High proportion of undiagnosed diabetes in patients surgically treated for infrarenal abdominal aortic aneurysm: findings from the multicentre Norwegian Aortic Aneurysm and Diabetes (ABANDIA) Study.

BACKGROUND: The aim was to investigate the total prevalence of known and undiagnosed diabetes mellitus (DM), and the association of DM with perioperative complications following elective, infrarenal, open surgical (OSR) or endovascular (EVAR), Abdominal Aortic Aneurysm (AAA) repair. METHODS: In this Norwegian prospective multicentre study, 877 patients underwent preoperative screening for DM by HbA1c measurements from November 2017 to December 2020. Diabetes was defined as screening detected HbA1c ≥ 48 mmol/mol (6.5%) or previously diagnosed diabetes. The association of DM with in-hospital complications, length of stay, and 30-day mortality rate were evaluated using adjusted and unadjusted logistic regression models. RESULTS: The total prevalence of DM was 15% (95% CI 13%,17%), of which 25% of the DM cases (95% CI 18%,33%) were undiagnosed upon admission for AAA surgery. The OSR to EVAR ratio was 52% versus 48%, with similar distribution among DM patients, and no differences in the prevalence of known and undiagnosed DM in the EVAR versus the OSR group. Total 30-day mortality rate was 0.6% (5/877). Sixty-six organ-related complications occurred in 58 (7%) of the patients. DM was not statistically significantly associated with a higher risk of in-hospital organ-related complications (OR 1.23, 95% CI 0.57,2.39, p = 0.57), procedure-related complications (OR 1.48, 95% CI 0.79,2.63, p = 0.20), 30-day mortality (p = 0.09) or length of stay (HR 1.06, 95% CI 0.88,1.28, p = 0.54). According to post-hoc-analyses, organ-related complications were more frequent in patients with newly diagnosed DM (n = 32) than in non-DM patients (OR 4.92; 95% CI 1.53,14.3, p = 0.005). CONCLUSION: Twenty-five percent of all DM cases were undiagnosed at the time of AAA surgery. Based on post-hoc analyses, undiagnosed DM seems to be associated with an increased risk of organ related complications following AAA surgery. This study suggests universal DM screening in AAA patients to reduce the number of DM patients being undiagnosed and to improve proactive diabetes care in this population. The results from post-hoc analyses should be confirmed in future studies.

Editor's Choice - The National Norwegian Carotid Study: Time from Symptom Onset to Surgery is too Long, Resulting in Additional Neurological Events.

OBJECTIVE/BACKGROUND: The objective was to observe for 1 year all patients in Norway operated on for symptomatic carotid stenosis with respect to (i) the time from the index event to surgery and neurological events during this time; (ii) the level in the healthcare system causing delay of surgical treatment; and (iii) the possible relationship between peri-operative use of platelet inhibitors and neurological events while awaiting surgery. METHODS: This was a prospective national multicentre study of a consecutive series of symptomatic patients. Patients were eligible for inclusion when referred for surgery. An index event was defined as the neurological event prompting contact with the healthcare system. All 15 departments in Norway performing carotid endarterectomy (CEA) participated. RESULTS: Three hundred and seventy one patients were eligible for inclusion between 1 April 2014 and 31 March 2015, and 368 patients (99.2%) were included. Fifty-four percent of the patients contacted their general practitioner on the day of the index event. Primary healthcare referred 84.2% of the patients to hospital on the same day as examined. In hospital median time from admission to referral for vascular surgery was 3 days. Median time between referral to the operating unit and actual CEA was 5 days. Overall, 61.7% of the patients were operated on within 2 weeks of the index event. Twelve patients (3.3%) suffered a new neurological event while awaiting surgery. The percentage of patients on dual antiplatelet therapy was lower (25.0%) in this group than among the other patients (62.6%) (p = .008). The combined 30 day mortality and stroke rate was 3.8%. CONCLUSION: This national study with almost complete inclusion and follow-up shows that the delays occur mainly at patient level and in hospital. The delay is associated with new neurological events. Dual antiplatelet therapy is associated with reduced risk of having a new neurological event before surgery.

Dysglycaemia in vascular surgery patients.

UNLABELLED: Oral glucose tolerance tests (OGTTs) have detected a pathologic glucose metabolism in up to 60% of patients with acute coronary syndromes. Only one-third of these were previously diagnosed. The purpose of this study was to determine the prevalence of abnormal glucose metabolism among vascular surgery patients. METHODS: Between October 2006 and September 2007, 465 consecutive patients admitted to the vascular surgery unit were asked to participate in the study; however, 121 declined. Among the patients included, 68 had previously known diabetes. A total of 276 patients performed an oral glucose tolerance test (OGTT). We categorised the findings based on fasting and 2-h plasma glucose levels into four groups: diabetes mellitus, impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and normal glucose metabolism. Information regarding the affected vascular bed and relevant medical history was also registered. RESULTS: Of the 276 patients who underwent OGTT, 66 (24%) had IGT, 23 (8%) had IFG and 33 (12%) had diabetes. As many as 17 of the 33 patients with newly diagnosed diabetes would have fulfilled the criteria for diagnosis based only on their fasting glucose levels. Including the patients with previously known diabetes, the prevalence of dysglycaemia was 55% and that of diabetes 29%. CONCLUSIONS: Total prevalence of dysglycaemia in vascular surgery patients corresponds well to that of acute coronary syndromes. The prevalence of unknown pathological glucose metabolism was 44% in our OGTT material. The use of fasting glucose as the sole diagnostic tool for diabetes would have resulted in the correct diagnosis in only half of the patients tested. OGTT should be considered as a routine investigation in non-diabetic vascular surgery patients. It remains to be seen whether early diagnosis and treatment of dysglycaemia in this patient group will influence the surgical treatment and outcome.

Improved patency and reduced intimal hyperplasia in PTFE grafts with luminal immobilized heparin compared with standard PTFE grafts at six months in a sheep model.

AIM: The aim of this study was to compare the performance of polytetrafluoroethylene (PTFE) grafts with luminal coating of immobilized heparin to that of standard PTFE grafts at six months. METHODS: Twenty-eight common carotid arteries in fourteen sheep were bypassed with heparin-coated PTFE grafts (6 mm diameter, 6 cm length) on one side and standard PTFE grafts on the other. The grafts were explanted after six months. The thickness of intimal hyperplasia (IH) in open grafts was measured with histomorphometrical methods. RESULTS: Two of 14 heparinized PTFE grafts and nine of 14 grafts in the control PTFE-group were occluded at explantation (P=0.006). Six-month patency rates for heparinized PTFE grafts and for standard PTFE grafts were 86% and 36%, respectively. Mean graft anastomotic IH thickness in open grafts were 0.074 mm for heparinized PTFE grafts and 0.259 mm for PTFE-grafts (P=0.006). CONCLUSION: PTFE grafts with luminal coating containing immobilized heparin had significantly better patency and recruited less intimal hyperplasia than standard PTFE grafts at six months.

Neutrophil CD64 as a marker for postoperative infection: a pilot study.

The aim of this pilot study was to evaluate the clinical utility of quantitative CD64 measurements to differentiate between systemic inflammation in response to surgical trauma and postoperative bacterial infection. In a consecutive series of 153 patients undergoing elective vascular surgery, peripheral venous blood samples were taken preoperatively on admission and postoperatively during the first 24h. The samples were analysed for C-reactive protein (CRP), total leucocyte counts (white blood cell (WBC)), serum procalcitonin (PCT) and neutrophil CD64 expression. Of the 153 patients, the focus is on those with (1) postoperative infection alone (group 1; n=1 4); (2) pre- and postoperative infection (group 2; n=6); and (3) postoperative fever with no other signs of infection (group 3; n=29). In group 1, all four markers were significantly increased in the 24h after surgery: CD64 (p=0.001), CRP (p=0.001), WBC (p=0.002) and PCT (p=0.012); in group 2, there was no significant difference in the CD64 (p=0.116), WBC (p=0.249) and PCT (p=0.138) values, whereas a marginal significance was shown for CRP (p=0.046); and the results for group 3 were similar to those of group 1. This pilot study suggests that the role of neutrophil CD64 measurements in facilitating the diagnosis of early postoperative infection merits further investigation.

Infusion of branched-chain amino acids and ammonium salts in rats with portacaval shunts.

During infusion into rats with a portacaval shunt of either ammonium (NH4+) salts alone or NH4+ salts combined with the three branched-chain amino acids (BCAAs) in equimolar quantities, we assessed neurologic function and measured plasma and brain ammonia and amino acid levels and the brain content of amine neurotransmitters and their metabolites. Survival was lengthened and neurologic function was preserved longer in rats receiving BCAAs. Infusion of BCAAs resulted in lower plasma and brain ammonia concentrations compared with rats receiving NH4+ salts alone. Plasma glutamine and alanine levels were higher in rats receiving BCAAs, suggesting increased ammonia detoxification. Loss of neurologic function, regardless of which solution was infused, eventually occurred and corresponded with decreased brain norepinephrine and increased brain alanine levels. These results suggest that BCAAs can protect against hyperammonemia by stimulating the peripheral detoxification of ammonia.

Percutaneous transluminal angioplasty with or without stenting for femoropopliteal occlusions? A randomized controlled study.

BACKGROUND: To investigate the-one year outcome of PTA and stenting and PTA alone for femoropopliteal occlusions. DESIGN: Randomized prospective study METHODS: 32 patients with femoropopliteal occlusions were randomized into two treatment groups: PTA and Strecker-stent (n=15) and PTA alone (n=17). The median age of the patients was 71 years. All patients had chronic limb ischaemia, 66% had tissue loss, 19% had rest pain and 15% had disabling claudication. The median ABPI was 0.45. The occlusion was confined to the superficial femoral artery in 30 cases and to the popliteal artery in 2 cases. The median length of the occlusions was 7.3 cm. Aspirin (ASA), 160 mg daily, was administrated postoperatively but no anticoagulation was used. The follow-up included: clinical examination, measurement of ABPI and control angiography at 12 months or earlier when necessary (20 patients). RESULTS: There was no mortality or limb loss as a consequence of the treatment. There were six (16%) immediate major complications in five patients. In the PTA group, one patient had a myocardial infarction and three patients needed arteriography due to bleeding. In the stent group, one patient required arteriography and embolectomy. The one-year mortality was 6% and there were no amputations. Four patients (two in each group) were operated on with a femorodistal bypass. The rate of clinical improvement was 71% after PTA and stent and 60% after PTA alone (p=0.17). An increased ABPI (>0.10) was shown in 50% of the stent group and 61% in the PTA group (p=0.17). Angiographic re-occlusions were seen in 33% and 75% in the stent and PTA groups respectively (p=0.17), while the rate of restenosis was significantly higher in the stent group (50% vs 25%) (p=0.033). CONCLUSIONS: Stenting following PTA for femoropopliteal occlusions does not significantly improve neither the clinical state nor the clinical/angiographic patency. The results do not justify any routine placement of stent following PTA in the successfully recanalized femoropopliteal arteries. The low rate of acceptance of a follow-up angiography indicates that this kind of study should preferably use duplex scanning instead of angiography for follow-up.

Vascular injuries in Sweden 1986-1990: the result of an enquiry.

In order to review the management of vascular trauma in Sweden all surgical and orthopedic departments were asked to report retrospectively vascular injuries occurring between 1986 and 1990. There were 294 injuries reported from 55 departments. The majority (approximately 80%) of the injuries were confined to the extremities. In the arms the injuries of the vessels were mostly simple, whereas in the legs they were more complex and correct treatment demanded extensive experience in vascular surgery. No less than 20% of the injuries were iatrogenic and half of them required reconstructive surgery. 55% of the iatrogenic injuries occurred during angiological examinations and treatments. Complex vascular injuries are often combined with fractures and soft tissue damage and required close cooperation between vascular and orthopedic surgeons. Advanced angiological examinations and treatments should only be performed in hospitals with vascular surgery facilities.

Visceral ischemia following aortic surgery.

Intestinal ischemia after aortic surgery is a rare (1-5%) complication, often with a fatal outcome (greater than 50%). During the period 1974-1987, 554 abdominal aortic operations were performed in our department. 17 patients (3%) were reoperated due to bowel ischemia, ten of these patients died. 12 patients were operated on due to aortic aneurysm (9 emergency operations) and 5 due to occlusive disease. A retrospective analysis of the files of the 17 patients was performed to try to identify the risk patient. Preoperative investigations demonstrated that the inferior mesenteric artery (IMA) was patent in 3 patients and occluded in 5 patients. As to the other 9 patients no information could be found (all with aneurysm). After the primary operation, 11 patients had persistent circulation via at least one of the hypogastric arteries and none of them had persistent circulation via the IMA. 11 patients had bloody diarrhea before reoperation and in 6 patients peritonitis was observed. Rectoscopy was performed in 8 patients and in 7 there was indication of ischemia. The most common finding among the laboratory tests was a rise in the creatinine level which was observed in 10 patients. Other laboratory tests such as blood gases, leucocytes, thrombocytes or temperature were of little predictive value per se. Patients operated on due to ruptured aortic aneurysm are risk patients. No other predictive symptom or sign was found to preoperatively identify the patient at risk for intestinal ischemia. An intraoperative method for evaluating the intestinal blood flow would be of great value when considering selective intestinal vascular reconstruction.

[Endovascular technique in aortic aneurysm. A promising alternative to open surgery]. / Endovaskulär teknik vid aortaaneurysm. Lovande alternativ till öppen kirurgi.

The article consists in a presentation of endovascular surgery for abdominal aortic aneurysm repair in 23 cases. Two cases required conversion to open surgery, but the procedure could be completed in the remaining 21 cases, with a current duration of follow-up of up to 30 months. There was early leakage in one case, and late leakage in five cases. Late conversion has been necessary in three instances, and supplementary endovascular measures have been required in a further two instances. All complications have occurred in those cases operated during the first half of the study period. Modification of the endoprosthesis used and increasing skill have reduced both operation time and the complication rate. Intensive care is no longer required, and the median duration of hospitalisation is three days. Follow-up with magnetic resonance imaging has yielded new and important information.

Homocysteine levels, haemostatic risk factors and patency rates after endovascular treatment of the common iliac arteries.

OBJECTIVES: To investigate the impact of clinical risk factors, plasma homocysteine and haemostatic variables on the results after endovascular treatment of symptomatic atherosclerosis of the common iliac artery. DESIGN: Prospective observational study. SETTING: University hospital. PATIENTS AND METHOD: The study included 139 technically successful interventions in 103 patients. Technical success was defined as < or = 30% residual stenosis as seen on the post treatment angiogram. Blood samples for analyses of fasting plasma values of homocysteine, fibrinogen, D-dimer, activated protein C resistance were drawn upon admission. Median follow-up for all procedures was 22 months (range 0-55 months). Patency was defined as freedom from > or = 50% restenosis or reocclusion. RESULTS: The technical success rate for all procedures was 93%. The 1-year cumulative primary patency rate based on intention to treat was 85%. Multivariate analysis revealed a significant independent association between patency rates and levels of fibrinogen and homocysteine and the nature of the lesion treated (stenosis vs. occlusion). CONCLUSION: The aetiology of restenoses and reocclusions is probably multifactorial. Procoagulant activity, the nature of the lesion treated and homocysteine levels within and above the upper range of normal limits are important risk factors for failure after endovascular treatment of the common iliac arteries.

Rat plasma clearance rate and organ distribution of beta-hexosaminidase isoenzymes from human serum.

beta-Hexosaminidase (EC 3.2.1.30) is markedly increased in human serum in liver disease, chronic alcoholism, and pregnancy. Knowledge of the clearance rate of plasma/serum beta-hexosaminidase is necessary to evaluate this increase. We studied the plasma clearance of beta-hexosaminidase isoenzymes (purified from human serum and placenta) after their infusion into rat circulation. A recently developed enzyme immunoassay method was used to measure the human beta-hexosaminidase isoenzymes; this method relies on both immunoreactivity and enzyme activity, so intact human isoenzymes were measured. In comparison with the placental isoenzymes (t1/2 less than 2 min), the serum forms showed a considerably slower clearance (t1/2 = 2-4 h). However, desialylation of the serum forms resulted in their rapid clearance (t1/2 less than 2 min). The organ localization of the enzyme eliminated from the circulation was investigated 24 h after infusion. Placental and native serum isoenzymes accumulated mainly in the liver and the spleen. Desialylated serum forms were almost exclusively localized to the liver.

Liver regeneration following 68% partial orthotopic liver transplantation in the rat.

Liver regeneration following transplantation in 'small for size' conditions is not fully understood. We therefore evaluated the regenerative response of transplanted partial liver grafts in outbred rats without the use of immunosuppression and compared it to liver regeneration following resection. The transplanted livers showed enhanced regeneration compared to controls. We suggest that this is caused by activation of the immune system.

The adhesion of labelled neutrophils on synthetic vascular grafts. An experimental porcine study.

The adhesion of neutrophils onto different vascular grafts was studied in vivo in a pig model. In acute experiments autologous 111In-labelled neutrophils were reinfused after end-to-side implantation of 5 cm, 6 mm internal diameter grafts. The dynamic deposition on each graft was determined for 300 min in vivo. Static measurements in vitro concluded the study. The adhesion was greater in Dacron and collagen coated Dacron grafts compared to expanded polytetrafluoroethylene (ePTFE) and to Dacron grafts coated with a polymer. The segmental activity along all the grafts increased towards the distal anastomosis. The results suggest different inflammatory response to various graft materials.

Healing characteristics of polymer-coated or collagen-treated Dacron grafts: an experimental porcine study.

The healing characteristics of polymer-coated Dacron grafts with or without heparin-bonding and collagen-coated Dacron grafts are compared with standard knitted Dacron grafts by implanting eight of each graft into pig iliac arteries. The grafts were implanted at random bilaterally with end-to-side anastomoses. The grafts were explanted after 1, 2 and 4 weeks and prepared for histological evaluation by in vivo fixation. Graft segments were investigated by light microscopy, scanning electron microscopy and transmission electron microscopy. The endothelial coverage, intimal thickness and healing characteristics were subjected to one-way analysis of variance. One week after surgery endothelial-like cells appeared close to the anastomoses and after 2 weeks a clear growing endothelial edge was observed in the collagen-coated grafts. After 4 weeks' implantation all grafts were patent and endothelial cells covered the grafts to a various extent. Collagen-coated grafts had significantly greater endothelial cell coverage compared with Dacron and polymer-coated grafts without heparin bonding (P < 0.05). Evaluation by transmission electron microscopy revealed the luminal coverage of the collagen-coated grafts to consist of organized smooth muscle cells and endothelial cells containing Weibel-Palade bodies. The smooth muscle cells in the other grafts were less organized and were covered by endothelial cells to a lesser degree. No differences were noted regarding the inflammatory response of the graft materials and no further positive effects were encountered by the addition of heparin to the polymer coating. The study demonstrates that various coating procedures and surface modulation of knitted Dacron grafts produce a graft which is impervious to blood but still allows tissue incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)

Indole amines and amino acids in various brain regions after infusion of branched chain amino acids into hepatectomized rats.

This study was designed to determine regional changes of amino acids and indole amines in the brain and possible interactions between amino acids and indole amines 18 h after hepatectomy in rats. Hepatectomy and glucose infusion alone resulted in a profound increase of most large neutral amino acids (LNAA) in plasma and in the brain except for the branched-chain amino acids (BCAA), which maintained normal or somewhat lower values in plasma. Hepatectomy and infusion of glucose combined with BCAA sharply reduced the plasma and brain amino acid concentrations of other LNAA. Simultaneously the concentrations of serotonin and 5-hydroxyindoleacetic acid were decreased in all brain regions. In both groups of hepatectomized rats there were regional variations of the amino acid and the indole amine concentrations in the brain, but the response to BCAA infusion was generally the same in all brain regions. No difference in survival between the 2 groups could be found.

Methionine sulfoximine prevents the accumulation of large neutral amino acids in brain of portacaval-shunted rats.

Portal-systemic shunting and hyperammonemia lead to an accumulation of the large neutral amino acids in brain and apparently alter transport of neutral amino acids across the blood-brain barrier. It has been proposed that portal-systemic shunting leads to a high brain concentration of glutamine, a product of cerebral ammonia detoxification, and thereby affects the transport of other neutral amino acids across the blood-brain barrier. To test this hypothesis, rats with a portacaval shunt were treated with L-methionine-dl-sulfoximine (MSO), an inhibitor of glutamine synthesis. Treatment with MSO resulted in lower concentrations of the neutral amino acids in brain of portacaval-shunted rats and a higher brain ammonia concentration, compared with untreated shunted rats. These results suggest that the accumulation of neutral amino acids in brain after portacaval shunt depends on the increased synthesis of glutamine in brain.

Effect of hyperammonemia and methionine sulfoximine on the kinetic parameters of blood-brain transport of leucine and phenylalanine.

The activity of the blood-brain neutral amino acid transport system is increased in rats infused with ammonium salts or rendered hyperammonemic by a portacaval anastomosis. This effect may be due to a direct action of ammonia or to some metabolic consequence of high ammonia levels, such as increased brain glutamine synthesis. To test these possibilities we evaluated the kinetic parameters of blood-brain transport of leucine and phenylalanine in control rats, in rats after continuous 24 h infusion of ammonium salts (NH4+ = 2.5 mmol X kg-1 X h-1), and in rats treated with methionine sulfoximine, an inhibitor of glutamine synthetase, before infusion of ammonium salts. In ammonia-infused rats without methionine sulfoximine treatment, the KD and Vmax of phenylalanine transport were increased, respectively, about 170% and 80% compared to controls, whereas the Km and Vmax of leucine transport were increased, respectively, about 100% and 200%. Electron microscopy demonstrated marked swelling of astrocytic processes around brain capillaries of ammonia-infused rats; however, capillary permeability to horseradish peroxidase apparently was not increased by ammonia infusion. Administration of methionine sulfoximine before ammonia infusion inhibited glutamine synthesis and prevented the changes in transport of leucine and phenylalanine, but apparently did not reverse the perivascular swelling. These results suggest that the ammonia-induced increase in the activity of transport of large neutral amino acids across the blood-brain barrier requires glutamine synthesis in brain, and is not a direct effect of ammonia.

The effects of ammonia tolerance tests on the cerebrospinal fluid concentrations of amino acids and indoleamines in patients with liver cirrhosis.

To study the effect of ammonia administration on amino acids and indoleamines in cerebrospinal fluid (CSF) and on amino acids, insulin, and glucagon in plasma in humans with liver cirrhosis, we performed seven ammonia tolerance tests on six patients with stable liver cirrhosis. The grade of encephalopathy was determined by psychometric tests. Only one of the patients had pronounced encephalopathy. The other patients had no or only slight encephalopathy. The plasma concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, and methionine decreased after the ammonia load, whereas no changes were found in the plasma concentrations of glucagon and insulin. In CSF the concentrations of glutamine, aromatic amino acids, and indoleamines increased only in the patient who had pronounced encephalopathy, whereas no changes were found in the other patients. The effect of an ammonia load on the concentrations of neutral amino acids in CSF in patients with pronounced encephalopathy remains to be demonstrated.