Leg ischaemia management collaboration (LIMb): study protocol for a prospective cohort study at a single UK centre.

INTRODUCTION: Severe limb ischaemia (SLI) is the end stage of peripheral arterial occlusive disease where the viability of the limb is threatened. Around 25% of patients with SLI will ultimately require a major lower limb amputation, which has a substantial adverse impact on quality of life. A newly established rapid-access vascular limb salvage clinic and modern revascularisation techniques may reduce amputation rate. The aim of this study was to investigate the 12-month amputation rate in a contemporary cohort of patients and compare this to a historical cohort. Secondary aims are to investigate the use of frailty and cognitive assessments, and cardiac MRI in risk-stratifying patients with SLI undergoing intervention and establish a biobank for future biomarker analyses. METHODS AND ANALYSIS: This single-centre prospective cohort study will recruit patients aged 18-110 years presenting with SLI. Those undergoing intervention will be eligible to undergo additional venepuncture (for biomarker analysis) and/or cardiac MRI. Those aged ≥65 years and undergoing intervention will also be eligible to undergo additional frailty and cognitive assessments. Follow-up will be at 12 and 24 months and subsequently via data linkage with NHS Digital to 10 years postrecruitment. Those undergoing cardiac MRI and/or frailty assessments will receive additional follow-up during the first 12 months to investigate for perioperative myocardial infarction and frailty-related outcomes, respectively. A sample size of 420 patients will be required to detect a 10% reduction in amputation rate in comparison to a similar sized historical cohort, with 90% power and 5% type I error rate. Statistical analysis of this comparison will be by adjusted and unadjusted logistic regression analyses. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the UK National Research Ethics Service (19/LO/0132). Results will be disseminated to participants via scientific meetings, peer-reviewed medical journals and social media. TRIAL REGISTRATION NUMBER: NCT04027244.

Transient heparin-induced platelet activation linked to generation of platelet 12-lipoxygenase. Findings from a randomised controlled trial.

Previously we demonstrated that heparin administration during carotid endarterectomy (CEA) caused a marked, but transient increase in platelet aggregation to arachidonic acid (AA) and adenosine diphosphate (ADP), despite effective platelet cyclo-oxygenase-1 (COX-1) inhibition with aspirin. Here we investigated the metabolism of AA via platelet 12-lipoxygenase (12-LOX) as a possible mediator of the observed transient aspirin resistance, and compared the effects of unfractionated (UFH) and low-molecular-weight (LMWH) heparin. A total of 43 aspirinated patients undergoing CEA were randomised in the trial to 5,000 IU UFH (n=22) or 2,500 IU LMWH (dalteparin, n=21). Platelet aggregation to AA (4x10⁻³) and ADP (3x10⁻6) was determined, and the products of the COX-1 and 12-LOX pathways; thromboxane B2 (TXB2) and 12-hydroxyeicosatretraenoic acid (12-HETE) were measured in plasma, and in material released from aggregating platelets.Aggregation to AA increased significantly (~10-fold) following heparinisation (p<0.0001), irrespective of heparin type (p=0.33). Significant, but smaller (~2-fold) increases in aggregation to ADP were also seen, which were significantly lower in the platelets of patients randomised to LMWH (p<0.0001). Plasma levels of TxB2 did not rise following heparinisation (p=0.93), but 12-HETE increased significantly in the patients' plasma, and released from platelets stimulated in vitro withADP, with both heparin types (p<0.0001). The magnitude of aggregation to ADP correlated with 12-HETE generation (p=0.03). Heparin administration during CEA generates AA that is metabolised to 12-HETE via the 12-LOX pathway, possibly explaining the phenomenon of transient heparin-induced platelet activation. LMWH has less effect on aggregation and 12-HETE generation than UFH when the platelets are stimulated with ADP.

Combined emergency abdominal aortic aneurysm repair and valve replacement in a patient with severe aortic stenosis.

Simultaneous open surgery has been advocated in the elective management of abdominal aortic aneurysm patients with significant ischemic heart disease, as staged procedures risk worsening myocardial ischemia or aortic rupture, depending on which is the first intervention. The argument for combined aneurysm and valve repair is less established. We describe the case of a 70-year-old female who while awaiting aortic valve replacement suffered rupture of an abdominal aortic aneurysm. The patient was successfully managed with emergency combined open abdominal aortic aneurysm repair and open aortic valve replacement. We would advocate that such a strategy be considered as a salvage technique in similarly difficult management dilemmas.

Periaortic inflammation after endovascular aneurysm repair.

BACKGROUND: The periaortitis seen with inflammatory abdominal aortic aneurysms usually resolves after repair by both open and endovascular techniques. Conversely, the de novo development of retroperitoneal fibrosis after endovascular aneurysm repair (EVAR) has also been rarely described, and we present a case and also review the literature. METHODS AND RESULTS: A 63-year-old man underwent EVAR for an asymptomatic, noninflammatory abdominal aortic aneurysm, presenting 9 months subsequently with left loin pain, raised inflammatory markers, and radiological evidence of periaortic inflammation causing significant left ureteric obstruction. Ureteric stenting resolved the hydronephrosis, and the periaortitis improved with combination of steroid and tamoxifen therapy. CONCLUSION: Periaortitis causing renal impairment after EVAR is a rare complication. Prompt recognition and ureteric stenting helps to prevent long-term renal damage. Steroid and tamoxifen therapy is recommended to treat and avoid recurrence of periaortitis.

Bile duct "clip-stones"--why a stitch in time could save nine.

A 32 year old female patient underwent laparoscopic cholecystectomy and in the post-operative phase was investigated after developing obstructive jaundice. ERCP revealed a stenosis at the junction of the cystic and common hepatic ducts and this was seen to be directly adjacent to the clips which had been used to ligate the cystic duct. The stricture was easily dilated with a balloon and all her symptoms improved and her liver function tests returned to normal. Eight years later she represented with a mid-common bile duct calculus. An ERCP was performed but the stone could not be dislodged or retrieved and when removed subsequently at open exploration it was found to have precipitated around two metal clips, which had migrated into the lumen of the common bile duct. We propose that the risk of this rare, yet previously reported complication, could be reduced by heeding the longstanding recommendation that only absorbable material be used in biliary surgery, and particularly when there is a short cystic duct.

"Masson's pseudoangiosarcoma" in a popliteal aneurysm: tumor or thrombus? Cause or effect?

A 44-year-old male presented to our vascular surgery unit with a partially thrombosed 22 mm popliteal aneurysm giving rise to progressive distal ischemia. Microscopy of embolus retrieved from the posterior tibial artery at bypass surgery revealed the unexpected finding of intravascular papillary endothelial hyperplasia (Masson's pseudoangiosarcoma).

Axillomesenteric bypass: an unusual solution to a difficult problem.

A 49-year-old woman presented with acute anuric renal failure and severe hypertension. Imaging revealed occlusion of the distal thoracic and abdominal aorta. Acute hemodialysis and reduction in blood pressure precipitated an acute exacerbation of previously undiagnosed mesenteric ischemia. Repeated episodes of flash pulmonary edema and a generally parlous clinical condition precluded thoracoabdominal reconstruction. As a result, a left axillomesenteric bypass was performed as a substitute, using a 6-mm externally ringed PTFE graft. She made an uneventful recovery, and her abdominal symptoms resolved swiftly. The patient remains symptom-free 12 months postoperatively. In this rare situation, extra-anatomic bypass provided an unorthodox but less-invasive solution to a difficult surgical problem.