Ultrasound screening for abdominal aortic aneurysm in high-risk women.

BACKGROUND: Population-wide ultrasound screening programmes for abdominal aortic aneurysm (AAA) for men have already been established in some countries. Women account for one third of aneurysm-related mortality and are four times more likely to experience an AAA rupture than men. Whole-population screening for AAA in women is unlikely to be clinically or economically effective. The aim of this study was to determine the outcomes of a targeted AAA screening programme for women at high risk of AAA. METHOD: Women aged 65-74 years deemed at high risk of having an AAA (current smokers, ex-smokers, or with a history of coronary artery disease) were invited to attend ultrasound screening (July 2016 to March 2019) for AAA in the Female Aneurysm screening STudy (FAST). Primary outcomes were attendance for screening and prevalence of AAA. Biometric data, medical history, quality of life (QoL) and aortic diameter on ultrasound imaging were recorded prospectively. RESULTS: Some 6037 women were invited and 5200 attended screening (86.7 per cent). Fifteen AAAs larger than 29 mm were detected (prevalence 0.29 (95 per cent c.i. 0.18 to 0.48) per cent). Current smokers had the highest prevalence (0.83 (95 per cent c.i. 0.34 to 1.89) per cent) but lowest attendance (75.2 per cent). Three AAAs greater than 5.5 cm were identified and referred for consideration of surgical repair; one woman underwent repair. There was a significant reduction in patient-reported QoL scores following screening. CONCLUSION: A low prevalence of AAA was detected in high-risk women, with lowest screening uptake in those at highest risk. Screening for AAA in high-risk women may not be beneficial.

Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting.

This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.

Shear Wave Elastography May Be Superior to Greyscale Median for the Identification of Carotid Plaque Vulnerability: A Comparison with Histology.

PURPOSE: There is a need to develop methods that reliably quantify characteristics associated with vulnerable carotid plaque. Greyscale median (GSM) and shear wave elastography (SWE) are two techniques that may improve individual plaque risk stratification. SWE, which quantifies Young's Modulus (YM) to estimate tissue stiffness, has been researched in the liver, breast, thyroid and prostate, but its use in carotid plaques is novel. MATERIALS AND METHODS: The aim of this study was to quantify YM and GSM of plaques and compare to histology. 25 patients (64% male) with a mean age of 76 underwent both clinical and SWE imaging. The mean GSM was quantified over a cardiac cycle. The mean YM was quantified in multiple regions within the plaque over 5 frames. Histological features were assessed following carotid endarterectomy. RESULTS: The mean YM of unstable plaques was significantly lower than that of stable plaques (50.0 kPa vs. 79.1 kPa; p = 0.027). The presence of intra-plaque hemorrhage, thrombus and increasing numbers of foam cells was also associated with a significantly lower YM. Plaque YM did not correlate well with plaque GSM (r =  .12). The mean plaque GSM was the same in both unstable and stable plaques. Fibrous plaques had a significantly higher GSM (p = 0.036). CONCLUSION: In conclusion, SWE provides additional information on plaque stiffness which may be of clinical benefit to help identify vulnerable plaque, and warrants further study.

A Novel Ultrasound-Based Carotid Plaque Risk Index Associated with the Presence of Cerebrovascular Symptoms.

PURPOSE: The purpose of this study was to determine the efficacy of a novel ultrasound-based carotid plaque risk index (CPRI) in predicting the presence of cerebrovascular symptoms in patients with carotid artery stenosis. MATERIALS AND METHODS: This was a cross-sectional, observational study involving 56 patients (mean age 76.6 years, 62.5 % male). Plaque grayscale median (GSM) and surface irregularity indices (SII) were measured in 82 stenosed carotid arteries (range 10 - 95 %) and combined with the degree of stenosis (DOS) in the form of (DOS*SII)/(1 + GSM). A reduced index DOS/(1 + GSM) not incorporating plaque surface irregularities was also investigated. Receiver operating characteristic curves (ROC) were used to study the diagnostic efficacy of CPRI, comparing against DOS and an equivalent risk index constructed using a conventional logistic regression based method with model parameters optimized to the dataset (CPRIlogistic). RESULTS: There were 42 stenosed carotid arteries with cerebrovascular symptoms, and 40 without symptoms. The presence of symptoms significantly correlated with DOS, GSM and SII (p < 0.01). The median CPRI of the symptomatic (asymptomatic) groups were 23.2 (9.2) compared with 0.71 (0.30) for CPRIlogistic (p < 0.01). The diagnostic performance of CPRI exceeded that of CPRIlogistic and DOS, and demonstrated a better separation of the symptomatic and asymptomatic groups. CONCLUSION: Our novel risk index combines quantitative measures of carotid plaque echogenicity and surface irregularities with the degree of stenosis. It is a better predictor of cerebrovascular symptoms than the degree of stenosis and could be valuable in studies and clinical trials aimed at identifying vulnerable carotid artery stenoses.

Reprinted article "Subintimal angioplasty of femoropopliteal artery occlusions: the long-term results".

The technique of subintimal angioplasty has been attempted on 200 consecutive femoropopliteal artery occlusions of median (range) length 11 (2-37) cm. The principle of the technique is to traverse the occlusion in the subintimal plane and recanalise by inflating the angioplasty balloon within the subintimal space. The technical success rate was 159/200 (80%) and was not significantly different for occlusions <10 cm (81%, n = 73), 11-20 cm (83%, n = 63) or >20 cm (68%, n = 23), p = 0.20. There were no deaths nor limb loss resulting from the procedure. The median (range) ankle-brachial pressure index increased from 0.61 (0.21-1.0) preangioplasty to 0.90 (0.26-1.50) postangioplasty. The actuarial haemodynamic patencies of technically successful procedures at 12 and 36 months were 71% and 58% respectively, the symptomatic patencies were 73% and 61%. A multiple regression analysis showed that smoking multiplied the risk of reocclusion by 2.70 (p < 0.001), each additional run-off vessel reduced the risk by 0.54 (p < 0.001) and the risk increased by 1.73 (p = 0.020) for every 10 cm of occlusion length. In conclusion, the technical success rate (80%) of subintimal angioplasty for femoropopliteal occlusions is unrelated to occlusion length and for all procedures, including technical failures, cumulative symptomatic and haemodynamic patencies of 46 and 48% can be achieved at 3 years. The factors influencing long-term patency were smoking, the number of calf run-off vessels and occlusion length.

Ultrasound measurement of aortic diameter in a national screening programme.

OBJECTIVE: Currently there is no universally accepted standard for ultrasound measurement of abdominal aortic aneurysm (AAA). The aim was to investigate the reliability and reproducibility of inner to inner (ITI) versus outer to outer (OTO) ultrasound measurement of AAA diameter. METHODS: A prospective study design was used to collect 60 random images of aorta (1.4-7.1 cm). Inner and outer wall diameter measurements were then performed by 13 qualified AAA screening technicians and 11 vascular sonographers. RESULTS: The mean (range) diameter for all 60 aortas by ITI was 3.91 cm (1.39-6.80) and by OTO was 4.18 cm (1.63-7.09), a significant mean difference of 0.27 cm (95% CI: 0.23-0.32 cm). The reproducibility coefficients for differences between technicians were 0.30 cm (95% CI: 0.24-0.36) for ITI and 0.42 cm (95% CI: 0.35-0.49) for OTO indicating significantly better repeatability using ITI. Finally, 15 images were measured twice in random order by all screeners and sonographers. For AAAs > 5 cm, repeatability was significantly better with ITI than OTO (0.14 vs. 0.21; p = 0.016). CONCLUSION: There was the expected difference in AAA diameter between the two methods (0.27 cm). However, ITI wall method was measurably more reproducible.

Extracranial and transcranial ultrasound assessment in patients with suspected positional 'vertebrobasilar ischaemia'.

OBJECTIVES: A diagnosis of 'positional' vertebrobasilar ischaemia is considered in patients presenting with dizziness/vertigo during lateral neck rotation/extension and is attributed to bony 'nipping' of the vertebral artery (VA). This study reviewed our experience with extracranial and transcranial ultrasound to determine whether a diagnosis of 'positional' vertebrobasilar ischaemia was associated with any changes in flow in the extracranial VA and the P1 segment of the posterior cerebral artery (PCA) during head turning. METHODS: A retrospective case note review was undertaken in 46 patients with an accessible window for transcranial Doppler who had undergone extracranial and transcranial assessment of flow velocity and flow directionality in the VA and PCA while the head was moved into positions that normally triggered the patient's symptoms. RESULTS: Positional 'vertebrobasilar symptoms' were triggered by lateral head rotation in 35 patients (76%), while 11 (24%) developed symptoms following neck extension. Only one patient was found to have a significant carotid stenosis (symptoms unchanged following carotid endarterectomy) and none had significant disease in the extracranial VAs. None of the patients exhibited any change in extracranial VA flow during head turning/extension and none had reversal of flow either. Similarly, there was no change observed in the PCA flow characteristics during head turning. The majority of patients (74%) were subsequently referred to the Ear, Nose and Throat (ENT) department, and 94% of the patients noted an improvement in symptoms following entry into a vestibular rehabilitation programme. CONCLUSIONS: A diagnosis of 'positional' vertebrobasilar ischaemia should be made with extreme caution and only after a specialist assessment in a Balance Centre.

Joint recommendations for reporting carotid ultrasound investigations in the United Kingdom.

At present in the United Kingdom a number of different criteria are used to grade disease in carotid ultrasound investigations. One main cause of this has been the difference in the method of grading angiograms used in the NASCET and ECST large carotid surgery trials. It is desirable that all centres reporting carotid ultrasound investigations report to the same standard. This paper presents recommendations for the reporting of ultrasound investigations of the extra cranial arteries produced by a Joint Working Group formed between the Vascular Society of Great Britain and Ireland, and the Society for Vascular Technology of Great Britain and Ireland. The recommended criteria are based on the NASCET method of grading carotid bulb disease. Key recommendations include recording peak systolic velocity (PSV) and end-diastolic velocity (EDV) in both internal and distal common carotid arteries; measuring all velocities at a Doppler angle of 45-60 degrees; the use of internal carotid PSV of >1.25 ms(-1) and >2.3 ms(-1) and a Peak Systolic Velocity Ratio of >2 and >4 to indicate >50% and >70% stenosis respectively; and the use of the St Mary's Ratio to grade >50% stenoses in deciles. General recommendations are also given for the acquisition, interpretation and reporting of the data.

The diagnosis and management of 689 chronic leg ulcers in a single-visit assessment clinic.

OBJECTIVES: accurate diagnosis is essential if patients with chronic leg ulceration are to receive optimal treatment. This prospective study describes the findings of a standardised assessment protocol and the initial management of a consecutive series of patients with chronic leg ulceration presenting to a single-visit leg ulcer assessment clinic. METHODS: between January 1993 and January 1999, a total of 555 patients (220 men and 335 women of median age 73, range 28-95 years) with 689 chronic leg ulcers were assessed. Full clinical assessment, ankle:brachial pressure index and lower limb venous duplex scan were performed according to a standardised protocol and diagnostic and management data were recorded prospectively on a computerised database. RESULTS: venous disease alone was responsible for 496 of 689 (72%) ulcers. Isolated superficial venous reflux (SVR) was identified in 52% of limbs and two-thirds of these had superficial venous surgery. Combined SVR and segmental deep venous reflux (DVR) was present in 13%, and full-length DVR was present in 33% of limbs. Nineteen (4%) limbs had deep venous stenosis or obstruction. Overall, superficial venous surgery was performed in 43% and compression bandages or hosiery alone were applied in 52% of limbs. Mixed arterio-venous ulceration was present in 100 (14.5%) limbs of which 56 had arterial revascularisation, 38 had superficial venous surgery and 23 had compression alone. Fifteen limbs with pure arterial ulceration had angioplasty (n=13) or simple dressings alone (n=2). Ulceration due to lymphoedema (n=17), mixed lymphoedema and venous reflux (n=11) and other causes (n=50) were managed by compression, dressings or skin grafting. CONCLUSIONS: a standardised protocol of clinical and duplex assessment can lead to a diagnosis in 97% of chronic leg ulcers. Duplex is essential to confirm or exclude potentially correctable venous disease and allow tailored surgical intervention for those patients who many benefit.

Role of superficial venous surgery in patients with combined superficial and segmental deep venous reflux.

OBJECTIVES: superficial venous surgery heals chronic venous ulceration (CVU) in the majority of patients with isolated superficial venous reflux (SVR). This study examines the role of superficial venous surgery in patients with combined SVR and segmental deep venous reflux (DVR). METHODS: combined SVR and segmental DVR was diagnosed by venous duplex in 53 limbs in 49 patients (24 men and 25 women of median age 66, range 27-90, years). Fourteen limbs had varicose veins (CEAP class 2-4) and 39 (74%) had active CVU (CEAP class 6). Duplex ultrasound was performed before and three months after local anaesthetic superficial venous surgery. Perforator vein surgery, skin grafting and compression bandaging or hosiery were not used. RESULTS: forty-two limbs with long saphenous vein (LSV) reflux underwent sapheno-femoral disconnection, 10 with short saphenous vein (SSV) reflux underwent sapheno-popliteal disconnection and one limb with LSV and SSV reflux had sapheno-femoral and sapheno-popliteal disconnection. Segmental DVR was confined to the superficial femoral vein (SFV) in 16 limbs, below knee popliteal vein (BKPV) in 25 and gastrocnemius vein (GV) in 12 limbs. Overall, duplex demonstrated post-operative resolution of segmental DVR in 26 of 53 (49%) limbs. Resolution of segmental SFV reflux occurred in 12 of 16 (75%) limbs compared with 14 of 37 (38%) limbs with segmental BKPV or GV reflux (p=0.018). Segmental DVR resolved in 19 of 39 (49%) limbs with CVU and ulcer healing occurred in 30 of 39 (77%) limbs at 12 months with a median time to healing of 61 (range 14-352) days. Segmental DVR resolved in 14 of 30 (47%) limbs with a healed ulcer: 7 of 9 (78%) limbs with SFV and 7 of 21 (33%) with BKPV or GV reflux (p=0.046). CONCLUSIONS: these data demonstrate that in patients with combined SVR and segmental DVR, superficial venous surgery alone corrects DVR in almost 50% of limbs and is associated with ulcer healing in 77% of limbs at 12 months. These findings suggest an extended role for superficial venous surgery in the management of patients with complicated venous disease.

Trypanosoma brucei 5'ETS A'-cleavage is directed by 3'-adjacent sequences, but not two U3 snoRNA-binding elements, which are all required for subsequent pre-small subunit rRNA processing events.

Trypanosoma brucei pre-rRNA processing commences by cleavage near the 5' end of 5.8 S sequences. The 5' external transcribed spacer (5'ETS) is removed from pre-small subunit (SSU) rRNAs by sequential cleavages at internal A' and A0 sites, and A1 at the 5' end of SSU rRNA. The A' and A0 sites positionally resemble the U3 small nucleolar RNA-dependent, primary pre-rRNA cleavages of vertebrates and yeast, respectively. Uniquely in T. brucei, two U3-crosslinkable 5'ETS sites are essential for SSU rRNA production: site1b is novel in its 3' location to the A' site, and site3 lies upstream of A0 in a position analogous to the yeast U3-binding site. Here, in vivo analysis of mutated 5'ETS sequences shows that sequences 5' to the A' site are not needed for A' cleavage or SSU rRNA production. A' cleavage is linked to, but is not sufficient to trigger, downstream pre-SSU rRNA processing events. These events require an intact 11 nt sequence, 3'-adjacent to A', which directs efficient and accurate A' cleavage. Neither the A' nearby site1b nor the site3 U3-binding elements affect A' processing, yet each is required for A0 and A1 cleavage, and SSU rRNA production. The same U3 3' hinge bases evidently bind a core element, UGUu/gGGU, within site1a and site3; the U3-site1b interaction is less reliant on base-pairing than the U3-site3 interaction. As yeast U3 5' hinge bases pair to 5'ETS sequences, it is clear that distinct U3 hinge regions can interact at both novel and related 5'ETS sites to promote 3'-proximal 5'ETS processing events in diverse organisms. The T. brucei data fit a model wherein processing factors assemble at the 5'ETS site1a to affect A' cleavage and stabilize a U3-site1b complex, which may work in concert with the downstream U3-site3 complex to assist processing events leading to ribosomal SSU production.

Characterization of an essential RNA secondary structure in the 3' untranslated region of the murine coronavirus genome.

We have previously identified a functionally essential bulged stem-loop in the 3' untranslated region of the positive-stranded RNA genome of mouse hepatitis virus. This 68-nucleotide structure is composed of six stem segments interrupted by five bulges, and its structure, but not its primary sequence, is entirely conserved in the related bovine coronavirus. The functional importance of individual stem segments of this stem-loop was characterized by genetic analysis using targeted RNA recombination. We also examined the effects of stem segment mutations on the replication of mouse hepatitis virus defective interfering RNAs. These studies were complemented by enzymatic and chemical probing of the stem-loop. Taken together, our results confirmed most of the previously proposed structure, but they revealed that the terminal loop and an internal loop are larger than originally thought. Three of the stem segments were found to be essential for viral replication. Further, our results suggest that the stem segment at the base of the stem-loop is an alternative base-pairing structure for part of a downstream, and partially overlapping, RNA pseudoknot that has recently been shown to be necessary for bovine coronavirus replication.

The clinical management and outcome of venous ulcers in legs with deep-venous obstruction.

OBJECTIVE: as a result of a serious complication from compression bandaging in a patient with venous ulceration and deep-vein obstruction, a policy of incremental compression in such limbs has been developed. The purpose of this retrospective study is to review the outcome of this policy. DESIGN: limbs with deep-venous obstruction (stenosis or occlusion) were treated initially with 3-layer compression bandaging and reviewed 24 h later. If 3-layer bandaging was tolerated, it was re-applied for a further 48 h. If there were no problems, then 4-layer bandaging was applied and the patient reviewed at 24 and 72 h. If 4-layer bandaging could not be tolerated, the limb was returned to 3-layer bandaging. RESULTS: of 325 limbs seen in a venous-ulcer clinic, 22 (7%) had deep-vein obstruction. Fifteen (68%) limbs were able to tolerate 4-layer bandaging, five (23%) could tolerate 3-layer bandaging and two limbs (9%) could only tolerate class 2 compression hosiery. The overall 1-year healing rate was 55%. There were no serious complications from bandaging. CONCLUSIONS: a protocol of incremental compression bandaging is safe in ulcerated legs with deep-vein obstruction and produces healing in up to 55% of cases.

Two 5'-ETS regions implicated in interactions with U3 snoRNA are required for small subunit rRNA maturation in Trypanosoma brucei.

Early pre-rRNA processing events were examined in the ancient protozoan parasite Trypanosoma brucei and found to have both distinctive and conserved features. Two 5'-ETS cleavages occur: A' and the newly discovered A0. A' and A0 appear related to vertebrate and yeast primary pre-RNA cleavage sites, respectively. However, trypanosomatid primary rRNA transcripts can first be processed at the ITS1/5.8S boundary and 5'-ETS sequences then removed by consecutive cleavages at A', A0 and A1 at the 5'-ETS/SSU rRNA junction. 5'-ETS sequences previously crosslinked to U3 snoRNA were tested for their roles in rRNA processing using our new tagged rRNA system. Two distinct A'-adjacent sequence elements, which may pair with U3 hinge bases, were specifically required for SSU rRNA production, as was a downstream element. The latter element appears conserved with the yeast 5'-ETS U3 binding sequence, required for A0, A1 and A2 cleavages, in that they both share 10 bases complementary with U3 hinge sequences and lie upstream from A0 and A1 sites located in a potential stem-loop structure. The distinctive positioning of putative trypanosomatid U3 binding sites with respect to A" and A0 cleavages suggests that different U3-dependent mechanisms may direct each processing event.

Use of colour duplex imaging to diagnose and guide angioplasty of lower limb arterial lesions.

BACKGROUND: The purpose of this study was to investigate whether colour duplex imaging alone could safely and effectively be used to diagnose lower limb arterial lesions and guide subsequent percutaneous transluminal angioplasty (PTA). METHODS: Patients with discrete lower limb arterial lesions, preferably stenoses, which could be visualized clearly by colour duplex imaging were selected for duplex-guided PTA. Duplex-guided PTA was performed in an operating theatre using conventional balloon catheters. RESULTS: Duplex imaging was used to diagnose and guide PTA of 55 arterial lesions in 50 legs of 45 patients. There were 53 stenoses and two occlusions. The median (range) ankle : brachial pressure index was 0. 86 (0.52-1.10) before dilatation and 1.00 (0.83-1.40) immediately after dilatation (P = 0.0001). There were no complications during or after any of the procedures and 46 of the 47 symptomatic legs were markedly improved at a median follow-up of 23 days. Radiographic imaging was not required for any of the procedures. CONCLUSION: It is possible to diagnose and angioplasty lower limb arterial lesions using colour duplex imaging alone.

Role of superficial venous surgery in the treatment of venous ulceration.

BACKGROUND: The aim of this study was to determine the ability of superficial venous surgery to heal venous ulcers in lower legs with isolated superficial venous incompetence. METHODS: This was a prospective study of patients recruited from a venous ulcer assessment clinic. Ulcers were considered venous if the ankle : brachial pressure index was greater than 0.8 and duplex imaging showed venous reflux. Patients with isolated superficial venous incompetence were offered saphenofemoral and/or saphenopopliteal surgery. Neither perforator surgery, skin grafting nor postoperative compression hosiery or bandaging was used. RESULTS: A total of 122 legs with normal deep veins underwent superficial venous surgery. Ninety procedures (74 per cent) were done under local and 32 (26 per cent) under general anaesthesia. Sixty operations (49 per cent) were done as a day case. The median time to healing was 18 (95 per cent confidence interval 14-21) weeks and the cumulative 6-, 12- and 18-month healing rates were 57, 74 and 82 per cent respectively. CONCLUSION: In patients with venous ulceration and isolated superficial venous incompetence, superficial venous surgery can produce ulcer healing in the majority of patients without the need for perforator surgery, postoperative compression bandaging or skin grafting.

Venous ulceration and continuous flow in the long saphenous vein.

OBJECTIVE: To determine the clinical significance of continuous flow in the long saphenous vein in limbs with venous ulceration. DESIGN: Retrospective review. PATIENTS AND METHODS: Review of 1608 consecutive limbs undergoing colour duplex scanning for venous disease over a 43 month period. RESULTS: Continuous flow in the long saphenous vein is seen in 8% of limbs with venous ulceration and in 37% of limbs with deep venous obstruction. Sixty-six per cent of ulcerated limbs with continuous flow in the long saphenous vein had deep venous obstruction, 27% had deep venous reflux with cellulitis and 7% had lymphoedema in addition to venous ulceration. CONCLUSION: Continuous flow in the long saphenous vein in patients with venous ulceration should alert the clinician to the possibility of deep venous obstruction. Such limbs should be treated by compression bandaging with extreme caution.

Colour-coded duplex imaging and dependent Doppler ultrasonography in the assessment of cruropedal vessels.

BACKGROUND: It has been suggested that ultrasonography could replace diagnostic arteriography in the assessment of patients who present with leg ischaemia. This study investigated a group of consecutive patients who had femorodistal bypass and who were assessed before operation with colour-coded duplex and dependent Doppler insonation alone. METHODS: Thirty-seven consecutive patients with critical lower limb ischaemia underwent surgical exploration with a view to femorodistal bypass. Results of preoperative colour-coded duplex and dependent Doppler insonation were compared with intraoperative arteriograms and surgical findings. RESULTS: There was very good agreement between colour-coded duplex imaging and dependent Doppler insonation with intraoperative angiography and surgical findings in the prediction of the optimal run-off vessel (kappa = 1.0) and the site of the distal anastomosis (kappa = 0.85; 95 per cent confidence interval 0.71-1.0). There was also very good agreement between dependent Doppler insonation and intraoperative arteriography (kappa = 1.0) in predicting pedal arch patency and the predominant feeding vessel. CONCLUSION: Assessment of leg arteries before femorodistal bypass can be performed accurately with non-invasive colour-coded duplex imaging and dependent Doppler insonation alone, thus obviating the need for preoperative arteriography.