Chronic deep vein thrombosis.

Deep vein thrombosis (DVT) is an important cause of short-term mortality and long-term morbidity. Although acute DVT is often well managed, there is uncertainty in the management of chronic DVT which is increasingly being noted among patients presenting with similar symptoms to their initial DVT. The presence of a residual venous clot can be a problem for both physicians and patients fearing the risk of emboli to the same extent as the acute DVT. There are also issues in the accurate diagnosis and appropriate management of chronic DVT, which is the focus of the second part of this review.

Iliofemoral deep vein thrombosis and the problem of post-thrombotic syndrome.

Deep vein thrombosis (DVT) is an important cause of short-term mortality and long-term morbidity. Among the different presentations of DVT, thrombus in the iliofemoral veins may be considered the severest form. Although anticoagulation is the mainstay of the management of iliofemoral thrombosis, despite adequate anticoagulant treatment, complications including post-thrombotic syndrome is not uncommon. The latter is often overlooked but can cause considerable morbidity to the affected individuals. Preventing this condition remains a challenge but recent clinical trials of catheter directed thrombolysis and elasticated compression stockings provide some advance in this context. In this article, with the aid of a clinical case, we review the particular considerations to take into account when managing patients with an iliofemoral DVT.

Multi-layer Flow-modulating Stents for Thoraco-abdominal and Peri-renal Aneurysms: The UK Pilot Study.

OBJECTIVE: There remains a population of patients with aortic aneurysms that cannot be treated by conventional endovascular means. Multi-layer flow modulating stents (MFMS) are a novel approach for the treatment of aortic aneurysm; this study reports outcomes of a UK pilot study of first-generation MFMS in thoraco-abdominal (TAAA) and perirenal aneurysms (PAA) in patients who were also unfit for open surgery. METHODS: Patients with TAAA and PAA unfit for open surgery and with no conventional options for endovascular repair were recruited. Follow-up included CTA at 1, 3, 6, and 12 months, then annually. Outcome measures included 30 day mortality, growth-free survival, branch vessel patency, complications, re-intervention, and maximal aortic diameter. RESULTS: MFMS were implanted in 14 patients (6 PAA, 8 TAAA) between October 2011 and March 2014 with one (7%) 30 day death and 11 (79%) surviving to 12 months. The median aneurysm growth was 9 mm in the first 12 months following implantation. On mean follow-up of 22.8 months, seven (50%) patients had died including one confirmed rupture. AAA diameter remained stable in only two of the surviving patients. Fifty of 51 covered aortic branches remained patent with no embolic episodes or symptoms of ischaemia in any patient. MFMS dislocation occurred in four patients, leading to re-intervention in two. A total of six re-interventions were performed in five patients (35%) with one post-re-intervention death. CONCLUSION: These first-generation MFMS were unstable and dislocated frequently. It is uncertain whether MFMS implantation influenced the natural history of these aneurysms as none decreased in size, but two remain stable after a mean of 22.8 months. Although side branch patency was maintained, our results do not support the continued use of these first-generation devices. Further development is needed if this technology is to have a role in treatment of aortic aneurysm.

Costs and resource utilization patterns in surgical site infections: a pre-COVID-19 perspective from France, Germany, Spain, and the UK.

BACKGROUND: Surgical site infections (SSIs), mainly caused by Staphylococcus aureus, pose a significant economic burden in Europe, leading to increased hospitalization duration, mortality, and treatment costs, particularly with drug-resistant strains such as meticillin-resistant S. aureus. AIM: To conduct a case-control study on the economic impact of S. aureus SSI in adult surgical patients across high-volume centres in France, Germany, Spain, and the UK, aiming to assess the overall and procedure-specific burden across Europe. METHODS: The SALT study is a multinational, retrospective cohort study with a nested case-control analysis focused on S. aureus SSI in Europe. The study included participants from France, Germany, Italy, Spain, and the UK who underwent invasive surgery in 2016 and employed a micro-costing approach to evaluate health economic factors, matching S. aureus SSI cases with controls. FINDINGS: In 2016, among 178,904 surgical patients in five European countries, 764 developed S. aureus SSI. Matching 744 cases to controls, the study revealed that S. aureus SSI cases incurred higher immediate hospitalization costs (€8,810), compared to controls (€6,032). Additionally, S. aureus SSI cases exhibited increased costs for readmissions within the first year post surgery (€7,961.6 versus €5,298.6), with significant differences observed. Factors associated with increased surgery-related costs included the cost of hospitalization immediately after surgery, first intensive care unit (ICU) admission within 12 months, and hospital readmission within 12 months, as identified through multivariable analysis. CONCLUSION: The higher rates of hospitalization, ICU admissions, and readmissions among S. aureus SSI cases highlight the severity of these infections and their impact on healthcare costs, emphasizing the potential benefits of evidence-based infection control measures and improved patient care to mitigate the economic burden.

A comparative study of carotid atherosclerotic plaque microvessel density and angiogenic growth factor expression in symptomatic versus asymptomatic patients.

OBJECTIVE: A challenge facing clinicians is identifying patients with asymptomatic carotid disease at risk of plaque instability. We hypothesise that locally released angiogenic growth factors contribute to plaque instability. METHODS: Carotid endarterectomy specimens from eight symptomatic and eight asymptomatic patients were interrogated for microvessel density and angiogenic growth factor expression histologically using immunofluorescence, and biochemically using quantitative real-time polymerase chain reaction (q-RT-PCR). Bio-Plex suspension array was used to assess circulating biomarkers in venous blood from the same patients and six healthy age-matched controls. RESULTS: Immunofluorescence demonstrated significantly greater neovessel density in symptomatic plaques (P=0.010) with elevated expression of hepatocyte growth factor (HGF) (P=0.001) and its receptor MET (P=0.011) than in asymptomatic plaques. The q-RT-PCR demonstrated up-regulation of Endoglin (CD105), HGF (P=0.001) and MET (P=0.011) in the plaques of symptomatic versus asymptomatic patients. Bio-Plex suspension array demonstrated elevated HGF (P=0.002) serum levels in symptomatic versus asymptomatic patients and healthy controls, and decreased platelet-derived growth factor (PDGF) (P=0.036) serum levels in symptomatic versus asymptomatic patients. CONCLUSION: Plaque instability may be mediated by HGF-induced formation of new microvessels, and decreased vessel stability resulting from decreased PDGF. Suspension array technology has the potential to identify circulating biomarkers that correlate with plaque rupture risk.

Bifurcated abdominal aortic endograft deployment via the carotid artery.

BACKGROUND: We report the use of the common carotid artery as an alternate access in endovascular therapy. METHODS/RESULTS: A 77-year-old man with an enlarging abdominal aortic aneurysm in whom previous attempts at standard endovascular repair had failed because of difficult iliac access underwent endovascular repair via the left common carotid artery. A custom-made Zenith infrarenal bifurcated stent graft was reverse-loaded on a thoracic distal delivery device and deployed in a caudal-to-cranial fashion. The patient made an uneventful recovery without any complications. Computed tomography confirmed exclusion of the aneurysm. CONCLUSION: This case report highlights the role of the common carotid artery as an access vessel for stent-graft deployment when standard access via the femoral and iliac routes is unachievable.

Contemporary management of aorto-iliac aneurysms in the endovascular era.

Up to 40% of abdominal aortic aneurysms have co-existing unilateral or bilateral iliac artery ectasia or aneurysm. These are associated with an increased risk of endoleak, morbidity and mortality following endoluminal repair. To reduce the adverse sequelae of internal iliac artery (IIA) occlusion, various open, endovascular and hybrid measures have been described to maintain perfusion to the pelvis. This review discusses the contemporary management of aorto-iliac aneurysm in the endovascular era with reference to the sequelae of IIA occlusion and the strategies to preserve IIA perfusion. Particular consideration is given to iliac bifurcation devices.

A systematic review of open versus endovascular repair of inflammatory abdominal aortic aneurysms.

INTRODUCTION: Inflammatory abdominal aortic aneurysms (IAAAs) have traditionally been treated by open surgical repair (OSR). Over the last decade, endovascular aneurysm repair (EVAR) has been increasingly employed. The optimal treatment option for IAAA remains unclear. This article aims to evaluate and compare outcomes of OSR and EVAR in IAAA repair. METHODS: All publications in the English language relating to IAAA were sought electronically using OVID and MEDLINE (1972-2008). Studies identifying 30-day mortality were considered. Periaortic inflammation (PAI), hydronephrosis and 1-year mortality were obtained from studies with at least 1-year computed tomography (CT) follow-up. Outcomes of OSR and EVAR were compared and analysed for statistical significance using Fisher's exact test. RESULTS: The results were obtained from 35 studies comprising 999 patients and 21 studies with 121 patients who underwent OSR and EVAR, respectively. One-year CT follow-up was available for 124 and 52 patients from the two groups, respectively. Thirty-day mortality after OSR was 6% (95% confidence interval (CI); 6-13) and 2% (95% CI; 0-7) after EVAR (p=0.1). At 1 year, PAI regressed in 73% (95% CI; 64-80) in the OSR group compared to 65% (95% CI; 49-77) of the EVAR group (p=0.7). Conversely, inflammation progressed in 1% and 4%, respectively (p=0.1). Forty-five patients undergoing OSR and 29 EVAR were found to have preoperative hydronephrosis. This regressed postoperatively in 69% (95% CI; 53.3-81.8) and 38% (95% CI; 20.6-57.7), respectively (p=0.01). Hydronephrosis progressed in 9% of patients after OSR and in 21% after EVAR (p=0.1). New-onset hydronephrosis developed in 6% undergoing OSR compared to 2% with EVAR (p=0.2). One-year all-cause mortality after OSR was 14% (95% CI; 6-18) compared to 2% (95% CI; 0-13) after EVAR (p=0.02). CONCLUSION: Either OSR or EVAR may be considered based on patient suitability. EVAR is associated with lower 1-year mortality compared to OSR. However, OSR may be preferred in those patients who have hydronephrosis and are deemed low risk.

Investigation of the composition of arterial plaques based on arterial waveforms and material properties.

Stroke is mainly caused by a narrowing of the carotid artery from a build-up of plaque. The risk of plaque rupture and subsequent stroke is dependent on plaque composition. Advances in imaging modalities offer a non-invasive means to assess the health of blood vessels and detect damage. However, the current diagnosis fails to identify patients with soft lipid plaque that are more susceptible to fissure, resulting in stroke. The aim of this study was to use waveform analysis to identify plaque composition and the risk of rupture. We have investigated pressure and flow by combining an artificial blood flow circuit with tubing containing different materials, to simulate plaques in a blood vessel. We used fat and bone to model lipid and calcification respectively to determine if the composition of plaques can be identified by arterial waveforms. We demonstrate that the arterial plaque models with different percentages of calcification and fat, results in significantly different arterial waveforms. These findings imply that arterial waveform analysis has the potential for further development to identify the vulnerable plaques prone to rupture. These findings could have implications for improved patient prognosis by speed of detection and a more appropriate treatment strategy.

Hepatic ischemia-reperfusion injury.

BACKGROUND: The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. DATA SOURCES: The entire world literature on the subject was searched via Medline. Keywords included reperfusion injury, transplantation, liver resection, nitric oxide, endothelin, cytokines, Kupffer cells, ischemic/ischaemic preconditioning, and nuclear factor-kappa B. CONCLUSIONS: An imbalance between endothelin and nitric oxide levels results in failure of the hepatic microcirculation at the onset of reperfusion. Activation of nuclear factor-kappa B in the liver promotes proinflammatory cytokine and adhesion molecule synthesis. These result in oxygen-derived free radical production and neutrophil recruitment, further contributing to cellular injury. Various therapeutic modalities acting on the above mediators have been successfully used to attenuate reperfusion injury in animal models of hepatic transplantation and resection. Application of the knowledge gained from animal models of hepatic ischemia-reperfusion to the clinical setting will improve the outcome of hepatic surgery.

[Non-parasitic splenic cysts]. / Le cisti non parassitarie della milza.

Nonparasitic cysts of the spleen are uncommon and often result from blunt abdominal trauma. Nonsurgical management of blunt splenic injuries increases the number of observations of the post-traumatic cysts. Complications (infection, rupture and hemorrhage) are lifethreatening, difficult to diagnose and require urgent surgical management. Until recently, splenectomy has been the primary choice of treatment of these cysts. Small (< 4 cm) asymptomatic post-traumatic pseudocysts stand a reasonable chance of involution with time (3-36 months) and so may be initially observed. Splenic preservation by partial splenectomy, enucleation or by marsupialization is actually recommended in children when technically feasible. Splenectomy is required for voluminous, central, multifocal cysts, in the presence of complications and in the adults with low immunologic risk. The Authors report 5 cases of large cysts successfully treated by splenectomy with one 12-year-old girl treated in emergency for infection by Salmonella.

Meta-analysis of retrojugular versus antejugular approach for carotid endarterectomy.

INTRODUCTION: The retrojugular approach for carotid endarterectomy (CEA) has been reported to have the advantages of shorter operative time and ease of dissection, especially in high carotid lesions. Controversial opinion exists with regard to its safety and benefits over the conventional antejugular approach. METHODS: A systematic review of electronic information sources was conducted to identify studies comparing outcomes of CEA performed with the retrojugular and antejugular approach. Synthesis of summary statistics was undertaken and fixed or random effects models were applied to combine outcome data. FINDINGS: A total of 6 studies reporting on a total of 740 CEAs (retrojugular approach: 333 patients; antejugular approach: 407 patients) entered our meta-analysis models. The retrojugular approach was found to be associated with a higher incidence of laryngeal nerve damage (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 1.46-7.07). No significant differences in the incidence of hypoglossal or accessory nerve damage were identified between the retrojugular and antejugular approach groups (OR: 1.09 and 11.51, 95% CI: 0.31-3.80 and 0.59-225.43). Cranial nerve damage persisting during the follow-up period was similar between the groups (OR: 2.96, 95% CI: 0.79-11.13). Perioperative stroke and mortality rates did not differ in patients treated with the retrojugular or antejugular approach (OR: 1.26 and 1.28, 95% CI: 0.31-5.21 and 0.25-6.50). CONCLUSIONS: Currently, there is no conclusive evidence to favour one approach over the other. Proof from a well designed randomised trial would help determine the role and benefits of the retrojugular approach in CEA.

Endothelial microparticles as conveyors of information in atherosclerotic disease.

Endothelial microparticles (EMPs) are complex submicron membrane-shed vesicles released into the circulation following endothelium cell activation or apoptosis. They are classified as either physiological or pathological, with anticoagulant or pro-inflammatory effects respectively. Endothelial dysfunction caused by inflammation is a key initiating event in atherosclerotic plaque formation. Athero-emboli, resulting from ruptured carotid plaques are a major cause of stroke. Current clinical techniques for arterial assessment, angiography and carotid ultrasound, give accurate information about stenosis but limited evidence on plaque composition, inflammation or vulnerability; as a result, patients with asymptomatic, or fragile carotid lesions, may not be identified and treated effectively. There is a need to discover novel biomarkers and develop more efficient diagnostic approaches in order to stratify patients at most risk of stroke, who would benefit from interventional surgery. Increasing evidence suggests that EMPs play an important role in the pathogenesis of cardiovascular disease, acting as a marker of damage, either exacerbating disease progression or triggering a repair response. In this regard, it has been suggested that EMPs have the potential to act as biomarkers of disease status. In this review, we will present the evidence to support this hypothesis and propose a novel concept for the development of a diagnostic device that could be implemented in the clinic.

An alternative to aorto-uni-iliac EVAR and femoro-femoral crossover in a patient having an aorto-iliac aneurysm with an occluded external iliac artery.

INTRODUCTION: An endovascular procedure for excluding an aorto-iliac aneurysm whilst simultaneously preserving one internal iliac artery is described in a patient with complex iliac pathology. REPORT: The procedure involved the use of Advanta V12 covered stents to bridge the gap between the contralateral limb of the main body of a custom-made Zenith stent graft and the internal iliac artery on the side of an external iliac artery occlusion. DISCUSSION: Minimal modifications to the standard design of modular stent grafts make it possible to treat high risk patient with complex pathology with minimal morbidity.

Intimal neovascularisation is a prominent feature of atherosclerotic plaques in diabetic patients with critical limb ischaemia.

INTRODUCTION: Neovascularisation of atherosclerotic plaques correlates with increased plaque instability and subsequent risk of vascular complications. Diabetics have widespread atherosclerotic involvement of the arterial tree and a more aggressive form of the disease culminating in increased plaque instability. This results in a greater incidence of ischaemic sequelae than in non-diabetics. Previous studies have examined neovascularisation as a marker of plaque instability in both the carotid and coronary territories and revealed a greater degree in both symptomatic and diabetic patients. This is the first study to examine intimal neovascularisation in lower limb peripheral arterial disease. METHODS: Arterial specimens were taken from 20 patients, ten of whom were type 2 diabetics, undergoing major lower limb amputation for unreconstructable critical ischaemia. Sections were stained with H&E for morphological assessment and inflammatory cell characterisation. Additional sections underwent immunohistochemical staining for CD31 and von-Willebrand Factor (vWF) and the number of intimal vessels per four 40x magnification fields assessed. RESULTS: There was a more prominent inflammatory infiltrate in diabetic subjects compared to non-diabetic controls. Diabetic patients had a greater degree of intimal neovascularisation compared to controls with a median of 11.5 and 2.0 vessels per field respectively (P<0.05). Sub-group analysis revealed that diabetic patients medicating with HMG-CoA Reductase inhibitors (Statins) had a greater degree of neovascularisation compared to those not taking this class of medication. CONCLUSION: Diabetic patients with critical limb ischaemia requiring amputation demonstrate a greater degree of plaque intimal neovascularisation and inflammatory infiltrate compared to their non-diabetic counterparts. This may explain the greater plaque instability and subsequent cardiovascular complications seen in these patients.

Expression of inducible nitric oxide synthase contributes to the development of pancreatitis following pancreatic ischaemia and reperfusion.

BACKGROUND: Inducible nitric oxide synthase (iNOS) activity is increased in experimentally induced acute pancreatitis. Increased expression of this isoform of nitric oxide synthase has been demonstrated in several organs subjected to ischaemia-reperfusion injury. The present experiment investigated the expression of iNOS and the effect of selective iNOS inhibition in pancreatic ischaemia-reperfusion. METHODS: Wistar rats (n = 40) were randomly and equally assigned to four groups. Groups 2 and 4 underwent 60 min of total pancreatic ischaemia followed by 6 h of reperfusion (I-R). Groups 1 and 3 underwent sham operation. The selective iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine (L-NIL) was administered to groups 3 and 4. Expression of iNOS was examined by immunohistochemistry. Other investigations included measurement of serum amylase activity and pancreatic wet : dry weight ratio, and histopathological examination. RESULTS: Eight of ten rats in group 2 (I-R only) expressed iNOS but none of the ten animals in group 1 (sham laparotomy) did so. Group 4 (I-R + L-NIL) animals had significantly lower serum amylase levels and wet : dry weight ratios than those in group 2 (I-R only). Microscopic evidence of pancreatic injury was present only in rats in group 2 (I-R only). CONCLUSION: Expression of iNOS during reperfusion following pancreatic ischaemia contributes significantly to the development of acute pancreatitis.

Duodenal webs--no age limit.

BACKGROUND: Duodenal webs usually give rise to symptoms of gastric outlet obstruction in infancy, but they occasionally present in adulthood. CASE OUTLINE: We report an 82-year-old woman with an unusual cause of gastric outlet obstruction. Peptic ulcer stricture or carcinoma were suspected, but a CT scan and upper gastrointestinal endoscopy revealed that her symptoms were the result of duodenal webs. The webs were successfully dilated at endoscopy. DISCUSSION: Duodenal webs may rarely account for gastric outlet obstruction in adults. Failure to visualise the second and third parts of the duodenum at endoscopy means that the diagnosis may be missed. Diclofenac and slow-release potassium tablets may have played an aetiological role in the formation of the webs in this patient.

Hepatic and mesenteric nitric oxide synthase expression in a rat model of CCl(4)-induced cirrhosis.

BACKGROUND: Cirrhosis and portal hypertension are frequently linked with changes in expression of nitric oxide synthase (NOS) and/or endotoxaemia. AIMS: This study tested the following hypothesis: that inducible (i)NOS activity is increased within the visceral circulation concurrently with decreased constitutive (c)NOS activity in the hepatic sinusoids and that the concentration of NO metabolites in portal blood is consequent on endotoxin concentration. MATERIALS AND METHODS: Plasma concentrations of (nitrite + nitrate) and endotoxin, together with hepatic and mesenteric NOS activity (arginine/citrulline method) and protein expression (histochemistry) plus portal and arterial blood pressure, were determined in rats made severely cirrhotic by intragastric CCl(4) over 14 weeks (n = 6) compared with age-matched controls (n = 5). The concentrations of [nitrite + nitrate] and endotoxin in portal plasma were also directly compared in rats made cirrhotic for a period of 8-14 weeks (n = 10). RESULTS: In rats with advanced cirrhosis, arterial [nitrite + nitrate] was 93.1 (22.4) micromol/L (mean, SEM) compared with 29.1 (6.1) micromol/L in controls (P < 0.05); portal plasma [NO(2)(-) + NO3(-)] was 127.1 (27.2) compared with 24.7 (4.7) micromol/L in controls (P < 0.05). Cirrhotic rats had higher endotoxin concentration in plasma compared with controls (systemic: 85.0 (24.5) versus 1.7 (0.2) EU/ml, P < 0.05; portal: 180.3 (47.9) versus 1.7 (0.2) EU/ml, P < 0.05). The same severely cirrhotic rats possessed decreased cNOS activity in liver (2.95 [0.40] versus 5.29 [0.85] pmol/min/g; P < 0.05) and increased iNOS activity in mesentery (4.83 [1.23] versus 1.47 [0.15] pmol/min/g; P < 0.05) compared with controls. Histochemical observations confirmed these findings. Rats given CCl(4) for a period of 8-14 weeks possessed high endotoxin concentration in portal plasma, with correspondingly high [nitrite + nitrate] (r(2) = 0.954; P < 0.001). CONCLUSIONS: An endotoxin-induced increase in mesenteric iNOS activity and a decrease in hepatic cNOS activity may account for, respectively, the hyperdynamic visceral circulation and the increased intrahepatic resistance of cirrhosis.