Anticoagulation in embolic acute limb ischaemia-an observational study.

The management of embolic acute limb ischaemia commonly involves determining aetiology and performing emergency invasive procedures. This detailed study aimed to determine the impact of manipulation of anticoagulation in the aetiology of emboli in acute limb ischaemia and determine the efficacy of primary anticoagulation therapy vs. invasive interventions. Material and methods: Data collection was conducted at a single institution on a cohort of patients presenting consecutively with embolic acute limb ischaemia over one year. Two groups were compared, one receiving anticoagulation as primary therapy with those undergoing invasive treatment as the internal comparison group. Results: A likely haematological causation was identified in 22 of 38 presentations, related to interruption of anticoagulation in cardiac conditions, the majority atrial fibrillation (n=12), or hypercoagulable states (n=10). Limb salvage was pursued in 36 patients employing anticoagulation (n=19) or surgical embolectomy (n=17) as the primary therapy in upper and lower limbs (n=17 vs n=19 respectively). Despite delays often well beyond six hours and a range of ischaemic severity in both groups, 35 of 36 patients achieved full or substantive restoration of function with improved perfusion. Regarding anatomical distribution of arterial disease and therapy, three patients with multi-level disease proceeded to embolectomy following anticoagulation. Embolectomy was undertaken most often for proximal emboli and more profound paralysis. Conclusions: Anticoagulation and coagulopathy are commonly implicated in the aetiology of arterial emboli, with omission of effective anticoagulation in atrial fibrillation being associated in almost 1/3 of presentations. Whilst more profound limb paralysis and proximal or multi-level disease tended to be managed surgically, primary anticoagulation therapy alone or with a secondary embolectomy was effective across the spectrum of ischaemia severity and despite significant delays beyond guideline recommendations.

Coil Embolization of Femoral Pseudoaneurysms in Intravenous Drug Users: An Additional Treatment Modality.

BACKGROUND: This report describes our centers' experience of a new approach using coil embolization for femoral pseudoaneurysms (PSAs) in intravenous drug users (IVDUs). Current treatment options for this challenging patient group include femoral/external iliac artery ligation and excision of the PSA, with or without revascularization. Radiological thrombin injection, endoluminal stent grafting, and coil embolization have not been widely studied in this patient group and are most commonly reserved for sterile PSAs. METHODS: A series of 6 patients who presented to the vascular surgical department with IVDU-related PSA were treated with coil embolization. We present here their clinical course and outcomes. Ethical approval was not required. RESULTS: Coil embolization alone did not result in a satisfactory outcome. Thirty-three percent of patients required vessel ligation following their initial treatment with coil embolization. However, all patients initially managed with coil embolization, whether as a definitive treatment or temporizing measure to surgery, were discharged home, mobilizing well, with Doppler signals at the ankle. Postoperative claudication was present in 17% of patients. There were no amputations as a direct result of coil embolization. The amputation in this series resulted from triple-vessel ligation without revascularization in a patient mistaken as having a groin abscess. CONCLUSIONS: Coil embolization is a potential, less invasive treatment option in selected cases of IVDU PSA. It offers an alternative therapeutic intervention, adding to the armamentarium available to tackle these often challenging patients.

Approaches for Identifying Novel Targets in Precision Medicine: Lessons from DNA Repair.

Genome stability is maintained by a number of elegant mechanisms, which sense and repair damaged DNA. Germline defects that compromise genomic integrity result in cancer predisposition, exemplified by rare syndromes caused by mutations in certain DNA repair genes. These individuals often exhibit other symptoms including progeria and neurodegeneration. Paradoxically, some of these deleterious genetic alterations provide novel therapeutic opportunities to target cancer cells; an excellent example of such an approach being the recent development of poly (ADP-ribose) polymerase inhibitors as the first 'synthetic lethal' medicine for patients with BRCA-mutant cancers. The therapeutic exploitation of synthetic lethal interactions has enabled a novel approach to personalised medicine based on continued molecular profiling of patient and tumour material. This profiling may also aid clinicians in the identification of specific drug resistance mechanisms following relapse, and enable appropriate modification of the therapeutic regimen. This chapter focuses on therapeutic strategies designed to target aspects of the DNA damage response, and examines emerging themes demonstrating mechanistic overlap between DNA repair and neurodegeneration.

Thromboprophylaxis prescribing among junior doctors: the impact of educational interventions.

BACKGROUND: Venous thromboembolism (VTE) prophylaxis in an important aspect of the care of hospitalised patients, for which the National Institute for Health and Care Excellence (NICE) has issued guidance. Guidance compliance continues to be a concern. Junior doctors are the main group responsible for prescribing thromboprophylaxis. We aimed to compare local pharmacological thromboprophylaxis prescribing against NICE guidelines in a surgical department at a district general hospital, and determine whether interventions aimed at improving compliance were effective. METHODS: Over four months, a two cycle audit of prescribing patterns for VTE prophylaxis was performed using data collected at four intervals: 1. Baseline 2. Following pro-forma introduction and feedback 3. A second baseline data collection. 4. Following VTE prophylaxis teaching. RESULTS: A total of 394 admissions were included. Correct identification and prescribing for at-risk patients ranged between 76 and 93 %, whilst risk assessment documentation and explanation to patients occurred in fewer than 50 and 66 % respectively. Prescribing and risk assessment improved in the first cycle (chi2 = 6.75, p = 0.009 and chi2 = 10.70, p = 0.001 respectively), a consequence of one specialty improving following additional feedback. Teaching was not associated with improvements. Overall compliance with NICE guidelines was achieved in no more than 25 % of admissions. CONCLUSIONS: Despite junior doctors generally prescribing VTE thromboprophylaxis appropriately, overall compliance with guidelines remained poor regardless of educational interventions. Verbal feedback was the only intervention associated with modest improvements. A pressurised work environment may limit the impact of educational interventions. Guidance simplification or devolving responsibility to other members of staff may improve compliance.

The influence of connective tissue disease in the management of lower limb ischemia.

INTRODUCTION: Vascular intervention for patients with connective tissue disease (CTD) and symptomatic limbs, particularly with tissue loss, is associated with poor outcomes. The aims of our study were to compare outcomes from arterial interventions for patients with CTD versus overall results for our unit and analyse available baseline patient characteristics to determine whether any features were associated with poor prognosis. METHODS: We retrieved data from a prospectively maintained database of all patients undergoing interventions on the vascular unit since 1984. The database included coding for CTD and tissue loss at presentation. Information was retrieved for each patient with CTD identified for a period of 2 years postoperatively. Additional data were retrieved from patient's notes. RESULTS: CTD was identified in 23 patients, 12 men and 11 women, with a median age of 68 years (range 42-84). The majority of patients suffered from rheumatoid arthritis. Of 13 patients who presented with peripheral arterial disease (PAD) and associated tissue loss, 12 underwent arterial procedures, and 1 had a primary amputation. Of 5 endovascular procedures performed, 4 failed, 2 immediately and 2 subsequently. Seven patients had major amputations at 6 months. At 2 years, 11 of 13 patients (84.6%) had major amputations, and of the remaining 2, 1 had persisting ulceration. In comparison, of the 10 patients presenting with critical limb ischemia without tissue loss, there was 1 amputation, which occurred at 12 months, and 1 patient died, a limb loss/death rate at 24 months of 20%. A backward binary logistic regression analysis showed that neither gender nor age had a significant effect in predicting limb loss, but tissue loss at presentation was associated with a significantly higher rate of amputation. CONCLUSIONS: Patients with CTD and PAD who present with lower limb tissue loss appear to be at greater risk of limb loss after vascular intervention compared with the general vascular population managed by our unit. CTD patients with no tissue loss had outcomes comparable to the general vascular population. We suggest that the management of patients with CTD and PAD presenting with lower limb tissue loss should include focused, aggressive treatment of underlying inflammation and nutrition.

Data recording aids in acute admissions.

PURPOSE: Clinical data capture and transfer are becoming more important as hospital practices change. Medical record pro-formas are widely used but their efficacy in acute settings is unclear. This paper aims to assess whether pro-forma and aide-memoire recording aids influence data collection in acute medical and surgical admission records completed by junior doctors. DESIGN/METHODOLOGY/APPROACH: During October 2007 to January 2008, 150 medical and 150 surgical admission records were randomly selected. Each was analysed using Royal College of Physicians guidelines. Surgical record deficiencies were highlighted in an aide-memoire printed on all A4 admission sheets. One year later, the exercise was repeated for 199 admissions. FINDINGS: Initial assessment demonstrated similar data capture rates, 77.4 per cent and 75.9 per cent for medicine and surgery respectively (Z = -0.74, p = 0.458). Following the aide-memoire's introduction, surgical information recording improved relatively, 70.5 per cent and 73.9 per cent respectively (Z = 2.01, p = 0.045). One from 11 aide-memoire categories was associated with improvement following clinical training. There was an overall fall in admission record quality during 2008-9 vs 2007-8. RESEARCH LIMITATIONS/IMPLICATIONS: The study compared performance among two groups of doctors working simultaneously in separate wards, representing four months' activity. PRACTICAL IMPLICATIONS: Hospital managers and clinicians should be mindful that innovations successful in elective clinical practice might not be transferable to an acute setting. ORIGINALITY/VALUE: This audit shows that in an acute setting, over one-quarter of clinical admission data were not captured and devices aimed at improving data capture had no demonstrable effect. The authors suggest that in current hospital practice, focussed clinical training is more likely to improve patient admission records than employing recording aids.

A diabetic foot service established by a department of vascular surgery: an observational study.

BACKGROUND: The mechanism by which the multidisciplinary approach to diabetic foot disease reduces amputation rates is unclear. Ischemia, sepsis, and necrosis represent aspects of severe diabetic foot disease amenable to intervention. In 2006, a vascular unit introduced a rapid access service for severe foot disease, augmenting the established community provision. This study aimed to determine whether concurrent changes in amputation rates were observed, and to identify areas that may have influenced outcomes. METHODS: Unit data prospectively collected during 4 years for patients with lower-limb disease were compared with data retrieved over 2 years before the foot service. Outcome measurements were major amputations, foot surgery, vascular interventions, admissions, and length of stay. RESULTS: Major amputation rates associated with diabetes peaked in 2005 at 24.7/10,000 vs. 1.07/10,000 in 2009; (relative risk = 0.043, 95% confidence interval = 0.006-0.322). The proportion of diabetic to nondiabetic amputations decreased; foot surgery rates also dropped (53.7/10,000 in 2006 vs. 7.5/10,000 in 2009). The number of open revascularization procedures decreased, but the rates of endovascular procedures remained generally constant. Hospital admission rates decreased after initially peaking, and the length of stay was unchanged (16 vs. 15.5 days in 2004 and 2009, respectively). CONCLUSIONS: The integration of a vascular unit with community care has been associated with improved outcomes for patients with diabetic foot disease. Improvements were not related to the increased number of vascular procedures or hospitalizations, but did coincide with a greater proportion of patients attending the foot unit. The referral of patients to the unit facilitates the rapid management of severe disease, reducing delays deleterious to outcomes.

Improved limb salvage for patients with vascular disease and tissue loss associated with new model of provision targeted at the diabetic foot.

AIMS: The establishment of a vascular surgeon-led emergency diabetic foot service in 2006 has evolved to provide lower limb wound care for patients with and without diabetes. We aimed to determine whether the service was associated with sustained, improved limb salvage rates for the whole population, analyse key aspects of service provision and compare outcomes against published studies. METHODS: The vascular unit serves a largely rural population of approximately 240,000. Data was collected prospectively on lower limb amputations, arterial and minor surgical interventions from 2006 to 2015, and retrospectively retrieved for 2004-2005, prior to service commencement. Data was also collected on referral patterns, volume of patient admissions and attendances, and delays. Lower limb amputation rates were compared against published data and analysis of admission trends and delays employed non-parametric tests. RESULTS: Age/gender adjusted major lower limb amputations for the populations with and without diabetes were 412/100,000 in 2004 and 15/100,000 in 2005 respectively. Following service introduction, major amputations reduced and since 2012 have been sustained at between 15-44/100,000 and 1-3/100,000 for patients with and without diabetes respectively, comparing favourably with published data. Vascular interventions have remained static, but referrals of patients directly to the service and numbers of minor procedures have increased. CONCLUSIONS: The sustained decreases in all major lower limb amputations that have coincided with the development of a core team approach to providing rapid access and comprehensive care for patients with emergency diabetic foot problems may indicate that this service design benefits patients with and without diabetes.

C-Branched pyrrolidines from 2-C-acetylmethyl-glycosylazides. Reduction of imines formed by monosaccharide ring opening.

Reduction of the protected 2-C-acetylmethyl-beta-glucopyranosyl azide derivative 1 produced the corresponding beta-glucosylamine 3. Rather than forming a conformationally strained 1,2-trans-fused bicyclic imine, we propose that the beta-glycosylamine underwent anomerization to an acyclic imine (4) followed by an intramolecular ring closure by the 5-hydroxy group. The resultant 2-C-acetylmethyl-alpha-glucopyranosylamine 5, which possesses the 1,2-cis-configuration was immediately converted to a bicyclic imine (2) in excellent yield. Attempts to selectively reduce the C=N double bond of 2 using sodium borohydride and cyanoborohydride failed to produce bicyclic amine 6. Instead, compound 6 underwent another ring-opening elimination and further reduction to produce a C-branched pyrrolidine (8) in good yield. Catalytic hydrogenation of 1 and 2 also provided the C-branched pyrrolidine (10).

An evaluation of the efficacy of methods used in screening for lower-limb arterial disease in diabetes.

OBJECTIVE: Foot-related disease is the most common cause for hospital admission among the diabetic population. Lower-limb peripheral arterial occlusive disease (PAOD) is a major risk factor in diabetic foot disease. Screening for PAOD commonly includes foot pulses and the ankle-brachial pressure index (ABPI) and/or the toe-brachial pressure index (TBI), but concerns persist regarding their accuracy. We evaluated the efficacy of several commonly used screening methods in different subject populations. RESEARCH DESIGN AND METHODS: We studied 130 limbs in 68 individuals with no critical ischemia over 8 months. Limbs were grouped on the basis of the presence or absence of diabetes, clinically detectable peripheral neuropathy, and PAOD identified on color duplex imaging. Comparative analyses of foot pulses, the ABPI, the TBI, and distal Doppler waveform analysis were performed. RESULTS: Foot pulses, the TBI, and qualitative waveform analyses were highly sensitive screening methods in individuals with and without diabetes. However, detectable peripheral neuropathy was associated with a reduced sensitivity and poor specificity of foot pulses, a reduction in sensitivity of the ABPI (71 to 38%), and a reduction in specificity of the TBI (81 to 61%) and qualitative waveform analysis (96 to 66%). Quantitative analysis failed to detect disease with severely damped and low-intensity signals. CONCLUSIONS: Screening tools that are effective in screening for lower-limb PAOD in the nondiabetic population are less efficacious in diabetes, particularly in the presence of detectable peripheral neuropathy. Qualitative waveform analysis and the TBI were demonstrated to be more effective screening methods than the ABPI and foot pulses particularly in high-risk limbs with detectable peripheral neuropathy.

Welsh Surgical Society Spring Meeting, 6-7 May 2010.

The 55th meeting of the Welsh Surgical Society was held at the Education Centre, Nevill Hall Hospital, Abergavenny. The prize medals were announced and presented to Simon Weaver (Registrar prize and his second Welsh Surgical Society prize) and Rachel Pollock (Junior prize) by Mr P Braithwaite, former President of the Society. Six of the best were chosen from 34 abstracts selected for presentation at the meeting.

Triazole-fused sugars from nitroalkene-containing C-glycosides by a tandem 1,3-dipolar cycloaddition and intramolecular Michael addition.

A synthetic method to triazole-fused sugars by treatment of nitroalkene-containing C-glycosides with sodium azide is described. Initial experiments conducted at room temperature gave only the 1,3-dipolar cycloaddition products. However, at elevated reaction temperature the tandem beta-elimination/cycloaddition/Michael addition yielded 1,5-disubstituted triazole-fused sugars.

Missed diagnosis of ankle pseudoaneurysm following ankle arthroscopy: a case report.

BACKGROUND: Pseudoaneurysm formation is rare complication after arthroscopy with incidence of 0.008%, easy to misdiagnose. Its potential catastrophic sequelae should not be underestimated. CASE PRESENTATION: We present a case of missed diagnosis of traumatic anterior tibial artery pseudoaneurysm in a 39 years old female, instead treated as post operative arthroscopy infection. The diagnosis was confirmed with a duplex ultrasound scan and referred to the vascular surgeon with successful out come. CONCLUSION: In view of rare presentation this complication, it is easily missed. According to one study, incidence of anatomic variations of anterior tibial artery range from 2.4 to 12%. Because of this anatomical variation in course along with other factors, pseudoaneurysm formation at ankle is relatively high. In this report, we discuss the diagnosis, anatomical variations of anterior tibial artery and prevention of this complication following arthroscopy. We believe that surgeons operating in this region should take into account these anatomical variations preoperatively.

One-pot synthesis of highly functionalized morphans from C-glycosides.

Highly functionalized morphan derivatives were synthesized from nitroalkene 2'-(oxoalkyl)-C-glycosides by a tandem reaction that created three (two C-N and one C-C) new bonds and four stereogenic centers in a one-pot procedure under very mild conditions without the use of expensive reagents. The transformation was achieved from a beta-elimination/Michael addition cascade, followed by Michael addition of the amine and intramolecular enamination. In the presence of sodium cyanoborohydride the iminium intermediate was reduced in situ to afford the desired morphans.

Synthesis of iminoalditol analogues of galactofuranosides and their activities against glycosidases.

Iminoalditol analogues of galactofuranosides were synthesized from 1-C-(2'-oxo-propyl)-1,4-dideoxy-1,4-imino-d-galactosides and different amines by reductive amination, followed by removal of protecting groups. The activity of these compounds against galactosidases and other glycosidases was investigated. The best inhibitor against beta-galactosidase (bovine liver) is a diastereomeric mixture of an iminoalditol (10h), which contains a hydrophobic hexadecyl aglycon (R=C(16)H(33)), whereas no significant inhibitory activity was observed with compounds having a hydrophilic aglycon. Surprisingly, activation of alpha-galactosidase (coffee bean) by 10h was also observed. Because these results were obtained from a mixture of iminoalditols, the inhibition and activation of glycosidases could result from different diastereomers.

The influence of diabetes and lower limb arterial disease on cutaneous foot perfusion.

OBJECTIVE: Peripheral arterial occlusive disease and peripheral neuropathy are major risk factors in diabetic foot disease. We evaluated the relative influences of noncritical lower limb arterial disease and peripheral neuropathy on cutaneous foot perfusion in diabetes. METHOD: Toe-brachial pressure indices, transcutaneous oxygen, and carbon dioxide tensions at foot and chest sites were measured in individuals with diabetes, with or without detectable peripheral neuropathy and with or without significant arterial disease on color duplex imaging. Subjects without diabetes, with and without arterial disease, were used as controls. RESULTS: A total of 130 limbs were studied during an 8-month period. Toe-brachial pressure indices reflected the presence of arterial disease in all groups. Foot transcutaneous oxygen values were reduced in diabetes and correlated with chest transcutaneous oxygen values. Low foot transcutaneous oxygen with elevated transcutaneous carbon dioxide values were only demonstrated in individuals with diabetes, arterial disease, and peripheral neuropathy. Toe-brachial pressure indices demonstrated a positive correlation with foot transcutaneous oxygen values, but values >1.2 demonstrated a negative correlation. CONCLUSIONS: We demonstrated two influences on cutaneous foot perfusion in diabetes: (1) a global microcirculatory dysfunction, reflected in low chest and foot transcutaneous oxygen values, and (2) macrovascular disease as indicated by reduced toe-brachial pressure indices and foot transcutaneous oxygen values. Further, the results demonstrated that in diabetic individuals without critical limb ischemia, impaired foot perfusion secondary to arterial disease is amplified significantly by coexisting microcirculatory disease.

New treatments for diabetic neuropathic foot ulceration: views from a wound healing unit.

The management of diabetic foot ulceration remains problematic despite advances in treatments. The evidence for many treatments is lacking and clinical experience remains important. Current diabetic foot ulcer management and an evaluation of new therapies are discussed. Research in wound healing and diabetic foot disease can complement each other in accurately evaluating and treating diabetic foot ulceration. This would aid in formulating personalized therapies, tailoring treatments to optimize the ulcer healing environment.