Re-amputation and survival following toe amputation: outcome data from a tertiary referral centre.

PURPOSE: Toe amputation is a commonly performed procedure for irreversible foot sepsis. However, outcome and predictors of outcome are poorly understood. Our aim was to determine survival and rate of progression to further amputation following index toe amputation. METHODS: Consecutive patients between 2010 and 2015 were included. Progression to further minor amputation, major amputation or death was recorded. Multivariable Cox regression analyses were undertaken to determine independent predictors of outcome and survival. RESULTS: One hundred forty-six patients were included, with mean age of 65 years. Fifty-five (37.7%) patients underwent hallux amputation, while 91 (62.3%) underwent amputation of non-hallux digit(s). Following index toe amputation, 63 (43.2%) patients progressed to further minor or major ipsilateral amputation, median time to which was 36 months. Twenty-one patients (14.4%) progressed to major ipsilateral amputation. Patients undergoing index non-hallux amputation were significantly more likely to require further minor amputation (P = 0.050); however, the rate of major amputation between hallux (14.5%) and non-hallux (14.3%) groups was similar. Overall, 5-year ipsilateral amputation-free (iAFS) was 39.6 ± 4.1%, ipsilateral major amputation-free (iMAFS) was 55.9 ± 4.1% and overall survival (OS) was 64.3 ± 4.0% and did not differ between index amputation sites. CONCLUSION: Almost half of patients undergoing toe amputation required further digital amputation. However, limb preservation rates are high, and a majority of patients are alive at 5-year follow-up. There was no significant difference in outcome between patients undergoing hallux and non-hallux primary procedures. Overall, increasing age remains the only independent predictor of iMAFS and OS.

Diagnostic Performance of Ankle-Brachial Pressure Index in Lower Extremity Arterial Disease.

Introduction Ankle-brachial pressure indices (ABIs) continue to form the basis of diagnostics for lower extremity arterial disease (LEAD). However, there remains a paucity of data to support its accuracy. This study aims to evaluate its diagnostic sensitivity and specificity using established arterial-imaging modalities as a benchmark. Methods In this retrospective study, a regional, prospectively maintained, vascular laboratory database was interrogated to identify referred patients with arterial disease who underwent concomitant assessment with ABI and lower limb arterial duplex ultrasound (DUS). Duplex acted as the reference standard. Those who had peripheral computed tomography angiogram (CTA) within 3 months of initial assessment were included in a subgroup analysis to correlate ABI with CTA. The primary end point was the sensitivity and specificity of ABI compared with DUS as the reference standard. Results Concomitant assessment was performed in 438 limbs (250 patients) over a 27-month period. The ABI was normal (0.9 to 1.4) in 196 limbs (44.9%) and abnormal in the remaining 241 limbs (55.1%). False-positive results occurred in 83 out of 241 limbs (34.4%), and false-negative results occurred in 54 limbs out of 196 (27.5%). True-positive results were 158 out of 241 limbs (65.6%), whereas true-negative results were 142 out of 196 limbs (72.4%). ABI using DUS as a benchmark identified a sensitivity for peripheral artery disease of 72.3% and a specificity of 69.3%. Concomitant CTA imaging was available in 200 limbs. The sensitivity and specificity of ABI correlated with CTA were 65.5 and 68.8%, respectively. Conclusion ABIs have a moderate predictive value in the diagnosis of LEAD. Normal range outcomes cannot be taken to infer the absence of LEAD and, as such, further arterial imaging in the form of DUS or angiography should be strongly considered in those with suspected underlying disease requiring intervention. Further noninvasive tests such as exercise studies or pulse volume waveforms should be considered, if diagnostic uncertainty exists, in those requiring nonoperative intervention and risk factor control.

Investigating the Potential and Pitfalls of EV-Encapsulated MicroRNAs as Circulating Biomarkers of Breast Cancer.

Extracellular vesicles (EVs) shuttle microRNA (miRNA) throughout the circulation and are believed to represent a fingerprint of the releasing cell. We isolated and characterized serum EVs of breast tumour-bearing animals, breast cancer (BC) patients, and healthy controls. EVs were characterized using transmission electron microscopy (TEM), protein quantification, western blotting, and nanoparticle tracking analysis (NTA). Absolute quantitative (AQ)-PCR was employed to analyse EV-miR-451a expression. Isolated EVs had the appropriate morphology and size. Patient sera contained significantly more EVs than did healthy controls. In tumour-bearing animals, a correlation between serum EV number and tumour burden was observed. There was no significant relationship between EV protein yield and EV quantity determined by NTA, highlighting the requirement for direct quantification. Using AQ-PCR to relate miRNA copy number to EV yield, a significant increase in miRNA-451a copies/EV was detected in BC patient sera, suggesting potential as a novel biomarker of breast cancer.

Patients referred for arteriovenous fistula construction: a retrospective outcome analysis.

OBJECTIVES: With lower rates of sepsis and re-interventions, arteriovenous fistula (AVF) is the preferred vascular access modality. The aim of this study is to evaluate the outcomes of patients referred for AVF construction at a single center in Cork, Ireland. METHODS: The current study is a single-center retrospective review of all patients who underwent AVF creation between 2015 and 2017. Additionally, the kidney disease clinical patient management system was used to provide statistics on AVF use in Ireland. RESULTS: 39.3% of hemodialysis patients in Ireland use an AVF for vascular access. Regional use ranged from 50 to 20% across Irish hemodialysis centers. At Cork University Hospital, 192 AVFs were created. The population was 69.3% male (n = 133), 30.7% female (n = 59) with a mean (±SEM) age of 58.8 ± 1.03 years. 69.5% of females received a brachiocephalic AVF (BCAVF) while 13.6% had a radiocephalic AVF (RCAVF) constructed. Significance was seen when comparing gender and AVF type (p < 0.001). Fifty-four percent of the fistulae were brachiocephalic (n = 103), 33% were radiocephalic (n = 63), and 4% were brachiobasilic (n = 8). BCAVF patients (62.7 ± 1.2 years) were significantly older than patients receiving a RCAVF (54.5 ± 1.9 years, p < 0.001). A post-operative thrill or continuous flow on Doppler was present in 99% of patients (n = 190) with maturation and complication rates of 82.7% (n = 153) and 5.7% (n = 11) respectively. 69.9% of AVFs were needled for hemodialysis (n = 114). CONCLUSIONS: AVF outcomes at this center are consistent with reported statistics in the literature. Patient age, sex, and diabetic status may influence the use of proximal AVF. AVF creation rates in Ireland are below international reported recommendations.

Compression therapy following ClariVein® ablation therapy: a randomised controlled trial of COMpression Therapy Following MechanO-Chemical Ablation (COMMOCA).

BACKGROUND: Endovenous treatment of varicose veins has increased in popularity over the last decade. There remains, however, a degree of uncertainty regarding the role of compression bandaging or hosiery following this intervention. The National Institute for Clinical Excellence Guideline Development Group has advocated further research to evaluate the clinical and cost-effectiveness of this post-procedure intervention. In addition to this, the duration of compression bandaging also warrants clarification. METHODS: Ethical approval for the study was obtained from the Singhealth Centralised Institutional Review Board (CIRB Ref: 2017/2710). Consent to enter the study will be sought from each participant only after a full explanation has been given, an information leaflet offered and time allowed for consideration. Signed participant consent will be obtained. Patients will be randomised to either compression (group A) or no compression (group B). The primary aim of the study is to assess the patient's pain scores for the first 10 days post procedure using a visual analogue scale. Secondary aims include an assessment of patient compliance with compression, quality of life scores, clinical effectiveness, rates of bruising and phlebitis, time taken to return to normal activities, patient satisfaction and occlusion rate at 6 months. DISCUSSION: The purpose of this study is to examine the effect of compression therapy in patients having mechano-chemical ablation (MOCA) therapy for truncal incompetence of their varicose veins using the ClariVein® device. This study may provide clarification on the role of compression therapy in patients undergoing MOCA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03685838. Registered on 26 September 2018.

The changing cost of breast cancer care: lessons from a centralised modern cancer centre.

BACKGROUND: The cost of new cancer technologies has been the subject of intense debate in recent years. There have been significant advances in therapeutic techniques for breast cancer over the past 20 years. This has been accompanied by the concentration of services in designated cancer centres. The aim of this study was to examine the changing cost of breast cancer management over an 18-year period and identify factors underlying this. METHODS: We use breast cancer services data from Galway University Hospital in 1995-1996, 2005-2006 and 2011-2012 to examine the changing pattern of care costs and survival. RESULTS: The number of patients treated for breast cancer rose from 200 in 1995-1996, to 411 in 2005-2006 and 563 in 2011-2012. Two-year survival rose in line with national figures from 84 to 89.78 and 92.07%, in the three-time periods respectively. Adjusting for inflation, the average cost per patient rose from €14,710 (95% C.I., €13,398 to €16,022) in 1995-1996 to €30,405 (95% C.I., €38,620 to €32,189) in 2005-2006, before falling to €14,458 (C.I., €13,343 to €15,572) in 2011-2012. We found significant changes in the pattern of costs, with some rising in relative and absolute terms while others fell as new therapies became available and/or moved off patent. CONCLUSION: Within an evolving context where services are centralised, new therapies emerge and subsequently come off patent, our understanding of the value of cancer therapies continues to evolve. This has important implications for the evaluation of new therapies and broader policy initiatives in this area.

Exosome-encapsulated microRNAs as circulating biomarkers for breast cancer.

Breast cancer is a highly prevalent disease, accounting for 29% of invasive cancers in women. Survival from this disease depends on the stage at diagnosis, with patients who are detected earlier having more favourable outcomes. It is because of this that research groups are focusing on the development of a blood-based biomarker for breast cancer. Such biomarkers may facilitate the detection of breast cancer in its infancy before it has spread beyond the primary site. MicroRNAs (miRNAs) have shown immense potential in this setting. These short, non-coding RNA sequences have been shown to be dysregulated in breast cancer. Despite showing immense promise, miRNAs have not been successfully implemented in the clinical setting due to a lack of a standardised approach which has resulted in conflicting results. These challenges may be addressed at least in part through the study of exosomes. The biomarker potential for exosomes holds huge promise and may revolutionise the way in which we diagnose and manage breast cancer. These nanovesicles may be isolated from a variety of bodily fluids, including serum, and their miRNA content has been shown to reflect that of the parent breast cancer cell. This review will highlight the nomenclature and defining characteristics of exosomes, and current methods of isolation of serum-derived exosomes. Initial promising reports on the potential utility of exosomal miRNAs to be used as breast cancer biomarkers will also be addressed.