The Utility of Sirolimus Eluting Balloons in the Setting of Chronic Limb Threatening Ischaemia in Asian Patients from Singapore - 12 Months Results of the PRISTINE Registry.

PURPOSE: The aim of PRISTINE was to evaluate the 6 and 12 months safety and efficacy of the Selution Sustained Limus Release (SLR)™ sirolimus-coated balloon for treatment of complex lower limb occlusive lesions (TASC II C & D) in patients with chronic limb threatening ischemia (CLTI) from Singapore. METHODS: PRISTINE was a prospective, non-randomized, single arm, observational, multi-investigator, single-center clinical study. Complication-free survival at 30 days was the safety clinical endpoint. Immediate technical success (ability to cross and dilate the lesion and achieve residual angiographic stenosis < 30%), 6-month primary vessel patency, limb salvage, clinically driven target lesion revascularization (TLR) and amputation free survival (AFS) were the efficacy endpoints of interest. RESULTS: Seventy five patients were included. There were 50 (68.0%) males; mean age, 69.0 ± 10.7 years. CLTI severity was based on the Rutherford Scale (R5 = 51; R6 = 17). Significant co-morbidities included diabetes mellitus (n = 68; 91.0%) and end-stage renal failure (n = 28; 37.0%). 112 atherosclerotic lesions were treated (TASC II D = 58 (52%); 76 (67%) de novo). There was 100% technical success. Mean lesion length treated was 22.4 ± 13.9 cm. Primary vessel patencies at 6 and 12 months were 64/86 (74%) and 43/74 (58%) and freedom from clinically driven TLR were 72/86 (84%) and 55/74 (74%) respectively. AFS was 61/73 (84.0%; five deaths and seven major lower extremity amputation) at 6-months. Mean Rutherford score improved from 5.1 ± 0.55 at baseline to 1.1 ± 2.05 (p < 0.05) at one year and there was a wound healing rate of 38/48 (79%) at the same timepoint. CONCLUSIONS: The Selution SLR™ drug eluting balloon is safe and efficacious in treating highly complex infra-inguinal atherosclerotic lesions in an otherwise challenging frail population of CLTI patients with a high incidence of diabetes and end-stage renal failure. It is associated with highly satisfactory acute technical and clinical success, 12-month target lesion patency and AFS. LEVEL OF EVIDENCE: Level 2b, Individual Cohort Study.

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.

Neurodevelopmental outcomes in neonatal extracorporeal membrane oxygenation survivors: An institutional perspective.

AIM: To describe the neurodevelopmental outcomes following extracorporeal membrane oxygenation (ECMO) in early infancy. METHODS: Thirty-seven patients who had survived following ECMO support from 2008 to 2018 had their neurodevelopmental outcomes assessed and analysed using the Bayley Scales of Infant and Toddler Development. Developmental outcome was defined as impairment in any of the developmental domains of motor function, cognition and language with mild impairment being 1-2 standard deviations below the test mean, moderate being 2-3 standard deviations below and severe being greater than 3 standard deviations below. RESULTS: Of these 37 patients, the median age at admission to Paediatric Intensive Care Unit was 0.4 months (interquartile range 2.8 months) with all of the study patients having an underlying diagnosis of congenital cardiac disease and 37/40 (92.5%) ECMO runs occurring in the immediate post-operative period. Of the 29 patients who had had follow-up at 12 months of age or older, 3 (10.3%) had severe impairment, 4 (13.8%) had moderate impairment, 12 (41.3%) had mild impairment and 10 (34.5%) had no impairment. Gross motor function was most significantly impacted in 18/29 (62.1%) patients, of which 7/18 (38.9%) had severe impairment. This was followed by impairment of receptive language in 8/29 (27.6%) patients and expressive language in 6/29 (20.1%) patients. CONCLUSIONS: One in four infants undergoing ECMO treatment in early infancy has moderate to severe neurodevelopmental impairment. Gross motor and language are the most affected developmental domains.

Accessory Vein Obliteration and Balloon-Assisted Maturation for Immature Arteriovenous Fistulas for Haemodialysis: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to examine outcomes of immature arteriovenous fistula salvage using balloon angioplasty (PTA) without and with accessory vein obliteration (PTA + VO). MATERIALS AND METHODS: PubMed and Embase were accessed on 21 September 2020 to retrieve cohort studies on adult patients with end-stage renal failure (ESRF) requiring dialysis. Risk of bias was assessed using Newcastle-Ottawa Scale. Studies were pooled into PTA or PTA + VO arms, with outcomes (technical/clinical success, primary/secondary post-intervention patency until 12 months) reported as event rates with 95% confidence intervals. Random-effects model and maximum likelihood meta-regression were used for meta-analysis. RESULTS: Fourteen studies (1030 participants) were included. The between-subgroup difference in outcomes was largely non-significant (p > 0.050). CONCLUSION: The evidence does not support balloon angioplasty with concomitant accessory vein obliteration for immature fistula salvage.

[Clinical features of Chinese patients with Takotsubo syndrome].

Objective: To analyze the characteristics, diagnosis and treatment status of Takotsubo syndrome (TTS) of Chinese patients. Methods: Complete literature review was performed to summarize Chinese TTS cases between 2007 and 2018. Results: A total of 131 literatures were included including 160 TTS patients (age (58.3±14.7) years). There were 137 female patients (85.6%) in this cohort, the age was (59.6±14.0) years. There were 124 cases (77.5%) of stress-evoking factors, of which 83 cases (66.9%) were self-stress factors. There were 97 cases (60.6%) complained of chest pain and 15 cases (9.4%) with syncope. Forty-eight cases (30.0%) presented with cardiogenic shock. CK-MB and cTnT/I increased in 109 cases (80.1%). There were 124 cases (77.5%) presented with ST segment elevation on electrocardiogram, which were common in lead V2-V5. Echocardiography results were available in 128 cases (80.0%), reduced left ventricular ejection fraction (<50%) was reported in 78 cases (73.6%). Coronary angiography was performed in 133 patients (83.1%), of which 126 patients (94.7%) had normal coronary arteries or single non-significant stenosis. One hundred and thirty-eight patients (87.3%) were apical type. The misdiagnosis rate on admission was 96.9% (155/160), of which 141 cases (88.1%) were misdiagnosed as acute myocardial infarction. Nitroglycerin was used in 36 patients (30.3%). Angiotensin converting enzyme inhibitor or angiotensin Ⅱ receptor antagonist were used in 38 patients (31.9%). ß blockers were used in 46 patients (38.7 %). Dopamine was used in 22 cases (18.5%) and norepinephrine was used in 12 cases (10.1%). Intra-aortic balloon counter pulsation was used in 5 cases (3.1%). Cardiopulmonary resuscitation was performed in 9 cases (5.6%). Cardiac function recovery time was 7 (6, 15) days. The average InterTAK diagnosis score was (51.5±18.1) points, and value was>70 points in 2 cases (1.3%). There were 92 patients in the high-risk group, and there were 3 recurrent TTS cases. Five patients died. Conclusions: TTS incidence tends to be young and dominates in female in China. The misdiagnosis rate is extremely high on admission. Most patients are treated with medication.

Registry to investigate the efficacy and safety of the VenaBlock© VeIn SEaling system for VaRicose veins in SingApore - Six months results of the RIVIERA trial.

BACKGROUND: The Venablock© Venous Closure System (Invamed, Ankara, Turkey) is a novel cyanoacrylate-based non-thermal non-tumescent embolization device to block refluxing truncal veins for chronic venous insufficiency and varicose veins. The aim was to prospectively evaluate the safety and 6 months efficacy of Venablock© for the treatment of primary great saphenous vein (GSV) and small saphenous vein (SSV) incompetency in a multi-ethnic cohort from Singapore. METHODS: This was a single arm, single investigator prospective study of 29 patients (39 limbs, 39 truncal veins) recruited over a 5-month period (August 2019 to February 2020), who were treated with the Venablock© device at a tertiary vascular unit in Singapore. Patients with symptomatic varicose veins (C2-6) and had truncal reflux > 0.5 second on venous Duplex ultrasound were included. Follow-up occurred at 2 weeks, 3 and 6 months with dedicated quality of life questionnaires and a targeted Duplex ultrasound performed to check for continued venous occlusion. RESULT: Mean age was 61.4 (±11.0) years and mean BMI was 26.2 (±5.7) kg/m2. 11/29 (37.9%) were males. Most common CEAP class treated was 2 (12/29, 41.3%). Mean diameter of treated GSV was 5.7 (±2.0) mm, 4.8 (±1.7) mm and 4.2 (±1.3) mm for the proximal, mid and distal above knee segments respectively. Mean time from access puncture to sheath removal was 23.4 (±10.0) mins. Vein occlusion at 2 weeks, 3 and 6 months was 39/39 (100%), 39/39 (100%) and 36/37 (97.2%) respectively. 5/29 (17.2%) developed puncture site infections, of which 3/29 (7.7%) required formal surgical drainage. 3/29 (7.7%) developed phlebitis. At 6 months, revised Venous Clinical Severity Score improved from 5.2 (±3.5) to 2.1 (±2.9; p < .001); EuroQol-5 Dimension score, from 7.4 (±2.1) to 5.7 (±1.4; p < .001); Aberdeen Varicose Vein Questionnaire score, from 18.1 (±15.5) to 7.9 (±8.9; p = .007); and Chronic Venous Insufficiency Questionnaire, from 18.6 (±16.2) to 4.5 (±6.3; p < .001). CONCLUSION: Venablock© is a safe and efficacious option of treating truncal venous insufficiency in a multi-ethnic Asian cohort from Singapore in the short term. There is a significant improvement in QoL. Longer follow-up is required to assess the durability of this technique, in particular the higher puncture site infection rates observed compared to other glue-based therapies.

A review of the Turned-down Onto Pericapsular-tissue Hemisectioned Amputated Toe (TOPHAT) flap for wound coverage during ray amputations of the toes.

INTRODUCTION: Exposure of the adjacent Metatarsal-Phalangeal Joint (MTPJ) commonly occurs after application of Topical Negative Pressure Wound Therapy (TNPWT) for a ray amputation wound. This is due to mechanical soft tissue erosion or trauma to the adjacent digital artery from direct pressure effect. This results in toe gangrene requiring a ray amputation and ultimately a larger wound bed. We describe the use of the Turned-down Onto Pericapsular-tissue Hemisectioned Amputated Toe (TOPHAT) flap - a filleted toe flap to protect the adjacent MTPJ capsule combined with a novel Negative Pressure Wound Therapy with instillation and dwell-time (NPWTi-d) dressing technique. The flap protects the adjacent joint capsule and reduces the wound burden whilst allowing the wound to benefit from TNPWT, thereby accelerating wound healing. MATERIAL AND METHODS: A retrospective review was conducted of patients with toe gangrene requiring ray amputation that underwent the TOPHAT flap on in our institution from 2019 and 2020. Complications such as wound dehiscence, hematoma, flap necrosis and secondary infection were recorded. Other outcomes recorded were time taken to final skin grafting and time taken for complete wound epithelialization. RESULTS: 9 patients underwent treatment with the TOPHAT flap. 2 patients had flap necrosis. 7 patients progressed to definitive skin coverage with skin grafting. One patient subsequently had progressive arterial disease despite successful skin grafting and required above knee amputation. The mean time to final skin grafting and complete wound epithelialization was 49.5 days and 107.5 days respectively. All patients were satisfied with the outcomes and were able to return to their pre-morbid function. CONCLUSIONS: The TOPHAT flap has a consistent vascular supply that provides durable soft tissue coverage. It is a robust and easily reproducible technique to accelerate wound healing after ray amputations even in patients with peripheral vascular disease.

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.

Helical stent (SUPERA™) and drug-coated balloon (Passeo-18 Lux™) for recurrent cephalic arch stenosis: Rationale and design of arch V SUPERA-LUX Study.

BACKGROUND: The treatment options for cephalic arch stenosis are limited and standard of care remains at crossroads - none are ideal and there is currently no gold standard. Endovascular techniques are now the preferred primary therapeutic option because they are minimally invasive and better tolerated by haemodialysis patients who have multiple comorbidities. However, conventional plain old balloon angioplasty, bare metal stenting and stent grafts all have their limitations. The aim of this trial is to evaluate whether the helical SUPERA™ stent (Abbott Vascular, Santa Clara, CA, USA), which has a higher degree of flexibility and resistance to compressive forces compared to traditionally laser-cut nitinol stents, combined with a drug-coated balloon (Biotronik Passeo-18 Lux™) to minimize the neointimal hyperplasia effect, can improve patency and reduce reintervention rates. METHODS AND RESULTS: Arch V SUPERA-LUX is a pilot investigator-initiated single-centre, single-arm prospective study. Twenty patients with a brachiocephalic fistula within 6 months of initial plain old balloon angioplasty for significant cephalic arch stenosis will be recruited for treatment with SUPERA and drug-coated balloon. The primary objectives are immediate angiographic and procedural success, primary patency and functional fistula at 1 week, 8 weeks, 6 and 12 months. The results from eight patients treated prospectively as proof of concept have shown primary patency of 83.3% at 1 year with 100% technical and procedural success rates. Enrolment for the Arch V SUPERA-LUX study is expected to be completed at the end of 2019. CONCLUSION: The Arch V SUPERA-LUX study is the first trial to evaluate whether SUPERA stent implantation and drug-coated balloon use can provide superior protection against restenosis compared to traditional angioplasty, bare metal stents and stent grafts in recurrent cephalic arch stenosis. Initial pilot results are encouraging but longer follow-up is required to truly test this technique. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov NCT03891693.

Case report of a type III endoleak presenting only decades after endovascular aortic repair.

INTRODUCTION: Type III endoleaks are a rare but potentially life-threatening complication post endovascular aortic aneurysm repair (EVAR). CASE REPORT: A 91-year-old Chinese female, presented to our accident and emergency department for severe back and abdominal pain. She had previously undergone an EVAR procedure twenty years ago for a 6.5 cm diameter infra-renal abdominal aortic aneurysm. A CT aortogram revealed a type III endoleak, with the contralateral limb found to be disconnected from the main graft body. She was successfully treated by relining the graft using an endovascular technique. DISCUSSION: The case highlights the need for life-long stent-graft surveillance. We discuss early generation stent-grafts, type III endoleak treatment options and the current long-term data for late EVAR-related complications. CONCLUSION: For patients who had undergone EVAR, type III endoleaks can present only decades later and pose a significant risk of aneurysmal rupture.

Foxo transcription factors in T cell biology and tumor immunity.

The evolutionally conserved forkhead box O (Foxo) family of transcription factors is pivotal in the control of nutrient sensing and stress responses. Recent studies have revealed that the Foxo proteins have been rewired to regulate highly specialized T cell activities. Here, we review the latest advances in the understanding of how Foxo transcription factors control T cell biology, including T cell trafficking, naive T cell homeostasis, effector and memory responses, as well as the differentiation and function of regulatory T cells. We also discuss the emerging evidence on Foxo-mediated regulation in antitumor immunity. Future work will further explore how the Foxo-dependent programs in T cells can be exploited for cancer immunotherapy.

Autophagy suppresses the proliferation of renal carcinoma cell.

OBJECTIVE: To investigate the effetcs of autophagy on the proliferation of renal carcinoma (RCCs). MATERIALS AND METHODS: Authophagy related protein 7 (Atg7)-overexpressing and knockdown RCC cell lines were established using lentiviral transfection and shRNA interference, respectively. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (MTT) was used to determine the Cell growth rate, and western blot was used to determine the expression of protein. In order to establish xenograft animal models, stable transfected cells were injected into nude mice. After that those mice were used to detect the effect of autophagy on the growth of RCC in vivo. RESULTS: Atg7 overexpression could up-regulate the level of LC3II in RCC cell lines, while Atg7-knockdown suppressed the expression of light chain 3 II (LC3II) in RCC cell lines. Atg7-overexpression cells exhibited a decreased growth profile, while suppressing the expression of Atg7 could accelerate the growth of RCC formed tumors. CONCLUSIONS: Our data indicated that autophagy could suppress the growth of RCC cells in vivo and in vitro, and autophagy appeared to be a new therapeutic target for treating advanced renal cell carcinoma.

Ets transcription factor GABP controls T cell homeostasis and immunity.

Peripheral T cells are maintained in the absence of vigorous stimuli, and respond to antigenic stimulation by initiating cell cycle progression and functional differentiation. Here we show that depletion of the Ets family transcription factor GA-binding protein (GABP) in T cells impairs T-cell homeostasis. In addition, GABP is critically required for antigen-stimulated T-cell responses in vitro and in vivo. Transcriptome and genome-wide GABP-binding site analyses identify GABP direct targets encoding proteins involved in cellular redox balance and DNA replication, including the Mcm replicative helicases. These findings show that GABP has a nonredundant role in the control of T-cell homeostasis and immunity.

Needs of exploring the burden of recent onset seizures due to neurocysticercosis and challenges in southeast Asia focusing on scenario in Malaysia.

Seizures due to neurocysticercosis (NCC) is a neglected human-to-human transmitted disorder and an emerging problem worldwide. A substantial portion of recent onset seizures is known to be attributed to NCC in Taenia solium (T. solium) endemic areas where populations which neither raise pigs nor eat pig meat are also at risk. High prevalence of NCC causing epilepsy has been reported in the underdeveloped areas of Southeast Asia (SEA) however, only fragmentary information on its incidence is available in countries like Malaysia. In Malaysia T. solium infection was previously thought to be infrequent due to Muslim population majority and the religious prohibition of consuming pork, but it is not totally absent. There is an evident lack of knowledge and awareness of the actual burden, routes of transmission, and the impact of NCC in this region. The problem is assumed to be more prevalent particularly in cities because of the frequent inflow of possibly T. solium infected individuals or carriers among those who migrate from neighboring endemic countries to Malaysia. The issue of imported cases that are likely to be emerging in Malaysia is highlighted here. An accurate quantification of regional burdens of epilepsy due to NCC in Malaysia is warranted considering the disease emergence in its neighboring countries. It is suggested that the importance of NCC be recognized through quantification of its burden, and also to collect epidemiological data for its subsequent elimination in line of World Health Organization's mission for control of cysticercosis as a neglected tropical disease. In this review the need as well as a strategy for neuro-care center screening of epilepsy cases, and various issues with possible explanations are discussed. It is also proposed that NCC be declared as a reportable disease which is one of the eradicable public health problems in SEA.

HLA Mismatching Favoring Host-Versus-Graft NK Cell Activity Via KIR3DL1 Is Associated With Improved Outcomes Following Lung Transplantation.

Chronic lung allograft dysfunction (CLAD) is linked to rejection and limits survival following lung transplantation. HLA-Bw4 recipients of HLA-Bw6 grafts have enhanced host-versus-graft (HVG) natural killer (NK) cell activity mediated by killer cell immunoglobulin-like receptor (KIR)3DL1 ligand. Because NK cells may promote tolerance by depleting antigen-presenting cells, we hypothesized improved outcomes for HLA-Bw4 recipients of HLA-Bw6 grafts. We evaluated differences in acute cellular rejection and CLAD-free survival across 252 KIR3DL1+ recipients from University of California, San Francisco (UCSF). For validation, we assessed survival and freedom from bronchiolitis obliterans syndrome (BOS), retransplantation, or death in 12 845 non-KIR typed recipients from the United Network for Organ Sharing (UNOS) registry. Cox proportional hazards models were adjusted for age, gender, ethnicity, transplant type, and HLA mismatching. HVG-capable subjects in the UCSF cohort had a decreased risk of CLAD or death (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.36-0.88) and decreased early lymphocytic bronchitis. The HVG effect was not significant in subjects with genotypes predicting low KIR3DL1 expression. In the UNOS cohort, HVG-capable subjects had a decreased risk of BOS, retransplant, or death (HR 0.95, 95% CI 0.91-0.99). Survival improved with the higher-affinity Bw4-80I ligand and in Bw4 homozygotes. Improved outcomes in HVG-capable recipients are consistent with a protective NK cell role. Augmentation of NK activity could supplement current immunosuppression techniques.

Corrigendum: Fluidic Logic Used in a Systems Approach to Enable Integrated Single-Cell Functional Analysis.

[This corrects the article on p. 70 in vol. 4, PMID: 27709111.].