Irene C Kuo, M.D.

• Chief, Wilmer Eye Institute - White Marsh
• Associate Professor of Ophthalmology

https://www.hopkinsmedicine.org/profiles/results/directory/profile/0015722/irene-kuo

This artifact often results from insufficient injection of flushing media; therefore medicine for vertigo buy cheap combivent 100mcg line, operators should be careful not to interpret this artifact as real tissue structure medicine 94 purchase combivent online now. Contrast medium is optically transparent and is typically used to remove blood from the lumen (choice B) medicine interaction checker cheap 100mcg combivent. Thrombus medications 126 discount combivent online, or plaque rupture complicated with thrombus accumulation medications an 627 generic combivent 100mcg on line, often appears as a lobulated intraluminal mass that attaches to the lacerated plaque surface or is floating within the lumen (choices A and C) symptoms rheumatoid arthritis cheap combivent 100 mcg without prescription. Red thrombus (red blood cell-rich thrombus) is typically observed as a high backscattering and high attenuation structure, whereas white thrombus (platelet-rich thrombus) is seen as a less backscattering and homogeneous mass with less signal attenuation. The color scale from red to yellow indicates increasing algorithm probability of a lipid component of the vessel wall (choice B). At present, the ability of coronary spectroscopy to detect and differentiate various other plaque components or pathological features of plaque vulnerability remains to be determined. Emerging Clinical Applications of Physiologic and Intravascular Imaging Tools Olivia Y. Herein we describe emerging clinical applications of in vivo physiologic and imaging modalities in the settings of stable ischemic heart disease, symptomatic myocardial ischemia without obstructive epicardial atherosclerosis, and acute coronary syndromes. Physiologic assessment can also help simplify and determine the overall interventional approach for complex bifurcation lesions by converting them into a predominantly single lesion. The primary end point was the rate of a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization within 1-year after the procedure. Nevertheless, we discuss below the evidence derived from anatomic lesion assessment. The angiographic 2-dimensional images cannot account for the multiple factors that produce resistance to coronary blood flow and loss of pressure across a stenosis. The eccentric and irregular stenosis (upper panel) shows arrows designating entrance effects, friction, and zones of turbulence accounting for separation energy loss. The calculation of pressure loss (P) across a stenosis (lower right panel) incorporates length (l), areas stenosis (As), reference area (An), flow (Q), and coefficients of viscous friction and laminar separation (f1 and f2) as contributors to resistance and hence pressure loss. Current Concepts of Integrated Coronary Physiology in the Catheterization Laboratory. Therefore, adjunctive imaging and physiology modalities have emerged as highly useful tools allowing operators to more confidently and accurately evaluate lesions and direct revascularization. Randomized clinical trials directed toward invasive physiologic and anatomic assessment for left main disease are warranted. Patients with non-obstructive atherosclerosis have longterm outcomes similar to those with obstructive coronary artery disease; anginal symptoms in these patients have been associated with increased mortality, higher frequency of emergency room visits and hospitalizations, increased costs, and worse quality of life when compared to normal subjects. For patients presenting with angina but no flow limiting coronary lesions, we recommend coronary reactivity testing, first with acetylcholine and then with adenosine. If this occurs without notable findings in response to acetylcholine, then the patient has endothelium-independent microvascular dysfunction. On the other hand, if it occurs with vasoconstriction to acetylcholine, then the patient is considered to have both endothelial and microvascular dysfunction. Angina pectoris and myocardial ischemia in the absence of obstructive coronary artery disease: practical considerations for diagnostic tests. Several indices have been developed to evaluate microvascular function in patients with and without epicardial disease. Endothelial dysfunction is a common cause of microvascular disease and angina in patients with no significant coronary atherosclerotic lesions. Endothelial function testing requires pharmacological interrogation of the endothelium using intracoronary acetylcholine (off-label use) and thus is generally performed in specialized centers or in research protocols. In patients with endothelial dysfunction, acetylcholine paradoxically fails to cause vasodilatation and may even result in vasoconstriction through interaction on muscarinic receptors of arterial smooth muscle cells. Patients with severe vasospasm may demonstrate complete obliteration of the coronary artery that can be quickly reversed with nitroglycerin. Myocardial Bridging While only a minority of myocardial bridges will cause myocardial ischemia, identification of those with hemodynamic relevance is of paramount importance in the diagnosis and management of symptomatic patients. Similar to fixed coronary stenoses, the angiographic severity of myocardial bridge does not correlate well with its functional relevance. On the other hand, the physiology of myocardial bridging is significantly different and more complex compared to that of fixed stenoses. During systole, myocardial compression results in highly resistive microcirculation and markedly higher intracoronary pressure, which is observed as a negative pressure gradient across the myocardial bridge where distal pressure is higher than aortic pressure. As a myocardial bridge is a dynamic stenosis that depends on the contractile status of the myocardium and the length of diastole, the hemodynamic consequences of myocardial bridging may only get expressed under stress during increased inotropy and tachycardia, which shortens the diastolic period. Furthermore, innovations in hybrid intravascular imaging and multi-modality fusion may facilitate precise morphologic visualization and phenotypic characterization of culprit lesions. Assessing Pathogenesis of the Culprit Lesion Intravascular imaging has allowed in vivo evaluation of ruptured thin cap fibroatheromas and plaque erosions, which are the most common precursors of coronary occlusions resulting in fatal acute myocardial infarctions. Depending on the clinical setting, a conservative approach of medical management and watchful waiting with possible imaging follow up has been shown to have excellent clinical and angiographic outcome. For those with acute, ongoing or recurrent ischemia, revascularization is indicated to restore the coronary blood flow and reduce infarct size. There are 3 options: 1) conservative stenting to cover only the entry door and segments showing severe lumen compromise, which may result in residual distal dissection, 2) aggressive stenting that may result in a "full metal jacket" due to propagation of an intramural hematoma, or 3) coronary artery bypass grafting for unstable patients with left main involvement or multiple severe and long dissections. Spontaneous Coronary Artery Dissection Long-Term Follow-Up of a Large Series of Patients Prospectively Managed With a "Conservative" Therapeutic Strategy. In critical angiographic stenosis (>90% diameter stenosis by visual assessment), particularly in a symptomatic patient with evidence of myocardial ischemia, further intravascular physiologic testing is not required to decide on hemodynamic lesion severity. Whether physiologically guided spot stenting or anatomically guided "normal to normal" stenting results in superior outcomes has not been prospectively investigated. Intravascular imaging co-registered with angiography can accurately measure required stent diameter and length, inform the decision of how aggressively to prepare the lesion prior to stenting, and direct poststent optimization with noncompliant balloon dilatation or adjunctive stenting. At the time of stent implantation, intravascular imaging can identify stent underexpansion, edge dissections, strut malapposition, tissue prolapse and incomplete lesion coverage. Bioresorbable scaffolds due to their larger strut size, are associated with a higher incidence of postprocedural side branch obstruction. Strut Malapposition Malapposition, also known as incomplete stent apposition, occurs when there is no contact between the stent struts and the lumen wall. The extent of strut malapposition can be measured as the distance between the strut and the vessel wall, taking into account strut thickness and intravascular imaging resolution limits. Malapposition can occur acutely after stent deployment or develop over time from positive arterial remodeling or thrombus resolution, and are categorized accordingly. Tissue Prolapse Tissue prolapse occurs after stent implantation where the tissue of the arterial wall and plaque protrudes between the stent struts. Edge Dissections A classification system for intimal tears was proposed by the Coronary Angioplasty Registry to help manage dissections observed after balloon angioplasty. Minor tears are categorized as type A or B dissections and are considered to be clinically benign. While highgrade edge dissections continue to be intervened upon, there is no consensus on the optimal management of low grade and angiographically silent edge dissections, so it remains to be seen whether edge dissections that are observed only on intravascular imaging are clinically relevant. Stent Fracture Fracturing of metallic stents is relatively uncommon with a reported rate of about 4%;113 however, there are heightened concerns about stent fractures in the bioresorbable scaffolds. Patients with recurrent angina symptoms and non-obstructive coronary artery disease may benefit from microvascular function testing and endothelial function assessment to guide targeted medical therapy. Intravascular imaging plays an important role in visualizing plaque characteristics and optimizing stent deployment to reduce the risk of in-stent stenosis and thrombosis. It has therefore become critical for clinicians to understand the potential applications of adjunctive diagnostic tools in the cardiac catheterization laboratory in order to best incorporate these modalities into their current practice. Physiological assessment of coronary artery disease in the cardiac catheterization laboratory: a scientific statement from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology. Current concepts of integrated coronary physiology in the catheterization laboratory. Intravascular imaging tools in the cardiac catheterization laboratory: comprehensive assessment of anatomy and physiology. Hyperemic stenosis resistance index for evaluation of functional coronary lesion severity. Improvement in coronary haemodynamics after percutaneous coronary intervention: assessment using instantaneous wave-free ratio. Diagnostic classification of the instantaneous wave-free ratio is equivalent to fract Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study ional flow reserve and is not improved with adenosine administration. Clinical potential of intravascular ultrasound for physiological assessment of coronary stenosis: relationship between quantitative ultrasound tomography and pressure-derived fractional flow reserve. Intravascular ultrasound criteria for the assessment of the functional significance of intermediate coronary artery stenoses and comparison with fractional flow reserve. Outcomes of percutaneous coronary intervention in intermediate coronary artery disease: fractional flow reserve-guided versus intravascular ultrasound-guided. Correlation between fractional flow reserve and intravascular ultrasound lumen area in intermediate coronary artery stenosis. Preintervention angiographic and intravascular ultrasound predictors for side branch compromise after a single-stent crossover technique. How good are experienced interventional cardiologists at predicting the functional significance of intermediate or equivocal left main coronary artery stenoses Intravascular ultrasoundguided treatment for angiographically indeterminate left main coronary artery disease: a long-term follow-up study. Correlations between fractional flow reserve and intravascular ultrasound in patients with an ambiguous left main coronary artery stenosis. Intravascular ultrasound-derived minimal lumen area criteria for functionally significant left main coronary artery stenosis. Optimizing outcomes during left main percutaneous coronary intervention with intravascular ultrasound and fractional flow reserve: the current state of evidence. Angina pectoris and myocardial ischemia in the absence of obstructive coronary artery 34. Myocardial bridging: contemporary understanding of pathophysiology with implications for diagnostic and therapeutic strategies. High wall shear stress proximal to myocardial bridging and atherosclerosis: intracoronary ultrasound and pressure measurements. New signs characteristic of myocardial bridging demonstrated by intracoronary ultrasound and Doppler. Comparison of intravascular ultrasound and angiography in the assessment of myocardial bridging. Abnormal regional myocardial flow in myocardial bridging of the left anterior descending coronary artery. Importance of diastolic fractional flow reserve and dobutamine challenge in physiologic assessment of myocardial bridging. Intramyocardial muscle bridging of the coronary artery-an examination of a diastolic "spike and dome" pattern of coronary flow velocity. Effects of dobutamine on coronary stenosis physiology and morphology: comparison with intracoronary adenosine. Diastolic fractional flow reserve to assess the functional severity of moderate coronary artery stenoses: comparison with fractional flow reserve and coronary flow velocity reserve. Functional, angiographic and intracoronary Doppler flow characteristics in symptomatic patients with myocardial bridging: effect of shortterm intravenous beta-blocker medication. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopathology. Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography. Spontaneous coronary artery dissection: long-term follow-up of a large series of patients prospectively managed with a "conservative" therapeutic strategy. Diagnosis of spontaneous coronary artery dissection by optical coherence tomography. Predictors of subacute stent thrombosis: results of a systematic intravascular ultrasound study. Impact of intravascular ultrasound guidance on long-term clinical outcomes in patients treated with drugeluting stent for bifurcation lesions: data from a Korean multicenter bifurcation registry. Kissing balloon or sequential dilation of the side branch and main vessel for provisional stenting of bifurcations: lessons from micro-computed tomography and 64. Percutaneous revascularization of left main: role of imaging, techniques, and adjunct pharmacology. Frequency-domain optical coherence tomography assessment of unprotected left main coronary artery disease-a comparison with intravascular ultrasound. The index of microcirculatory resistance predicts myocardial infarction related to percutaneous coronary intervention. Meta-analysis of randomized studies comparing intravascular ultrasound versus angiographic guidance of percutaneous coronary intervention in predrug-eluting stent era. Intravascular ultrasound guidance improves angiographic and clinical outcome of stent implantation for long coronary artery stenoses: final results of a 82. The effect of complete percutaneous revascularisation with and without intravascular ultrasound guidance in the drugeluting stent era. Late stent malapposition after drug-eluting stent implantation: an intravascular ultrasound analysis with long-term follow-up. Natural consequence of postintervention stent malapposition, thrombus, tissue prolapse, and dissection assessed by optical coherence tomography at mid-term 91. Late incomplete stent apposition after sirolimus-eluting stent implantation: a serial intravascular ultrasound analysis.

The average resorption time of poly-l-lactic acid is 1 year medicine ball exercises buy generic combivent, as indicated by gel permeation chromatography symptoms checklist trusted 100 mcg combivent. Regions previously occupied by polymeric struts are replaced by functional connective tissue at 2 years treatment vaginitis purchase genuine combivent on-line. The first-generation device eluted everolimus medicine jokes order combivent 100mcg with visa, whereas the secondgeneration scaffold elutes Myolimus xerostomia medications that cause order combivent pills in toronto. Polylactides are relatively hydrophilic; thus water diffuses into the less dense amorphous regions of the implant and hydrolyzes the ester bonds treatment 3 phases malnourished children best buy combivent. The second stage is characterized by continuous cleavage of the amorphous tie chains, reducing the radial strength of the scaffold and leading to structural discontinuities. The end products of magnesium-based scaffolds are elemental magnesium and inorganic salts. Only very complex lesion subsets, such as very long or heavily calcified lesions, chronic total occlusions, left main disease, and large bifurcations, were excluded. Device thrombosis rates in these smaller vessels were significantly different, reaching 4. This subanalysis demonstrates the importance of vessel sizing, suggesting avoidance of vessels >2. C In-segment late lumen loss at 1 year was the efficacy end point and the primary end point. The primary end point was angiographic in-segment late lumen loss powered for noninferiority with a margin of 0. In-segment late lumen loss (in-device + 5-mm proximal and distal edge vascular responses) was 0. The firstgeneration device eluted everolimus, whereas the second-generation scaffold elutes Myolimus. The scaffold design incorporates sinusoidal in-phase hoops with straight connectors and a strut thickness of 150 m, and the expected strut resorption is 1 year, as indicated in porcine models. Multislice computed tomography was performed at 12 months and repeated at 24 months, whereas clinical end points were assessed at 30 days, 6 months, and annually for up to 5 years. Drug-Coated Balloon Technologies: Technical Features and Clinical Applications Juan F. Experimental data showed that a repeated intracoronary bolus injection of a taxane-iopromide formulation resulted in significant reduction of neointimal proliferation in the porcine model of restenosis. Early experimental data confirmed that paclitaxel transfer into the vessel wall occurs rapidly following balloon inflation. Several experimental studies suggest that the presence of paclitaxel deposits on the surface of the vessel wall contribute to the biologic process of sustained local drug delivery. Interestingly, at 7 days, vessel wall concentrations began to equalize to the vessel surface levels, providing an explanation regarding the lack of tissue toxic effects despite the apparent supratherapeutic tissue levels found in pharmacokinetic studies. Bench data suggest that during balloon transit to the target lesion, approximately 10% to 15% of the drug is lost into the bloodstream. In the absence of the stent, the vessel healing profile is characterized by neointimal inhibition, presence of fibrin, and smooth muscle cell loss persistent over 90 days and resolving at 180 days. However, it has also been described that these particles are usually small and unlikely to be trapped into the distal microcirculation. Experimental data also suggest that microembolization is a rare finding and perhaps clinically irrelevant. However, due to the potential clinical adverse events derived from this phenomenon, the clinical introduction of these technologies for the treatment of specific critical vascular territories (eg, below the knee) has been slow and limited. In long femoropopliteal lesions, the regular use of metallic stents has resulted in high mechanical and clinical failures rates. Two large-scale randomized controlled trials have already completed 12month clinical follow-up (Table 32-2). In this study, despite that both the safety (freedom from death, amputation, and reintervention) and efficacy primary end points were met, clinical efficacy was not demonstrated. Those results demonstrate remarkable overall effectiveness and safety for patients treated with this technology in this lesion subset. Parallel to the development of more aggressive recanalization techniques, the use of femoropopliteal stenting continues to increase. The optimal treatment of this condition remains elusive as multiple modalities have failed to provide durable results. A single-center prospective registry, including 39 patients, reported a 1-year primary patency rate of 92. Clearly, the scientific data are still scarce, and the costbenefit analysis of this approach deserves further evaluation. In the randomized groups, the primary end point, percent stenosis at 12 months, was similar in both cohorts. Further investigation in larger, prospective, statistically powered randomized trials is warranted. The management of long calcified lesions in multiple small-caliber, low-flow arteries with a highresistance outflow bed influences tissue pharmacokinetics. If the artery significantly tapers in a long diseased segment, drug delivery and distribution may not be uniform. In addition, the presence of multiple lesions throughout the length of an artery and few anatomic landmarks may lead to geographic miss. It is not clear whether these complex biologic components affect drug pharmacokinetics. Especially among patients with poor vascular runoff, the dislodgment of a large amount of particles may lead to the mechanical occlusion of microvessels vital for tissue survival. In addition, paclitaxel accumulation in hypoxic tissue may either delay or worsen healing in patients with evidence of tissue loss. A subgroup of patients with lesions 10 cm in length underwent angiographic follow-up. It has been hypothesized that the small size of the arteries causing increased friction and higher drug losses may be responsible for these findings. Clinical adoption involving other indication will largely depend on the evolution of these technologies toward safer and more predictable local drug delivery devices. Significant technologic improvements are under development and include low-dose, low-particulate coating technologies and sirolimus-based local drug delivery devices. Acute cardiac tolerance of current contrast media and the new taxane protaxel using iopromide as carrier during porcine coronary angiography and stenting. Successful inhibition of neointimal proliferation in the porcine coronary stent model. Addition of paclitaxel to contrast media prevents restenosis after coronary stent implantation. Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. Inhibition of restenosis in femoropopliteal arteries: paclitaxel-coated versus uncoated balloon: femoral paclitaxel randomized pilot trial. Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: an autopsy study. Paclitaxel coated balloons for coronary artery interventions: a comprehensive review of preclinical and clinical data. Vascular, downstream, and pharmacokinetic responses to treatment with a low dose drug-coated balloon in a swine femoral artery model. Do pharmacokinetics explain persistent restenosis inhibition by a single dose of paclitaxel Vascular effects of paclitaxel following drug-eluting balloon angioplasty in a porcine coronary model: the importance of excipients. Mechanisms of tissue uptake and retention of paclitaxel-coated balloons: impact on neointimal proliferation and healing. Specific binding to intracellular proteins determines arterial transport properties for rapamycin and paclitaxel. Intravascular drug release kinetics dictate arterial drug deposition, retention, and distribution. Inhibition of neointimal proliferation after bare metal stent implantation with low-pressure drug delivery using a paclitaxel-coated balloon in porcine coronary arteries. Long-term follow-up after treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Effectiveness of paclitaxel-eluting balloon catheter in patients with sirolimus-eluting stent restenosis. A multicenter randomized comparison of paclitaxel-coated balloon catheter with conventional balloon angioplasty in patients with bare-metal stent restenosis and drugeluting stent restenosis. Long-term efficacy and safety of paclitaxel-eluting balloon for the treatment of drug-eluting stent restenosis: 3-year results of a randomized controlled trial. Comparison among drug-eluting balloon, drug-eluting stent, and plain balloon angioplasty for the treatment of instent restenosis: a network meta-analysis of 11 randomized, controlled trials. Drug-coated balloon angioplasty for drug-eluting stent restenosis: insight from randomized controlled trials. Paclitaxel-eluting balloon versus everolimus-eluting stent for treatment of drug-eluting stent restenosis. A multicenter randomized comparison of drug-eluting balloon plus bare-metal stent versus baremetal stent versus drug-eluting stent in bifurcation lesions treated with a single-stenting technique: six-month angiographic and 12-month clinical results of the drug-eluting balloon in bifurcations trial. Elutax paclitaxel-eluting balloon followed by bare-metal stent compared with Xience V drug-eluting stent in the treatment of de novo coronary stenosis: a randomized trial. Stent coverage and neointimal proliferation in bare metal stents postdilated with a paclitaxel-eluting balloon versus everolimus-eluting stents: prospective randomized study using optical coherence tomography at 6-month follow-up. Comparison of two different paclitaxel-coated balloon catheters in the porcine coronary restenosis model. Prospective randomised trial evaluating a paclitaxel-coated balloon in patients treated with endothelial progenitor cell capturing stents for de novo coronary artery disease. How to use the drug-eluting balloon: recommendations by the German consensus group. SeQuent Please World Wide registry: clinical results of SeQuent Please paclitaxel-coated balloon angioplasty in a large-scale, prospective registry study. Local paclitaxel induces late lumen enlargement in coronary arteries after balloon angioplasty. Influence of stent fracture on the long-term patency in the femoro-popliteal artery: experience of 4 years. Paclitaxel-coated versus uncoated balloon angioplasty reduces target lesion revascularization in patients with femoropopliteal arterial disease: a meta-analysis of randomized trials. Conventional balloon angioplasty versus peripheral cutting balloon angioplasty for treatment of femoropopliteal artery in-stent restenosis: initial experience. Drug-coated balloon angioplasty after directional atherectomy improves outcome in restenotic femoropopliteal arteries. Combined treatment of heavy calcified femoro-popliteal lesions using directional atherectomy and a paclitaxel coated balloon: one-year single centre clinical results. Prospective trial of infrapopliteal artery balloon angioplasty for critical limb ischemia: angiographic and clinical results. Angiographic patency and clinical outcome after balloon-angioplasty for extensive infrapopliteal arterial disease. Endovascular revascularization of below-the-knee arteries: prospective short-term angiographic and clinical follow-up. First experience with drugeluting balloons in infrapopliteal arteries restenosis rate and clinical outcome. Which of the following paclitaxel formulations is more effective in maintaining the drug in the vessel wall for a longer time Does not preclude re-intervention of the treated segment in case restenosis occurs 4. A Solid phase drug provides a reproducible pharmacokinetic profile after balloon delivery and the drug stays in the vessel wall after the balloon inflation for a longer time compared with liquid phase drug that diffuses quickly into tissues. Addition of a carrier to crystalline paclitaxel keeps the drug in the vessel wall for a longer time and enhances drug intake. Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome. Resistance to antiproliferative drugs shares the same molecular mechanisms observed in chemotherapy resistance in oncologic medicine. Within the arterial vessel, the fluid velocity is maximal in the middle of the lumen and minimal in proximity to the vessel wall due to viscosity forces. Role of endothelial shear stress in stent restenosis and thrombosis: pathophysiologic mechanisms and implications for clinical translation. The antiproliferative drugs associated with the greatest effects are paclitaxel and limus family drugs. Pclitaxel acts by stabilizing the microtubule polymer and blocking the progression of mitosis, triggering apoptosis or reverting to the G phase of the cell cycle without reaching the cell division phase. Stent implantation failure was demonstrated to be associated with significant polymer damage. Bifurcation lesions have been associated with a high risk of polymer damage, nonuniform drug release, and focal restenosis. Local vascular inflammation induced by vessel barotrauma following intracoronary stent implantation is a critical factor influencing the burden of subsequent neointimal hyperplastic response. Farb et al9 demonstrated that early after stent implantation, features of acute inflammation at the interface of the stent and arterial wall were almost always present. The main trigger for arterial chronic inflammation is represented by the presence of the durable polymer. The pathology of neoatherosclerosis in human coronary implants baremetal and drug-eluting stents.

In this test medications and grapefruit purchase combivent paypal, a section of tissue (biopsy) from a diseased organ is overlain with fluorescent-tagged antibodies to specific immunoglobulin or complement 7r medications buy 100 mcg combivent free shipping. This test is used routinely on kidney biopsies to separate the various types of glomerulonephritis medicine for anxiety cheap combivent line. The amount of enzyme (most often quantified by the amount of a colored product) is proportional to the amount of component to be measured medicine information cheap combivent express. Such tests are most important in the evaluation of relative and absolute immune deficiencies symptoms 8 weeks pregnant discount combivent 100mcg visa. A shows red blood cells as they normally appear on a smear: as individual units medications that cause weight loss buy 100mcg combivent amex, separate from one another. If this were to happen in vivo, the patient would suffer rapid and severe hemolysis. They can take many forms, including developmental, inflammatory, and neoplastic conditions involving various organ systems. Specific diseases in this chapter are classified into the immune deficiencies and the four basic types of allergy. Immune Deficiency Diseases Immune deficiencies are manifested as an increased susceptibility to infections-that is, more frequent and severe infections. If the deficiency is in the immunoglobulins (B-cell system), infections such as pneumonia, produced by pyogenic bacteria, occur. If the deficiency is in the cell-mediated immune system, infections produced by a variety of weak, opportunistic pathogens, including bacteria, fungi, viruses, and protozoa, occur. Inherited deficiency of the immunoglobulin system can be substantiated by finding very low levels of serum gamma globulin (agammaglobulinemia). Deficiencies of the T-cell immune system are demonstrated by absence of skin reactivity to substances that commonly cause a delayed hypersensitivity reaction. A delayed hypersensitivity skin test is performed by placing the antigen in or on the skin and checking in 1 to 2 days for the typical raised, firm, delayed hypersensitivity reaction. T-cell deficiencies can also adversely affect antibody production if the deficiency involves T-helper cells. Delayed (cell-mediated) hypersensitivity to microorganisms such as occurs in tuberculosis and fungal diseases can be evaluated by skin tests in which the antigen (killed microorganisms) is injected into the skin and, when positive, a delayed (48 to 72 hours) wheal and flare inflammatory reaction ensues. Contact dermatitis is most often diagnosed by good detective work, but suspected allergens may be tested by placing them on the skin (patch test). Autoimmune diseases are varied and complex, and their clinical features often overlap. Laboratory tests are confirmatory and best used when the pretest probability is high (clinical features suggest autoimmune disease prior to ordering the test). Anaphylactic-Atopic Allergies (Type I) Anaphylactic-atopic allergies are caused by the release of chemicals called vasoactive amines. These substances include histamine from tissue mast cells or blood basophils, which produce the most immediate reaction, and other substances that cause slightly more delayed reactions. As a group, these substances produce the following effects: (1) contraction of most nonvascular smooth muscle, producing effects such as bronchial constriction leading to asthmatic breathing; (2) vasodilation, which locally leads to increased blood flow and systemically may lead to shock; (3) increased vascular permeability, which leads to edema such as is seen in the raised wheals of urticaria of the skin or the swollen nasal mucosa of hay fever; and (4) stimulation of secretory activity of some glands, such as the increased mucus secretion in the bronchus in asthma and increased nasal secretions in hay fever. Specific Diseases A typical laboratory finding in this group of diseases is an increase in eosinophils in the blood or tissue and IgE in the plasma. Eosinophilia suggests atopic allergy, but it also may be found in some immune complex diseases. A raised edematous lesion with a red border (wheal and flare) reaches a maximum about 15 minutes after intradermal injection of the allergen being tested. Asthma and Allergic Rhinitis (Hay Fever) Because many allergens are airborne, the respiratory tract is a common site for type I hypersensitivity reactions to them. The portion of the tract affected presumably reflects individual differences of unknown nature. Both rhinitis and asthma can be triggered by nonallergic mechanisms in susceptible individuals. Asthma involves the bronchi and produces three effects: (1) broncho constriction, resulting from the contraction of the smooth muscle layers of bronchial and bronchiolar segments of the tract; (2) edema, resulting from vasodilation and increased permeability of bronchial vessels; and (3) increased bronchial secretion of thick, tenacious mucoid material. If secretions are not inhibited by drugs or removed by expectoration, their accumulation can impede air flow. The chief mechanical difficulty experienced in bronchial asthma is increased resistance to air flow manifested by wheezing. Generally, attacks are episodic, but the occasional asthma patient may experience a persistence of symptoms for 24 hours or more and fail to respond to medication. This condition of prolonged and unresponsive asthmatic distress is termed status asthmaticus. The patient exhibits very labored breathing with great respiratory effort, dyspnea, harassing cough, and sometimes cyanosis. Anxiety is great, and sleeplessness, extreme fatigue, exhaustion, dehydration, and disorientation develop. Allergic rhinitis is marked by edema and hypersecretion by the mucosal lining of the nasopharyngeal cavities, producing partial blockage of the airways with intense nasal and postnasal discharge. Edema may affect the mucosa of the paranasal sinuses, reducing their drainage, and it may close the eustachian tube. Secondary infection and inflammation of the sinuses (sinusitis) and the middle ear (otitis media) may result. These are masses of redundant edematous mucosa, which may obstruct breathing and occur more frequently with nonallergic (intrinsic) rhinitis and asthma. The allergens of hay fever are seasonal plant pollens including ragweed pollen (late summer and early autumn) and tree and grass pollens (spring and early summer). Ubiquitous Urticaria (Hives) and Angioedema Urticaria is a type I hypersensitivity reaction that is recognized on the skin by slightly raised, flat, well-demarcated, edematous patches with a congested border. Urticaria develops rapidly after exposure to an allergen and is associated with pruritus. Urticaria may be caused by an anaphylactic reaction in the skin to allergens that may have been introduced into the skin (injected drugs or insect stings) or, more often, by allergens that have been ingested and distributed throughout the body after alimentary absorption. A great variety of foods are known to cause urticaria-shellfish, strawberries, and tomatoes being common examples. Some foods, notably bacterially contaminated dark meat fish, contain histamine or histamine-releasing substances, thus causing urticaria and even more serious reactions, by a non-immune mechanism rather than an IgE-mediated mechanism. Mosquito bites cause a wheal as a result of nonspecific irritants in the saliva of the mosquito, whereas stinging insects (mainly Trymenoptera) inject allergens into the skin with rear stingers rather than mouth parts. It also is an edematous eruption, but it is more widespread and involves the deep dermis. Often it affects the lips, tongue, face, or even the pharynx, perhaps blocking the airway. A gastrointestinal reaction begins shortly after eating specific foods to which the person is allergic. The direct Coombs test is used to detect antibodies on the surface of red blood cells. Erythroblastosis Fetalis the hemolytic disorder of the newborn known as erythroblastosis fetalis is caused by immunologic incompatibility between mother and child and usually involves the Rh antigen of red blood cells. This antigen is expressed as an autosomal dominant trait present on the erythrocytes of 85% of the population. Consequently, the first pregnancy of a woman with an Rh-incompatible fetus is uncomplicated. By the time of birth, the child has suffered from continuous hemolysis and may be jaundiced from excess bilirubin, as well as anemic and edematous. The hemolysis is often accentuated just after birth, at which time the infant no longer has the help of the placenta in removing bilirubin. Consequently, blood of the infant is often exchanged for Rh-negative blood in an exchange transfusion. Erythroblastosis fetalis can be prevented by injecting mothers with human gamma globulin containing anti-Rh antibodies within 72 hours after delivery of the first and subsequent Rh-positive children. Because of this now routine preventive measure, erythroblastosis fetalis is not nearly as common as it once was. An Rh-negative individual does not have anti-Rh antibodies unless previously sensitized. A person with the A antigen on red blood cells has anti-B antibody as a natural phenomenon. Within seconds to minutes after exposure to the allergen, the patient feels an itching of the scalp, tongue, and throat followed by generalized flushing and headache. Difficulty in breathing begins and is joined shortly thereafter by precipitous drop in blood pressure and body temperature. If early reversal is not instituted, the train of events may lead to death from shock within 15 minutes of allergic exposure. Treatment is immediate subcutaneous administration of epinephrine, which causes vasoconstriction, thereby reversing systemic shock. The more common allergens that cause anaphylaxis are pollens, foods, chemicals, venoms from stinging insects, foreign sera such as diphtheria or tetanus antitoxins, and drugs such as penicillin. These blood transfusion reactions are prevented by typing and cross-matching of blood before transfusion. The frequent involvement of renal glomeruli in immune complex diseases is often associated with loss of protein and red blood cells in the urine and variable degrees of renal failure. More severe forms result in a generalized vasculitis with involvement of many organs. Local injection of soluble antigen in an animal previously sensitized by the same antigen produces an acute inflammation at the site of inoculation. Histologically, the reaction shows evidence of cell necrosis, infiltration with neutrophils, and vasculitis, all sequelae of the acute inflammatory reaction. Arthus reactions are reported very rarely following vaccination with diphtheria or tetanus toxoid. Serum Sickness Serum sickness is the prototype of a systemic Arthus- Autoimmune Hemolytic Anemia and Thrombocytopenia Many spontaneously occurring hemolytic anemias and thrombocytopenias are cytotoxic-type hypersensitivity reactions. The reactions may be mild, with agglutinated cells being prematurely removed by the spleen. Autoimmune hemolytic anemias can be detected by the direct Coombs test, in which red cells coated with an antibody are observed to agglutinate in vitro with the addition of antihuman globulin serum. Sometimes drugs attach to the cell surface and become part of the antigen, in which case the drug is a hapten. The horse serum was used as a source of antibodies to toxins such as tetanus toxin or diphtheria; however, the protective effect was often offset by the harmful effect produced when the patient developed antibodies to the horse serum. Although horse serum is rarely used anymore, the same reaction can be seen with drugs such as penicillin. Symptoms are fever, painful joints, enlarged lymph nodes and spleen, and frequently an allergic urticaria. Usually, after suspending administration of the offending material, the patient recovers with no permanent damage. Modern vaccines and other therapeutics rarely contain serum components from other species. However, serum sickness does sometimes occur after infusion of some drugs including antibiotics. The renal disturbance is first seen 1 to 4 weeks after apparent recovery from the acute streptococcal infection. Immune complexes are caught on the glomerular basement membrane, where they fix complement and promote an inflammatory process that compromises the filtering function of the glomerulus. Recovery is the rule, probably because the antigenic stimulation of the streptococcal infection subsides. Chronic glomerulonephritis results from a variety of antigens and is often low grade but persistent, eventually leading to renal failure. The antigen is usually not identified, although hepatitis virus B or C is implicated in about 35% of cases. The tuberculin skin test is an example of a typical subacute reaction, with development of a red, firm lump at the site of injection of tuberculin in a sensitized individual. Internal delayed hypersensitivity reactions are quite variable in appearance but are all characterized by a chronic inflammatory cell reaction, with predominance of lymphocytes and with variable degrees of tissue destruction. It is an acute or chronic delayed-type hypersensitive response to allergens placed on the skin surface. However, the range of agents that cause contact dermatitis is very large and includes many topically applied drugs, cosmetics, paints, dyes, plastics, plants, and some metal jewelry. The lesion varies from simple erythema discretely localized to the area of allergen contact to the more edematous, pruritic, vesicular dermatitis seen with poison ivy. It is sometimes difficult to distinguish the reaction caused by direct irritants from that produced by allergens. A cross section of a small artery; the vessel wall is intensely inflamed and necrotic. Specific Diseases to discover the allergen or to remove it from the environment once discovered. Treatment consists of removing the cause plus topical hydrocortisone ointments to reduce inflammation. Infections Manifested Primarily as Delayed Hypersensitivity Reactions Some microorganisms tend to stimulate cell-mediated immunity.

The pathophysiology of vascular disease involves derangements in endothelial aquapel glass treatment 100mcg combivent fast delivery, vascular smooth muscle cell symptoms pregnancy buy discount combivent 100mcg on line, and platelet function treatment 2 stroke cost of combivent. It has been shown that diabetes is a clinical predictor of nonresponse to aspirin and clopidogrel therapy treatment regimen purchase combivent with american express, suggesting that patients with diabetes may require more aggressive antiplatelet regimens treatment quad tendonitis purchase combivent line. In a study that included over 12 medicine runny nose purchase genuine combivent on line,000 patients with diabetes undergoing stent implantation (bare metal and first- and secondgeneration drug-eluting stents), diabetes was an independent risk factor for restenosis (odds ratio, 1. Cumulative incidence of mortality (A), myocardial infarction (B), and target vessel revascularization (C) at 3 years in the matched cohort of patients with diabetes. Drug-eluting or bare-metal stenting in patients with diabetes mellitus: results from the Massachusetts Data Analysis Center Registry. In this mixed treatment comparative meta-analysis of 42 trials with over 10,000 patients with diabetes, all of the drug-eluting stents showed a reduction in target vessel revascularization compared with bare metal stents. The efficacy varied between stents, with everolimus-eluting stents having the lowest rate of target vessel revascularization compared to zotarolimus, sirolimus, and paclitaxel stents. Complicating the interpretation of the initial studies, which compared the outcomes of surgical versus percutaneous modalities of revascularization in the patient with diabetes, are the recent advances in both surgical and percutaneous techniques and materials. However, these findings must be interpreted with caution in view of a small subset of patients with diabetes, use of first-generation drugeluting stents, and an overall trial that did not meet its primary end point. Careful peri- and intraprocedural management can often mitigate some of the acute risk, and here we discuss strategies that we believe are helpful to consider. Patients with diabetes should be in a euvolemic state prior to and following use of iodinated contrast agents. Volume depletion increases the risk for contrast-mediated renal insufficiency, which is a concern in patients with diabetes, particularly in those with chronic kidney disease. We recommend that diuretics be held the morning of the scheduled procedure, and if there is any baseline renal impairment, we consider withholding angiotensin-converting enzyme inhibitors. Our practice is to withhold metformin at least 24 hours prior to the procedure, if possible, and to withhold it for a minimum of 72 hours after the procedure. In addition, we routinely hold oral hypoglycemic agents and short-acting insulin preparations. After the procedure, we administer a high volume of hydration with saline infusion (minimum 1-2 L), maintaining euvolemia with furosemide as needed (with positive or negative fluid balance at 12-24 hours after procedure determined by filling pressures). Serum electrolytes and creatinine are routinely measured on the day after the procedure. Transradial catheterization is associated with a lower incidence of bleeding and vascular complications when compared with the transfemoral route,56 and this is preferred, especially in the patient with diabetes and peripheral arterial disease. Since diabetic patients are at increased risk for repeat revascularization, drug-eluting stents are our preferred revascularization strategy. Heart disease and stroke statistics-2015 update: a report from the American Heart Association. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Assessment of subclinical coronary atherosclerosis in asymptomatic patients with type 2 diabetes mellitus with single photon emission computed tomography and coronary computed tomography angiography. Comparison of in-hospital and one-year outcomes in patients with and without diabetes mellitus undergoing percutaneous catheter intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry). Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. Effects of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials. Relationship between aspirin and clopidogrel responses in acute coronary syndrome and clinical predictors of non response. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial I. Glycemic control in type 1 diabetes and long-term risk of cardiovascular events or death after coronary artery bypass grafting. Long-term prognosis in patients with type 1 and 2 diabetes mellitus after coronary artery bypass grafting. Percutaneous coronary interventions for non-acute coronary artery disease: a quantitative 20-year synopsis and a network meta-analysis. Restenosis after arterial injury caused by coronary stenting in patients with diabetes mellitus. Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography. Multiple predictors of coronary restenosis after drug-eluting stent implantation in patients with diabetes. Drug eluting and bare metal stents in people with and without diabetes: collaborative network metaanalysis. Outcomes with various drug eluting or bare metal stents in patients with diabetes mellitus: mixed treatment comparison analysis of 22 844 patient years of follow-up from randomised trials. Coronary artery bypass graft surgery vs percutaneous interventions in coronary revascularization: a systematic review. Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials. Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. Effectiveness of percutaneious coronary intervention with drug-eluting stents compared with bypass surgery in diabetics with multivessel coronary disease: comprehensive systematic review and meta-analysis of randomized clinical data. Superior long-term patency of saphenous vein conduits compared with drug-eluting stents D. Compared with bare metal stents, drug-eluting stents reduce the incidence of which of the following in patients with diabetes A 45-year-old man with unstable angina and a 90% stenosis in the mid right coronary artery B. A 60-year-old woman with rheumatoid arthritis on steroids, unstable angina, and a 70% discrete stenosis in the proximal circumflex artery and 90% ulcerated stenosis in the proximal right coronary artery C. A 55-year-old man with stable angina and an 80% stenosis in the proximal left anterior descending artery, a 100% stenosis in the proximal right coronary artery, and a 70% stenosis in the proximal left circumflex artery D. C Bare metal stents were developed to reduce the incidence of restenosis following balloon angioplasty. Neointimal proliferation within the stent became an important limitation, leading to restenosis and need for subsequent revascularization, particularly in diabetic patients. Drug-eluting stents were developed to decrease the incidence neointimal proliferation and restenosis. The body of data accrued to date has clearly established this invasive, nonsurgical procedure as the treatment of choice in symptomatic patients with moderate to severe mitral stenosis (mitral valve area <1. Among the multiple variables, valve morphology and severity of associated mitral regurgitation have, to a large extent, remained the principal determinants in patient selection. With successful balloon valve enlargement, there is generally a 2-fold increase in the mitral valve area and an associated dramatic fall in transmitral valve gradient, left atrial pressure, and pulmonary artery pressure. Therefore, patients with unfavorable mitral morphology are, in general, better served with mitral valve replacement (but not surgical commissurotomy). In our experience, the risk of resultant severe mitral regurgitation is minimal with the use of cautionary balloon sizing approach and the controlled stepwise dilation technique. In patients with nonpedunculated thrombi in the left atrial cavity, one may elect to administer long-term (3-6 months) warfarin therapy (targeting an international normalized ratio between 2 and 2. These include the antegrade (transvenous) approaches with 1 or 2 balloon catheters through 1 or 2 interatrial septal punctures29,30 or the retrograde (transarterial) approaches with transseptal wiring or without transseptal access. There is, however, persuasive evidence that the Inoue-balloon approach is technically less demanding and clearly simpler to perform; hence, it has a shorter irradiation and procedural time and is safer than the double-balloon approach. These have resulted in a nearly 100% technical success rate and a significant diminution in complications despite the presence of a significant number of technically demanding scenarios and high-risk comorbid conditions. Transseptal puncture must not only be executed safely to avoid cardiac perforation but also made at an appropriate interatrial septal site to facilitate balloon crossing of the stenosed mitral valve. To perform transseptal procedure, biplane fluoroscopic equipment is preferable, but single-plane fluoroscopy is usually sufficient. The instruments used for the procedure include a Brockenbrough needle and a 7- or 8-Fr transseptal catheter. The use of an outer sheath is optional, but its utility is recommended, especially for inexperienced operators, for 2 reasons: (1) to prevent inadvertent perforation of the dilator by the needle during its insertion, and (2) to prevent left atrial perforation during insertion of the catheter/needle into the left atrium; the sheath tip works as a safety stopper at the septum. Landmarks for Optimal Puncture Site the puncture target site is usually located at the cross point of (1) a horizontal line crossing the center of the mitral annulus (M-line) and (2) a vertical line, assumed to divide the interatrial septum into anterior and posterior halves ("midline"). For example, in patients with giant left atria, the operator is often forced to make the interatrial septal puncture more caudal to the horizontal M-line. In patients with a more vertically oriented left ventricle and a relatively small left atrium, the operator may need to make the puncture site slightly more cephalad to the M-line and lateral to the vertical midline. The angiogram is also used as a road map during transseptal puncture and balloon catheter manipulation. A, pigtail catheter tip; L, left atrial lateral border; T10, 10th thoracic vertebra. Because the septum lies within the superimposed area between the 2 atria in both methods, the medial atrial silhouette (usually the left atrium) is used as the posterior limit (not necessarily the posterior border) because there is no septum beyond this silhouette. Infrequently, such as in patients with giant left atria or distorted cardiac anatomy, the right atrial border is medial to that of the left atrium, and thus, the right atrial border is used as the posterior limit. The "midline" (broken line) is the vertical line crossing at the midpoint between T and L. Therefore, a pigtail catheter is placed with its tip in the noncoronary sinus of Valsalva, touching the aortic valve. Confirmation of Optimal Puncture Site Frontal View Under frontal view, the needle-fitted transseptal catheter placed in the superior cava inserted from the right femoral vein is slowly withdrawn to align the catheter/needle on the midline. Reshaping of the distal Brockenbrough needle to make it more curved may be necessary to align the catheter tip with the midline. The needle tip should be constantly kept concealed slightly (2-3 mm) within the catheter tip before needle puncture. The catheter tip should not be set medial to the midline to avoid puncturing the aorta, tricuspid valve, or coronary sinus. More importantly, the puncture site thus made is too close to the mitral valve, and this makes balloon crossing of the mitral valve difficult or even impossible. Slight lateral deviation of the puncture site to the midline is permissible, especially in patients with relatively small left atria. It is important to note that there may not be septum in an area near the inferior (caudal) border of the left atrium because the atrium often bulges caudally beyond the true septal boundary. Because the catheter tip is away from the aorta, tricuspid valve, coronary sinus, and left atrial posterior border, needle puncture at this point pierces only the septum unless the puncture is made too caudally near the caudal edge of the left atrium in frontal view. Confirmation of Catheter Tip at Septum When setting of the catheter/needle at the septum is in doubt, septal flush or stain method may be used to examine the catheter/needle tip position. This is done by injecting a small amount of pure contrast medium contained in a 5mL syringe attached to the proximal needle end. The optimal puncture site (P, arrowhead) is at the curved segment of the septal outline (right). If no blood is aspirated, the needle either has dissected the higher septum or is caught in the thickened septum (usually, in the muscular septum). If the catheter/needle is caught in the septum, it should be carefully forced across the septum. With pressure monitoring, it is not possible to differentiate high septal dissection from needle entrapment in the thick septum. This is another reason why the authors perform the transseptal puncture without constant pressure monitoring. If there is no or little resistance, the catheter/needle is advanced forward slightly into the left atrium. Then, the catheter alone is advanced until the tip of the sheath meets a resistance at the septum, while the needle is being withdrawn. On needle removal, heparin, 100 U/kg body weight, is given immediately through the catheter. Our balloon catheter selection methods have evolved from our continuing efforts to minimize this complication. Table 41-2 Catheter Selection and Balloon Sizing Based on Patient Height and Valvular Status Pretesting for Balloon-Syringe Mismatch Although the volume predefined by red marks on the syringe and its corresponding balloon size at full inflation have been tested by the manufacturer, balloon-syringe mismatch may occur. Although this mismatch is usually mild, gross mismatch may take place when the catheter and the syringe are from different packages. The mismatch, if undetected, may result in either underinflation or overinflation of the balloon. Therefore, before inserting the balloon catheter into each patient, the diameters of balloon inflated by injection of diluted contrast medium should be confirmed using a test; the balloon diameter chosen for the first inflation and the nominal diameter of the balloon should be compared. After insertion of the coiled-tip guide wire into the left atrium, the shorter subcutaneous track is then well stretched with an artery forceps alongside the wire. This is followed by use of the 12-Fr dilator, which is also used to dilate the atrial septum.

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