Super-resolution SRS microscopy with A-PoD.

Stimulated Raman scattering (SRS) offers the ability to image metabolic dynamics with high signal-to-noise ratio. However, its spatial resolution is limited by the numerical aperture of the imaging objective and the scattering cross-section of molecules. To achieve super-resolved SRS imaging, we developed a deconvolution algorithm, adaptive moment estimation (Adam) optimization-based pointillism deconvolution (A-PoD) and demonstrated a spatial resolution of lower than 59 nm on the membrane of a single lipid droplet (LD). We applied A-PoD to spatially correlated multiphoton fluorescence imaging and deuterium oxide (D2O)-probed SRS (DO-SRS) imaging from diverse samples to compare nanoscopic distributions of proteins and lipids in cells and subcellular organelles. We successfully differentiated newly synthesized lipids in LDs using A-PoD-coupled DO-SRS. The A-PoD-enhanced DO-SRS imaging method was also applied to reveal metabolic changes in brain samples from Drosophila on different diets. This new approach allows us to quantitatively measure the nanoscopic colocalization of biomolecules and metabolic dynamics in organelles.

A high-throughput technique to map cell images to cell positions using a 3D imaging flow cytometer.

We develop a high-throughput technique to relate positions of individual cells to their three-dimensional (3D) imaging features with single-cell resolution. The technique is particularly suitable for nonadherent cells where existing spatial biology methodologies relating cell properties to their positions in a solid tissue do not apply. Our design consists of two parts, as follows: recording 3D cell images at high throughput (500 to 1,000 cells/s) using a custom 3D imaging flow cytometer (3D-IFC) and dispensing cells in a first-in-first-out (FIFO) manner using a robotic cell placement platform (CPP). To prevent errors due to violations of the FIFO principle, we invented a method that uses marker beads and DNA sequencing software to detect errors. Experiments with human cancer cell lines demonstrate the feasibility of mapping 3D side scattering and fluorescent images, as well as two-dimensional (2D) transmission images of cells to their locations on the membrane filter for around 100,000 cells in less than 10 min. While the current work uses our specially designed 3D imaging flow cytometer to produce 3D cell images, our methodology can support other imaging modalities. The technology and method form a bridge between single-cell image analysis and single-cell molecular analysis.

Complete revascularization in stable multivessel coronary artery disease: A real world analysis from the British Columbia Cardiac Registry.

BACKGROUND: More than half of patients undergoing percutaneous coronary intervention (PCI) have multivessel disease (MVD). The prognostic significance of PCI in stable patients has recently been debated, but little data exists about the potential benefit of complete revascularization (CR) in stable MVD. We investigated the prognostic benefit of CR in patients undergoing PCI for stable disease. METHODS: We compared CR versus incomplete revascularization (IR) in 8,436 patients with MVD. The primary outcome was all-cause mortality at 5 years. RESULTS: A total of 1,399 patients (17%) underwent CR during the index PCI procedure for stable disease. CR was associated with lower mortality (6.2 vs. 10.7%, p < .001) and lower repeat revascularization at 5 years (12.7 vs. 18.4%, p < .001). Multivariable-adjusted analyses indicated that CR was associated with lower mortality (HR = 0.73, 95% CI: 0.58-0.91, p = .005) and repeat revascularization at 5 years (HR = 0.78, 95% CI: 0.66-0.93, p = .005). These findings were also confirmed in propensity-matched cohorts. Subgroup analyses indicated that CR conferred survival in older patients, male patients, absence of renal disease, greater angina (CCS Class III-IV) and heart failure (NYHA Class III-IV) symptoms, and greater burden of coronary disease. In sensitivity analyses where patients with subsequent repeat revascularization events were excluded, CR remained a strong predictor for lower mortality (HR = 0.69, 95% CI: 0.54-0.89, p = .004). CONCLUSIONS: In this study of stable patients with MVD, CR was an independent predictor of long-term survival. This benefit was specifically seen in higher risk patient groups and indicates that CR may benefit selected stable patients with MVD.

The Impact of Pre-Procedural Renal Impairment on Outcomes Following Percutaneous Coronary Intervention: An Analysis of 45,287 Patients From the British Columbia Cardiac Registry.

BACKGROUND: Renal disease confers a strong independent risk for morbidity and mortality after percutaneous coronary intervention (PCI). We evaluated the relationship between baseline pre-procedural renal function and outcomes following PCI. METHODS: We examined 45,287 patients who underwent PCI in British Columbia. We evaluated all-cause mortality and target vessel revascularisation (TVR) at 2 years. Pre-procedural renal impairment was categorised by creatinine clearance (CrCl, mL/min): CrCl≥90 (n=14,876), 90>CrCl≥60 (n=10,219), 60>CrCl≥30 (n=14,876), 30>CrCl≥0 (n=2,594) and dialysis (n=579). RESULTS: Declining CrCl values less than 60 mL/min were progressively associated with greater mortality: 60>eGFR≥30 (HR=2.01, 95% CI 1.71-2.37, p<0.001); 30>eGFR≥0 (HR=4.10, 95% CI 3.39-4.95, p<0.001); and dialysis (HR=6.22, 95% CI 5.07-7.63, p<0.001). A reduction in eGFR was not associated with TVR in non-dialysis patients. However, dialysis was a strong independent predictor for TVR (HR=1.69, 95% CI 1.37-2.08, p<0.001). This was confirmed in propensity-matched analyses where, dialysis was strongly associated with TVR (HR=1.53, 95% CI 1.24-1.89, p<0.001). This association was consistently seen in stratified analyses for diabetic versus non-diabetic patients; stent length >30 mm versus <30 mm; stent diameter >3 mm versus <3 mm; and receipt of bare metal stents versus drug-eluting stents. CONCLUSIONS: This study indicates the association with declining renal function and mortality in patients undergoing PCI. Whilst renal disease was not associated with increased TVR in non-dialysis patients, dialysis-dependence was a strong independent predictor for increased TVR.

DO-SRS imaging of metabolic dynamics in aging Drosophila.

Emerging studies have shown that lipid metabolism plays an important role in aging. High resolution in situ imaging of lipid metabolic dynamics inside cells and tissues affords a novel and potent approach for understanding many biological processes such as aging. Here we established a new optical imaging platform that combines D2O-probed stimulated Raman scattering (DO-SRS) imaging microscopy and a Drosophila model to directly visualize metabolic activities in situ during aging. The sub-cellular spatial distribution of de novo lipogenesis in the fat body was quantitatively imaged and examined. We discovered a dramatic decrease in lipid turnover in 35-day-old flies. Decreases in protein turnover occurred earlier than lipids (25-day vs. 35-day), and there are many proteins localized on the cell and lipid droplet membrane. This suggests that protein metabolism may act as a prerequisite for lipid metabolism during aging. This alteration of maintenance of protein turnover indicates disrupted lipid metabolism. We further found a significantly higher lipid turnover rate in large LDs, indicating more active metabolism in large LDs, suggesting that large and small LDs play different roles in metabolism to maintain cellular homeostasis. This is the first study that directly visualizes spatiotemporal alterations of lipid (and protein) metabolism in Drosophila during the aging process. Our study not only demonstrates a new imaging platform for studying lipid metabolism, but also unravels the important interconnections between lipid metabolism and aging.

Outcomes and complications in scleral-fixated intraocular lens implantations.

PURPOSE: This study compares outcomes and complications of scleral-fixated intraocular lens implantation between 2 levels of surgeons. METHODS: A retrospective case series of patients undergoing scleral-fixated intraocular lens implantation at Prince of Wales Hospital, Hong Kong, between May 2012 and April 2017 were reviewed. Data collected included age, gender, affected eye, preoperative and postoperative visual acuities, refractive target and outcome, surgeon profile, operative details including method of scleral fixation, intraoperative and postoperative complications and length of follow-up. RESULTS: Ninety eyes of 90 patients were included for analyses. The mean LogMAR visual acuities were 1.17 ± 0.70 at postoperative week 1, 0.81 ± 0.56 at 1 month, 0.66 ± 0.55 at 3 months, 0.56 ± 0.59 at 6 months, and 0.51 ± 0.60 at 1 year, respectively. After adjusting for age at operation, operative time, axial length, subspecialty of the surgeon and preoperative LogMAR, surgeon seniority was not significantly associated with final visual outcomes. There was no statistically significant difference between the mean improvement in visual acuities between eyes operated by consultants and fellows under direct supervision of a senior surgeon. CONCLUSION: Scleral-fixated intraocular lens implantation is safe and effective in improving visual acuity in aphakic adults without capsular support. Under good supervision, fellows were able to produce comparable results compared with experienced specialists.

The prognostic impact of revascularization strategy in acute myocardial infarction and cardiogenic shock: Insights from the British Columbia Cardiac Registry.

BACKGROUND: In patients with acute myocardial infarction (AMI) and cardiogenic shock (CS), percutaneous coronary intervention (PCI) of the culprit vessel is associated with improved outcomes. A large majority of these patients have multivessel disease (MVD). Whether or not PCI of non-culprit disease in the acute setting improves outcomes continues to be debated. We evaluated the prognostic impact of revascularization strategy for patients presenting with AMI and CS. METHODS: We compared culprit vessel intervention (CVI) versus multivessel intervention in 649 patients with AMI, CS, and MVD enrolled in the British Columbia Cardiac Registry. We evaluated mortality at 30 days and 1 year. RESULTS: CVI was associated with lower mortality at 30 days (23.7% vs. 34.5%, P = 0.004) and 1 year (32.6% vs. 44.3%, P = 0.003). CVI was an independent predictor for survival at 30 days (HR = 0.63, 95% CI: 0.45-0.88, P = 0.009) and 1 year (HR = 0.72, 95% CI: 0.54-0.96, P = 0.027). These findings were confirmed in propensity-matched cohorts. Subgroup analyses indicated that CVI was associated with lower mortality in patients aged <80 years; non-diabetics; and those presenting with ST-elevation MI. When analyzing non-culprit anatomy, PCI of non-culprit LAD disease was associated with higher 1-year mortality (HR = 1.51, 95% CI: 1.13-2.01, P = 0.006), primarily with non-culprit proximal LAD disease (HR = 1.82, 95% CI: 1.20-2.76, P = 0.005). However, PCI of non-culprit non-proximal LAD, LCx, and RCA disease was not associated with mortality. CONCLUSIONS: In patients with AMI and CS, a strategy of CVI appears to be associated with lower mortality. These findings are consistent with recently published randomized-controlled trial data.

Angiographic appearance of spontaneous coronary artery dissection with intramural hematoma proven on intracoronary imaging.

BACKGROUND: The pathognomonic appearance of multiple radiolucent lumen on angiography is used to diagnose spontaneous coronary artery dissection (SCAD). However, this finding is absent in >70% of SCAD, in which case optical coherence tomography (OCT) or intravascular ultrasound (IVUS) is useful to assess arterial wall integrity. METHODS: We report the angiographic appearance of SCAD that were proven on intracoronary imaging with OCT or IVUS. Our angiographic classification and algorithm for SCAD diagnosis was previously reported. Patients with type 1 SCAD (multiple radiolucent lumen) do not require OCT/IVUS, whereas, it was recommended for those with suspected type 2 (diffuse stenosis) or 3 (mimic atherosclerosis) SCAD. RESULTS: Twenty-two consecutive patients with non-type 1 angiographic SCAD in 25 coronary arteries (22 OCT and 4 IVUS) were studied. Mean age was 52.9 ± 9.9 years, 89.5% were women, and 16/22 (72.7%) had underlying fibromuscular dysplasia. Sixteen SCAD arteries were type 2 SCAD, and nine were type 3. All 25 SCAD arteries had intramural hematoma and intimomedial membrane separation with double lumen on OCT or IVUS. The mean visual angiographic stenosis was 74.6 ± 17.5% (range 40-100%). Dissected segments were long with mean qualitative coronary analysis (QCA) length 45.2 ± 29.2 mm, especially in patients with type 2 SCAD (mean QCA length 58.3 ± 29.0 mm). The mean QCA length in type 3 SCAD lesions was 22.1 ± 5.7 mm. CONCLUSIONS: Intracoronary imaging confirms that SCAD may appear angiographically without multiple radiolucent lumen. Angiographers should be familiar with angiographic SCAD variants to improve SCAD diagnosis, and utilize intracoronary imaging when the diagnosis is uncertain.

Long-term outcomes following drug-eluting stents versus bare metal stents for primary percutaneous coronary intervention: A real-world analysis of 11,181 patients from the british columbia cardiac registry.

BACKGROUND: Drug eluting stents (DES) are associated with reduced risk of restenosis when compared with bare metal stents (BMS). Their use in ST-elevation myocardial infarction (STEMI) is debated, owing to concerns about stent thrombosis. There are limited real-world data comparing DES versus BMS in STEMI. We conducted an observational analysis in this setting and rigorously adjusted for treatment selection bias. METHODS: We analyzed 11,181 consecutive patients with acute STEMI who received either DES or BMS during 2008-2014 in the British Columbia Cardiac Registry. We analyzed target vessel revascularization (TVR) and mortality at 2 years. RESULTS: Multivariable-adjusted, propensity-matched and inverse probability-treatment weighted analyses found DES to be associated with early and late survival up to 2 years but not TVR. However, when adjusting for measured and unmeasured confounders, instrumental variable (IV) analyses demonstrated that DES use was associated with reduced TVR up to 2 years (Δ = -6.7%, 95% CI: -10.0%, -3.4%, P < 0.001). DES use was not associated with mortality at 1 year (Δ = -2.3%, 95% CI: -5.0%, 0.4%, P = 0.100) but associated with reduced mortality at 2 years (Δ = -5.4%, 95% CI: -8.3%, -2.5%, P < 0.001). Stratified IV analyses indicated that this long-term survival benefit was largely attributable to the second generation DES. CONCLUSIONS: In this study of patients with STEMI, when adjusting for measured and unmeasured factors, DES use was associated with reduced TVR and long-term survival beyond 1 year. This long-term survival was largely attributable to the second generation DES. These real-world data are reassuring and support the use of DES for STEMI. © 2016 Wiley Periodicals, Inc.

Embolic protection device use and its association with procedural safety and long-term outcomes following saphenous vein graft intervention: An analysis from the British Columbia Cardiac registry.

BACKGROUND: Embolic protection devices (EPDs) have been designed and introduced to reduce distal embolization and peri-procedural myocardial infarction during saphenous vein graft (SVG) intervention. Current guidelines give a class I recommendation to EPD use during SVG intervention when technically feasible. However, the routine use of these devices has recently been debated. METHODS: We analyzed 1,359 patients undergoing isolated SVG intervention between 2008 and 2013 in the British Columbia Cardiac Registry. We analyzed (a) post-procedural TIMI flow; and (b) target vessel revascularization (TVR) and mortality at 1 and 2 years. RESULTS: EPD use was an independent predictor of post-procedural TIMI 2/3 flow (OR = 2.38, 95% CI: 1.51-3.74, P < 0.001). At 1 year, EPD use was an independent predictor for lower TVR (HR = 0.35, 95% CI: 0.14-0.85, P = 0.021) and a trend towards lower mortality (HR = 0.45, 95% CI: 0.18-1.10, P = 0.082). These associations were lost at 2 years where EPD use was not predictive of mortality (HR = 0.62, 95% CI: 0.33-1.17, P = 0.144) or TVR (HR = 0.70, 95% CI: 0.41-1.17, P = 0.176). These findings were confirmed in propensity-matched and inverse probability treatment weighted analyses. CONCLUSIONS: In this analysis of patients undergoing SVG intervention, EPD use was a strong predictor for improved post-procedural TIMI flow. Whilst EPD use was associated with lower TVR and a trend for lower mortality at 1 year, these associations were lost at 2 years. These findings would appear to support the use of EPD for SVG intervention. © 2015 Wiley Periodicals, Inc.

Rapidly growing cardiac mass: a rare case of left atrial intramural hematoma complicating coronary artery stenting.

Formation of an intramural left atrial hematoma (ILAH) is a rare complication of coronary artery stenting. Rapid diagnosis with noninvasive multimodality imaging can potentially be lifesaving. We report a case of ILAH that resulted in left ventricular inflow obstruction and pericardial tamponade in a 55-year-old male who presented with hemodynamic instability and worsening dyspnea three weeks after seemingly uncomplicated left circumflex artery stenting. We demonstrate features on transthoracic echocardiography with contrast and cardiac computed tomography that were used for diagnosis and management.

Culprit lesion thrombus burden after manual thrombectomy or percutaneous coronary intervention-alone in ST-segment elevation myocardial infarction: the optical coherence tomography sub-study of the TOTAL (ThrOmbecTomy versus PCI ALone) trial.

AIMS: Manual thrombectomy has been proposed as a strategy to reduce thrombus burden during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the effectiveness of manual thrombectomy in reducing thrombus burden is uncertain. In this substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial, we compared the thrombus burden at the culprit lesion using optical coherence tomography (OCT) in patients treated with thrombectomy vs. PCI-alone. METHODS AND RESULTS: The TOTAL trial (N = 10 732) was an international, multicentre, randomized trial of thrombectomy (using the Export catheter, Medtronic Cardiovascular, Santa Rosa, CA, USA) in STEMI patients treated with primary PCI. The OCT substudy prospectively enrolled 214 patients from 13 sites in 5 countries. Optical coherence tomography was performed immediately after thrombectomy or PCI-alone and then repeated after stent deployment. Thrombus quantification was performed by an independent core laboratory blinded to treatment assignment. The primary outcome of pre-stent thrombus burden as a percentage of segment analysed was 2.36% (95% CI: 1.73-3.22) in the thrombectomy group and 2.88% (95% CI: 2.12-3.90) in the PCI-alone group (P = 0.373). Absolute pre-stent thrombus volume was not different (2.99 vs. 3.74 mm(3), P = 0.329). Other secondary outcomes of pre-stent quadrants of thrombus, post-stent atherothrombotic burden, and post-stent atherothrombotic volume were not different between groups. CONCLUSION: Manual thrombectomy did not reduce pre-stent thrombus burden at the culprit lesion compared with PCI-alone. Both strategies were associated with low thrombus burden at the lesion site after the initial intervention to restore flow.

Stroke in the TOTAL trial: a randomized trial of routine thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction.

AIMS: TOTAL (N = 10 732), a randomized trial of routine manual thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction, showed no difference in the primary efficacy outcome but a significant increase in stroke. We sought to understand these findings. METHODS AND RESULTS: A detailed analysis of stroke timing, stroke severity, and stroke subtype was performed. Strokes were adjudicated by neurologists blinded to treatment assignment. Stroke within 30 days, the primary safety outcome, was increased [33 (0.7%) vs. 16 (0.3%), hazard ratio (HR) 2.06; 95% confidence interval (CI) 1.13-3.75]. The difference in stroke was apparent within 48 h [15 (0.3%) vs. 5 (0.1%), HR 3.00; 95% CI 1.09-8.25]. There was an increase in strokes within 180 days with minor or no disability (Rankin 0-2) [18 (0.4%) vs. 13 (0.3%) HR 1.38; 95% CI 0.68-2.82] and in strokes with major disability or fatal (Rankin 3-6) [35 (0.7%) vs. 13 (0.3%), HR 2.69; 95% CI 1.42-5.08]. Most of the absolute difference was due to an increase in ischaemic strokes within 180 days [37 (0.7%) vs. 21 (0.4%), HR 1.71; 95% CI 1.03-3.00], but there was also an increase in haemorrhagic strokes [10 (0.2%) vs. 2 (0.04%), HR 4.98; 95% CI 1.09-22.7]. Patients that had a stroke had a mortality of 30.8% within 180 days vs. 3.4% without a stroke (P < 0.001). A meta-analysis of randomized trials (N = 21 173) showed an increase in risk of stroke (odds ratio 1.59; 95% CI 1.11-2.27) but a trend towards reduction in mortality odds ratio (odds ratio 0.87; 95% CI 0.76-1.00). CONCLUSION: Thrombectomy was associated with a significant increase in stroke. Based on these findings, future trials must carefully collect stroke to determine safety in addition to efficacy.

Ischaemic and inflammatory injury in renal graft from brain death donation: an update review.

Renal transplantation remains an important therapy in treating renal failure and can be considered to be a curative treatment. The demand for renal grafts outstrips supply available each year, making it increasingly important to look at improving the treatment of both renal grafts and recipients, and thereby improving patient outcomes and increasing the pool of potential donor grafts. Important to this, however, is knowledge of the underlying mechanisms leading to damage to the graft and rejection from the recipient. This includes ischaemia and consequently the priming of the organ during storage for ischaemia reperfusion injury (IRI) on implantation and the importance of the innate immune system which can be activated via multiple pathways, often via TLR-4, and the consequent production of danger-associated molecular patterns. This makes the time period involving both explantation and storage an important therapeutic window for improving outcomes. Other windows explored include treatment of IRI and improvement in immunosuppressive therapy. The multiple windows of potential therapeutic input have spawned a large body of work exploring both the underlying mechanisms and also how to exploit these mechanisms to improve overall outcomes and to allow for more marginal organs to be used.

Necroptosis and parthanatos are involved in remote lung injury after receiving ischemic renal allografts in rats.

Early renal graft injury could result in remote pulmonary injury due to kidney-lung cross talk. Here we studied the possible role of regulated necrosis in remote lung injury in a rat allogeneic transplantation model. In vitro, human lung epithelial cell A549 was challenged with TNF-α and conditioned medium from human kidney proximal tubular cells (HK-2) after hypothermia-hypoxia insults. In vivo, the Brown-Norway rat renal grafts were extracted and stored in 4 °C Soltran preserving solution for up to 24 h and transplanted into Lewis rat recipients, and the lungs were harvested on day 1 and day 4 after grafting for further analysis. Ischemia-reperfusion injury in the renal allograft caused pulmonary injury following engraftment. PARP-1 (marker for parthanatos) and receptor interacting protein kinase 1 (Rip1) and Rip3 (markers for necroptosis) expression was significantly enhanced in the lung. TUNEL assays showed increased cell death of lung cells. This was significantly reduced after treatment with necrostatin-1 (nec-1) or/and 3-aminobenzamide (3-AB). Acute immune rejection exacerbated the remote lung injury and 3-AB or/and Nec-1 combined with cyclosporine A conferred optimal lung protection. Thus, renal graft injury triggered remote lung injury, likely through regulated necrosis. This study could provide the molecular basis for combination therapy targeting both pathways of regulated necrosis to treat such complications after renal transplantation.

Radial versus femoral access for elderly patients with acute coronary syndrome undergoing coronary angiography and intervention: insights from the RIVAL trial.

BACKGROUND: Radial access for percutaneous coronary intervention is associated with lower rates of access site complications and bleeding. However, elderly patients have more complex vascular anatomy and radial access may be more challenging in this population. There remains uncertainty regarding the role of radial access in elderly patients undergoing cardiac catheterization. METHODS AND RESULTS: The RIVAL trial randomized patients with acute coronary syndromes undergoing cardiac catheterization to radial versus femoral access. In this analysis, the rates of access site complications and access site cross-over were compared across different age groups. Among the 7,021 patients, 1035 (15%) were ≥75 years of age. Across all age categories, radial access was consistently associated with higher rates of access site cross over and lower rates of major access site complications, with no significant interaction between age and access site. Radial access was associated with lower rates of major vascular access site complications in patients ≥75 years of age (3.6% vs 6.6%; P = .03) and in patients <75 years of age (1.0% vs 3.2%; P < .001; P value for interaction = .2). The rates of access site crossover were higher with radial access among patients ≥75 (12.5% vs 2.6%; P < .001) and <75 (6.7% vs 1.9%; P < .001; P value for interaction = .9). There were no significant differences in the primary composite outcome (death, myocardial infarction, stroke or non coronary artery bypass graft major bleeding) or its individual components in either age group. In patients ≥75 years of age undergoing primary percutaneous coronary intervention, there was no significant difference in procedure time (120 vs 115 minutes; P = .3). CONCLUSIONS: Consistent with the overall RIVAL trial population, elderly patients undergoing cardiac catheterization have lower rates of major bleeding or access site complications and higher rates of access site crossover with radial access compared to femoral access.

The role of interleukin 17 in tumour proliferation, angiogenesis, and metastasis.

With 7.6 million deaths globally, cancer according to the World Health Organisation is still one of the leading causes of death worldwide. Interleukin 17 (IL-17) is a cytokine produced by Th17 cells, a T helper cell subset developed from an activated CD4+ T-cell. Whilst the importance of IL-17 in human autoimmune disease, inflammation, and pathogen defence reactions has already been established, its potential role in cancer progression still needs to be updated. Interestingly studies have demonstrated that IL-17 plays an intricate role in the pathophysiology of cancer, from tumorigenesis, proliferation, angiogenesis, and metastasis, to adapting the tumour in its ability to confer upon itself both immune, and chemotherapy resistance. This review will look into IL-17 and summarise the current information and data on its role in the pathophysiology of cancer as well as its potential application in the overall management of the disease.

Outcomes following antegrade-only versus retrograde chronic total occlusion percutaneous coronary intervention: insights from the CCTOP registry.

Background: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can be performed using an antegrade-only (AO) approach or a retrograde approach (RA). Whether an RA carries a higher risk of complications needs further investigation. Methods: The Canadian CTO PCI (CCTOP) was a multicenter, prospective, investigator-initiated cohort study conducted at 6 experienced centers across Canada between March 2014 and October 2019. Patients who underwent an RA were compared to AO patients. The primary endpoint was in-hospital major adverse cardiac events (MACE), defined as death, any post-PCI cardiac enzyme elevation, urgent revascularization, and tamponade. A multivariable analysis was performed to control for potential confounders. Results: A total of 1033 patients were included in the study, and an RA was used in 48.4% of the cases. The RA was associated with higher lesions complexity (J-CTO score 2.7 ± 1.1 vs 2.3 ± 1.1, P < .001) and lower technical success (81.2% vs 91.5%, P < .001). The risk of in-hospital MACE was higher with the RA (10.2% vs 4.7%, P < .001), and all deaths occurred in the RA group (0.8% vs 0%, P = .038). In the multivariable model, the RA remained associated with an increased risk of MACE (OR, 2.25; 95% CI, 1.26 to 4.02). Conclusions: Our experience confirms that the RA is associated with an independent increased risk of in-hospital MACE when compared with an AO approach.

Multi-molecular hyperspectral PRM-SRS microscopy.

Lipids play crucial roles in many biological processes. Mapping spatial distributions and examining the metabolic dynamics of different lipid subtypes in cells and tissues are critical to better understanding their roles in aging and diseases. Commonly used imaging methods (such as mass spectrometry-based, fluorescence labeling, conventional optical imaging) can disrupt the native environment of cells/tissues, have limited spatial or spectral resolution, or cannot distinguish different lipid subtypes. Here we present a hyperspectral imaging platform that integrates a Penalized Reference Matching algorithm with Stimulated Raman Scattering (PRM-SRS) microscopy. Using this platform, we visualize and identify high density lipoprotein particles in human kidney, a high cholesterol to phosphatidylethanolamine ratio inside granule cells of mouse hippocampus, and subcellular distributions of sphingosine and cardiolipin in human brain. Our PRM-SRS displays unique advantages of enhanced chemical specificity, subcellular resolution, and fast data processing in distinguishing lipid subtypes in different organs and species.

Intracoronary imaging of coronary fibromuscular dysplasia with OCT and IVUS.

Fibromuscular dysplasia (FMD) is a segmental non-atherosclerotic, non-inflammatory vasculopathy typically of small- to medium-muscular arteries. Coronary FMD (CFMD) is believed to be rare. However, we have found an association between spontaneous coronary artery dissection (SCAD) and FMD as the cause of myocardial infarction in ∼25% of young women age <50 years. It is plausible that pre-existing CFMD predisposed these women to SCAD. Definitive diagnosis of CFMD entails autopsy that is obviously impractical, and prior angiographic description does not differentiate superimposed SCAD from obliterative arteriopathy of CFMD. Adjunctive intravascular ultrasound or optical coherence tomography may aid the diagnosis of CFMD and we report the first of such novel images.