Narrowing Of Vessels Research Articles

Correlation of Red Blood Cell Distribution Width with The Severity of Coronary Artery Disease

Atherosclerosis causing occlusion of coronary vessels by building up of plaque leading to narrowing of vessels supplying heart and causing coronary artery disease, which is the leading and common cause of mortality around the globe. Objective: To find the correlation of Red Cell Distribution Width (RDW) and severity of Coronary Artery Disease (CAD) lesions Methods: A number of 280 patients in total, admitted to cardiology department who presented with chest pain and diagnosed as angina, positive treadmill test and who underwent angiography and were found to have CAD, were enrolled in the study over a period of one year. Modified Gensini score (MGS) is used for assessment of severity of CAD. Each patient was assessed in relation to severity of CAD using MGS scoring system. Results: Out of 280 patients, 218 were assigned to Group A and 70 were assigned to Group B. Mean age of presentation were (52.34± 13.90 vs 50.8± 11.63 years). Male subjects were predominant overall with ratio of 2.63:1. RDW was assessed and was seen to be significantly elevated in Group A in comparison to Group B (14.98± 1.59 vs 13.82 ± 0.91p= <0.0001). After assessing MGS in relation to severity of CAD, significant correlation was observed. RDW was found to be increasing as MGS score increased (14.46± 0.65 vs 14.98± 1.00 vs 15.02± 0.88, p= <0.0001) Conclusions: It was concluded that RDW is a parameter which is cost effective, very easy, readily and urgently available for the assessment and stratification of patients presenting with coronary artery disease.

Association between Blood Copper Levels and the Incidence of Ischemic Heart Disease

Background: Ischemic heart disease is one of the interrelated disease amongst cardiovascular disease group. Pathophysiological model of ischemic heart disease and myocardial ischemia are caused by obstructive atherosclerotic plaque, which involves the narrowing of small blood vessels that oxygenate the heart muscle by the build-up of plaque. Diet plays an important role in ischemic heart disease. Copper, an essential trace metal micronutrient, is required for myocardial angiogenesis action. Copper deficiency leads to cardiac mitochondrial structural defect and interference in oxidative phosphorylation.
 Aims: This study aims to examine the association between blood copper levels amd the incidence of ischemic heart disease.
 Methods: A total of 30 patients in cardiovascular clinic in Universitas Sumatera Utara Hospital in Medan, Indonesia from September 2021 until January 2022 were included in this cross-sectional study, with descriptive analytics. Demographic data, smoking behavior, supplement consumption, anthropometry measurements, body mass index, medical history were collected. Food frequency questionnaire (semiquantitative FFQ) was used to obtain food recall data. Blood level of copper were analysed in Prodia Clinical Laboratory.
 Results: Out of 30 patients in this study, 70% were male with a mean age of 60.6 years old. Research subjects who had risk factor of smoking were as much as 33.3%. Comorbidities such as dyslipidemia and diabetes mellitus were apparent, which were 63.3% and 30%, respectively. Sixty percent of the subjects were sedentary with mean body mass index 25.9 kg/m2. Median level of copper consumed daily was 1400 mcg/day and mean blood copper level was 1034,5 mg/L. Based on the blood copper level analysis of the subjects, we found an insignificant negative correlation between blood copper level with the incidence of ischemic heart disease (r = -0.050; p <0.795).
 Conclusion: This study found no association between blood copper levels and the incidence of ischemic heart disease.

The Relationship between Alcohol Consumption and Cardiovascular Disease in Adults: Meta-Analysis

Background: Alcoholic drink is a type of drink that contains ingredients similar to alcohol, usually ethyl alcohol or ethanol. Cardiovascular disease or also known as heart disease, generally refers to conditions that involve narrowing or blocking of blood vessels. The cardiovascular effects of alcohol consumption seen in observational studies continue to be hotly debated in the thematic literature and popular media. The purpose of this study was to analyze the relationship between alcohol consumption and cardiovascular disease in adultsSubjects and Method: This is a meta-analysis study using PRISMA flowchart guidelines and the articles were published in English from 2013 to 2022. The article search was conducted using the PICO model, Population: Adults, Intervention: Alcohol consumption. Comparison: No Consumption of alcoholic beverages. Articles obtained from the PubMed, Google Scholar and ScienceDirect databases. Based on the database, there were 9 articles that met the inclusion criteria. The analysis was carried out using Revman 5.3. software.Results: There were 9 articles from Asia, North America, and Europe, 2 articles from South Korea, 2 articles from China, 1 article from Japan, 1 article from the United States (USA), 1 article from England, 1 article from Spain and 1 article from Eastern Europe. Based on the results of the forest plot using a cohort study, it showed that someone who consumes alcohol has a high risk of cardiovascular disease by 2.83 times compared to someone who does not consume alcohol which is associated with cardiovascular disease (aHR = 2.83; CI 95% = 2.67 to 3.00; p <0.001).Conclusion: Adults who consume alcohol are at risk for cardiovascular disease. Keywords: cardiovascular, alcoholic drink, heart disease Correspondence:Moh Maulana. Medical Record Study Program, Jember Polytechnic. Jl. Mastrip, East Krajan, Sumbersari 68121, East Java. Email: maulana.rosy21@gmail.com. Mobile: +62 851-5667-1759.

Pathophysiology of Atherosclerosis.

Atherosclerosis is the main risk factor for cardiovascular disease (CVD), which is the leading cause of mortality worldwide. Atherosclerosis is initiated by endothelium activation and, followed by a cascade of events (accumulation of lipids, fibrous elements, and calcification), triggers the vessel narrowing and activation of inflammatory pathways. The resultant atheroma plaque, along with these processes, results in cardiovascular complications. This review focuses on the different stages of atherosclerosis development, ranging from endothelial dysfunction to plaque rupture. In addition, the post-transcriptional regulation and modulation of atheroma plaque by microRNAs and lncRNAs, the role of microbiota, and the importance of sex as a crucial risk factor in atherosclerosis are covered here in order to provide a global view of the disease.

Pre-angioplasty instantaneous wave-free ratio pullback predicts hemodynamic outcome in diffuse coronary artery disease

Background: Serial stenoses or diffuse vessel narrowing hamper pressure wire–guided management of coronary stenoses. Characterization of functional relevance of individual stenoses or narrowed segments constitutes an unmet need in ischemia-driven percutaneous revascularization. Aim of the Study: To perform hemodynamic mapping of the entire vessel using pullback technique of a pressure guidewire with continuous instantaneous wave-free ratio (iFR) measurement compared coronary angiography aiming to minimize the procedure, decrease number and length of stents used. Materials and Methods: This study was conducted on 40 patients presented with diffuse coronary artery disease and undergoing elective PCI. Diagnostic coronary angiography using the routine angiographic projections was done with assessment of non-obstructive coronary lesions by 2D quantitative coronary angiography and iFR pullback measurement Results: Percentage of difference between probable sig lesions via pullback technique and No of actual sig lesions for studied group, was (59.5%). The difference was statistically highly significant p=0.0001. Conclusion: Compared with angiography alone, availability of iFR pullback data significantly decreased the number and length of hemodynamically significant lesions identified for revascularization.

Plaque Characteristics in Young Adults With Symptomatic Intracranial Atherosclerotic Stenosis: A Preliminary Study.

PurposeTo determine how intracranial vascular wall and atherosclerosis plaque characteristics differ between young and old adults with sICAS.MethodsEighty-four consecutive patients with sICAS who underwent high-resolution magnetic resonance imaging (HRMRI) from December 2017 to July 2020 were retrospectively collected. These participants were divided into young adult group (18–50 years, n = 28) and old adult group (>50 years, n = 56). Reviewers were blinded to any clinical information and HRMRI scans were analyzed for qualitative and quantitative indicators of vascular walls and plaque at the maximal lumen narrowing site using the independent-sample t-test, Mann–Whitney U-test, chi-square test or Fisher exact test, and logistic regression analysis.ResultsYoung patients with sICAS had significantly smaller maximum wall thickness (1.45 ± 0.38 vs.1.75 ± 0.51 mm2, P = 0.003), higher prevalence of positive remodeling (53.57 vs. 21.43%, P = 0.003), and lower prevalence of diabetes mellitus (14.29 vs. 35.71%, P = 0.04) than old patients. Plaque burden and other plaque features were comparable between young and old patients.ConclusionYoung patients with sICAS have smaller maximum wall thickness and greater ability to reconstruct, and are more likely to show positive remodeling, which may lead to some atherosclerotic lesions being missed. Young patients with evidence of vessel narrowing should be carefully examined for presence of high-risk atherosclerotic plaque.

Therapy of moderate cognitive impairment and asthenia in patients with cerebrovascular pathology: results of a prospective observational study

Obtaining additional data on the efficacy and safety of the drug Prospekta in the treatment of moderate cognitive impairment (MCI) and asthenia in patients with cerebrovascular disease (CVD). A prospective observational study in more than 40 Russian cities enrolled 232 patients (mean age 61.5±10.0 years) with mild cognitive impairment (MCI), asthenia on ongoing basic nootropic therapy. The presence of MCI was confirmed by the Montreal Cognitive Assessment Scale (MoCA), asthenia - by 10-point Visual Analog Scale (VAS). All patients were prescribed the nootropic medication Prospekta 2 tablets 2 times a day for 8 weeks in addition to the therapy they received. Ultrasound Doppler sonography of the main arteries of the head and magnetic resonance imaging (MRI) of the brain were also assessed. At the end of treatment, the Clinical Global Impression Efficacy Index (CGI-EI) was assessed and the safety of the treatment was evaluated. The baseline severity of cognitive impairment according to the MoCA scale was 21.6 points, severity of asthenia according to the VAS was 6.3 points. According to Doppler flowmetry findings, hemodynamically significant stenosis was revealed in 105 (49.3%) patients, and narrowing of the main vessels without changes in hemodynamic parameters was revealed in 108 (50.7%) patients. According to MRI results, single vascular lesions in the brain matter were detected in 102 (44.0%) patients. The medications with nootropic effect were administered to 144 (62.1%) patients. A positive therapeutic response as improvement of cognitive functions was seen in 93.3% of patients after 8 weeks of taking Prospekta, including 39.4% of patients who had cognitive functions restored to the normal level. No side effects were registered during the observational study. The nootropic medication Prospekta is effective and safe in treatment of MCI in patients with asthenia with CVD, and improves cognitive function in patients with asthenia with CVD, both in monotherapy and in combination with other nootropic agents.

Advances in the treatment of ST Elevation Myocardial Infarction in the UK.

The treatment of acute coronary occlusion with Primary PCI has been a major factor in improving outcomes of patients suffering STEMI in the last 15 years, and is the standard treatment for patients suffering STEMI in the UK.Treatment is beneficial for patients presenting within 12 hours of the onset of symptoms, with the goal being opening of the occluded artery within 150 min of the call for help.Opening of the occluded artery is typically completed with a drug-eluting stent followed by administration of antiplatelet medications for 12 months. Procedures are performed using the radial artery which is associated with improved outcomes compared to vascular access via the femoral artery.Evidence is growing to support full revascularisation including the treatment of severe narrowing in other blood vessels as well as the culprit vessel.

Development of a Sugical Support Robot Capable of Palpation

In order to add a palpation function to a surgical robot, we developed a micro forceps mechanism driven by hydraulic pressure. Therefore, viscoelasticity modeling of the measurement target was investigated using the micro-forceps mechanism, and viscoelasticity measurements of an arteriosclerosis model were performed. Arteriosclerosis can be roughly divided into arterial narrowing, lipid content, and arterial stiffening. Plaque composed of fat causes narrowing of blood vessels, and the amount of lipid in the plaque determines whether the plaque fails or not. Therefore, we created a model that varies the degree of stenosis and the amount of lipid with reference to the characteristics of atherosclerosis, and measured the viscoelasticity of changes in arterial stiffness. As a result, the superiority of the three-element Maxwell model and the difference in viscoelasticity in each experiment of the arteriosclerosis model were measured.

On the Use of Micro-Computed Tomography for Pre-Clinical Testing of Cardiovascular Devices that Treat Intravascular Calcium

Micro-computed tomography (µCT) is a powerful, non-destructive tool that generates three-dimensional images of objects using penetrative X-rays. µCT is useful when imaging hardened, biological tissues and is particularly useful when studying the efficacy of cardiovascular devices for the treatment of intravascular calcium (IVC). IVC is an advanced state of atherosclerosis that commonly afflicts the elderly and is associated with vessel hardening (i.e., calcification) and narrowing. If left untreated, adverse events due to IVC include myocardial infarction, stroke, and amputation. However, because of its high strength and the fragility of the surrounding artery, IVC is difficult to treat. Further, device innovations are stymied because of the lack of readily available, pre-clinical models. Currently, the best model of IVC is diseased cadaveric and endarterectomy tissue, but the morphological inconsistencies of these tissues require a standardized approach when used for evaluating IVC treatments. We report a generalized approach that employs µCT to enable qualitative and quantitative analyses of the treatment effect of new devices on IVC tissue. This approach consists of 1) specimen screening, storage, and preparation, 2) pre-, peri-, and post-treatment µCT imaging, and 3) image analysis of IVC morphology and treatment effect. Various examples are provided to guide future bioengineering and medical device testing applications in this space.

Surveillance utilizes multi-omics in cardiovascular disease: Diet and its potentiality in Preventive index

Cardiovascular Disease (CVD) is characterized by multidimensional risks including drug, diet, lifestyle, stress, and metabolomics diseases which cause mortality and morbidity depending on age and status of chronic diseases. However, emerging evidence indicated it is preventable health complications that depend on risk management along with lifestyle change, and personalized medication that include alternative measures like Diet use following molecular diagnostic and imaging analysis. CVD is mainly attributed to the narrowing of blood vessels through atherosclerotic lesions and/or thrombosis. Hypertension, obesity, and hyperlipidemia are major risk factors for the development of CVD and treating these diseases is essential in slowing down progression of CVD. Inflammation appears to play a pivotal role in CVD and can be measured through a simple blood assay (CRP). Multi-omics approaches have been essential in the development of treatments for CVD, in the prevention of CVD, and in the diagnosis of CVD. There are many outcomes available to help with diagnosing CVD and omics platforms have helped scientists and clinician develop these diagnostic tools. Radiomics has played a key part in the diagnosis of CVD as being able to view the diseased heart is essential in determining CVD progression and the treatment options suitable for that secondary disease related. Nutrigenomics is emerging as the future of medicine such as utilizing treatment strategy innovation instead of medications, but it is still in its infancy. Nutrigenomics will open the doors to different therapeutic drug targets and allow us the ability to be more specific in our treatment options. There are only a few gene-diet interactions documented that increase a person’s chances of developing CVD. Curating an individual diet and treatment plan based on somebody’s genetic disposition or skewed immune responses following personalized diagnosis will be essential in the survival of these severe CVD patients. Key issues referring to risk surveillance and prevention is a distant approach which reflects several factors: for example, what type of tools can be used to conduct diagnosis, molecular diagnostic tools detect what type of biomarkers are present prior to prescribing the personalized diet and to ensure diagnostic accuracy. Recently, increasing findings emphasize dual aspects of diet such as immune enhancers and modulators in which gut microbiota has been proven to play a major factor in development of CVD. The future direction of omics studies will foster the ability to test the impact of gut microbiome of a patient with CVD following diet driven organ protection as well as prescribe essential components of the diet that can be adjusted with proper probiotic medication. Proper diet adjustments can correct the organ dysfunction that occurred due to interaction between molecular mismatch and cellular damage following stress-mediated damage or chronic disease. Further micro-scale assays and molecular diagnostic techniques following nutrigenomics application to the patient could be beneficial to allow patient’ care shift from physician driven and clinic based to self-management with knowledge based at home treatment programs that work by envisioning molecular reprogramming and rejuvenation of damaged organ. These at home treatments can be utilized with development of radiological data with innovation of software. The aim of the short review is to visualize the current role of nutrigenomics and diet formulation for integrative care (e.g., diagnosis, prevention, and treatment of CVD) which would take advantage of earlier prevention synchronized with current medical tests, imaging techniques. Health economy like management can reduce medical cost with disease prevention disease and could modulate the following: enhance knowledge-based interaction between body and diet, discuss cognitive enhancement how sensing with molecular behavior under image-management platform, monitor drug surveillance of current treatment options in CVD and the pitfalls of current omics application and data transformation needs for patient care in the future.

Estimating the Association of Ultrasonographical Placental Grading in Utero to Gestational Age and Feto-maternal outcomes in Hypertensive Disorders of Pregnancy

Background: Worldwide, about 5-8% of all pregnant females are affected by hypertensive disorders. In rural India, the incidence is 10%. This entity has become a significant cause of maternal mortality and morbidity, resulting in 10-15% of all maternal fatalities in developing nations, particularly in developing nations. Hence, identifying this entity in pregnant females and its timely management is vital for both mother and baby. Gestational hypertension can cause placental insufficiency due to narrowing and occlusion of uteroplacental vessels leading to intrauterine growth retardation. This study aims to detect placental grading by ultrasonography in the third trimester in cases of hypertensive disorders of pregnancy and to assess its correlation with fetal-maternal outcomes.
 Methodology: This will be a cross-sectional study carried out in the Department of Obstetrics and Gynecology, AVBRH, Wardha. About 130 pregnant normotensive females and 130 hypertensive pregnant females will be included in the study. Baseline data such as age, sex, parity, routine laboratory data, PIH profile, sonography scans will be collected. All the patients will be followed till delivery, and feto-maternal outcomes will be assessed. Data will be analyzed with appropriate statistical tests.
 Expected Outcome: A significant correlation is expected between higher placental grading in hypertensive pregnant females compared to normotensive patients and will have a significant association with perinatal and fetal morbidity.

Radiotherapy alone for pediatric patients with craniopharyngioma.

Radiotherapy alone, without tumor-directed surgery, may be appropriate for selected patients with craniopharyngioma reducing the risks associated with neurosurgery. Understanding outcomes for patients with craniopharyngioma treated with radiotherapy alone will further refine patient selection and treatment options. Since 2002, 13 children, adolescents and young adults, with craniopharyngioma were treated with radiotherapy alone and followed for disease control and functional outcomes at a single institution. The median age at treatment was 13years (range, 3-21years). All patients received 54Gy/54Gy(RBE) in 30 fractions. Five patients were treated with intensity-modulated photon therapy, four with passively scattered proton therapy, and four with intensity-modulated proton therapy. With a median follow-up of 5years (range 3months-14years), all patients were alive. One experienced tumor progression 8.5years after treatment. No significant changes in vision, hearing or neurologic function attributed to radiotherapy. Hormone deficiencies and body mass index were within the expected range at baseline and 5years after treatment. There was no evidence of cognitive decline based on assessment of IQ, memory and attention. Unexpected complications included single cases of out-of-field malignancy, white matter changes, large vessel narrowing, and pontine capillary telangiectasia. Six patients had sphenoid bone abnormalities on follow-up imaging attributed to radiotherapy. Radiotherapy alone is an important treatment option to consider when radical resection is contraindicated, or surgical intervention is not required to alleviate symptoms. Disease control and functional outcomes are excellent after radiation therapy alone in appropriately selected patients.

Transcranial Doppler Velocities and Angiographic Vasospasm after SAH: A Diagnostic Accuracy Study.

After aneurysmal SAH, transcranial Doppler is commonly used to monitor cerebral vasospasm. The diagnostic accuracy of transcranial Doppler flow velocity values in detecting angiographic vasospasm in patients requiring urgent endovascular intervention has not been established. We performed a retrospective analysis of a consecutive series of patients with aneurysmal SAH who underwent transcranial Doppler (index test) within 24 hours of conventional angiography (reference test). The judgment of 33%, 50%, and 66% degree of vessel narrowing on angiography was independently established by multiple neuroendovascular clinicians. Vessel-specific per-segment and per-patient transcranial Doppler velocities were studied using receiver operating characteristic curves, the Youden index, and minimal acceptable sensitivity models. Optimal mean flow-velocity thresholds were explored to calculate sensitivity and specificity using a per-patient judgment of vasospasm of at least 50% angiographic narrowing in any large arterial segment except A1. In 221 patients, vasospasm was found in 15%, 8%, and 4% of arteries when the degree of reference angiographic luminal narrowing was 33%, 50%, and 66%, respectively. Mean flow velocities were significantly higher in vasospastic segments (P = . 001), but per-segment exploratory analyses yielded unsound mean flow velocity thresholds. The Youden and minimal acceptable sensitivity models proposed mean flow velocity thresholds of approximately 160 cm/s for the anterior circulation and 80 cm/s for the posterior circulation in the per-patient diagnosis of angiographic vasospasm (≥50%), yielding a sensitivity of 80%-90% (95% CI, 0.77-0.96), but with a corresponding specificity of 50% (95% CI, 0.40-0.56). In this study, a threshold transcranial Doppler mean flow-velocity value that would accurately diagnose ≥50% angiographic vasospasm remained elusive.

Abstract 12338: Promotion of Arteriolar Differentiation of Vascular Endothelial Cells by PKD-1/CD36 Signaling-Mediated Chromatin Remodeling

Vessel narrowing and occlusions reduce blood supply to end tissues, leading to myocardial infarction in the heart or tissue loss in the peripheral vasculature. Effective approaches are needed to establish de novo arteriogenesis to treat these conditions. An essential first step is to understand mechanisms of arteriolar differentiation, in which transcriptional reprogramming of vascular endothelial cells (ECs) may be critical. Our previous studies indicate that protein kinase D (PKD-1) is required for arterial differentiation and plays an essential role in proarteriogenic reprogramming via transcriptional inhibition of antiangiogenic receptor CD36 via histone deacetylase HDAC7. We hypothesize that PKD-1/CD36 signaling initiates an epigenetic reprogramming of ECs for arteriolar differentiation via chromatin remodeling. To test this hypothesis, we isolated primary heart and lung ECs from wild-type control, EC-specific cd36 KO or pkd-1 KO mice. Total RNA was extracted for expression of arteriogenic genes by RT-qPCR. The proteins were collected for Western blotting and ChIP assays. Our results showed that when CD36 was downregulated in primary ECs from hearts and lungs, the expression levels of PKD-1 and arteriogenic genes EphB2 and DLL4 were significantly elevated compared to controls (p < 0.05). Intriguingly, we observed a significant increase in protein expression of neuropilin1. In contrast, in heart ECs from the EC-specific pkd-1 KO mice, arteriogenic gene expressions were downregulated whereas CD36 expression was significantly upregulated. Using the ChIP assay, we measured the interactions between H3K9 on the CD36, DLL4, or EphB2 promoters using ECs from EC-specific cd36 and pkd-1 KO mice. In conclusion, our results indicate that an epigenetic reprogramming regulates arteriolar differentiation at a transcriptional level by chromatin remodeling. PKD-1 signaling may dictate CD36 transcriptional levels, thereby reprogramming ECs for arteriolar differentiation by inducing an arteriogenic gene signature, which may contribute to de novo arteriogenesis under ischemic conditions.

Abstract 16747: Rapidly Lethal Dilated Cardiomyopathy Secondary To Generalized Arterial Calcification Of Infancy

Case Presentation: A previously healthy 3-month-old infant presented with cardiorespiratory arrest, from which she was successfully resuscitated. A dilated cardiomyopathy with severely depressed systolic function was diagnosed. ECG showed high voltage QRS complexes and generalized alteration of repolarization. In the following 12 hours, she suffered 2 other cardiac arrests, recuperated with defibrillation. Hemodinamic stability was achieved but brain death was diagnosed 36 hours after the onset of symptoms. Autopsy showed striking calcification of the right and left coronary arteries, with narrowing of the arterial lumen, causing extensive subendocardial infarction. Calcification also affected the aorta, pulmonary arteries, thyroid, kidney and other splanchnic arteries. Generalized arterial calcification of infancy (GACI) was diagnosed and a genetic study found two biallelic variants in ABCC6 gene: p.Arg1114Cys and p.Trp38Ser, both previously described in elastic pseudoxanthoma (PXE), but not in GACI. Genotyping of the healthy parents confirmed genetic segregation with biallelic variants. Discussion: GACI is an extremely rare genetic disease characterized by widespread arterial calcification and narrowing of large and medium-sized vessels. The usual clinical presentation is heart failure in fetal life or in the first months of infancy. In most cases it is lethal, with death occurring within a few hours or days after the onset of symptoms, although clinical involvement is highly variable and cases with long survival have been described. GACI is an autosomal recessive disease secondary to biallelic variants in the ENPP1 gene (67% of cases) and in the ABCC6 gene (9%). The variants found in our patient had not been previously described in GACI, just in PXE, a much milder disease with usually normal lifespan. This case confirms that both entities reflect two extremes of a clinical spectrum of ectopic calcification instead of two different disorders. The aim of presenting this case is to remind clinicians of this rare etiology in neonates or infants with dilated cardiomyopathy. In case of death, autopsy should always be requested. When this condition is diagnosed, genetic study will be positive in 75% of cases, allowing prenatal counseling.

Incidence of Stroke and Other Brain Imaging Findings in Adult Patients with Sickle Cell Disease: A Retrospective Study

Background: Vaso-occlusion and hemolytic anemia are the main features of sickle cell disease. Central Nervous system complications of sickle cell disease (SCD) can include silent cerebral infarcts (SCI), hemorrhagic or ischemic strokes, seizures and Moyamoya syndrome. SCI is the most common neurological complications in SCD. SCI patients have abnormal Magnetic Resonance Imaging (MRI) of the brain with normal neurological examination and no history of stroke. More precisely, Casella et al in the Silent Cerebral Infarct Multi-Center Clinical trial (SIT) defined infarct as MRI signal abnormality that was at least 3 mm in one dimension and that was visible in two planes on fluid-attenuated inversion recovery T2 -weighted images, as determined by agreement of two of the three study neuroradiologists. SCI in children is associated with lower Intelligence Quotient and increased risk of stroke.Methods: In this retrospective study we reviewed 100 adult patients at our Comprehensive Sickle Cell Center. We looked at the incidence of documented stroke and other neurological complications in SCD patients. We reviewed the hospital records of SCD patients for any incidental brain imaging (MRI brain or Computed Tomography(CT) brain) findings, done as inpatient or in the emergency room as part of hospital visits.Results: Out of the 100 patients, 14 patients had documented stroke. On the review of other 86 patients, 10 patients had MRI brain, 23 patients had CT brain, and 53 patients had no brain imaging record. Out of the 10 patients with MRI brain, 7 patient had significant findings- 3 patients had small vessel ischemic changes, 1 patient with chronic petechial hemorrhage of cerebellar vermis, 1 patient with ischemic changes and Chiari malformation type 1 (CTM 1), 1 patient with CTM 1 and non-specific white matter changes and 1 patient with CTM 1 alone. Out of the 22 CT of the brain and 1 CT angiogram of brain, 2 imaging showed ischemic changes and the angiogram showed large cerebral vessel narrowing. Therefore, on our review, 19 patients out of 100 were found to have stroke and 24 out of 100 had significant neurological findings. However, only 14 out of 19 patients had documented stroke. 7 out the 10 patients with MRI brain had significant incidental neurological findings. The number of adult SCD patients with neurological findings in our cohort could have been higher, if we had brain imaging record for the 53 other patients.Conclusion: This study shows that there is a heavy burden of neurological complications in SCD patients and SCI is under-diagnosed. MRI brain is superior to CT brain in detecting neurological complications in SCD patients. SIT showed that regular blood-transfusion significantly reduced the recurrence of cerebral infarct in children with SCI. Finding of SCI in adults also warrants consideration for follow up brain imaging, neurology referral and discussion of treatment modalities including chronic blood transfusion and hydroxyurea therapy. CTM 1 can also be associated with SCD. In CTM 1, tonsil herniates 5 millimeter or below foramen magnum. SCD may cause increased thickness of calvarium from extramedullary hematopoiesis in skull, which can result in cranio-cephalic disproportion with cerebellar ectopia and subsequent CTM 1. Because of high incidence of neurological complications in SCD patients, routine screening with MRI brain should be considered in adult SCD patients. DisclosuresIdowu: Forma Therapeutics, Inc.: Research Funding; Pfizer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ironwood: Research Funding.

FORCED CONVECTION IN A LID-DRIVEN NON-NEWTONIAN BLOOD FLOW THROUGH A STENOTIC ARTERY

Cardiovascular diseases are one of the major health concerns globally, mainly caused by inadequate blood flow in different body parts. The lack of blood flow is often due to abnormal narrowing of blood vessels, and a systematic technique to boost blood flow in these areas can help cure the disease. One such method uses elevated temperatures to influence blood flow in the concerned areas. This paper investigates this process, i.e. the forced convection, through blood flow in a stenotic region of a human artery. A part of the stenotic region is considered a porous medium and the top wall is subjected to a higher temperature with a lid moving from left to right. Blood is considered as a non-Newtonian fluid with the power law index varying from 0.5 to 1.5. The geometric properties are considered to match the problem of blood flow in the artery affected by stenosis. The Carreau-Yasuda model is used to represent the non-Newtonian fluid flow in porous media and the numerical analysis is carried out using the Lattice Boltzmann method. This problem is investigated to study the influence of the moving lid and other geometric properties on convection and flow properties such as velocity profiles, streamlines, isotherms and heat transfer.

Retinal Degeneration Associated With RPGRIP1: A Review of Natural History, Mutation Spectrum, and Genotype-Phenotype Correlation in 228 Patients.

Purpose: RPGRIP1 encodes a ciliary protein expressed in the photoreceptor connecting cilium. Mutations in this gene cause ∼5% of Leber congenital amaurosis (LCA) worldwide, but are also associated with cone–rod dystrophy (CRD) and retinitis pigmentosa (RP) phenotypes. Our purpose was to clinically characterize RPGRIP1 patients from our cohort, collect clinical data of additional RPGRIP1 patients reported previously in the literature, identify common clinical features, and seek genotype–phenotype correlations.Methods: Clinical data were collected from 16 patients of our cohort and 212 previously reported RPGRIP1 patients and included (when available) family history, best corrected visual acuity (BCVA), refraction, comprehensive ocular examination, optical coherence tomography (OCT) imaging, visual fields (VF), and full-field electroretinography (ffERG).Results: Out of 228 patients, the majority (197, 86%) were diagnosed with LCA, 18 (7%) with RP, and 13 (5%) with CRD. Age of onset was during early childhood (n = 133, average of 1.7 years). All patients but 6 had moderate hyperopia (n = 59, mean of 4.8D), and average BCVA was 0.06 Snellen (n = 124; only 10 patients had visual acuity [VA] > 0.10 Snellen). On funduscopy, narrowing of blood vessels was noted early in life. Most patients had mild bone spicule-like pigmentation starting in the midperiphery and later encroaching upon the posterior pole. OCT showed thinning of the outer nuclear layer (ONL), while cystoid changes and edema were relatively rare. VF were usually very constricted from early on. ffERG responses were non-detectable in the vast majority of cases. Most of the mutations are predicted to be null (363 alleles), and 93 alleles harbored missense mutations. Missense mutations were identified only in two regions: the RPGR-interacting domain and the C2 domains. Biallelic null mutations are mostly associated with a severe form of the disease, whereas biallelic missense mutations usually cause a milder disease (mostly CRD).Conclusion: Our results indicate that RPGRIP1 biallelic mutations usually cause severe retinal degeneration at an early age with a cone–rod pattern. However, most of the patients exhibit preservation of some (usually low) BCVA for a long period and can potentially benefit from gene therapy. Missense changes appear only in the conserved domains and are associated with a milder phenotype.

Safety of Irreversible Electroporation Ablation of the Pancreas.

To evaluate the safety of irreversible electroporation (IRE) on swine pancreatic tissue including its effects on peripancreatic vessels, bile ducts, and bowel. Eighteen Yorkshire pigs underwent IRE ablation of the pancreas successfully and without clinical complications. Contrast-enhanced computed tomography angiography and laboratory studies before the IRE ablation with follow-up computed tomography angiography, laboratory testing, and pathological examination up to 4 weeks postablation were performed. In a subset of cases, anatomic peripancreatic vessel narrowing was seen by 1 week postablation, persisting at 4 weeks postablation, without apparent functional impairment of blood flow. Laboratory studies revealed elevated amylase and lipase at 24 hours post-IRE, suggestive of acute pancreatitis, which normalized by 4 weeks post-IRE. There was extensive pancreatic tissue damage 24 hours after IRE with infiltration of immune cells, which was gradually replaced by fibrotic tissue. Ductal regeneration without loss of pancreatic acinar tissue and glandular function was observed at 1 and 4 weeks postablation. In our study, we demonstrated and confirmed the safety and minimal complications of IRE ablation in the pancreas and its surrounding vital structures. These results show the potential of IRE as an alternative treatment modality in patients with pancreatic cancer, especially those with locally advanced disease.