Outcome after 7 years of carotid artery stenting and endarterectomy in Sweden - single centre and national results.

OBJECTIVES: The aim was internal vascular centre quality-control measures to compare single-centre results with the national perspective, as well as analysing the Swedish results from carotid artery stenting (CAS) and comparing a relatively high-volume single centre with the Swedish Vascular Registry (Swedvasc) data. The second aim was to compare CAS and carotid artery endarterectomy (CEA) outcomes for the same 7-year period. DESIGN: Retrospective review of a single high-volume centre (Södersjukhuset (SÖS)) (approximately 30 CAS year(-1) approximately 90 CEA year(-1)) versus Swedvasc National data. MATERIALS AND METHODS: All consecutive selective patients treated with CAS at SÖS for a stenosis of the internal carotid artery (n = 208) or CEA (n = 552) between 2004 and 2011 were compared with all patients in Swedvasc registered for CAS (n = 258) and CEA (n = 6474). Primary outcome was 30-day frequency of stroke or death. Secondary outcome was stroke/death/acute myocardial infarction (AMI). RESULTS: The 30-day frequency of any stroke or death after CAS at SÖS compared to the national data was 2.9% and 7.4%, respectively (P = 0.04). The 30-day AMI/stroke/death frequency was 3.4% and 9.5%, respectively (P = 0.01). After CEA during the same time period, the Swedvasc national data had a 4.4% frequency of 30-day stroke and death and 5.8% for AMI/stroke/death. CONCLUSIONS: CAS is not as safe as CEA from a national perspective but our results indicate that a single centre can achieve acceptable results with CAS.

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Celiac trunk coverage in endovascular aneurysm repair.

BACKGROUND AND AIMS: This retrospective study was undertaken to examine the risks associated with obstruction of the coeliac trunk in the process of treating aneurysms with endografting. MATERIAL AND METHODS: 120 patients were treated by endografting for aneurysmal disease. Of these, a subgroup of 9 patients had their celiac trunk covered. If possible, a preoperative angiography was performed to evaluate collateral flow from the superior mesenteric artery. This was considered to predict the risk for ischemia. RESULTS: None of the patients had any severe clinical event of the celiac trunk occlusion or clinical signs of intestinal ischemia. Three patients had transient increase of liver enzymes. CONCLUSIONS: In cases where the distal landing zone of the descending thoracic aorta is to short for endografting, covering of the celiac trunk may be an option if no other surgical alter-native is apparent. Preoperative angiography to visualise the presence of collateral vessels from the superior mesenteric artery is recommended.

TEVAR and covering the celiac artery. Is it safe or not?

Thoracic endovascular aortic repair (TEVAR) is the treatment of choice for descending thoracic aortic aneurysms (TAA). However, not all patients with TAA can be treated with the endovascular technique. Insufficient proximal and/or distal sealing zone is the most common reason for open surgery in these patients. If the distal sealing zone above the celiac axis is too short, several endovascular alternatives are possible; hybrid procedures with TEVAR and open by-pass to the celiac artery, custom made stent-grafts with scallop or fenestration for the celiac artery, or intentional coverage of the celiac artery. In the latter case, adequate collateral supply to the upper gastrointestinal tract is crucial. Collateral arteries joining the celiac and the superior mesenteric arteries are well characterized in patients with chronic celiac stenosis or occlusion. Are these collateral pathways sufficient also for sudden iatrogenic closure of the celiac artery? By performing a preoperative angiography of the superior mesenteric artery with temporary balloon occlusion of the celiac artery, collateral capacity between the two vessels can be tested in advance. Exact positioning of the distal end of a large thoracic stent-graft can be challenging and require special considerations and techniques. Most case series in the literature support the efficacy and the safety of intentional celiac covering. However, there are also reports of ischemic foregut complications that could be associated to the procedure. Taken together, in the large majority of patients, it appears that intentional celiac coverage can be done safely provided that sufficient collateral function have been demonstrated in advance.

Remodeling of the thoracic aorta after stent grafting of type B dissection: a Swedish multicenter study.

AIM: Endovascular repair of complicated type B dissections has evolved as a promising alternative to open repair. Previous studies have indicated that continued false lumen flow is a predictor of continued aortic dilatation and risk of rupture during follow-up. This multicenter study was conducted to analyze the postoperative changes of the false lumen after endografting of complicated type B dissections. METHODS: All patients treated with endovascular stent grafts for thoracic type B dissections at 5 major Vascular Centers in Sweden were identified through local databases. Review of charts and all available pre- and postoperative CT scans were performed to identify demographics, indications for repair as well as postoperative changes of the aorta and false lumen. RESULTS: A total of 129 patients treated for type B dissections between 1994 and December 2005 were identified. Median radiological follow-up was 14 months. Fourteen patients died perioperatively leaving 115 patients available for analysis. Seventy-four of these had CT imaging of sufficient quality for morphological analysis. The vast majority of acute patients were treated for rupture or end-organ ischemia whereas most chronic patients were treated for asymptomatic aneurysms. In 80% of patients, the false lumen thrombosed along the stent graft but it remained perfused distal to the stent graft fixation in 50% of patients. Only 5% of patients presented with aortic enlargement of the stent grafted area when adequate proximal sealing was achieved. The distal, uncovered aorta displayed expansion in 16% of patients. CONCLUSIONS: The stent grafted thoracic aorta after type B dissection appears to be stabilized by covering the primary entry site with a stent graft in the majority of both acute and chronic dissections. The uncovered portion of the aorta distal to the stent graft, however, remains at risk of continuous dilatation. Stent grafting for complicated type B thoracic dissections seems to be a treatment option with reasonable morbidity and mortality even though the incidence of severe complications is still significant.

The effects of naloxone on cerebral blood flow and cerebral function during relative cerebral ischemia.

CBF and somatosensory evoked potentials (SEPs) were measured in a model of moderate cerebral ischemia in anesthetized spontaneously hypertensive rats. The rats were bled to reduce SEP amplitudes to about 50% of prebleeding control. The consequent blood pressure fall reduced CBF to 77% of control as measured by the laser-Doppler technique. Naloxone (5 mg kg-1 i.v. plus 25 mg kg-1 h-1 i.v. for 30 min) caused a significant increase in SEP amplitudes, while CBF did not change significantly. In addition, the latency of the first SEP component decreased toward prebleeding values. Heart rate (HR) decreased, but MABP was held constant by a pressure-regulating reservoir. In unbled rats, naloxone (5 mg kg-1 i.v.) caused a transient small increase in MABP and SEP amplitudes and decrease in HR. These results indicate that sensory input is regulated by opioid systems. Increased opioid activity may inhibit ascending sensory pathways during relative cerebral ischemia and thereby depress SEP responses. Thus, naloxone can release this inhibition and enhances SEP independently of CBF during relative cerebral ischemia. Similar mechanisms might explain the apparently beneficial effects of naloxone in some stroke models.

Esomeprazole 20 mg maintains symptom control in endoscopy-negative gastro-oesophageal reflux disease: a controlled trial of 'on-demand' therapy for 6 months.

BACKGROUND: Most patients with gastro-oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy. AIM: To assess the efficacy of 'on-demand' treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer. METHODS: In this multicentre, double-blind study, 342 endoscopy-negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4-week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted. RESULTS: All 342 patients (191 males), aged 19-79 (mean 49) years, were evaluable in the intention-to-treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on-demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1--3 consecutive days (esomeprazole) or 4--13 consecutive days (placebo). Use of antacids was > 2-fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles. CONCLUSIONS: On-demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy-negative GERD.

Differential responses in adrenal and renal nerves to CNS osmotic stimulation.

Hypertonic solutions act in the central nervous system (CNS) to increase mean arterial blood pressure (MAP) by activation of the sympathoadrenal axis. However, adrenal nerve activity (pre- and postganglionic nerve fibers) has not been determined during central osmotic stimulation. Therefore, these experiments evaluated adrenal (AdSNA) and renal (RSNA) sympathetic nerve activity, MAP, and heart rate (HR) following CNS administration of isotonic, hypertonic, and hypotonic sodium chloride solutions in chloralose-anesthetized rats. Injection of isotonic saline (5 microliters) did not alter MAP, HR, RSNA, or AdSNA. However, injection of hypertonic saline (5 microliters of 0.5 M) into the anteroventral portion of the third cerebral ventricle increased MAP (12 +/- 2 mmHg) and decreased HR (16 +/- 6 bpm). In addition, hypertonic saline significantly decreased RSNA (58 +/- 5% control), whereas AdSNA increased (158 +/- 10% control). Injection of hypotonic (5 microliters of 0.05 M) NaCl produced the opposite responses in RSNA (119 +/- 7% control) and AdSNA (86 +/- 5% control) and had no significant effect on MAP or HR. Furthermore, pre- and postganglionic adrenal nerve fibers responded similarly to changes in CNS osmolality. These results demonstrate that osmotic stimulation produces differential responses in RSNA and AdSNA, but not in pre- and postganglionic adrenal nerve fibers.

[Differentiated changes in the activity of the sympathetic nerves induced by glycopenia in spontaneously hypertensive rats]. / Differentsirovannye izmeneniia aktivnosti simpaticheskikh nervov, vyzvannye glikopeniei, u spontanno gipertenzivnykh krys.

2-deoxy-D-glucose (2-DG) evokes an increase in the efferent discharge rate of the adrenal nerve in anesthetized rats and rabbits. A 63% increase in adrenal sympathetic nerve activity (adrSNA) occurred within 15 min after 125 mg/kg 2-DG administration in alert animals, no changes being revealed in the renal sympathetic nerve activity (renSNA), blood pressure (BP) or the heart rate (HR). Additional administration of 375 mg/kg 2-DG (cumulative dose 500 mg/kg) led to an over 120% increase in the adrSNA and the 20 mm Hg increase in the BP, whereas renSNA only increased by 30%. These results indicate that 2-DG-induced neuroglycopenia evokes highly differential changes in adrenal and renSNA in alert SHR rats. Whether this explains an obvious response of the BP in SHR to 2-DG, remains to be determined.

Changes in sympathetic nerve activity during morphine abstinence in the rat.

The aim of the study was to examine sympathetic nerve activity, heart rate and blood pressure during naloxone-precipitated withdrawal reactions in morphine-dependent rats. In two groups of rats, one group conscious and the other anaesthetized with chloralose, renal sympathetic nerve activity (rSNA), heart rate (HR) and mean arterial blood pressure (MAP) were recorded before and during naloxone-precipitated abstinence. The conscious rats showed a biphasic pattern in the withdrawal responses. Initially, after small doses of naloxone, rSNA and HR increased and increased somatomotor activity including 'wet-dog' shakes were observed. However, upon further administration of naloxone, rSNA and HR promptly decreased while MAP increased. As rSNA was lowered, the withdrawal behaviour of the rats was markedly diminished and the animals rested calmly in the cages. In contrast, the anaesthetized group reacted with an immediate decrease in rSNA after the lowest dose of naloxone, followed by an increase in MAP and HR after higher doses of naloxone, although rSNA was still decreased. In both groups, rSNA remained below pre-naloxone control levels when the increased MAP was lowered to the pre-naloxone level with sodium nitroprusside, indicating a central origin of the sympathetic inhibition. It is concluded that naloxone elicits a biphasic rSNA response in the conscious, morphine-dependent rat. This includes an initial increase upon low naloxone doses followed by a pronounced inhibition of rSNA after higher doses. In chloralose-anaesthetized rats, rSNA declined already after low doses of naloxone. It is suggested that there might be a tonic, excitatory input on rSNA, mediated by the activation of opiate receptors by high levels of circulating morphine in the addicted animal. Naloxone will therefore decrease the tonic sympathetic nerve activity in these rats.

Role of opioid receptors in the long-lasting blood pressure depression after electric muscle stimulation in the hind leg of the rat.

In a previous study, electrically induced contractions of the gastrocnemius muscle in conscious spontaneously hypertensive rats were shown to induce a blood pressure reduction of 15-20 mmHg lasting several hours. We showed in that study that endogenous opioid systems were involved. In this study, drugs with selective affinity for different opioid receptors were used to analyse further the involvement of endogenous opioid systems in the post-stimulatory drop in blood pressure in spontaneously hypertensive rats. Prestimulatory intracerebroventricular administration of beta-FNA (a mu-receptor antagonist) did not significantly influence the response at all, nor did a lower intravenous dose of naloxone reverse the post-stimulatory drop in blood pressure. High-dose naloxone (15 mg kg-1) increased post-stimulatory blood pressure by around 10 mmHg. About 50% of the drop thus remained after this treatment. A similar, partial reversal of the decreased blood pressure was seen after intravenous administration of a delta-receptor antagonist, ICI 154,129. However, the depressor response was completely reversed by a low intravenous dose of MR 2266 BS (a kappa-receptor antagonist). These results suggest that the reduction in blood pressure after muscle stimulation is mainly mediated by the opioid kappa-receptor. A certain involvement of the delta-receptor is also indicated.

Vascular adrenergic responses in morphine-dependent rats.

The circulatory effects of morphine abstinence have recently been found to involve decreased renal sympathetic nerve activity and increased mean arterial pressure, induced by vasoconstriction. A direct influence of morphine withdrawal on the peripheral vasculature could possibly contribute to the increased resistance. Therefore, contractile responses to transmural nerve stimulation and to applied noradrenaline of peripheral arteries from morphine-dependent and untreated rats were examined in vitro under paired conditions. No increase in contractile response was observed after chronic morphine treatment, either on nerve stimulation or on applied noradrenaline. Instead the smooth muscle sensitivity to adrenergic stimulation was reduced. Consequently, the present study does not support a peripheral adrenergic origin of the vasoconstriction during naloxone-precipitated morphine abstinence.

Electrical stimulation of the gastrocnemius muscle in the spontaneously hypertensive rat increases the pain threshold: role of different serotonergic receptors.

In a previous study, prolonged low-frequency muscle stimulation in the hind leg of the fully conscious spontaneously hypertensive rat (SHR) was shown to induce a long-lasting reduction of blood pressure. It was also shown that opioid and serotonergic (5-HT) systems were involved. More recently, we have shown that the 5-HT1 receptors are involved in the post-stimulatory decrease in blood pressure. In the present study, the influence of this type of muscle stimulation on the pain threshold was investigated. Pain perception was measured as the squeak threshold to noxious electric pulses. After cessation of the stimulation, an analgesic response was elicited within 60 min and peak analgesia developed after 120 min, being 139 +/- 10% (P less than 0.01) of the prestimulatory control value. The increased pain threshold lasted for another 2 h. One group of SHR was pretreated with PCPA, a serotonin synthesis blocker, which completely abolished the post-stimulatory analgesia. To analyse further the involvement of different serotonin systems, drugs with selective affinity for 5-HT receptors were used. In one group a prestimulatory dose of metitepine maleate (a 5-HT1&2 receptor antagonist) abolished the post-stimulatory elevation of the pain threshold. The prolonged analgesic response was still present after prestimulatory treatment with ritanserin or ICS 205-930 (5-HT2 and 5-HT3 blocking agents respectively). In another group of experiments, the serotonin receptor antagonists were administered post-stimulation to animals with fully elicited analgesia. None of the antagonists used could reverse the elevation of pain threshold towards prestimulatory levels.(ABSTRACT TRUNCATED AT 250 WORDS)