Diabetic macular ischaemia- a new therapeutic target?

Diabetic macular ischaemia (DMI) is traditionally defined and graded based on the angiographic evidence of an enlarged and irregular foveal avascular zone. However, these anatomical changes are not surrogate markers for visual impairment. We postulate that there are vascular phenotypes of DMI based on the relative perfusion deficits of various retinal capillary plexuses and choriocapillaris. This review highlights several mechanistic pathways, including the role of hypoxia and the complex relation between neurons, glia, and microvasculature. The current animal models are reviewed, with shortcomings noted. Therefore, utilising the advancing technology of optical coherence tomography angiography (OCTA) to identify the reversible DMI phenotypes may be the key to successful therapeutic interventions for DMI. However, there is a need to standardise the nomenclature of OCTA perfusion status. Visual acuity is not an ideal endpoint for DMI clinical trials. New trial endpoints that represent disease progression need to be developed before irreversible vision loss in patients with DMI. Natural history studies are required to determine the course of each vascular and neuronal parameter to define the DMI phenotypes. These DMI phenotypes may also partly explain the development and recurrence of diabetic macular oedema. It is also currently unclear where and how DMI fits into the diabetic retinopathy severity scales, further highlighting the need to better define the progression of diabetic retinopathy and DMI based on both multimodal imaging and visual function. Finally, we discuss a complete set of proposed therapeutic pathways for DMI, including cell-based therapies that may provide restorative potential.     

Intervention rates and outcomes in medically managed uncomplicated descending thoracic aortic dissections

ObjectiveTo evaluate the long-term incidence and outcome of aortic interventions for medically managed uncomplicated thoracic aortic dissections.MethodsBetween January 2012 and December 2018, 91 patients were discharged home with an uncomplicated, medically treated aortic dissection (involving the descending aorta with or without aortic arch involvement, no ascending involvement). After a median period of 4 (first quartile: 2, third quartile: 11) months, 30 patients (33%) required an aortic intervention. Patient characteristics, radiographic, treatment, and follow-up data were compared for patients with and without aortic interventions. A competing risk regression model was analyzed to identify independent predictors of aortic intervention and to predict the risk for intervention.ResultsPatients who underwent aortic interventions had significantly larger thoracic (P = .041) and abdominal (P = .015) aortic diameters, the dissection was significantly longer (P = .035), there were more communications between both lumina (P = .040), and the first communication was significantly closer to the left subclavian artery (P = .049). A descending thoracic aortic diameter exceeding 45 mm was predictive for an aortic intervention (P = .001; subdistribution hazard ratio: 3.51). The risk for aortic intervention was 27% ± 10% and 36% ± 11% after 1 and 3 years, respectively. Fourteen patients (47%) underwent thoracic endovascular aortic repair, 11 patients (37%) thoracic endovascular aortic repair and left carotid to subclavian bypass, 3 patients (10%) total arch replacement with the frozen elephant trunk technique, and 2 patients (7%) thoracoabdominal aortic replacement. We observed no in-hospital mortality.ConclusionsThe need for secondary aortic interventions in patients with initially medically managed, uncomplicated descending aortic dissections is substantial. The full spectrum of aortic treatment options (endovascular, hybrid, conventional open surgical) is required in these patients.     

凉血通瘀方干预高血压大鼠急性脑出血模型对脑组织中差异miRNA表达的影响＊

目的 研究凉血通瘀方对高血压大鼠急性脑出血模型脑组织miRNA表达的影响，对差异表达的miRNA靶基因进行分析，探索凉血通瘀方可能的药效机制。方法 将自发性高血压大鼠随机分成对照组（B）和实验组（C）。适应性饲养一周后，C组灌胃凉血通瘀方，B组灌胃等体积生理盐水，连续5天，每天1次。构建脑出血模型后收集脑组织，借助全转录组测序技术获得miRNA表达量，与miRBase数据库比对获取已知miRNA，使用miRDeep2预测新miRNA。差异分析软件为DESeq2，筛选阈值为|log₂FC| ≥1 并且P <0.05。对显著差异表达的miRNA进行靶基因预测，对靶基因进行GO功能、KEGG通路富集和PPI网络分析。结果 实验组和对照组对比，共发现21个显著差异表达的miRNA，上调有9个，下调有12个，共预测得到1243个有统计学意义的靶基因。GO富集分析发现，生物过程中突触囊泡分泌的调节、神经递质分泌的调节和神经递质运输的调节占前三位，神经元投射终点、全膜、质膜区域和细胞投射则是主要的细胞成分。分子功能分别为小GTPase绑定、底物特异性跨膜转运蛋白活性和离子跨膜转运体活性。通路分析结果显示，靶基因在癌证通路、pI3K-Akt信号通路、人类乳头瘤病毒感染、神经活性配体-受体相互作用和MAPK通路等分布广泛。采用STRING网站和Cytoscape软件，根据MCC算法筛选出ADRA2C、CASR、CCL28、CCR1、DRD2、GNAT3、GRM2、DYNC1LI1、GABBR1、GNAI1等核心靶基因。结论 凉血通瘀方对脑出血急性期鼠脑组织内miRNA的表达有重要影响；显著差异表达miRNAs可能通过靶向核心基因调控凉血通瘀方干预急性脑出血的病理过程及预后。     

Perivascular fat attenuation for predicting adverse cardiac events in stable patients undergoing invasive coronary angiography

BackgroundInflammation surrounding the coronary arteries can be non-invasively assessed using pericoronary adipose tissue attenuation (PCAT). While PCAT holds promise for further risk stratification of patients with low coronary artery disease (CAD) prevalence, its value in higher risk populations remains unknown.MethodsCORE320 enrolled patients referred for invasive coronary angiography with known or suspected CAD. Coronary computed tomography angiography (CCTA) images were collected for 381 patients for whom clinical outcomes were assessed 5 years after enrollment. Using semi-automated image analysis software, PCAT was obtained and normalized for the right coronary (RCA), left anterior descending (LAD), and left circumflex arteries (LCx). The association between PCAT and major adverse cardiovascular events (MACE) during follow up was assessed using Cox regression models.ResultsThirty-seven patients were excluded due to technical failure. For the remaining 344 patients, median age was 62 (interquartile range, 55–68) with 59% having ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography. Mean attenuation values for PCAT in RCA, LAD, and LCx were ?74.9, ?74.2, and ?71.2, respectively. Hazard ratios and 95% confidence intervals (CI) for normalized PCAT in the RCA, LAD, and LCx for MACE were 0.96 (CI: 0.75–1.22, p ?= ?0.71), 1.31 (95% CI: 0.96–1.78, p ?= ?0.09), and 0.98 (95% CI: 0.78–1.22, p ?= ?0.84), respectively. For death, stroke, or myocardial infarction only, hazard ratios were 0.68 (0.44–1.07), 0.85 (0.56–1.29), and 0.57 (0.41–0.80), respectively.ConclusionsIn patients referred for invasive coronary angiography with suspected CAD, PCAT did not predict MACE during long term follow up. Further studies are needed to understand the relationship of PCAT with CAD risk.     

Trans-lesional fractional flow reserve gradient as derived from coronary CT improves patient management: ADVANCE registry

BackgroundThe role of change in fractional flow reserve derived from CT (FFR_CT) across coronary stenoses (ΔFFR_CT) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown.ObjectivesTo investigate the incremental value of ΔFFR_CT in predicting early revascularization and improving efficiency of catheter laboratory utilization.MaterialsPatients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFR_CT was measured 2 ?cm distal to stenosis. ΔFFR_CT was manually measured as the difference of FFR_CT across visible stenosis.ResultsOf 4730 patients (66 ?± ?10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFR_CT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26–1.35]; p ?< ?0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFR_CT. Among the 3 models (model 1: risk factors ?+ ?stenosis type and location ?+ ?CAD-RADS; model 2: model 1 ?+ ?FFR_CT; model 3: model 2 ?+ ?ΔFFR_CT), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86–0.88] vs 0.85 [0.84–0.86]; p ?< ?0.001), with the greatest incremental value for FFR_CT 0.71–0.80. ΔFFR_CT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFR_CT ≤0.8, a diagnostic strategy incorporating ΔFFR_CT >0.13, would potentially reduce ICA by 32.2% (1638–1110, p ?< ?0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%.ConclusionsΔFFR_CT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFR_CT, particularly for those with FFR_CT 0.71–0.80. ΔFFR_CT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization.     

Radiation-Free Thoracic Endovascular Aneurysm Repair with Fiberoptic and Electromagnetic Guidance: A Phantom Study

PurposeTo evaluate the feasibility and accuracy of a radiation-free implantation of a thoracic aortic stent graft employing fiberoptic and electromagnetic tracking in an anthropomorphic phantom.Materials and MethodsAn anthropomorphic phantom was manufactured based on computed tomography (CT) angiography data from a patient. An aortic stent graft application system was equipped with a fiber Bragg gratings and 3 electromagnetic sensors. The stent graft was navigated in the phantom by 3 interventionalists using the tracking data generated by both technologies. One implantation procedure was performed. The technical success of the procedure was evaluated using digital subtraction angiography and CT angiography (before and after the intervention). Tracking accuracy was determined at various anatomical landmarks based on separately acquired fluoroscopic images. The mean/maximum errors were measured for the stent graft application system and the tip/end of the stent graft.ResultsThe procedure resulted in technical success with a mean error below 3 mm for the entire application system and <2 mm for the position of the tip of the stent graft. Navigation/implantation and handling of the device were rated sufficiently accurate and on par with comparable, routinely used stent graft application systems.ConclusionsThe study demonstrates successful stent graft implantation during a thoracic endovascular aortic repair procedure employing advanced guidance techniques and avoiding fluoroscopic imaging. This is an essential step in facilitating the implantation of stent grafts and reducing the health risks associated with ionizing radiation during endovascular procedures.     

Assessing the Effects of Geniculate Artery Embolization in a Nonsurgical Animal Model of Osteoarthritis

PurposeTo create a nonsurgical animal model of osteoarthritis (OA) to evaluate the effects of embolotherapy during geniculate artery embolization (GAE).Materials and MethodsFluoroscopy-guided injections of 700 mg of sodium monoiodoacetate were performed into the left stifle in 6 rams. Kinematic data were collected before and after induction. At 10 weeks after induction, Subjects 1 and 4–6 underwent magnetic resonance (MR) imaging with dynamic contrast enhancement (DCE) and Subjects 1, 3, and 4–6 underwent angiography with angiographic scoring to identify regions with greatest disease severity for superselective embolization (75–250-μm microspheres). Target vessel size was measured. At 24 weeks after angiography, DCE-MR imaging, angiography, and euthanasia were performed, and bilateral stifles were harvested. Medial/lateral tibial and femoral condylar, patellar, and synovial samples were cut, preserved, decalcified, and scored using the Osteoarthritis Research Society International criteria. The stifle and synovium Whole-Organ Magnetic Resonance Imaging Score and Multicenter Osteoarthritis Study score were determined. The volume transfer constant (K_trans) and extracellular volume fraction (v_e) were calculated from DCE-MR imaging along the lateral synovial regions of interest.ResultsThe mean gross and microscopic pathological scores were elevated at 38 and 61, respectively. Mean synovitis score was elevated at 9.2. Mean pre-embolization and postembolization angiographic scores were 5 and 3.8, respectively. Mean superior, transverse, and inferior geniculate artery diameters were 3.1 mm ± 1.21, 2.0 mm ± 0.50, and 1.6 mm ± 0.41 mm, respectively. Mean pre-embolization and postembolization cartilage and synovitis scores were elevated at 35.13 and 73.3 and 5.5 and 9.2, respectively. The K_trans/v_e values of Subjects 4, 5, and 6 were elevated at 0.049/0.38, 0.074/0.53, and 0.065/0.51, respectively. Altered gait of the hind limb was observed in all subjects after induction, with reduced joint mobility. No skin necrosis or osteonecrosis was observed.ConclusionsA nonsurgical ovine animal knee OA model was created, which allowed the collection of angiographic, histopathological, MR imaging, and kinematic data to study the effects of GAE.     

Colonoscopy Versus Catheter Angiography for Lower Gastrointestinal Bleeding After Localization on CT Angiography

PurposeThe aim of this study was to compare catheter angiography (CA) and colonoscopy outcomes after successful CT angiographic (CTA) localization for patients with overt lower gastrointestinal bleeding (LGIB).MethodsSeventy-one consecutive patients from two institutions between 2010 and 2020 had both contrast extravasation on CTA imaging in the lower gastrointestinal tract and subsequent CA or colonoscopy. The primary outcome was confirmation of active bleeding during CA or colonoscopy (defined as confirmation yield). The secondary outcomes were to determine therapeutic yield (hemostatic therapy), time to procedure, rebleeding rate, and adverse outcome rates (defined as surgery, acute kidney injury, initiation of dialysis, and overall mortality). Univariate analyses and multivariable analyses with P < .05 were used to determine statistical significance.ResultsForty-four patients underwent CA and 27 underwent colonoscopy. CA had higher overall confirmation yield (55% vs 26%, P = .026), whereas therapeutic yields were similar (70% vs 56%, P = .214). Time to procedure was 5.1 ± 3.4 hours for CA and 15.5 ± 13.6 hours for colonoscopy (P < .001). On multivariable analysis, shorter time to procedure was the only statistically significant predictor of confirmation yield (P = .037) and therapeutic yield (P = .013), whereas procedure, hemoglobin, transfusions, and hemodynamic instability were not. Adverse events and rebleeding were not statistically different between patients who underwent CA and colonoscopy (P > .05).ConclusionsShorter time to procedure was the only statistically significant predictor of confirmation and therapeutic yield after CTA localization of LGIB. Because CA can be performed sooner than colonoscopy without increased rates of adverse outcomes or rebleeding, CA may be a reasonable first-line treatment option in patients with CTA localization of LGIB.