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1.
JACS Au ; 4(6): 2335-2342, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38938813

ABSTRACT

Recovering precious metals from electronic waste (e-waste) using microbes presents a sustainable methodology that can contribute toward the maintenance of planetary health. To better realize the potential of bioremediation using engineered microbes, enzymes that mediate the reduction of Au(III) to Au(0) have been the subject of intense research. In this study, we report the successful engineering of a metal reductase, MerA, whose cognate substrate is mercury(II), toward other precious metals such as Au(III) and Ag(I). The engineered variant, G415I, exhibited a 15-fold increase in catalytic efficiency (k cat/K M) in Au(III) reduction to Au(0) and a 200-fold increase in catalytic efficiency in Ag(I) reduction to Ag(0) with respect to the wild-type enzyme. The apparent shift in preference toward noncognate metal ions may be attributed to the energetics of valency preference. The improved Au(III) reductase has an apparent increased preference toward monovalent cations such as Au(I) and Ag(I), with respect to divalent cations such as Hg(II), the cognate substrate of the progenitor MerA (an increase in K M of 5.0-fold for Hg(II), compared to a decrease in K M of 5.8-fold for Au(III) and 1.8-fold for Ag(I), respectively). This study further extends the mechanistic understanding of Au(III) bioreduction that could proceed through the stabilization of Au(I) en route to Au(0) and suggests that the biosynthesis of Au nanoparticles with high efficiency can be realized through the engineering of promiscuous metal reductases for precious metal recovery from e-wastes.

2.
J Clin Microbiol ; 61(9): e0031623, 2023 09 21.
Article in English | MEDLINE | ID: mdl-37671882

ABSTRACT

NG-Test CARBA 5 (NG-Biotech) is a rapid in vitro multiplex immunoassay for the phenotypic detection and differentiation of the "big five" carbapenemase families (KPC, OXA-48-like, VIM, IMP, and NDM). Version 2 of this assay was evaluated alongside the Xpert Carba-R assay (Cepheid, Inc.), the modified carbapenem inactivation method (mCIM), and the CIMTris assay, with a collection of carbapenem-resistant non-fermenting Gram-negative bacilli comprising 138 Pseudomonas aeruginosa and 97 Acinetobacter baumannii isolates. Whole-genome sequencing (WGS) was used as the reference standard. For P. aeruginosa, NG-Test CARBA 5 produced an overall percentage agreement (OPA) with WGS of 97.1%, compared with 92.8% forXpert Carba-R and 90.6% for mCIM. For A. baumannii, as OXA-type carbapenemases (non-OXA-48) are not included, both the NG-Test CARBA 5 and Xpert Carba-R only had an OPA of 6.2%, while the CIMTris performed well with an OPA of 99.0%. The majority of A. baumannii isolates (95.9%) tested falsely positive for IMP on NG-Test CARBA 5; no IMP genes were found on WGS. No clear cause was found for this phenomenon; a cross-reacting protein antigen unique to A. baumannii is a possible culprit. NG-Test CARBA 5 performed well for carbapenemase detection in P. aeruginosa. However, results from A. baumannii isolates should be interpreted with caution.


Subject(s)
Bacterial Proteins , beta-Lactamases , Humans , Bacterial Proteins/genetics , beta-Lactamases/genetics , Whole Genome Sequencing , Carbapenems/pharmacology , Gram-Negative Bacteria/genetics , Pseudomonas aeruginosa/genetics
3.
Cardiovasc Intervent Radiol ; 45(11): 1663-1669, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35237860

ABSTRACT

PURPOSE: Drug-coated balloon angioplasty (DCBA) has been studied as a potentially superior option compared to conventional percutaneous transluminal angioplasty (PTA) in treating below-the-knee (BTK) arteries in chronic limb-threatening ischemia (CLTI). The aim of this study is to examine the cost-effectiveness of DCBA versus PTA in BTK arteries based on a randomized controlled trial. MATERIAL AND METHODS: A prospective economic study was embedded in a randomized controlled trial of 138 patients with CLTI. Resource use and health outcomes were assessed at baseline, and at 3, 6 and 12 months post-intervention. Costs were calculated from a societal perspective and health outcomes measured using quality-adjusted life years with probabilistic sensitivity analysis performed to account for subject heterogeneity. RESULTS: Compared with participants randomized to receive PTA, participants randomized to DCBA gained an average baseline-adjusted quality-adjusted life years (QALYs) of .012 while average total costs were USD$1854 higher; this translates to an incremental cost-effectiveness ratio (ICER) of US$154,500 additional cost per QALY gained. However, the estimate of ICER had substantial variance with only 48% of bootstrap ICERs meeting a benchmark threshold of US$57,705 (the average gross domestic product (GDP) per capita of Singapore). CONCLUSION: The use of DCBA in BTK arteries in CLTI patients was not cost-effective compared with PTA. LEVEL OF EVIDENCE: 2, Randomized trial.


Subject(s)
Angioplasty, Balloon , Chronic Limb-Threatening Ischemia , Humans , Cost-Benefit Analysis , Prospective Studies , Treatment Outcome , Angioplasty, Balloon/adverse effects , Popliteal Artery , Angioplasty , Ischemia/therapy
5.
Cardiovasc Intervent Radiol ; 45(5): 646-653, 2022 May.
Article in English | MEDLINE | ID: mdl-35059796

ABSTRACT

PURPOSE: To study the safety and efficacy of cutting balloon angioplasty (CBA) followed by paclitaxel drug-coated balloon (PCB) angioplasty for recurrent venous lesions in arteriovenous fistulas (AVFs). MATERIALS AND METHODS: We conducted a prospective single-arm cohort study of CBA followed by PCB angioplasty for recurrent AVF stenoses between September 2017 and April 2019. In total, 44 participants were recruited. Target lesions were included if they had recurred within 12 months post-angioplasty, were > = 0.5 cm upstream from the arteriovenous anastomosis, and did not involve the central veins. Up to two non-target lesions per circuit/participant with the same definition were allowed. Lesions were considered separate when there was an intervening 2-cm segment of normal vessel. Technical success was defined as complete lesion effacement on angioplasty. End-points of target and circuit patency were evaluated clinically at 3, 6, and 12 months post-procedure. RESULT: Technical success was 96% (42/44): Two participants were excluded from analysis due to the need for high-pressure balloon angioplasty as the target lesions did not efface with CBA. The median follow-up duration was 337.5 days. Mean stenosis pre- and post-angioplasty was 69.0% (51.6-84.8) and 20.8% (0-44.8), respectively. The target lesion primary, primary assisted and circuit patency for the entire study population (n = 42) were 61.6 ± 7.8%, 92.7 ± 4.0%, and 54.7 ± 7.9%, respectively, at 12 months. For participants without non-target lesions (n = 22), the rates were 77.3 ± 8.9%, 90.9 ± 6.1%, and 60.7 ± 11.0%, respectively, at 12 months. CONCLUSION: CBA followed by PCB angioplasty appears safe and feasible for treatment of recurrent venous lesions in dysfunctional AVFs.


Subject(s)
Angioplasty, Balloon , Arteriovenous Fistula , Arteriovenous Shunt, Surgical , Angioplasty, Balloon/methods , Coated Materials, Biocompatible , Cohort Studies , Constriction, Pathologic/therapy , Humans , Paclitaxel , Prospective Studies , Renal Dialysis , Treatment Outcome , Vascular Patency
6.
Eur Arch Otorhinolaryngol ; 279(6): 3139-3146, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34739578

ABSTRACT

BACKGROUND: The management of thyroid nodules ≥ 4 cm is controversial due to conflicting evidence on the prevalence of malignancy and diagnostic accuracy of fine-needle aspiration cytology (FNAC). Some literature recommends routine excision of large thyroid nodules due to high cytology false negative rates (FNR). We aim to investigate the diagnostic accuracy of FNAC, prevalence of malignancy in large (≥ 4 cm) thyroid nodules compared to nodules < 4 cm, and the clinical and ultrasound characteristics of those large nodules with false negative cytology. METHODS: This was a retrospective case-log review in a tertiary referral hospital. All thyroid nodules subjected to Ultrasound (US)-guided FNAC by the Interventional Radiology department between December 2011 and November 2017 were included. Data on patient demographics, thyroid US features, cytology findings, and surgical histology were collected and analyzed. Sensitivity, specificity, and FNR were calculated based on FNAC results and final post-operative histology. Factors associated with a false negative result were analyzed using univariate and multivariate analyses. RESULTS: A total of 4982 nodules were studied, including 4419 < 4 cm and 563 ≥ 4 cm. Malignancy rates were similar in both groups. For nodules ≥ 4 cm, FNAC sensitivity was 40%, specificity 100%, and FNR 6.6% compared to 4.2% in nodules < 4 cm. Within malignant nodules, there was a significantly higher proportion of follicular and Hurthle cell carcinomas in nodules ≥ 4 cm. Amongst nodules ≥ 4 cm, multivariate analysis revealed male gender to be an independent predictor of FNR (OR 3.32; 95% CI 1.29-8.59). CONCLUSION: Larger nodules ≥ 4 cm have a similar malignancy rate as nodules < 4 cm, and FNAC FNR is low at 6.6%. Management of large thyroid nodules should be individualized based on their clinical, sonographic and cytological features rather than routine surgery.


Subject(s)
Thyroid Neoplasms , Thyroid Nodule , Biopsy, Fine-Needle , Humans , Male , Retrospective Studies , Sensitivity and Specificity , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/surgery , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/surgery
7.
Trials ; 22(1): 945, 2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34930401

ABSTRACT

BACKGROUND: Percutaneous transluminal angioplasty is the current standard treatment for arteriovenous fistula (AVF) stenosis. The mid- and long-term patency with plain balloon angioplasty (PBA) is however far from satisfactory. While paclitaxel-coated balloon angioplasty has been shown to be superior to PBA, concern over its safety profile has recently arisen after a reported possible increased mortality risk with a meta-analysis of large lower limb studies. An angioplasty balloon with a new type of drug coating, the sirolimus-coated balloon (SCB), has been proven to improve patency in the coronary arteries. However, its effect on AV access has yet to be studied. METHODS/DESIGN: This is an investigator-initiated, prospective, multicenter, double-blinded, randomized controlled clinical trial to assess the effectiveness of SCB compared to PBA in improving the patency of AVF after angioplasty. A total of 170 patients with mature AVF that requires PTA due to AVF dysfunction will be randomly assigned to treatment with a SCB or PBA at a 1:1 ratio, stratified by location of AVF and followed up for up to 1 year. The inclusion criteria include [1] adult patient aged 21 to 85 years who requires balloon angioplasty for dysfunctional arteriovenous fistula [2]; matured AVF, defined as being in use for at least 1 month prior to the angioplasty; and [3] successful angioplasty of the underlying stenosis with PBA, defined as less than 30% residual stenosis on digital subtraction angiography (DSA) and restoration of thrill in the AVF on clinical examination. The exclusion criteria include thrombosed or partially thrombosed access circuit at the time of treatment, presence of symptomatic or angiographically significant central vein stenosis that requires treatment with more than 30% residual stenosis post angioplasty, and existing stent placement within the AVF circuit. The primary endpoint of the study is access circuit primary patency at 6 months. The secondary endpoints are target lesion primary patency; access circuit-assisted primary patency; access circuit secondary patency at 3, 6, and 12 months; target lesion restenosis rate at 6 months; total number of interventions; complication rate; and cost-effectiveness. The trial is supported by Concept Medical. DISCUSSION: This study will evaluate the clinical efficacy and safety of SCB compared to PBA in the treatment of AVF stenosis in hemodialysis patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04409912 . Registered on 1 June 2020.


Subject(s)
Angioplasty, Balloon , Sirolimus , Angioplasty, Balloon/adverse effects , Humans , Multicenter Studies as Topic , Paclitaxel , Prospective Studies , Randomized Controlled Trials as Topic , Renal Dialysis/adverse effects , Sirolimus/adverse effects
8.
Eur J Vasc Endovasc Surg ; 62(4): 610-621, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34362627

ABSTRACT

OBJECTIVE: To perform an individual patient data level meta-analysis of randomised controlled trials comparing drug coated balloon angioplasty (DCB) against conventional percutaneous transluminal angioplasty (PTA) in the treatment of dysfunctional haemodialysis venous access. METHODS: A search was conducted from inception to 13 November 2020. Kaplan-Meier curves comparing DCB with PTA by target lesion primary patency (TLPP) and access circuit primary patency (ACPP) were graphically reconstructed to retrieve patient level data. One stage meta-analyses with Cox models with random effects shared frailties were conducted to determine hazard ratios (HRs). Dynamic restricted mean survival times (RMST) were conducted in view of violation of the proportional hazards assumption. Conventional two stage meta-analyses and network meta-analyses under random effects Frequentist models were conducted to determine overall and comparative outcomes of paclitaxel concentrations used. Where outliers were consistently detected through outlier and influence analyses, sensitivity analyses excluding those studies were conducted. RESULTS: Among 10 RCTs (1 207 patients), HRs across all models favoured DCB (one stage shared frailty HR 0.62, 95% CI 0.53 - 0.73, p < .001; two stage random effects HR 0.60, 95% CI 0.42 - 0.86, p = .018, I2 = 65%) for TLPP. Evidence of time varying effects (p = .005) was found. TLPP RMST was + 3.54 months (25.0%) longer in DCB treated patients compared with PTA (p = .001) at three years. TLPP at six months, one year, and two years was 75.3% vs. 58.1%, 51.1% vs. 37.1%, and 31.4% vs. 26.0% for DCB and PTA, respectively. The P-Scores within the Frequentist network meta-analysis suggest that higher concentrations of paclitaxel were associated with better TLPP and ACPP. Among six RCTs (854 patients), the one stage model favoured DCB (shared frailty HR 0.72, 95% CI 0.60 - 0.87, p < .001) for ACPP. Conversely, the two stage random effects model demonstrated no significant difference (HR 0.76, 95% CI 0.35 - 1.67, p = .41, I2 = 81%). Sensitivity analysis excluding outliers significantly favoured DCB (HR 0.61, 95% CI 0.41 - 0.91, p = .027, I2 = 62%). CONCLUSION: Overall evidence suggests that DCB is favoured over PTA in TLPP and ACPP.


Subject(s)
Angioplasty, Balloon/instrumentation , Arteriovenous Shunt, Surgical/adverse effects , Cardiovascular Agents/administration & dosage , Coated Materials, Biocompatible , Graft Occlusion, Vascular/therapy , Renal Dialysis , Vascular Access Devices , Adult , Aged , Aged, 80 and over , Angioplasty, Balloon/adverse effects , Cardiovascular Agents/adverse effects , Female , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/physiopathology , Humans , Male , Middle Aged , Randomized Controlled Trials as Topic , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Vascular Patency
9.
Br J Radiol ; 94(1124): 20210061, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-34106779

ABSTRACT

Hepatic venous pressure gradient (HVPG) is the gold-standard for measurement of portal hypertension, a common cause for life-threatening conditions such as variceal bleeding and hepatic encephalopathy. HVPG also plays a crucial role in risk stratification, treatment selection and assessment of treatment response. Thus recognition of common pitfalls and unusual hepatic venous conditions is crucial. This article aims to provide a radiographical and clinical guide to HVPG with representative clinical cases.


Subject(s)
Hypertension, Portal/diagnostic imaging , Hypertension, Portal/physiopathology , Portal Pressure , Adult , Female , Humans , Male , Middle Aged
10.
J Vasc Interv Radiol ; 32(3): 369-375, 2021 03.
Article in English | MEDLINE | ID: mdl-33334667

ABSTRACT

PURPOSE: To investigate the use of a sirolimus drug-coated balloon (DCB) in the management of a thrombosed arteriovenous graft (AVG). MATERIALS AND METHODS: A single-center prospective pilot study was conducted between October 2018 and October 2019. Twenty patients (age = 67.0 years ± 10; male = 35%; mean time on dialysis = 31 months) with thrombosed upper limb AVG were enrolled. After successful pharmacomechanical thrombectomy and adequate treatment of the graft vein junction, sirolimus DCB angioplasty was performed at the graft vein junction. The patients were followed-up for 6 months, and all adverse events occurring during the study period were recorded. RESULTS: The primary circuit patency rates at 3 and 6 months were 76% and 65%, respectively, while the assisted-primary circuit patency rates at 3 and 6 months were 82% and 65%, respectively. The 3- and 6-month secondary circuit patency rates were 88% and 76%, respectively. Using Kaplan-Meier analyses, the estimated mean primary, assisted-primary, and secondary patencies were 285 days (95% confidence interval (CI) = 194-376 days), 319 days (95% CI = 221-416 days), and 409 days (95% CI = 333-485 days). No adverse event directly related to sirolimus DCB use was observed. CONCLUSIONS: The results of this pilot study suggest that the application of sirolimus DCB at the graft vein junction after the successful thrombectomy of AVG may be a feasible option to improve patency outcomes.


Subject(s)
Angioplasty, Balloon/instrumentation , Arteriovenous Shunt, Surgical/adverse effects , Blood Vessel Prosthesis Implantation/adverse effects , Cardiovascular Agents/administration & dosage , Coated Materials, Biocompatible , Graft Occlusion, Vascular/therapy , Renal Dialysis , Sirolimus/administration & dosage , Thrombosis/therapy , Vascular Access Devices , Aged , Angioplasty, Balloon/adverse effects , Female , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/physiopathology , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Recurrence , Risk Factors , Thrombectomy , Thrombosis/diagnostic imaging , Thrombosis/physiopathology , Time Factors , Treatment Outcome , Vascular Patency
11.
Abdom Radiol (NY) ; 46(4): 1737-1745, 2021 04.
Article in English | MEDLINE | ID: mdl-33052468

ABSTRACT

OBJECTIVE: To describe rates and management strategies of arterial dissections in transarterial chemoembolization (TACE) and Yttrium-90 selective internal radiotherapy (90Y SIRT) for primary and secondary liver tumours. MATERIALS AND METHODS: This retrospective review included 1377 hepatic angiographies between May 2010 and June 2015 in a single centre for TACE and 90Y SIRT of liver tumours. The angiogram results, management, treatment outcomes and follow-up angiography/imaging findings were recorded. RESULTS AND DISCUSSION: Twelve cases of arterial dissections (12/1377, 0.87%) were documented. Three dissections (3/633, 0.47%) occurred during TACE, seven (7/449, 1.56%) during pre-treatment planning angiographies (PTPA) for 90Y SIRT, and two (2/249, 0.80%) during the treatment procedure of 90Y SIRT. The preferred management strategy was to manoeuvre past the dissection and complete the procedure, which was achieved in six patients (50%). Angioplasty with stenting was performed in one patient. In three patients, the procedure was held off for up to 3 months to allow the dissection to heal before repeating the procedure. A dissection that occurred during PTPA was detected only when the patient returned for 90Y SIRT. PTPA was immediately repeated for this patient. The last patient opted for sorafenib. Residual 50% stenosis was seen in one patient on follow-up hepatic angiography, but he was otherwise asymptomatic. In the remaining patients, no residual dissection or clinical sequelae was observed on follow-up. CONCLUSION: Arterial dissection is a rare but important complication of transarterial locoregional therapy. Where possible, attempts should be made at completing the therapy. Deferring treatment can be considered as dissections usually heal within 3 months. LEVEL OF EVIDENCE: Level 4, case series.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/radiotherapy , Dissection , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/radiotherapy , Male , Retrospective Studies , Treatment Outcome , Yttrium Radioisotopes/therapeutic use
12.
J Vasc Access ; 22(3): 457-461, 2021 May.
Article in English | MEDLINE | ID: mdl-32715861

ABSTRACT

OBJECTIVES: Usual short- to mid-term vascular accesses for oncologic patients include the peripherally inserted central catheter and non-tunnelled centrally inserted central catheters, inserted in the supraclavicular or infraclavicular area. Peripherally inserted central catheters can be restrictive in active patients; supraclavicular non-tunnelled centrally inserted central catheters are not ideal in terms of exit site location and cosmesis, while infraclavicular non-tunnelled centrally inserted central catheters may be associated with puncture-related complications. In this pilot study, we have evaluated the off-label use of peripherally inserted central catheters as a tunnelled supraclavicular centrally inserted central catheter. METHODS: Ten patients were recruited for this prospective study. A non-cuffed, power injectable peripherally inserted central catheter was inserted via a short subcutaneous tunnel into the internal jugular vein using the peel-away sheath and introducer as a tunneller. Puncture wounds were closed with tissue glue. Patients were followed up for comfort scores, dwell time and complications. RESULTS: The median dwell time was 94 days (mean of 113 days). One catheter was removed due to systemic fungemia, resulting in an acceptable complication rate of 0.97 per 1000 catheter days.Mean patient-reported comfort scores was 16 (out of 20). Pressurised injections for computer tomography imaging were performed in five patients without complications. CONCLUSION: Despite limited numbers, this method appears to be safe and well accepted with low complication rates. This modified vascular access is low profile, easily concealed, readily removable and compatible with pressure injector and uses a commonly found catheter in a modified fashion. Larger prospective trials will be needed to ascertain if it can be a standard of care for oncological patients.


Subject(s)
Antineoplastic Agents/administration & dosage , Catheterization, Central Venous/instrumentation , Catheterization, Peripheral/instrumentation , Catheters, Indwelling , Central Venous Catheters , Contrast Media/administration & dosage , Neoplasms/drug therapy , Vena Cava, Inferior , Administration, Intravenous , Adult , Aged , Catheterization, Central Venous/adverse effects , Catheterization, Peripheral/adverse effects , Device Removal , Equipment Design , Humans , Injections, Intravenous , Middle Aged , Neoplasms/diagnostic imaging , Neoplasms/mortality , Pilot Projects , Prospective Studies , Punctures , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
13.
J Vasc Interv Radiol ; 31(12): 1969-1977.e1, 2020 12.
Article in English | MEDLINE | ID: mdl-33139186

ABSTRACT

PURPOSE: To review outcomes of patients with critical limb ischemia (CLI) who underwent conventional percutaneous transluminal angioplasty (PTA) as first-line treatment for revascularization. MATERIALS AND METHODS: Retrospective review of 3,303 angioplasty procedures on 2,402 limbs in 1,968 patients with CLI was conducted. Mean patient age was 68 years ± 11, and 1,057 patients (54%) were male. Diabetes mellitus (DM) was present in 1,736 patients (88%), and end-stage renal disease (ESRD) in 579 (29%). A majority of patients (90%) had tissue loss. Limb salvage rates were generated by Kaplan-Meier plot. Univariate and multivariate Cox regression analysis was conducted to investigate associations between clinical predictors and time-to-event outcome. RESULTS: Limb salvage rates at 1, 3, 5, and 10 years were 75%, 73%, 72%, and 62%, respectively, and overall survival rates were 79%, 64%, 56%, and 34%, respectively. In multivariable Cox regression analysis with the outcome of major amputation, significant predictors included age < 69 years (P = .032), Malay race (P = .029), DM (P < .001), history of cerebral vascular disease (P = .003), ESRD (P < .001), Rutherford classification (P = .042), repeat intervention (P = .034), and number of straight-line flows (P < .001) and plantar arch integrity (P < .001) on completion angiography. Significant associations with mortality were age < 69 years (P < .001), male sex (P = .030), Malay race (P = .027), history of ischemic heart disease (P < .001), ESRD (P < .001), and repeat intervention (P < .001). CONCLUSIONS: PTA as first-line revascularization for patients with CLI is safe and effective. Further studies are suggested to validate the outcome predictive model.


Subject(s)
Angioplasty, Balloon , Ischemia/therapy , Limb Salvage , Peripheral Arterial Disease/therapy , Aged , Amputation, Surgical , Angioplasty, Balloon/adverse effects , Angioplasty, Balloon/instrumentation , Angioplasty, Balloon/mortality , Comorbidity , Critical Illness , Databases, Factual , Female , Humans , Ischemia/diagnostic imaging , Ischemia/mortality , Limb Salvage/adverse effects , Limb Salvage/mortality , Male , Middle Aged , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/mortality , Retrospective Studies , Risk Assessment , Risk Factors , Singapore , Stents , Tertiary Care Centers , Time Factors , Treatment Outcome
14.
J Radiol Case Rep ; 14(4): 8-20, 2020 Apr.
Article in English | MEDLINE | ID: mdl-33082919

ABSTRACT

Stenting is necessary when vascular patency is not adequately achieved with angioplasty alone. Common causes of pseudoaneurysms are iatrogenic and traumatic. We describe a case of a perforated left subclavian vein Gianturco stent causing a pseudoaneurysm of the left common carotid artery in a patient with granulomatosis with polyangiitis, detected 8 years after stent insertion.


Subject(s)
Aneurysm, False , Granulomatosis with Polyangiitis , Aneurysm, False/etiology , Granulomatosis with Polyangiitis/complications , Humans , Stents/adverse effects , Subclavian Artery , Subclavian Vein
15.
Ultrasound ; 28(3): 155-163, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32831888

ABSTRACT

INTRODUCTION: The aim of this study was to identify the ultrasound features which are associated with malignancy in subcentimetre thyroid nodules. METHODS: This retrospective study included 454 thyroid nodules <10 mm in size in 413 patients from 2012 to 2016, which were subjected to fine needle aspiration cytology. Each nodule was classified according to the ultrasound patterns of the 2015 American Thyroid Association guidelines and the high suspicion ultrasound features (solid, hypo-echogenicity, irregular margins, microcalcifications, taller-than-wide, interrupted rim calcifications, and extrathyroidal extension) were identified for evaluation of their diagnostic performance. RESULTS: Of the American Thyroid Association high suspicion ultrasound features, univariate analysis showed that hypo-echogenicity (sensitivity 81.6% (95% CI 65.7-92.3%), specificity 50.0% (95% CI 43.4-56.6%)), irregular margins (sensitivity 34.2% (95% CI 19.6-51.4%), specificity 92.2% (95% CI 88.0-95.3%)), microcalcifications (sensitivity 23.7% (95% CI 11.4-40.2%), specificity 91.0% (95% CI 86.5-94.3%)), and taller-than-wide (sensitivity 23.7% (95% CI 11.4-40.2%), specificity 92.2% (95% CI 88.0-95.3%)) were significantly associated with a malignant diagnosis. Amongst the above features, subsequent multivariate analysis identified a combination of hypo-echogenicity and irregular margins as significantly associated with malignancy. Our malignancy rates based on American Thyroid Association ultrasound patterns from benign to high suspicion were 0.0, 8.3, 3.9, 15.7, and 40.4%, respectively. The American Thyroid Association high suspicion ultrasound pattern had a sensitivity of 50.0% (95% CI 33.4-66.7%) and specificity of 84.5% (95% CI 79.2-88.9%). CONCLUSION: The presence of both hypo-echogenicity and irregular margins was significantly associated with malignancy in subcentimetre thyroid nodules in our study. Hence, subcentimetre nodules which are hypoechoic with irregular margins may warrant further follow-up.

16.
ACS Synth Biol ; 9(7): 1725-1735, 2020 07 17.
Article in English | MEDLINE | ID: mdl-32497424

ABSTRACT

Terminal deoxynucleotidyl transferase (TdT) catalyzes template free incorporation of arbitrary nucleotides onto single-stranded DNA. Due to this unique feature, TdT is widely used in biotechnology and clinical applications. One particularly tantalizing use is the synthesis of long de novo DNA molecules by TdT-mediated iterative incorporation of a 3' reversibly blocked nucleotide, followed by deblocking. However, wild-type (WT) TdT is not optimized for the incorporation of 3' modified nucleotides, and TdT engineering is hampered by the fact that TdT is marginally stable and only present in mesophilic organisms. We sought to first evolve a thermostable TdT variant to serve as backbone for subsequent evolution to enable efficient incorporation of 3'-modified nucleotides. A thermostable variant would be a good starting point for such an effort, as evolution to incorporate bulky modified nucleotides generally results in lowered stability. In addition, a thermostable TdT would also be useful when blunt dsDNA is a substrate as higher temperature could be used to melt dsDNA. Here, we developed an assay to identify thermostable TdT variants. After screening about 10 000 TdT mutants, we identified a variant, named TdT3-2, that is 10 °C more thermostable than WT TdT, while preserving the catalytic properties of the WT enzyme.


Subject(s)
DNA Nucleotidylexotransferase/chemistry , DNA Nucleotidylexotransferase/genetics , Mutant Proteins/chemistry , Protein Engineering/methods , Temperature , Amino Acid Sequence , Animals , Catalysis , Cattle , DNA Nucleotidylexotransferase/isolation & purification , DNA, Single-Stranded/chemistry , DNA-Directed DNA Polymerase/chemistry , DNA-Directed DNA Polymerase/genetics , DNA-Directed DNA Polymerase/isolation & purification , Escherichia coli/genetics , Escherichia coli/metabolism , Kinetics , Mutagenesis , Oligonucleotides/chemistry , Plasmids/genetics
17.
Cardiovasc Intervent Radiol ; 43(7): 963-970, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32409998

ABSTRACT

PURPOSE: The exact significance of type 2 endoleaks (T2ELs) and the indication and efficacy of treatment are widely debated. We report our experience with managing T2ELs in a tertiary Asian centre. MATERIALS AND METHODS: This was a retrospective study of patients who underwent endovascular abdominal aortic aneurysm repair (EVAR) between February 2006 and December 2016. Patients with T2ELs were identified, and their data were analysed. RESULTS: A total of 156 patients underwent EVAR, of which 67 (42.9%) developed T2ELs. Seven were lost to follow-up. The remaining 60 patients had a mean follow-up period of 50.3 ± 33.9 months-34 (56.7%) experienced T2ELs early and the rest (43.3%) had late T2ELs. Forty-one patients had isolated T2EL, whilst 19 had concomitant T1EL and/or T3EL. Spontaneous resolution occurred in 25 patients (41.7%). All T2ELs with stable sac size were on continued surveillance. Amongst those with persistent T2ELs associated with sac growth (n = 17), 14 underwent intervention, of which 7 (50%) received > 1 embolisation procedure. A total of 16 transarterial embolisation and 8 translumbar embolisation procedures were performed. Technical success rate was 75%. In the intervention group, 5 (35.7%) had complete and sustained resolution, 7 had persistent/recurrent T2ELs but stable sac size, and 2 had progressive sac expansion. Overall mortality due to sac rupture occurred in 2 patients with concomitant T2EL and T1EL/T3EL. CONCLUSION: T2ELs are common, albeit mostly benign if occurring in isolation and not in association with sac growth. Achieving complete T2EL resolution with embolisation is difficult even with reinterventions. LEVEL OF EVIDENCE: Level 2B, retrospective study.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Embolization, Therapeutic/methods , Endoleak/therapy , Aged , Angiography, Digital Subtraction/methods , Endoleak/diagnostic imaging , Female , Humans , Male , Retrospective Studies , Treatment Outcome
18.
Singapore Med J ; 60(4): 188-192, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31069400

ABSTRACT

INTRODUCTION: This study aimed to assess safety, local tumour progression (LTP) and risk factors for LTP after radiofrequency ablation (RFA) of liver tumours in a single centre. METHODS: All consecutive patients treated with RFA for liver tumours between January 2009 and October 2012 were included. Previously treated lesions that progressed were excluded. Using electronic medical records, the following data was captured: patient demographics, pre-procedural laboratory results, Child-Pugh status, tumour characteristics, development of tumoral seeding, RFA complications and LTP. Possible risk factors for LTP were identified using Cox regression. RESULTS: In total, 555 liver tumours were treated in 337 patients. 483 (87.0%) hepatocellular carcinomas, 52 (9.4%) colorectal metastases and 20 (3.6%) other tumour types were treated. Mean tumour size was 2.1 ± 1.1 (range 0.4-6.8) cm. Mean follow-up duration was 387 days. 416 (75.0%) lesions had no LTP at the last imaging. 70 (12.6%) patients had minor complications requiring observation, while 7 (1.3%) patients had significant complications requiring prolonged hospitalisation or further interventions. Only one case of tumour seeding was detected. Using multivariate Cox regression, the following factors were statistically significant in predicting LTP: hilar location (relative ratio [RR] 3.988), colorectal metastases (RR 2.075), size (RR 1.290) and younger age (RR 0.982). CONCLUSION: RFA of liver tumours is safe and effective, with a low significant complication rate of 1.3%. Hilar lesions are most prone to LTP, followed by lesions that were larger in size and colorectal metastases. 75.0% of patients showed no LTP at the last follow-up.


Subject(s)
Carcinoma, Hepatocellular/surgery , Disease Progression , Liver Neoplasms/surgery , Radiofrequency Ablation/methods , Aged , Female , Humans , Male , Middle Aged , Neoplasm Seeding , Radiofrequency Ablation/adverse effects , Retrospective Studies , Risk Factors
19.
Obes Res Clin Pract ; 13(4): 404-407, 2019.
Article in English | MEDLINE | ID: mdl-30975589

ABSTRACT

Data on attitudes and perceptions towards obesity are lacking in Asia. Participants who attended an obesity public forum were surveyed concerning obesity and its treatment options. Although obesity is generally accepted as a disease with biological underpinnings such as hormonal imbalances and slow metabolic rate, it is also regarded as an issue of personal responsibility. 65.1% believed that weight-loss medications are dangerous. 20.6% thought that pharmacotherapy is effective for weight loss, whereas 41.1% were unsure. Most believed that bariatric surgery could improve health (81.9%) and diabetes control (74.0%) although 64.1% were unsure of its risks.


Subject(s)
Attitude to Health/ethnology , Obesity/psychology , Public Opinion , Anti-Obesity Agents/therapeutic use , Bariatric Surgery/psychology , Female , Humans , Male , Middle Aged , Obesity/ethnology , Obesity/therapy , Perception , Risk Factors , Singapore/ethnology , Weight Loss/physiology
20.
Ultrasound ; 27(1): 64-68, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30774700

ABSTRACT

In light of the rising rate of incidentally detected subcentimetre thyroid nodules due to improved surveillance and diagnostic imaging, the decision of whether to perform fine needle aspiration cytology is increasingly pertinent. We aim to assess (1) the sampling adequacy of fine needle aspiration cytology, (2) malignancy rate, (3) thyroidectomy rate and (4) diagnostic accuracy of fine needle aspiration cytology. A total of 245 subcentimetre nodules in 220 patients underwent fine needle aspiration cytology between 2011 and 2014. Medical records were reviewed for cytology results, subsequent management and histopathological results in the event the patient underwent thyroidectomy. Sampling adequacy was calculated as the percentage of diagnostic results (Bethesda II-VI). Malignancy rate was defined as the percentage of Bethesda IV-VI diagnoses. Amongst patients with Bethesda IV-VI diagnoses who underwent thyroidectomy, their cytology reports were correlated with post-operative histopathological findings. The sampling adequacy of fine needle aspiration cytology was 77.1%. Malignancy rate (Bethesda IV-VI) was 9.7%. The respective malignancy rates in the < 5 mm nodule group and ≥ 5 mm nodule group were 6.67 and 10.0%. In total, 79.2% (19/24) of the malignant nodules underwent surgical excision. The rest declined surgery and/or were lost to follow-up. Amongst the malignant nodules which were surgically resected, 84.2% (16/19) had definitive malignant histology. Five of these demonstrated multifocal carcinoma and/or extrathyroidal extension of carcinoma on histology. Initial fine needle aspiration cytology and subsequent histopathological diagnoses matched in all cases except for three that had false-positive fine needle aspiration cytology results. Majority of our patients with suspicious cytology results subsequently underwent thyroidectomy, notwithstanding the relatively lower diagnostic accuracy of fine needle aspiration cytology in subcentimetre thyroid nodules.

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