Reliability of tomographic 3D ultrasound in measuring internal carotid artery plaque volume.

BACKGROUND: Tomographic 3D ultrasound (t3DUS) is a promise imaging technique for quantifying carotid plaque through measuring the degree of stenosis and plaque volume. Carotid plaque volume (CPV) could add benefit in predicting the potential risk of stroke. PURPOSE: To assess the reproducibility and accuracy of t3DUS for measuring CPV within the internal carotid artery in patients undergoing carotid endarterectomy. MATERIAL AND METHODS: t3DUS was used to obtain CPV in vivo from 25 symptomatic patients prior to surgery. Ex vivo CPV from the carotid endarterectomy specimen was then measured using a validated saline displacement method as a reference standard. CPV for each patient was measured twice using both methods (total n = 50 per technique). Intraclass correlation coefficient (ICC) and Bland-Altman plot were used to establish bias and limit of agreement between CPV measurements. RESULTS: There was an excellent agreement between t3DUS and reference test with respect to measuring CPV with an ICC value of 0.98 (95% confidence interval = 0.97-0.99, P < 0.001). Bias in measurements was 0.02 ± 0.11 cm3 (95% limit of agreement = -0.19 to 0.25). Intra-observer agreement of t3DUS CPV measurements was excellent with an ICC value of 0.95 (95% confidence interval = 0.92-0.97, P < 0.001). Bias in measurements was 0.004 ± 0.07 cm3 (95% limit of agreement = -0.14 to 0.15). CONCLUSION: t3DUS is a reproducible imaging method and showed excellent agreement with the reference standard with respect to measuring CPV. These findings suggest that t3DUS has the potential to be a valuable non-invasive tool for assessing carotid plaque burden and predicting the risk of stroke.

Tomographic 3D ultrasound for grading stenosis of superficial femoral artery.

INTRODUCTION: Treatment decision of lower extremity peripheral arterial disease (PAD) is governed by the severity of stenosis. Tomographic 3D ultrasound (t3DUS) is a reliable imaging technique for measuring vessel stenosis. In this study we attempted to provide a precise measurement of superficial femoral artery (SFA) stenosis using t3DUS in patients with PAD. METHODS: t3DUS was used to measure maximum stenosis percentage in SFA from 50 patients with lower extremity PAD. The maximum stenosed segment in SFA was defined using Duplex 2DUS aliasing was noted. The peak systolic velocity (PSV) was measured at the maximum stenotic site and proximal to aliasing for calculating the velocity ratio. The association between blood flow velocity ratio and the degree of stenosis measured using Duplex 2DUS and t3DUS, respectively, was assessed using Spearman rank correlation. RESULTS: There was a strong positive correlation between velocity ratio and degree of stenosis in SFA measured using t3DUS (correlation value (r) = 0.99, p < 0.001). The correlation between Stenosis percentage and velocity ratio in SFA are as followed: <50:<2; 50-54:2-2.4; 55-59:2.5-2.9; 60-64:3-3.4; 65-69:3.5-3.9; 70-74:4-4.4; 75-79:4.5-4.9; >80:>5.t3DUS can be used to provide precise measurement of the severity of SFA stenosis in patients with lower extremities arterial disease. The established criteria for grading SFA stenosis in this study can be applied to the current practice alongside Duplex 2DUS as it showed a strong positive correlation with velocity ratio. Further studies investigating the sensitivity and specificity of t3DUS in the assessment of stenosis in lower limbs arteries are required.

Diagnostic Accuracy of Point-of-care Tests Used to Detect Arterial Disease in Diabetes: TEsting for Arterial Disease in Diabetes (TrEAD) Study.

OBJECTIVE: We compared the diagnostic performance of a novel point-of-care duplex ultrasound test (podiatry ankle duplex scan; PAD-scan) against commonly used bedside tests for the detection of PAD in diabetes. BACKGROUND: PAD is a major risk factor for diabetic foot ulceration and amputation. Its diagnosis is fundamental though challenging. Although a variety of bedside tests are available, there is no agreement as to which is the most useful. PAD-scan may be advantageous over current tests as it allows for vessel visualization and more accurate arterial waveform assessment. However, its accuracy has not been previously evaluated. METHODS: From March to October 2019, we recruited 305 patients from 2 diabetic foot clinics. The diagnostic performance of ankle-brachial pressure index, toe-brachial pressure index, transcutaneous pressure of oxygen, pulse palpation, and ankle waveform assessment using PAD-scan and Doppler devices (audible and visual waveform assessment) were assessed. The reference test was a full lower limb duplex ultrasound. RESULTS: Based on the reference test, 202 (66.2%) patients had evidence of PAD. PAD-scan had a significantly higher sensitivity [95%, confidence interval (CI) 90%-97%) as compared to all other tests. Particularly low sensitivities were seen with pulse palpation (43%, CI 36%-50%) and transcutaneous pressure of oxygen (31%, CI 24%-38%). PAD-scan had a lower specificity (77%, CI 67%-84%) compared to toe-brachial pressure index (86%, CI 78%-93%; P < 0.001), but not statistically different when compared to all other tests. CONCLUSIONS: PAD-scan has superior diagnostic utility and is a valid first line investigation.

Facile Preparation and Analytical Utility of ZnO/Date Palm Fiber Nanocomposites in Lead Removal from Environmental Water Samples.

This study reports a facile approach for preparing low-cost, eco-friendly nanocomposites of ZnO nanoparticles (NPs) and date palm tree fiber (DPF) as a biomass sorbent. The hypothesis of this research work is the formation of an outstanding adsorbent based on the date palm fiber and ZnO nanoparticles. ZnO NP/DPF nanocomposites were synthesized by mixing the synthesized ZnO NPs and DPF in different mass ratios and evaluating their efficacy in adsorbing Pb2+ from aqueous solutions. The structure and surface morphology of the developed ZnO NP/DPF nanocomposite were critically characterized by XRD, FESEM, and TEM techniques. Compared to ZnO NPs, the ZnO NP/DPF nanocomposites displayed significantly enhanced Pb2+ uptake. Pb2+ adsorption was confirmed via various isotherm and kinetic models and thermodynamics. The computed Langmuir sorption capacity (qm) was found to be 88.76 mg/g (R2 > 0.998), and the pseudo-second-order R2 > 0.999 model was most appropriate for describing Pb2+ adsorption. Impregnating the biomass with ZnO NPs enhanced the spontaneity of the process, and the value (−56.55 kJ/mol) of ΔH displayed the exothermic characteristics of Pb2+ retention. Only the loaded ZnO NP/DPF achieved the removal of a high percentage (84.92%) of Pb2+ from the environmental water sample (seawater). This finding suggests the use of ZnO NP/DPF nanocomposites for removing heavy metals from environmental water samples to purify the samples.

Incidence of Enteric Fever in a Pediatric Cohort in North India: Comparison with Estimates from 20 Years Earlier.

BACKGROUND: An earlier cohort in 1995-1996 showed a very high burden of typhoid in Delhi. Our aim was to estimate the current overall and age-specific incidence of culture-confirmed enteric fever among children aged 6 months to 15 years in Delhi. METHODS: We enrolled a cohort of 6000 children aged 6 months to <14 years in South Delhi and followed them up weekly for 24 months or until 15 completed years of child age, whichever was earlier. Blood culture to confirm enteric fever was done in children with ≥3 consecutive days of fever. RESULTS: We recorded a total of 14 650 episodes of fever in the 11 510 person-years (PY) of follow-up. A total of 81 fever episodes were positive for enteric fever. The incidence (95% confidence interval) of all enteric fever was 703.7 (560.5-874.7) per 100 000 PY. The incidences of typhoid and paratyphoid fevers were 608.1 (95% confidence interval, 481.1-768.7) and 111.7 (59.5-191.1) per 100 000 PY, respectively, highest among children aged 10-15 years. CONCLUSIONS: Despite a 35% reduction in incidence compared with the 1995-1996 cohort, our study suggested a substantial burden of enteric fever in the population. Continued efforts to improve water, sanitation, and hygiene parameters along with implementation of novel vaccination strategies and disease surveillance can help achieve the goal of disease elimination.

Quality by design (Qbd) assisted development of phytosomal gel of aloe vera extract for topical delivery.

The aim of the current study was to develop the phytosomal gel of aloe vera extract for improved topical delivery. Aloe vera extract loaded phytosomal system was developed by fixing the amount of aloe vera extract and ethanol and by varying the concentration of lecithin (0.15-0.25% w/v) and speed of rotation (80-120 rpm). Different formulation batches were prepared as per the Design expert software. A 22 Factorial design was applied to optimize the formulation on the basis of vesicular size and entrapment efficiency. Developed formulations were evaluated for vesicular size, entrapment efficiency, PDI, zeta potential and in-vitro release. Further stability studies were also performed. For the optimized formulation (F09), vesicular size, entrapment efficiency and PDI were found as 123.1 ± 1.44 nm, 95.67 ± 0.27% and 0.98 ± 0.06. Zeta potential of -11.9 mV and drug release of 56.91 ± 4.1% obtained in 24 h. Drug release kinetics from the phytosomes follows Higuchi model. TEM micrograph confirms the uniform structure of phytosomes. Phytosomal gel of optimized phytosomal formulation (F09) was developed with 1% Carbopol 934 and physically characterized on the basis of pH, viscosity, homogeneity and drug content. Ex-vivo permeation study showed the better permeation and flux profile of phytosomal gel with the conventional aloe vera extract gel. Also, studies on phytosomal formulation and gel showed stability up-to 3 months. Thus overall, it can be concluded that the phytosomal gel is a good carrier for topical delivery of herbal extract such as aloe vera.

Arterial spectral waveform analysis in the prediction of diabetic foot ulcer healing.

OBJECTIVE: We assessed the association between (1) severity of vessel wall calcification, (2) number of patent vessels at the ankle and (3) arterial spectral waveform features, as assessed on a focused ankle Duplex ultrasound (DUS), and healing at 12-months in a cohort of patients who had their diabetic foot ulcers conservatively managed. RESEARCH DESIGN AND METHODS: Scans performed on 50 limbs in 48 patients were included for analysis. Patient health records were prospectively reviewed for 12-months to assess for the outcome of ulcer healing. RESULTS: We identified that the number of waveform components, peak systolic velocity, systolic rise time and long forward flow as well as the number of vessels patent at the ankle on DUS, may be useful independent predictors of healing, as noted by the trend towards statistical significance. CONCLUSION: Arterial spectral waveform features may be useful in predicting the chance of diabetic foot ulcer healing.

Chronic venous insufficiency: a new concept to understand pathophysiology at the microvascular level - a pilot study.

OBJECTIVES: The real mechanism for the development of the later stages of chronic venous insufficiency still remains unclear. Venous hypervolemia and microvascular ischemia have been reported to be the consequences of venous insufficiency. The aim of this study was to investigate the effects of induced venous hypovolemia by dorsiflexion exercise in patients with venous leg ulcers. METHODS: Thirty-six participants, all of whom had an ankle brachial pressure index between 0.8 and 1.2 mmHg, were chosen for this study. The participants were divided into two groups: Group A, a non-exercise group and Group B which performed regular exercise in the form of dorsiflexion. The basic assessment, including the history and examination, ankle-brachial pressure index (ABPI), Duplex scan and tcPO2 measurements, was performed on two occasions at the beginning of the trial and after three months. RESULTS: The tcPO2 level was low in the beginning in all the subjects, but the picture was different at the end of the trial. There was a significant increase in the tcPO2 level (p<0.001) in the patients who performed exercise while there was no difference in the measurements (p>0.05) in the non-exercise group. CONCLUSIONS: Induced venous hypovolemia through regular evacuation of the peripheral venous system improved tissue oxygenation at skin level. Venous hypervolemia may be the main contributing factor for the development of venous hypoxia and microvascular ischemia.

An investigation of skin perfusion in venous leg ulcer after exercise.

INTRODUCTION: A venous leg ulcer (VLU) has a major impact on the quality of life and functional ability of individuals, but no single treatment is yet effective. This study investigates the changes induced by dorsiflexion exercise on skin perfusion in VLU patients to achieve a better understanding of venous ulcer pathophysiology. METHODS: Seventy-eight venous leg ulcer patients were randomised into four groups. The non-exercise groups included a control group (n = 18) and a compression therapy group (n = 20) and the exercise groups included an exercise-only group (n = 20) and a compression and exercise group (n = 20). The exercise groups were expected to perform exercise for three months. Measurements included transcutaneous oximetry (tcPO2) and laser Doppler flowmetry (LDF). Skin perfusion measurements for all groups were taken twice: at the beginning and end of the three-month period. RESULTS: Initially, all participants showed a low level of tcPO2. The exercise groups showed a significant increase after three months of exercise (p<0.001), the tcPO2 level remained the same in the non-exercise groups. The LDF parameters decreased significantly (p<0.001) in the compression and exercise group and decreased to a lesser extent in the exercise-only group. There were no LDF changes in the non-exercise groups. CONCLUSIONS: Perfusion measurements showed significant changes after three months of regular exercise. We conclude that exercise has a significant effect on tissue perfusion parameters in venous leg ulcer and this effect may play a role in understanding the pathophysiology of VLU.

The impact of a focused vascular lower limb arterial duplex (F-VLAD) scan in management decisions for acute limb ischaemia.

OBJECTIVE: To establish the diagnostic accuracy of a 'focused vascular lower limb arterial duplex scan (F-VLAD)' developed to facilitate rapid decision-making for acute limb ischaemia (ALI). METHODS: Ten cases of ALI were identified from our patient database; clinical details, history and examination findings were extracted from the clinical notes. Original 'full' duplex ultrasound (DUS) pictorial reports were 're-formatted' to include only anatomical segments included in the 'F-VLAD' scan. The series of 10 reports were emailed to 1741 vascular surgeons. Each recipient received a random mixture of full and F-VLAD scans. Participants were asked regarding next step in management and confidence in decision-making (Likert scale; 1 strongly disagree, 5 strongly agree). The cases were again sent out to the same database and respondents were asked as to the cause of ischaemia (embolic or thrombosis). RESULTS: Eighty-one participants responded to the first survey and 43 participants to the second survey. Participants felt more confident making decisions regarding management using the full duplex report compared to the F-VLAD report (4 (3-4) vs 3 (2-4), median (IQR); p<0.001). However, there was no significant difference in diagnostic accuracy (differentiating embolus from thrombosis) when comparing the F-VLAD and full DUS reports (85.4% vs 88.3%; p=0.461). F-VLAD and 'full' DUS reports had comparable sensitivity (85.1% vs 86.8%), specificity (85.6% vs 89.2%),positive predictive value (PPV) (80.4% vs 81.9%) and negative predictive value (NPV) (89.2% vs 92.2%), respectively. CONCLUSION: The F-VLAD scan has comparable accuracy to a traditional full DUS in diagnosing the underlying aetiology of ALI. This may facilitate surgeon-performed point-of-care DUS.

Potential identification of a claudicant group vulnerable to acute kidney injury.

This observational study aimed to investigate the relationship between renal injury, endothelial function and oxidative stress in claudicants undergoing maximal treadmill exercise. Twenty patients with claudication were identified in whom the urinary N-acetyl-ß-D-glucosaminidase (ß-NAG)/creatinine ratio, plasma oxidative state and endothelial function were tested pre- and post-maximal treadmill walking exercise. Of the 20 participants in this study, the urinary NAG/creatinine (Cr) rose from a pre-exercise level of 8.9, 6.7 to 14.3 (µmol/L/mmol Cr; median, IQR) to 12.9, 9.1 to 17.7 post exercise (p = 0.0003, Mann Whitney U test). Of the 20 participants, eight participants had a rise of the NAG/Cr ratio post exercise whereas 12 did not. Participants with a rise in the NAG/Cr ratio post exercise had a greater ability to increase endothelial reactivity (%; median, IQR; 2.56, 0.1 to 3.7) cf. (0.1, -4.8 to 0.9, p = 0.03); they also walked further (metres; median, IQR; 415, 208 to 908) cf. (170, 100 to 315, p = 0.04), had a lower pre-exercise H2O2 (median, IQR; 1.9, 1.4 to 2.3 cf. 2.7, 2.1 to 3.3; p = 0.04) and a greater rise in H2O2 post exercise (18.8, -1.5 to 129.7 cf., -7.7, -13.9 to -2.0, p = 0.04). The mechanism by which the phenotypically distinct sub-group of patients with intermittent claudication who experience a NAG/Cr rise involves complex interactions between systemic oxidative stress and endothelial function. Implications on cardiovascular risk in this group requires further investigation.

Randomized study of teaching ultrasound-guided vascular cannulation using a phantom and the freehand versus needle guide-assisted puncture techniques.

PURPOSE: The task of ultrasound-guided vessel cannulation can be technically difficult. Needle guides have been designed to facilitate vessel puncture. We aimed to identify and compare the learning curves of participants performing vessel puncture with conventional freehand (FH) and needle guide-assisted (NG) techniques. METHODS: Thirty-six participants were randomly allocated to either the FH or the NG group. They were asked to consecutively perform as many as 30 vessel punctures on a simulated phantom model. Quantitative metrics (time taken and number of skin and posterior-wall punctures) were recorded and compared between the two groups. The cumulative sum and moving F-test statistical methods were used to delineate the learning curves. RESULTS: There was a significantly lower rate of posterior-wall punctures in the NG group than in the FH group (15% versus 26%; p < 0.0001). Participants in the NG group also performed significantly fewer skin punctures than did those in the FH group (mean, 405 versus 515; p < 0.0001). Cumulative sum statistical method analysis showed that participants in the NG group surmounted the learning curve earlier (13 attempts; interquartile range, 10.3-17.0) than did those in the FH group (19 attempts; interquartile range, 15.0-27.5). The number of attempts to surmount the learning curve was significantly less for the FH group (7.2 versus 16 attempts; p = 0.007) when using the moving F-test. CONCLUSIONS: The NG puncture allows a greater number of trainees to cross the learning threshold and offers the advantages of fewer posterior-wall punctures and skin punctures. The use of NG puncture may result in a shorter path to proficiency, allowing trainees to attempt needle puncture earlier and with a greater degree of safety.

Challenges in the diagnosis and management of spontaneous bile duct perforation: A case report and review of literature.

We report a case of 14-year-old male, who presented to us with complaints of severe pain in abdomen, vomiting, and inability to pass feces and flatus. He was diagnosed as a case of peritonitis after careful history, examination, and investigations. The exact cause of peritonitis was not known. Exploratory laparotomy was done, and it was found that there was perforation of the right hepatic duct about 1 cm proximal to its confluence with the left hepatic duct. Perforation was closed around the T-tube. Postoperative T-tube cholangiogram was done after 3 weeks which confirmed the free passage of dye into the duodenum, and there was no leakage of dye. T-Tube was removed 4 weeks after the operation, and the patient was discharged in satisfactory condition. Postoperative follow-up was done for 3 months, and it was uneventful.

Evaluating the benefits of machine learning for diagnosing deep vein thrombosis compared to gold standard ultrasound- a feasibility study.

BACKGROUND: This study evaluates the feasibility of remote deep venous thrombosis (DVT) diagnosis via ultrasound sequences facilitated by ThinkSono Guidance, an artificial intelligence (AI)-app, for point-of-care ultrasound (POCUS). AIM: The aim is to assess the effectiveness of AI-guided POCUS conducted by non-specialists in capturing valid ultrasound images for remote diagnosis of DVT. DESIGN & SETTING: Over a 3.5-month period, patients with suspected DVT underwent AI-guided POCUS conducted by non-specialists using a handheld ultrasound probe connected to the app. These ultrasound sequences were uploaded to a cloud-dashboard for remote specialist review. Additionally, participants received a formal DVT scans. METHOD: Patients underwent AI-guided POCUS using handheld probes connected to the AI-app, followed by formal DVT scans. Ultrasound sequences acquired during the AI-guided scan were uploaded to a cloud-dashboard for remote specialist review, where image quality was assessed, and diagnoses were provided. RESULTS: Among 91 predominantly elderly female participants, 18% of scans were incomplete. Of the rest, 91% had sufficient quality, with 64% categorised by remote clinicians as "compressible" or "incompressible." Sensitivity and specificity for adequately imaged scans were 100% and 91%, respectively. Notably, 53% were low risk, potentially obviating formal scans. CONCLUSION: ThinkSono Guidance effectively directed non-specialists, streamlining DVT diagnosis and treatment. It may reduce the need for formal scans, particularly with negative findings, and extend diagnostic capabilities to primary care. The study highlights AI-assisted POCUS potential in improving DVT assessment.

Early Ultrasound Surveillance of Newly-Created Hemodialysis Arteriovenous Fistula.

Introduction: We assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention. Methods: Consenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling. Results: Of 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9-77.3]; elbow, 66.7% [48.9-84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan's findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data. Conclusion: Early ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation.

Doppler ultrasound surveillance of recently formed haemodialysis arteriovenous fistula: the SONAR observational cohort study.

Background: Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. Objective: To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. Design: A prospective multicentre observational cohort study (the 'SONAR' study). Setting: Seventeen haemodialysis centres in the UK. Participants: Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Intervention: Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Main outcome measures: Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. Results: A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas' non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset (n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Conclusions: Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. Trial Registration: This trial is registered as ISRCTN36033877 and ISRCTN17399438. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.

For people with advanced kidney disease, haemodialysis is best provided by an 'arteriovenous fistula', which is created surgically by joining a vein onto an artery at the wrist or elbow. However, these take about 2 months to develop fully ('mature'), and as many as 3 out of 10 fail to do so. We asked whether we could use early ultrasound scanning of the fistula to identify those that are unlikely to mature. This would allow us to decide whether it would be practical to run a large, randomised trial to find out if using early ultrasound allows us to 'rescue' fistulas that would otherwise fail. We invited adults to undergo serial ultrasound scanning of their fistula in the first few weeks after it was created. We then analysed whether we could use the data from the early scans to identify those fistulas that were not going to mature by week 10. Of the 333 fistulas that were created, about two-thirds reached maturity by week 10. We found that an ultrasound scan 4 weeks after fistula creation could reliably identify those fistulas that were going to mature. However, of those fistulas predicted to fail, about one-third did eventually mature without further intervention, and even without knowing what the early scans showed, another third were successfully rescued by surgery or X-ray-guided treatment at a later stage. Performing an early ultrasound scan on a fistula can provide reassurance that it will mature and deliver trouble-free dialysis. However, because scans are poor at identifying fistulas that are unlikely to mature, we would not recommend their use to justify early surgery or X-ray-guided treatment in the expectation that this will improve outcomes.

The unfolded protein response regulator GRP78 is a novel predictive biomarker in colorectal cancer.

Adjuvant fluoropyrimidine-based (5-FU) chemotherapy is a mainstay of treatment for colorectal cancer (CRC), but only provides benefit for a subset of patients. To improve stratification we examined (for the first time in CRC), whether analysis of GRP78 expression provides a predictive biomarker and performed functional studies to examine the role of GRP78 in sensitivity to 5-FU. 396 CRC patient samples were collected in a prospective uniform manner and GRP78 expression was determined by immunohistochemistry on tissue microarrays using a well-validated antibody. Expression was correlated with clinicopathological parameters and survival. The role of GRP78 in 5-FU sensitivity was examined in CRC cells using siRNA, drug inhibition and flow cytometry. GRP78 expression was significantly elevated in cancer tissue (p < 0.0001), and correlated with depth of invasion (p = 0.029) and stage (p = 0.032). Increased overall 5-year survival was associated with high GRP78 expression (p = 0.036). Patients with stage II cancers treated by surgery alone, with high GRP78 also had improved survival (71% v 50%; p = 0.032). Stage III patients with high GRP78 showed significant benefit from adjuvant chemotherapy (52% vs. 28%; p = 0.026), whereas patients with low GRP78 failed to benefit (28% vs. 32%; p = 0.805). Low GRP78 was an independent prognostic indicator of reduced overall 5-year survival (p = 0.004; HR = 1.551; 95%CI 1.155-2.082). In vitro, inhibition of GRP78 reduces apoptosis in response to 5-FU in p53 wild-type cells. GRP78 expression may provide a simple additional risk stratification to inform the adjuvant treatment of CRC and future studies should combine analysis with determination of p53 status.

Ultrasonic Nonlinearity Experiment due to Plastic Deformation of Aluminum Plate Due to Bending Damage.

The nonlinear ultrasonic evaluation technique is useful for assessing micro-defects and microstructure changes caused by fatigue or bending damage. In particular, the guided wave is advantageous for long-distance testing such as piping and plate. Despite these advantages, the study of nonlinear guided wave propagation has received relatively less attention compared to bulk wave techniques. Furthermore, there is a lack of research on the correlation between nonlinear parameters and material properties. In this study, the relationship between nonlinear parameters and plastic deformation resulting from bending damage was experimentally investigated using Lamb waves. The findings indicated an increase in the nonlinear parameter for the specimen, which was loaded within the elastic limit. Inversely, regions of maximum deflection in specimens with plastic deformation exhibited a decrease in the nonlinear parameter. This research is expected to be helpful for maintenance technology in the nuclear power plant and aerospace fields that require high reliability and accuracy.

Reliability and Accuracy of Tomographic 3-D Ultrasound for Grading Vessel Stenosis: A Phantom Study.

The aim of this phantom study was to assess the accuracy of 3-D tomographic ultrasound (t3DUS) for grading stenosis, using the manufacturer's measurements as the gold standard. The percentage of maximum stenosis was obtained using 2-D ultrasound (2DUS) and t3DUS imaging techniques on a peripheral vascular phantom, including channels with 50%, 75% and 90% stenosis. The inter-observer reproducibility of t3DUS for grading stenosis was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Mean and mean differences were used to evaluate the accuracy of 2DUS and t3DUS in measuring maximum stenosis in all channels. Inter-operator agreement was excellent, with an ICC value of 0.99 (95% confidence interval: 0.994-0.998, p < 0.001). Bias in measurements was -0.59 ± 2.01% (95% limits of agreement: 4.54, 3.36). The mean difference (MD) between maximum stenosis measurements and reference values for all channels was lower in t3DUS than in 2DUS (t3DUS MD: +1.01%, diameter reduction 2DUS MD: -6.10%; area reduction 2DUS MD: +8.20%). Tomographic 3DUS is a reproducible and accurate imaging method for grading stenosis. The current B-mode 2DUS stenosis grading criteria used in vascular assessment may be underestimating or overestimating the percentage stenosis. Further phantom and human studies investigating the reliability of t3DUS for grading stenosis and other metrics including plaque volume are required.

Probiotics for the Chemoprotective Role against the Toxic Effect of Cancer Chemotherapy.

BACKGROUND: Chemo- and radiation therapy-based clinical management of different types of cancers is associated with toxicity and several side effects. Therefore, there is always an unmet need to explore agents that reduce such risk factors. Among these, natural products have attracted much attention because of their potent antioxidant and antitumor effects. In the past, some breakthrough outcomes established that various bacteria in the human intestinal gut are bearing growth-promoting attributes and suppressing the conversion of pro-carcinogens into carcinogens. Hence probiotics integrated approaches are nowadays being explored as rationalized therapeutics in the clinical management of cancer. METHODS: Here, published literature was explored to review chemoprotective roles of probiotics against toxic and side effects of chemotherapeutics. RESULTS: Apart from excellent anti-cancer abilities, probiotics alleviate toxicity & side effects of chemotherapeutics, with a high degree of safety and efficiency. CONCLUSION: Preclinical and clinical evidence suggests that due to the chemoprotective roles of probiotics against side effects and toxicity of chemotherapeutics, their integration in chemotherapy would be a judicious approach.