoms after the examination was shorter for colonoscopy (11:00 hours, IQR 2:54 - 20:00) than for CTC (22:00 hours; IQR 5:30 - 47:00; P < 0.001). Abdominal complaints were reported more frequently after CTC. Anxiety, pain, and quality of life worsened during the screening process, with no differences between the two examinations. CONCLUSIONS: Compared with colonoscopy, CTC screening required less time and allowed screenees to return to their daily activities more quickly. In contrast, CTC was associated with a twofold longer duration of screening-related symptoms. Feelings of anxiety, pain, and quality of life scores were similar during colonoscopy and CTC screening. These results should be incorporated into cost-effectiveness analyses of CRC screening techniques.

Value of magnetic resonance venography and computed tomographic venography in lower extremity chronic venous disease.

For the treatment of chronic venous disease (CVD) of the lower extremity, identification of the underlying venous pathologies is essential. Traditionally, the pathologies to detect with imaging have been centred on insufficiency and reflux of the superficial, perforator and deep veins of the leg. More recently, stenosis and obstruction of the deep veins of the pelvis and abdomen (i.e. inferior vena cava, common and external iliac veins) have been identified as significant underlying pathologies in CVD. Accurate detection of stenotic and/or occlusive venous disease expands the treatment options for patients with CVD. In most cases, imaging of venous disease is performed with duplex ultrasound. In this article we discuss the existing evidence and potential value of computed tomographic venography and magnetic resonance venography to contribute in accurately identifying chronic venous disease, in particular chronic venous obstruction.

Spinal cord function monitoring during endovascular treatment of thoracoabdominal aneurysms: implications for staged procedures.

AIM: Spinal cord ischemia is a well-known complication in the treatment of thoracoabdominal aneurysms (TAAA). Despite the fact that endovascular treatment of TAAA is less invasive, spinal cord ischemia rate is not reduced if compared to open repair. METHODS: We report the results of our experience of spinal cord function monitoring by measuring motor evoked potentials (MEP) during endovascular treatment of TAAA type II and III. Depending on the level of the MEPs the decision is made whether to stage the procedure or not. We treated ten patients according to this protocol. RESULTS: In two patients, MEPs decreased 50% or more and procedures were staged. Both experienced no neurological complications after first and second procedure. No MEPs decrease was seen during the second procedures. One of the other eight patients had a temporary right lower leg pararesis. CONCLUSION: In conclusion we state that our first experience demonstrates the value of assessing spinal cord function during extensive endovascular TAAA repair with subsequent strategies to prevent paraplegia.

Unit costs in population-based colorectal cancer screening using CT colonography performed in university hospitals in The Netherlands.

OBJECTIVES: Computed tomography (CT) colonography cost assumptions so far ranged from 346 to 594 per procedure, based on clinical CT reimbursement rates. The aim of our study was to estimate the costs in a screening situation. METHODS: Data were collected within an invitational population-based CRC screening trial (n = 2,920, age 50-75 years) with a dedicated CT-screening setting. Unit costs were calculated per action, per invitee and per participant (depending on adherence) and per individual with detected advanced neoplasia. Sensitivity analyses were performed, and alternative scenarios were considered. RESULTS: Of the invitees, 47.2 % were reminded, 38.8 % scheduled for an intake, 37.2 % scheduled for CT colonography, 33.6 % underwent CT colonography and 1.1 % needed a re-examination. Lesions ≥ 10 mm were detected in 2.9 % of the invitees. Invitation costs were Euro 5.57. Costs per CT colonography (intake to results) were Euro 144.00. Extra costs of communication of positive results were Euro 9.00. Average costs of invitational-based CT colonography screening were Euro 56.97 per invitee, Euro 169.40 per participant and Euro 2,772.51 per individual with detected advanced neoplasia. CONCLUSIONS: Dutch costs of CT-screening were substantially lower than the cost assumptions that were used in published cost-effectiveness analyses on CT colonography screening. This finding indicates that previous cost-effectiveness analyses should be updated, at least for the Dutch situation.