Metabolic Phenotyping in Venous Disease: The Need for Standardization.

Venous thromboembolism (VTE), chronic venous disease (CVD), and venous leg ulceration (VLU) are clinical manifestations of a poorly functioning venous system. Though common, much is unknown of the pathophysiology and progression of these conditions. Metabolic phenotyping has been employed to explore mechanistic pathways involved in venous disease. A systematic literature review was performed: full text, primary research articles on the applications of nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) in human participants and animals were included for qualitative synthesis. Seventeen studies applying metabolic phenotyping to venous disease were identified: six on CVD, two on VLU, and nine on VTE; both animal (n = 6) and human (n = 10) experimental designs were reported, with one study including both. NMR, MS, and MS imaging were employed to characterize serum, plasma, urine, wound fluid, and tissue. Metabolites found to be upregulated in CVD included lipids, branched chain amino acids (BCAA), glutamate, taurine, lactate, and myo-inositol identified in vein tissue. Upregulated metabolites in VLU included lactate, BCAA, lysine, 3-hydroxybutyrate, and glutamate identified in wound fluid and ulcer biopsies. VTE cases were associated with reduced carnitine levels, upregulated aromatic amino acids, 3-hydroxybutyrate, BCAA, and lipids in plasma, serum, thrombus, and vein wall; kynurenine and tricarboxylic acid pathway dysfunction were reported. Future research should focus on targeted studies with internal and external validation.

Deep Vein Thrombosis Exhibits Characteristic Serum and Vein Wall Metabolic Phenotypes in the Inferior Vena Cava Ligation Mouse Model.

OBJECTIVES: Deep vein thrombosis (DVT) is a major health problem, responsible for significant morbidity and mortality. The identification of a simple and effective diagnostic biomarker of DVT remains a challenge. Metabolomics have recently emerged as a new powerful scientific tool to characterise metabolic phenotypes of complex diseases and investigate small molecules in biofluids. The aim of the study was to identify the blood and vein wall metabolomic signature of DVT in a murine experimental model. METHODS: An established inferior vena cava ligation mouse model of DVT (n=10) was used and compared with sham surgery controls (n=10). Comprehensive untargeted metabolic profiling of serum and vein wall extracts was undertaken using liquid chromatography coupled mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Multivariate and univariate statistical analysis demonstrated a differential metabolic profile when comparing DVT mice and control animals. Serum from DVT mice was characterised by differential concentrations of adenosine (decreased in DVT mice 9.6 fold), adenine (decreased 10.6 fold), and tricyclic acid cycle (TCA) intermediates, including citrate, succinate, and fumarate (1.5, 2.3, and 2.8 fold decreases, respectively). l-carnitine was found to be of greater abundance in the serum of DVT animals (67.0 fold change). A number of lipid moiety classes, including sphingomyelins, phosphatidylcholines, and triglycerides, were differentially abundant. Several metabolites were found in vein wall, including acetylcarnitine (increased in DVT mice 1.9 fold), adenosine (increased 2.2 fold), and ceramide (increased 2.7 fold). Correlation analysis illustrated the biochemical relationships between assigned metabolites, with the discriminatory molecules being highly correlated with each other, in both serum and vein wall. CONCLUSIONS: The present findings demonstrate that metabolic dysregulations in DVT centre on energy metabolism, sphingolipid, and adenosine metabolism, representing a DVT specific metabolite signature in a murine experimental model.

Manual high-dose regional intraoperative thrombolysis of lower extremity emboli after open repair of a ruptured abdominal aortic aneurysm.

We describe a case of high-dose regional intraoperative thrombolysis subsequent to mechanical thrombectomy for the treatment of postoperative distal extremity embolization of the right lower limb owing to open repair of a ruptured abdominal aortic aneurysm. Mechanical thrombectomy was performed from the popliteal artery but residual embolic occlusion of all three tibial arteries remained. The limb was elevated, exsanguinated, and a blood cuff was placed below the knee and inflated to suprasystolic pressure to isolate the limb from systemic circulation. An 18-gauge infusion catheter was introduced to the exposed dorsalis pedis artery. Subsequently, the exposed great saphenous vein was cannulated and drained. A total of 100 mg of recombinant tissue-type plasminogen activator diluted in 500 mL of saline was infused into the anterior tibial artery with a slow hand infusion for 30 minutes. The infusion was continuously collected through the great saphenous cannulation and a closed loop was confirmed by angiogram. The limb was flushed with heparin and saline solution. Infusion catheter was extracted and the great saphenous vein was ligated. Blood cuff was removed, arterial flow was re-established, and a postprocedural arteriogram confirmed successful revascularization. This method may be an alternative to microtibial embolectomy at the foot ankle level after severe lower limb embolization after acute open repair of a ruptured abdominal aortic aneurysm.

Fenestrated and branched endografts for the treatment of thoracoabdominal aortic aneurysms: a systematic review.

PURPOSE: To offer a critical review of the current literature on the use of fenestrated and branched stent-grafts in patients with thoracoabdominal aortic aneurysms (TAAA). METHODS: A thorough search of the English-language literature published between January 2000 and September 2009 identified reports of endovascular procedures using fenestrated and/or branched endografts as the intended repair strategy in patients with TAAA. Studies were selected based on specific inclusion criteria: (1) >3 high-risk patients with preoperative diagnosis of TAAA, (2) the intended treatment strategy was an endovascular repair using a fenestrated or branched endograft or both, and (3) patient demographics and outcome data (technical success rate, 30-day mortality, and follow-up length) were clearly stated. From 47 articles initially identified, 7 studies were included in the statistical analysis encompassing 155 patients (mean age 74.4 years, range 41-86) with TAAA averaging 69.2 mm in diameter. The mean follow-up was 11.8 months, and the majority of patients had Crawford type IV aneurysms. Outcome measures of eligible studies were tabulated and then analyzed cumulatively. RESULTS: Technical success was achieved in 94.2% (n = 146) of the 155 patients. Twenty-three (18.4%) primary endoleaks were reported. The 30-day mortality was 7.1% (n = 11), while the 1-year survival rate was 82.6% (n = 128). Three (1.9%) patients developed permanent paraplegia and 2 (1.3%) developed permanent paraparesis; renal failure was reported in 9 (5.8%). Overall follow-up mortality was 16.1% (n = 25). CONCLUSION: Endovascular treatment with fenestrated or/and branched stent-grafts is a new therapeutic option with encouraging results for patients considered unfit for conventional open repair. However, prolonged follow-up studies are needed in order to draw robust conclusions.

A systematic review of clinical prediction scores for deep vein thrombosis.

Objective Diagnosis of deep vein thrombosis remains a challenging problem. Various clinical prediction rules have been developed in order to improve diagnosis and decision making in relation to deep vein thrombosis. The purpose of this review is to summarise the available clinical scores and describe their applicability and limitations. Methods A systematic search of PubMed, MEDLINE and EMBASE databases was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance using the keywords: clinical score, clinical prediction rule, risk assessment, clinical probability, pretest probability, diagnostic score and medical Subject Heading terms: 'Venous Thromboembolism/diagnosis' OR 'Venous Thrombosis/diagnosis'. Both development and validation studies were eligible for inclusion. Results The search strategy returned a total of 2036 articles, of which 102 articles met a priori criteria for inclusion. Eight different diagnostic scores were identified. The development of these scores differs in respect of the population included (hospital inpatients, hospital outpatients or primary care patients), the exclusion criteria, the inclusion of distal deep vein thrombosis and the use of D-dimer. The reliability and applicability of the scores in the context of specific subgroups (inpatients, cancer patients, elderly patients and those with recurrent deep vein thrombosis) remains controversial. Conclusion Detailed knowledge of the development of the various clinical prediction scores for deep vein thrombosis is essential in understanding the power, generalisability and limitations of these clinical tools.

Alerts in mobile healthcare applications: requirements and pilot study.

Recent advances in mobile technologies have greatly extended traditional communication technologies to mobile devices. At the same time, healthcare environments are by nature "mobile" where doctors and nurses do not have fixed workspaces. Irregular and exceptional events are generated in daily hospital routines, such as operations rescheduling, laboratory/examination results, and adverse drug events. These events may create requests that should be delivered to the appropriate person at the appropriate time. Those requests that are classified as urgent are referred to as alerts. Efficient routing and monitoring of alerts are keys to quality and cost-effective healthcare services. Presently, these are generally handled in an ad hoc manner. In this paper, we propose the use of a healthcare alert management system to handle these alert messages systematically. We develop a model for specifying alerts that are associated with medical tasks and a set of parameters for their routing. We design an alert monitor that matches medical staff and their mobile devices to receive alerts, based on the requirements of these alerts. We also propose a mechanism to handle and reroute, if necessary, an alert message when it has not been acknowledged within a specific deadline.

Superior mesenteric artery dissection after extracorporeal shockwave lithotripsy.

The use of shockwave lithotripsy is currently the mainstay of treatment in renal calculosis. Several complications including vessel injuries have been implied to extracorporeal shockwave lithotripsy. We report an isolated dissection of the superior mesenteric artery in a 60-year-old male presenting with abdominal pain which occurred three days after extracorporeal shockwave lithotripsy. The patient was treated conservatively and the abdominal pain subsided 24 hours later. The patient's history, the course of his disease, and the timing may suggest a correlation between the dissection and the ESWL.