A Randomized Controlled Trial of Endovenous Laser Ablation Versus Mechanochemical Ablation With ClariVein in the Management of Superficial Venous Incompetence (LAMA Trial).

OBJECTIVE: This RCT compares the clinical, technical and quality of life outcomes after EVLA and MOCA. SUMMARY OF BACKGROUND DATA: Thermal ablation is the current mainstay treatment for SVI. Newer nonthermal methods of treatment have been developed which do not require the use of tumescent anesthesia. The potential advantages of these newer methods should be tested in RCTs to ascertain their role in the future treatments of SVI. METHODS: This single-center RCT enrolled patients with symptomatic, unilateral, single-axis SVI. Eligible patients were equally randomized to either EVLA or MOCA, both with concomitant phlebectomy when necessary. The joint primary outcomes were intraprocedural axial ablation pain scores and anatomical occlusion at 1 year. Secondary outcomes included postprocedural pain, venous clinical severity score (VCSS), quality of life (Aberdeen varicose veins questionnaire and EuroQol 5-domain utility index), patient satisfaction and complication rates. RESULTS: One hundred fifty patients were randomized equally between the 2 interventions. Both groups reported low intraprocedural pain scores; on a 100 mm visual analog scale, pain during axial EVLA was 22 (9-44) compared to 15 (9-29) during MOCA; P = 0.210. At 1 year, duplex derived anatomical occlusion rates after EVLA were 63/69 (91%) compared to 53/69 (77%) in the MOCA group; P = 0.020. Both groups experienced significant improvement in VCSS and AVVQ after treatment, without a significant difference between groups. Median VCSS improved from 6 (5-8) to 0 (0-1) at one year; P < 0.001. Median AVVQ improved from 13.8 (10.0-17.7) to 2.0 (0.0-4.9); P < 0.001. One patient in the MOCA group experienced DVT. CONCLUSIONS: Both EVLA and MOCA were highly efficacious in treating SVI; patients improved significantly in terms of disease severity, symptoms, and QoL. Both resulted in low procedural pain with a short recovery time. Axial occlusion rates were higher after EVLA. Long term follow-up is warranted to assess the effect of recanalization on the rate of clinical recurrence.

A randomised clinical trial of ultrasound guided cannulation of difficult fistulae for dialysis access.

BACKGROUND: Arteriovenous fistulae (AVF) are preferred for dialysis access but require accurate cannulation for effective dialysis. Evidence supports improvements in cannulation and complication rates using ultrasound guidance (USG) in cannulating other sites. This mixed methods, randomised controlled trial aimed to assess effects of USG during AVF cannulation. METHODS: Participants with difficult to cannulate AVF had each cannulation event randomised to USG or standard technique (no USG). The primary outcome was the incidence and number of additional needle passes. Secondary outcomes included: the incidence and number of additional skin punctures; time to achieve two needle cannulation; pain associated with cannulation; local complications. Qualitative outcomes were assessed using patient and staff questionnaires. RESULTS: Thirty-two participants had 346 cannulation events randomised (170 to USG and 176 to standard cannulation). USG resulted in a significant reduction in additional needle passes (72 vs 99 p = 0.007) and additional skin punctures (10 vs 25 p = 0.016.) but prolonged time to cannulation (p > 0.001). There was no difference in pain score (p = 0.705) or complications between groups. Questionnaires demonstrated that USG cannulation is acceptable to patients and staff. CONCLUSION: USG cannulation of AVF is more accurate and no more painful than non-image guided cannulation, but prolonged time to cannulation. Some of the excess time involved may be due to the trial being performed early in cannulating staff's learning curve with the USG technique. Further work to elucidate which patients gain most benefit from USG cannulation and the effect of USG on cannulation complications and AVF patency is warranted.

A Randomised Clinical Trial of Buffered Tumescent Local Anaesthesia During Endothermal Ablation for Superficial Venous Incompetence.

OBJECTIVE/BACKGROUND: Endovenous thermal ablation (EVTA) is the recommended first line intervention for superficial venous incompetence (SVI). While the infiltration of perivenous tumescent local anaesthesia (TLA) is key to procedural success, it is paradoxically the predominant source of patient reported discomfort. This randomised controlled trial investigates the potential to reduce peri-procedural pain and improve patient reported outcome measures (PROMs), including quality of life (QoL) using TLA buffered to physiological pH. METHODS: Patients undergoing great saphenous vein EVTA with concomitant phlebectomies were randomised to either standard (ST) or buffered (BT) TLA. Follow up assessments were performed at weeks 1, 6, and 12. The primary outcome was patient reported peri-procedural pain on a 100 mm visual analogue scale (VAS). Secondary outcomes were one week post-procedural pain VAS and analgesia use, QoL (disease specific: Aberdeen Varicose Vein Questionnaire [AVVQ]; generic: Short Form-36 [SF-36] and EuroQol 5 Dimensions Questionnaire [EQ-5D]), patient satisfaction VAS, technical success on duplex ultrasound (DUS) examination, and complications. RESULTS: Ninety-seven patients were randomised: 50 to ST and 47 to BT. The groups had comparable baseline demographics, Clinical Etiologic Anatomic Pathological, Venous Clinical Severity Score, QoL, and DUS parameters. Equally, intra-procedural parameters (volume of TLA, length of ablation, and linear energy delivered) were also comparable. Peri-procedural pain scores were significantly lower in the BT group with a mean ± SD score of 2.86 ± 3.57 versus 4.44 ± 2.94 (p = .001). Pain scores and analgesia use over the subsequent week were equivalent. SF-36 Bodily Pain domain scores were significantly better in the BT group at week 1 (77 vs. 62; p = .008). AVVQ, SF-36, and EQ-5D scores were otherwise similar between the groups throughout follow up, significantly improving over baseline. Technical success was high in both groups, with no major complications and few minor complications. CONCLUSION: Buffered TLA offers a significantly lower peri-procedural pain experience for patients undergoing EVTA and should replace current tumescent formulae.

Defining the optimum tumescent anaesthesia solution in endovenous laser ablation.

Objectives To produce a tumescent anaesthesia solution with physiological pH for endovenous thermal ablation and evaluate its influence on peri- and postoperative pain, clinical and quality of life outcomes, and technical success. Methods Tumescent anaesthetic solution (0.1% lidocaine with 1:2,000,000 epinephrine) was titrated to physiological pH by buffering with 2 ml incremental aliquots of 8.4% sodium bicarbonate. Patients undergoing great saphenous vein endovenous laser ablation and ambulatory phlebectomy were studied before and after introduction of buffered tumescent anaesthetic. Primary outcome was perioperative pain measured on a 10 cm visual analogue scale. Secondary outcomes were daily pain scores during the first postoperative week, complications, time to return to normal activity, patient satisfaction, generic and disease-specific quality of life, and technical success. Patients were assessed at baseline, and at 1, 6 and 12 weeks following the procedure. Results A physiological pH was achieved with the addition of 10 ml of 8.4% sodium bicarbonate to 1 l of standard tumescent anaesthetic solution. Sixty-two patients undergoing great saphenous vein endovenous laser ablation with phlebectomy were recruited before and after the introduction of buffered tumescent anaesthetic solution. Baseline and operative characteristics were well matched. The buffered solution was associated with significantly lower (median (interquartile range)) periprocedural pain scores (1 (0.25-2.25) versus 4 (3-6), p < 0.001) and postoperative pain score at the end of the treatment day (1.8 (0.3-2.8) versus 3.0 (1.2-5.2), p = 0.033). There were no significant differences in postoperative pain scores between the groups at any other time. There were no significant differences in other clinical outcomes between the groups. Both groups demonstrated significant improvements in generic and disease-specific quality of life, with no intergroup differences. Both groups demonstrated 100% ultrasonographic technical success at all time points. Conclusions Buffering of tumescent anaesthetic solution during endovenous thermal ablation is a simple, safe, inexpensive and effective means of reducing perioperative and early postoperative pain.

A systematic review of the compression regimes used in randomised clinical trials following endovenous ablation.

Objectives There is insufficient evidence to inform guidelines on the optimal compression strategy following ablation for varicose veins. This study aimed to identify the practice of key opinion leaders performing randomised clinical trials involving endovenous ablation. Method A systematic review of MEDLINE/EMBASE/CENTRAL was performed identifying the compression strategies used in randomised clinical trials where at least one comparator arm underwent endovenous ablation. Results Thirty-four randomised clinical trials were identified. At least 14 different compression products were used, with at least 6 different pressures in 7 different regimes with durations from 2 to 84 days. There was no evidence of any convergence of practice over time. Conclusions A lack of evidence as to the optimal strategy for compression has resulted in a marked variation in clinical practice. There is no suggestion that this variation is becoming less over time indicating that experience is not helping to form a consensus and, therefore, further research is required.

Endovenous laser ablation versus mechanochemical ablation with ClariVein(®) in the management of superficial venous insufficiency (LAMA trial): study protocol for a randomised controlled trial.

BACKGROUND: Endovenous thermal techniques, such as endovenous laser ablation (EVLA), are the recommended treatment for truncal varicose veins. However, a disadvantage of thermal techniques is that it requires the administration of tumescent anaesthesia, which can be uncomfortable. Non-thermal, non-tumescent techniques, such as mechanochemical ablation (MOCA) have potential benefits. MOCA combines physical damage to endothelium using a rotating wire, with the infusion of a liquid sclerosant. Preliminary experiences with MOCA showed good results and less post-procedural pain. METHODS/DESIGN: The Laser Ablation versus Mechanochemical Ablation (LAMA) trial is a single-centre randomised controlled trial in which 140 patients will be randomly allocated to EVLA or MOCA. All patients with primary truncal superficial venous insufficiency (SVI) who meet the eligibility criteria will be invited to participate in this trial. The primary outcomes are intra-procedural pain and technical efficacy at 1 year, defined as complete occlusion of target vein segment and assessed using duplex ultrasound. Secondary outcomes are post-procedural pain, analgesia use, procedure time, clinical severity, generic and disease-specific quality of life, bruising, complications, satisfaction, cosmesis, time taken to return to daily activities and/or work, and cost-effectiveness analysis following EVLA or MOCA. Both groups will be evaluated on an intention-to-treat basis. DISCUSSION: The aim of the LAMA trial is to establish whether MOCA is superior to the current first-line treatment, EVLA. The two main hypotheses are that MOCA may cause less initial pain and disability allowing a more acceptable treatment with an enhanced recovery. The second hypothesis is that this may come at a cost of decreased efficacy, which may lead to increased recurrence and affect longer term quality of life, increasing the requirement for secondary procedures. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02627846 , registered 8 December 2015 EudraCT number: 2015-000730-30 REC ref: 15/YH/0207 R&D ref: R1788.

Laser; best practice techniques and evidence.

Laser ablation involves the delivery of laser light through a glass fibre placed into the lumen of a refluxing vein. This energy is converted into heat inducing a permanent, non-thrombotic occlusion. This highly effective and safe approach has significant advantages over traditional surgical treatment and has driven the endovenous revolution in the management of varicose veins. This chapter will explore the mechanism of action, present the evidence of laser' clinical and cost effectiveness, and analyse specific and generic aspects of laser ablation technique.

The associations between metals/metalloids concentrations in blood plasma of Hong Kong residents and their seafood diet, smoking habit, body mass index and age.

The concentrations of metals/metalloids in blood plasma collected from 111 healthy residents (51 female, 60 male) in Hong Kong (obtained from the Hong Kong Red Cross Blood Transfusion Service, from March to April 2008) were quantified by means of a double-focusing sector field inductively coupled plasma optical emission spectrometer (ICP-OES). Results showed that concentrations of these toxic metals such as Hg, Cd, and Pb in Hong Kong residents were not serious when compared with other countries. Males accumulated significantly higher (p < 0.05 or 0.01) Fe (female 0.92 mg/L; male 1.28), Sn (0.44 µg/L; 0.60), Cr (0.77; 0.90), Hg (1.01; 1.73), and Pb (23.4; 31.6) than females. Smokers accumulated significantly higher (p < 0.05) Cd (smoker 0.27 µg/L; nonsmoker 0.17) and Pb (32.8; 17.6) than nonsmokers. Positive correlations were found between concentrations of As, Cd, Pb, and Hg, with respect to seafood diet habit, body mass index (BMI), and age. More intensive studies involving more samples are needed before a more definite conclusion can be drawn, especially on the causal relationships between concentrations of metals/metalloids with dietary preference and lifestyle of the general public.

Robotic adherent cell injection for characterizing cell-cell communication.

Compared to robotic injection of suspended cells (e.g., embryos and oocytes), fewer attempts were made to automate the injection of adherent cells (e.g., cancer cells and cardiomyocytes) due to their smaller size, highly irregular morphology, small thickness (a few micrometers thick), and large variations in thickness across cells. This paper presents a robotic system for automated microinjection of adherent cells. The system is embedded with several new capabilities: automatically locating micropipette tips; robustly detecting the contact of micropipette tip with cell culturing surface and directly with cell membrane; and precisely compensating for accumulative positioning errors. These new capabilities make it practical to perform adherent cell microinjection truly via computer mouse clicking in front of a computer monitor, on hundreds and thousands of cells per experiment (versus a few to tens of cells as state of the art). System operation speed, success rate, and cell viability rate were quantitatively evaluated based on robotic microinjection of over 4000 cells. This paper also reports the use of the new robotic system to perform cell-cell communication studies using large sample sizes. The gap junction function in a cardiac muscle cell line (HL-1 cells), for the first time, was quantified with the system.

Towards a global understanding and standardisation of education and training in microsurgery.

With an increasing emphasis on microsurgery skill acquisition through simulated training, the need has been identified for standardised training programmes in microsurgery. We have reviewed microsurgery training courses available across the six continents of the World. Data was collected of relevant published output from PubMed, MEDLINE (Ovid), and EMBASE (Ovid) searches, and from information available on the Internet of up to six established microsurgery course from each of the six continents of the World. Fellowships and courses that concentrate on flap harvesting rather than microsurgical techniques were excluded. We identified 27 centres offering 39 courses. Total course length ranged from 20 hours to 1,950 hours. Student-to-teacher ratios ranged from 2:1 to 8:1. Only two-thirds of courses offered in-vivo animal models. Instructions in microvascular end-to-end and end-to-side anastomoses were common, but peripheral nerve repair or free groin flap transfer were not consistently offered. Methods of assessment ranged from no formal assessment, where an instructor monitored and gave instant feedback, through immediate assessment of patency and critique on quality of repair, to delayed re-assessment of patency after a 12 to 24 hours period. Globally, training in microsurgery is heterogeneous, with variations primarily due to resource and regulation of animal experimentation. Despite some merit to diversity in curricula, there should be a global minimum standard for microsurgery training.

A systematic review of evidence for education and training interventions in microsurgery.

Over the past decade, driven by advances in educational theory and pressures for efficiency in the clinical environment, there has been a shift in surgical education and training towards enhanced simulation training. Microsurgery is a technical skill with a steep competency learning curve on which the clinical outcome greatly depends. This paper investigates the evidence for educational and training interventions of traditional microsurgical skills courses in order to establish the best evidence practice in education and training and curriculum design. A systematic review of MEDLINE, EMBASE, and PubMed databases was performed to identify randomized control trials looking at educational and training interventions that objectively improved microsurgical skill acquisition, and these were critically appraised using the BestBETs group methodology. The databases search yielded 1,148, 1,460, and 2,277 citations respectively. These were then further limited to randomized controlled trials from which abstract reviews reduced the number to 5 relevant randomised controlled clinical trials. The best evidence supported a laboratory based low fidelity model microsurgical skills curriculum. There was strong evidence that technical skills acquired on low fidelity models transfers to improved performance on higher fidelity human cadaver models and that self directed practice leads to improved technical performance. Although there is significant paucity in the literature to support current microsurgical education and training practices, simulated training on low fidelity models in microsurgery is an effective intervention that leads to acquisition of transferable skills and improved technical performance. Further research to identify educational interventions associated with accelerated skill acquisition is required.

Quantitative analysis of locomotive behavior of human sperm head and tail.

Sperm selection plays a significant role in in vitro fertilization (IVF). Approaches for assessing sperm quality include noninvasive techniques based on sperm morphology and motility as well as invasive techniques for checking DNA integrity. In 2006, a new device using hyaluronic acid (HA)-coated dish for sperm selection was cleared by the Food and Drug Administration (FDA) and entered IVF clinics. In this technique, only sperms with DNA integrity bind to the HA droplet, after which these bound sperm stop revealing head motion and their tail movement becomes more vigorous. However, selecting a single sperm cell from among HA-bound sperms is ad hoc in IVF clinics. Different from existing sperm tracking algorithms that are largely limited to tracking sperm head only and are only able to track one sperm at a time, this paper presents a multisperm tracking algorithm that tracks both sperm heads and low-contrast sperm tails. The tracking results confirm a significant correlation between sperm head velocity and tail beating amplitude, demonstrate that sperms bound to HA generally have a higher velocity (before binding) than those sperms that are not able to bind to HA microdots, and quantitatively reveal that HA-bound sperms' tail beating amplitudes are different among HA-bound sperms.

Controlled aspiration and positioning of biological cells in a micropipette.

Manipulating single cells with a micropipette is the oldest, yet still a widely used technique. This paper discusses the aspiration of a single cell into a micropipette and positioning the cell accurately to a target position inside the micropipette. Due to the small volume of a single cell (picoliter) and nonlinear dynamics involved, these tasks have high skill requirements and are labor intensive in manual operation that is solely based on trial and error and has high failure rates. We present automated techniques in this paper for achieving these tasks via computer vision microscopy and closed-loop motion control. Computer vision algorithms were developed to detect and track a single cell outside and inside a micropipette for automated single-cell aspiration. A closed-loop robust controller integrating the dynamics of cell motion was designed to accurately and efficiently position the cell to a target position inside the micropipette. The system achieved high success rates of 98% for cell detection and 97% for cell tracking (n = 100). The automated system also demonstrated its capability of aspirating a single cell into a micropipette within 2 s (versus 10 s by highly skilled operators) and accurately positioning the cell inside the micropipette within 8 s (versus 25 s by highly skilled operators).

Three-dimensional rotation of mouse embryos.

Research and clinical applications, such as microinjection and polar-body biopsy involve 3-D rotation of mammalian oocytes/embryos. In these cell manipulation tasks, the polar body of an embryo/oocyte must be made visible and properly oriented under optical microscopy. Cell rotation in conventional manual operation by skilled professionals is based on trial and error, such as through repeated vacuum aspiration and release. The randomness of this manual procedure, its poor reproducibility, and inconsistency across operators entail a systematic technique for automated, noninvasive, 3-D rotational control of single cells. This paper reports a system that tracks the polar body of mouse embryos in real time and controls multiple motion control devices to conduct automated 3-D rotational control of mouse embryos. Experimental results demonstrated the system's capability for polar-body orientation with a high success rate of 90%, an accuracy of 1.9 °, and an average speed of 22.8 s/cell (versus averagely 40 s/cell in manual operation).

Lipopolysaccharide-induced nigral inflammation leads to increased IL-1ß tissue content and expression of astrocytic glial cell line-derived neurotrophic factor.

Reactive gliosis and inflammatory change is a key component of nigral dopaminergic cell death in Parkinson's disease (PD). Astrocyte derived glial cell line-derived neurotrophic factor (GDNF) promotes the survival and growth of dopaminergic neurones and it protects against or reverses nigral degeneration induced by 6-OHDA and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rodents and primates. But the effect of increased levels of pro-inflammatory cytokines on the release of GDNF is unknown. This study examined the relationship between release of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and the expression of GDNF in rats following nigral lipopolysaccharide (LPS) administration. Acute nigral administration of LPS led to marked elevation of IL-1ß but insignificant TNF-α tissue content and to a prominent expression of GDNF immunoreactivity in astrocytes but not microglia. The results suggest that inflammation is not only involved in neuronal loss but could promote neuronal survival through increased release of GDNF following up-regulation of IL-1ß.

Robotic ICSI (intracytoplasmic sperm injection).

This paper is the first report of robotic intracytoplasmic sperm injection (ICSI). ICSI is a clinical procedure performed worldwide in fertility clinics, requiring pick-up of a single sperm and insertion of it into an oocyte (i.e., egg cell). Since its invention 20 years ago, ICSI has been conducted manually by a handful of highly skilled embryologists; however, success rates vary significantly among clinics due to poor reproducibility and inconsistency across operators. We leverage our work in robotic cell injection to realize robotic ICSI and aim ultimately, to standardize how clinical ICSI is performed. This paper presents some of the technical aspects of our robotic ICSI system, including a cell holding device, motion control, and computer vision algorithms. The system performs visual tracking of single sperm, robotic immobilization of sperm, aspiration of sperm with picoliter volume, and insertion of sperm into an oocyte with a high degree of reproducibility. The system requires minimal human involvement (requiring only a few computer mouse clicks), and is human operator skill independent. Using the hamster oocyte-human sperm model in preliminary trials, the robotic system demonstrated a high success rate of 90.0% and survival rate of 90.7% (n=120).

Halogenated POPs and PAHs in blood plasma of Hong Kong residents.

The objective of this study was to quantify organic chlorinated pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs) in blood plasma collected from 111 healthy residents in Hong Kong to assess the levels of these pollutants in the general population during the period of March to April, 2008. Concentrations of these residues in blood plasma obtained from the Hong Kong Red Cross Blood Transfusion Service were determined by gas chromatography-mass spectrometry. Naphthalene, phenanthrene, p,p'-DDE, PCB-180, and PBDE-47 were detected in 100% of the participants. Females had significantly greater concentrations of acenaphthylene (female: 93.3 ng/g lipid; male: 39.8, p < 0.05), anthracene (22.3; 15.3, p < 0.05), fluoranthene (138; 125, p < 0.05), p,p'-DDE, p,p'-DDT, PCB-183, BDE-99 than males. Blood of smokers contained significantly greater (p < 0.05) concentrations of acenaphthene, benzo(a)pyrene, p,p'-DDE, p,p'-DDT, PCB-138, BDE-47, and BDE-99 than did blood of nonsmokers. Positive correlations were found between concentrations of each class of pollutant, with respect to seafood diet habit, Body Mass Index (BMI), and age. Concentrations of HCHs and DDTs in blood plasma of healthy Hong Kong residents were greater than those of other countries, and it was found that smoking, consumption of a seafood diet, BMI, and age could influence concentrations in human blood.