Comparison of pharmacological thrombolysis with mechanical thrombectomy in thrombosed arteriovenous fistulas and grafts: a systemic review and meta-analysis.

AIM: To compare the effectiveness and safety of pharmacological thrombolysis and mechanical thrombectomy. MATERIAL AND METHODS: This review was conducted in accordance with the PRISMA guidelines. Pooled proportions and subgroup analysis were calculated for primary and secondary patency rates, technical success, clinical success, major and minor complications rates. RESULTS: This systematic review identified a total of 6,492 studies of which 17 studies were included for analysis. A total of 1,089 patients comprising 451 (41.4 %) and 638 (58.6 %) patients who underwent thrombolysis and mechanical thrombectomy procedures, respectively, were analysed. No significant differences were observed between thrombolysis and mechanical thrombectomy procedures in terms of technical success, clinical success, major and minor complications rates, primary and secondary patency rates; however, subgroup analysis of overall arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs) demonstrated a significantly higher rate of major complications within the AVF group (p=0.0248). CONCLUSION: The present meta-analysis suggests that pharmacological thrombolysis and mechanical thrombectomy procedures are similarly effective and safe; however, AVFs are subject to higher major complications compared to AVGs.

Deeper may not be better: relationship between catheter dysfunction and location of the catheter tip in right-sided tunnelled haemodialysis catheters.

AIM: To examine the relationship between catheter tip location and catheter dysfunction in the context of tunnelled central venous catheters (CVCs) for haemodialysis. MATERIALS AND METHODS: This was a retrospective study of 993 haemodialysis patients who underwent insertion of tunnelled CVCs of step-tip design via the right internal jugular vein (IJV). Based on intra-procedural radiographs, the catheter tip was characterised as being in the superior vena cava (SVC), cavo-atrial junction (CAJ), or deep right atrium (DRA). Patients were tracked for 90 days post-procedure for complications resulting in catheter replacement, and these were compared between cohorts. Statistical analysis was performed with Pearson's chi-square and Fisher's exact tests for categorical variables and two-sample t-test and one-way analysis of variance (ANOVA) for continuous variables. RESULTS: Ninety-five patients (9.6%) experienced catheter dysfunction necessitating replacement within 90 days of insertion. Tip location in SVC was associated with lower occurrence of catheter dysfunction (1.9%) as compared with the CAJ (8%) and DRA (11%; p=0.049). Catheter replacement due to other complications (catheter-associated bacteraemia, cuff dislodgement, exit-site infection, external catheter damage) showed no statistically significant relation to location of the CVC tip. CONCLUSION: When utilising tunnelled CVCs with a step-tip design inserted via the right IJV, location of the catheter tip in the SVC is associated with reduced occurrence of catheter dysfunction as compared to either the CAJ or DRA.

Does reducing radiation levels for procedures affect image quality and radiation to proceduralists? A double-blinded randomised study of two protocols.

AIM: To evaluate the ultra-lose dose imaging protocol (ULDP), compared to the standard low-dose imaging protocol (LDP), which are used for haemodialysis access, in terms of radiation exposure and image quality. MATERIAL AND METHODS: This was a single-centre, institutional review board-approved, prospective, double-blinded randomised controlled study to compare radiation exposure and image quality of the ULDP and LDP. Ten proceduralists, two radiographers, and 11 nurses were enrolled. Radiation exposure during 80 procedures (40 angioplasties and 40 thrombolysis) was recorded (direct radiation to patients from protocol report and scattered radiation to participants from the RaySafe i2 real-time dosimetry system). Baseline characteristics of procedure were recorded. Image quality was assessed subjectively using questionnaires based on the five-point Likert scale after each procedure. RESULTS: Compared with LDP, the use of ULDP was associated with a significantly lower rate of radiation exposure to proceduralists, patients, and scrub nurses (0.506±0.430 versus 0.847±0.965 µSv/s, p=0.044; 0.571±1.284 versus 1.284±1.007 mGy/s, p<0.001; and 0.052±0.071 versus 0.141±0.185 µSv/s, p=0.005, respectively). No significant difference in image quality or duration of procedure was observed (all p values >0.05). CONCLUSION: Compared with LDP, the use of ULDP was associated with a significantly lower rate of radiation exposure to proceduralists, patients, and scrub nurses without compromising the image quality or duration of procedure.

Planning and coordination of the radiological response to the coronavirus disease 2019 (COVID-19) pandemic: the Singapore experience.

Coronavirus disease 2019 (COVID-19) has spread fast and extensively around the world, with significant mortality and morbidity. As this is a respiratory infection, chest radiography and computed tomography (CT) are important imaging techniques in the work-up of this disease. Given its highly infectious nature, cross-infection within the healthcare setting and radiology departments needs to be addressed actively and prevented. We describe the response of radiology departments in Singapore to this pandemic, in terms of diagnosis, re-configuration of the department, re-organisation and segregation of staff, infection control, managerial, and leadership issues.

Screening for impaired renal function in outpatients before iodinated contrast injection: Comparing the Choyke questionnaire with a rapid point-of-care-test.

RATIONALE AND PURPOSE: To determine the usefulness of the Choyke questionnaire with a creatinine point-of-care test (POCT) to detect impaired renal function amongst outpatients receiving intravenous iodinated contrast in a tertiary centre. MATERIALS AND METHODS: Between July and December 2012, 1361 outpatients had their serum creatinine determined by POCT and answered the Chokye questionnaire just before their examination. RESULTS: Four hundred and eighty (35.2%) patients had at least one 'Yes' response. Forty-four patients (3.2%) had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and 14 patients (1.0%) have eGFR <45 mL/min/1.73 m(2). Sensitivity, specificity, positive predictive value and negative predictive value of the Choyke criteria in detecting patients with eGFR <60 mL/min/1.73 m(2) are respectively: 65.9%, 65.8%, 6.0% and 98.3% and to detect eGFR <45 mL/min/1.73 m(2): 92.9%, 65.3%, 2.7% and 99.9%. Only 'Yes' responses to 'Have you ever been told you have renal problems?' and 'Do you have diabetes mellitus?' were statistically significant in predicting eGFR <45 mL/min/1.73 m(2), with odds ratio 98.7 and 4.4 respectively. CONCLUSION: The Choyke questionnaire has excellent sensitivity and moderate-to-good specificity in detecting patients with <45 mL/min/1.73 m(2), below this level it has been shown that risk of contrast induced nephropathy increases significantly, making it an effective screening tool. Also the use of POCT can potentially reduce waiting time.

Adipocytes contribute to resistance of human melanoma cells to chemotherapy and targeted therapy.

Epidemiological evidence has linked the development and progression of several cancers including melanoma with obesity. However, whether obesity impinges on responses of cancer cells to treatment remains less understood. Here we report that human adipocytes contribute to resistance of melanoma cells to various therapeutic agents. Exposure to media from adipocyte cultures (adipocyte media) increased cell proliferation and reduced sensitivity of melanoma cells to apoptosis induced by diverse chemotherapeutic drugs, including the DNA-damaging drug cisplatin, the microtubuletargeting agent docetaxel, and the histone deacetylase inhibitor SAHA. This was associated with increased activation of PI3K/Akt and MEK/ERK signaling, and was attenuated by a PI3K or MEK inhibitor. The effect of adipocyte media on melanoma cells was, at least in part, due to the interaction between the adipokine leptin and its long form receptor OB-Rb, in that immunodepletion of leptin in adipocyte media or siRNA knockdown of OB-Rb in melanoma cells reversed the increase in Akt and ERK activation, enhancement in cell proliferation, and importantly, protection of melanoma cells against the drugs. In support, recombinant leptin partially recapitulated the effect of adipocyte media on melanoma cells. Of note, OB-Rb was increased on the surface of melanoma cells compared to melanocytes, whereas leptin short form receptors appeared to be suppressed post-transcriptionally, suggesting that OB-Rb was selectively upregulated in melanoma cells. Collectively, these results indicate that adipocytes contribute to the resistance of melanoma cells to chemotherapeutic drugs and agents targeting the PI3K/Akt and MEK/ERK pathways, and suggest that inhibition of the leptin/ OB-Rb system may be useful to improve the efficacy of multiple therapeutic approaches in the treatment of melanoma.

Effective dose estimates for cone beam computed tomography in interventional radiology.

OBJECTIVES: To compare radiation doses in cone beam computed tomography (CBCT) with those of multi-detector computed tomography (MDCT) using manufacturers' standard protocols. METHODS: Dose-levels in head and abdominal imaging were evaluated using a dosimetric phantom. Effective dose estimates were performed by placing thermoluminescent dosimeters in the phantom. Selected protocols for two CBCT systems and comparable protocols for one MDCT system were evaluated. Organ doses were measured and effective doses derived by applying the International Commission on Radiological Protection 2007 tissue weighting factors. RESULTS: Effective doses estimated for the head protocol were 4.4 and 5.4 mSv for the two CBCT systems respectively and 4.3 mSv for MDCT. Eye doses for one CBCT system and MDCT were comparable (173.6 and 148.4 mGy respectively) but significantly higher compared with the second CBCT (44.6 mGy). Two abdominal protocols were evaluated for each system; the effective doses estimated were 15.0 and 18.6 mSv, 25.4 and 37.0 mSv, and 9.8 and 13.5 mSv, respectively, for each of the CBCT and MDCT systems. CONCLUSIONS: The study demonstrated comparable dose-levels for CBCT and MDCT systems in head studies, but higher dose levels for CBCT in abdominal studies. There was a significant difference in eye doses observed between the CBCT systems. KEY POINTS: • Cone beam computed tomography (CBCT) is increasingly utilised in interventional radiology. • Effective doses for selected CBCT and MDCT protocols were estimated and compared. • Dose levels in CBCT and MDCT were comparable for head studies. • Dose levels were higher in CBCT for abdominal studies.

Adjuvant hepatic intra-arterial iodine-131-lipiodol following curative resection of hepatocellular carcinoma: a prospective randomized trial.

BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.

Computed tomography hepatic arteriography has a hepatic falciform artery detection rate that is much higher than that of digital subtraction angiography and 99mTc-MAA SPECT/CT: implications for planning 90Y radioembolization?

PURPOSE: To compare the hepatic falciform artery (HFA) detection rates of digital subtraction angiography (DSA), computed tomography hepatic arteriography (CTHA) and 99mTc-macroaggregated albumin (99mTc-MAA) single photon emission computed tomography with integrated CT (SPECT/CT) and to correlate HFA patency with complication rates of yttrium-90 (90Y) radioembolization. MATERIAL AND METHODS: From August 2008 to November 2010, 79 patients (range 23-83 years, mean 62.3 years; 67 male) underwent pre-treatment DSA, CTHA and 99mTc-MAA scintigraphy (planar/SPECT/CT) to assess suitability for radioembolization with 90Y resin microspheres. Thirty-seven patients were excluded from the study, because CTHA was performed with a catheter position that did not result in opacification of the liver parenchyma adjacent to the falciform ligament. DSA, CTHA and 99mTc-MAA SPECT/CT images and medical records were retrospectively reviewed. RESULTS: A patent HFA was detected in 22 of 42 patients (52.3%). The HFA detection rates of DSA, CTHA and 99mTc-MAA SPECT/CT were 11.9%, 52.3% and 13.3%, respectively (p<0.0001). An origin from the segment 4 artery was seen in 51.7% of HFAs. Prophylactic HFA coil-embolization prior to 90Y microspheres infusion was performed in 2 patients. Of the patients who underwent radioembolization with a patent HFA, none developed supra-umbilical radiation dermatitis. One patient experienced epigastric pain attributed to post-embolization syndrome and was managed conservatively. CONCLUSION: The HFA detection rate of CTHA is superior to that of DSA and 99mTc-MAA SPECT/CT. Complications related to non-target radiation of the HFA vascular territory rarely occur, even in patients undergoing radioembolization with a patent HFA.

Suppression of PP2A is critical for protection of melanoma cells upon endoplasmic reticulum stress.

Endoplasmic reticulum (ER) stress triggers apoptosis by activating Bim in diverse types of cells, which involves dephosphorylation of Bim(EL) by protein phosphatase 2A (PP2A). However, melanoma cells are largely resistant to ER stress-induced apoptosis, suggesting that Bim activation is suppressed in melanoma cells undergoing ER stress. We show here that ER stress reduces PP2A activity leading to increased ERK activation and subsequent phosphorylation and proteasomal degradation of Bim(EL). Despite sustained upregulation of Bim at the transcriptional level, the Bim(EL) protein expression was downregulated after an initial increase in melanoma cells subjected to pharmacological ER stress. This was mediated by increased activity of ERK, whereas the phosphatase activity of PP2A was reduced by ER stress in melanoma cells. The increase in ERK activation was, at least in part, due to reduced dephosphorylation by PP2A, which was associated with downregulation of the PP2A catalytic C subunit. Notably, instead of direct dephosphorylation of Bim(EL), PP2A inhibited its phosphorylation indirectly through dephosphorylation of ERK in melanoma cells. Taken together, these results identify downregualtion of PP2A activity as an important protective mechanism of melanoma cells against ER stress-induced apoptosis.

Fluoroscopy-guided, transcervical, selective salpingography and fallopian tube recanalisation.

This study is a retrospective review of the transcervical fluoroscopy-guided fallopian tube recanalisation (FTR) procedures done in a multi-ethnic south-east Asian population, over 9 years. A total of 100 patients with infertility and documented proximal tubal obstruction (PTO) were referred for FTR. On-table hysterosalpingography under sedation demonstrated true PTO in 96 patients. At selective-salpingography, the PTO cleared in 16 patients; 78 required FTR and two had fimbrial blockage. The technical success rate of FTR was 86.8% and the post-FTR pregnancy rate was 36.84% at a mean follow-up interval of 12.2 months. There were no major, immediate procedure-related complications. There was an ectopic pregnancy in a single treated patient. Fluoroscopy-guided FTR is a safe treatment option in patients with infertility from PTO, with high technical success rate, low complication rate and increased chances of pregnancy; therefore it should be preferred before attempting more expensive and resource-intensive procedures.

Ministry of health clinical practice guidelines: clinical blood transfusion.

The Health Sciences Authority (HSA) and the Ministry of Health (MOH) publish clinical practice guidelines on Clinical Blood Transfusion to provide doctors and patients in Singapore with evidence-based guidance for blood transfusion. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the HSA-MOH clinical practice guidelines on Clinical Blood Transfusion, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=25700). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIP(L) from degradation by the E3 ligase itch in human melanoma cells.

Past studies have identified a number of distinct mechanisms that contribute to the resistance of melanoma cells against apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). In this report we show that cystatin B is another endogenous inhibitor of TRAIL-induced apoptosis. Cystatin B-deficient melanoma cell lines established by shRNA knockdown displayed increased apoptosis that was associated with enhanced activation of caspase-8 induced by TRAIL. This was not related to the inhibitory effect of cystatin B on the lysosomal cysteine proteases, cathepsin B and L, as they did not have a role in TRAIL-induced apoptosis in most melanoma cell lines even when cystatin B was inhibited. Instead, sensitization of melanoma cells to TRAIL-induced apoptosis by inhibition of cystatin B appeared associated with decreased stability of FLIP(L) as the levels of FLIP(L) were reduced because of shortened half-life time in melanoma cells deficient in cystatin B. In contrast, over-expression of cystatin B increased the levels of FLIP(L), decreased the amount of the E3 ligase Itch associated with FLIP(L), and reduced FLIP(L) ubiquitination. Inhibition of Itch by siRNA restored the levels of FLIP(L) and blocked sensitization to TRAIL-induced apoptosis associated with deficiency in cystatin B. Taken together, these results indicate that cystatin B regulates Itch-mediated degradation of FLIP(L) and thereby TRAIL-induced apoptosis in melanoma cells.

Apoptosis of human melanoma cells induced by inhibition of B-RAFV600E involves preferential splicing of bimS.

Bim is known to be critical in killing of melanoma cells by inhibition of the RAF/MEK/ERK pathway. However, the potential role of the most potent apoptosis-inducing isoform of Bim, Bim(S), remains largely unappreciated. Here, we show that inhibition of the mutant B-RAF(V600E) triggers preferential splicing to produce Bim(S), which is particularly important in induction of apoptosis in B-RAF(V600E) melanoma cells. Although the specific B-RAF(V600E) inhibitor PLX4720 upregulates all three major isoforms of Bim, Bim(EL), Bim(L), and Bim(S), at the protein and mRNA levels in B-RAF(V600E) melanoma cells, the increase in the ratios of Bim(S) mRNA to Bim(EL) and Bim(L) mRNA indicates that it favours Bim(S) splicing. Consistently, enforced expression of B-RAF(V600E) in wild-type B-RAF melanoma cells and melanocytes inhibits Bim(S) expression. The splicing factor SRp55 appears necessary for the increase in Bim(S) splicing, as SRp55 is upregulated, and its inhibition by small interfering RNA blocks induction of Bim(S) and apoptosis induced by PLX4720. The PLX4720-induced, SRp55-mediated increase in Bim(S) splicing is also mirrored in freshly isolated B-RAF(V600E) melanoma cells. These results identify a key mechanism for induction of apoptosis by PLX4720, and are instructive for sensitizing melanoma cells to B-RAF(V600E) inhibitors.

Endovascular aortic repair: the experience of two tertiary institutions in Singapore.

INTRODUCTION: Endovascular aortic repair (EVAR) has gained prominence as a means of treating aortic disease, with lower perioperative morbidity and mortality compared to open surgery. This article aimed to describe the experience of two tertiary hospitals in a Southeast Asian population. METHODS: A retrospective review of 100 consecutive patients undergoing EVAR in two hospitals in Singapore was conducted. This included patients undergoing elective as well as emergency repair. RESULTS: The mean duration of follow-up was 31.8 months. The mean aneurysm size was 6.3 cm and the mean length of stay was 12.1 days. 64 percent of the patients were of American Society of Anesthesiologists class III or above. The deployment success was 98 percent. Major complications (acute myocardial infarction, pneumonia, cerebrovascular accidents, renal failure, colonic infarction and spinal cord infarction) occurred in 18 patients. Perioperative mortality occurred in six percent of cases. The endoleak rate was 28 percent. Both patients with colonic infarction had a single patent internal iliac artery post-procedure, and end-stage renal failure. CONCLUSION: Our results are comparable to published experiences in aortic stenting. Our population possibly had a higher incidence of short common iliac arteries. Revascularisation of internal iliac arteries should be considered for patients with end-stage renal failure and a single patent internal iliac artery.

Use of magnetic resonance imaging in evaluation of placental invasion.

AIM: To review and describe the magnetic resonance imaging (MRI) features in patients with suspected placental invasion and correlate the findings with surgery and pathology findings. MATERIALS AND METHODS: A retrospective review was undertaken of the MRI images of seven consecutive patients with ultrasound findings suspicious for placental invasion. Two experienced MRI radiologists, blinded to the pathology and surgery findings, reviewed the MRI. The pathology or surgical findings were used as the reference standard to establish accuracy and concordance with the MRI findings. RESULTS: Three MRI features described in an earlier series were consistently present in the patients with placental invasion: lower uterine bulging, heterogeneous placenta, and dark intraplacental linear bands on T2-weighted images. CONCLUSION: MRI features, which were described in patients with placental invasion in an earlier series, were useful in establishing the presence and depth of placental invasion.

Novel oral anticoagulants.

Oral anticoagulants have been used widely for the treatment of venous thromboembolism and stroke prevention. The vitamin K antagonists (VKAs), such as warfarin, have been around for the last 65 years and its efficacy as thromboprophylaxis remained largely unchallenged, at least until recently. Nonetheless, the VKAs have significant limitations with marked inter- and intra-individual variability, requiring regular monitoring and have important food and drug interactions. Thus, there is an unmet need, with the quest for alternative oral anticoagulants with stable pharmacokinetics and pharmacodynamics that do not need monitoring. The novel oral anticoagulants are in 2 broad drug classes - the oral direct thrombin inhibitors and oral factor Xa inihibitors. This review article provides an overview of the pharmacology and describes the most recent published data on clinical trials with the new oral anticoagulants, which are in the more advanced stages of clinical development.

CT appearance of complications related to thoracic endovascular aortic repair (TEVAR): a pictorial essay.

Thoracic endovascular aortic repair (TEVAR) is a recognized treatment for various diseases involving the thoracic aorta. Patients treated with TEVAR require lifelong surveillance for potential complications, with CT being highly utilized in most centres. Endoleak is the most common complication and can be detected using CT. However, other complications such as stent strut perforations and end organ ischemia can also be detected on CT. The purpose of this pictorial essay is to illustrate the CT appearance of post-TEVAR complications encountered in our institution and to highlight their significance.