Large-caliber Vessels Research Articles

FREQUÊNCIA DA HOSPITALIZAÇÃO DOS CASOS DE EMBOLIA E TROMBOSE ARTERIAL EM MONTES CLAROS

Arterial thrombosis occurs when the formation of a blood clot completely blocks or impairs the flow of blood from an artery, which are the medium and large caliber vessels in our body responsible for transporting oxygen- and nutrient-rich blood to the tissues. This is a quantitative descriptive study whose data were collected in the Ministry of Health's online program TABNET-DATASUS, related to the municipality of Montes Claros, Minas Gerais. The selected variables were hospitalization by year of processing, age group, sex, color/race, and deaths during the period from 2017 to 2021. It is noted that with the analysis of the results obtained and the literature, that with advancing age, changes occur in normal aging, making individuals more prone to develop diseases, added to unhealthy habits and/or decompensated chronic diseases throughout life becomes even more predisposed.

Defining angioinvasion and lymphatic invasion in papillary thyroid carcinoma: morphological criteria, utility of D2-40/CD31/ERG immunohistochemistry and correlation with clinicopathological characteristics.

While CAP and ICCR protocols mandate the separation of angioinvasion (AI) and lymphatic invasion (LI) in thyroid carcinoma, distinction between them can be difficult. Because the presence of AI is used to stratify patients with papillary thyroid carcinoma (PTC), there is a need to accurately diagnose AI and LI. AI and LI were evaluated in 162 cases of PTC (n = 155) and high-grade differentiated thyroid carcinoma, papillary phenotype (HGDTCp, n = seven) using haematoxylin and eosin (H&E), D2-40 and CD31/ERG. In encapsulated carcinomas, vascular invasion (VI) was only of AI nature. Infiltrative carcinomas showed LI (46 of 131, 35%) and AI (19 of 131, 16%). The frequency of nodal metastasis (NM) and large volume of NM was 93 and 85%, respectively, in tumours with LI, and 39 and 26%, respectively, in those without LI. Luminal red blood cells and smooth muscle in the wall of large-calibre vessels were not reliable criteria to exclude LI and were seen in 23 and 6% of LI, respectively. LI was an independent predictor for NM, whereas AI is an independent predictor for distant metastasis at presentation in PTC/HGDTCp. VI in encapsulated carcinomas, including follicular variant PTC, is only of AI nature, confirming the position of this variant as a close entity to follicular carcinoma rather than classic PTC, whereas infiltrative PTC/HGDTCp may have LI or, less frequently, AI. As no morphological features reliably distinguish LI from AI, D2-40 and CD31/ERG immunostains should be considered for separating AI from LI when dealing with vascular invasion in an infiltrative PTC.

Abnormal vascular structure and function within brain metastases is linked to pembrolizumab resistance.

We recently conducted a phase 2 trial (NCT028865685) evaluating intracranial efficacy of pembrolizumab for brain metastases (BM) of diverse histologies. Our study met its primary efficacy endpoint and illustrates that pembrolizumab exerts promising activity in a select group of patients with BM. Given the importance of aberrant vasculature in mediating immunosuppression, we explored the relationship between immune checkpoint inhibitor (ICI) efficacy and vascular architecture in the hopes of identifying potential mechanisms of intracranial ICI response or resistance for BM. Using Vessel Architectural Imaging, a histologically validated quantitative metric for in vivo tumor vascular physiology, we analyzed dual-echo DSC/DCE MRI for 44 patients on trial. Tumor and peri-tumor cerebral blood volume/flow, vessel size, arterial and venous dominance, and vascular permeability were measured before and after treatment with pembrolizumab. BM that progressed on ICI were characterized by a highly aberrant vasculature dominated by large-caliber vessels. In contrast, ICI-responsive BM possessed a more structurally balanced vasculature consisting of both small and large vessels, and there was a trend toward a decrease in under-perfused tissue, suggesting a reversal of the negative effects of hypoxia. In the peri-tumor region, the development of smaller blood vessels, consistent with neo-angiogenesis, was associated with tumor growth before radiographic evidence of contrast enhancement on anatomical MRI. This study, one of the largest functional imaging studies for BM, suggests that vascular architecture is linked with ICI efficacy. Studies identifying modulators of vascular architecture, and effects on immune activity, are warranted and may inform future combination treatments.

Vascular Complications Following Transcatheter Aortic Valve Implantation, Using MANTA (Collagen Plug-Based) versus PROSTAR (Suture-Based), from a French Single-Center Retrospective Registry.

TAVI requires a large-bore arteriotomy. Closure is usually performed by the suture system. Some studies report a vascular complication rate of up to 21%. MANTA is a recently developed percutaneous closure system dedicated to large caliber vessels based on an anchoring system. Early studies report a lower rate of vascular complications with MANTA devices. This single-center retrospective study included all patients who underwent femoral TAVI at the Brest University Hospital from 20 November 2019 to 31 March 2021. The primary endpoint is the rate of vascular complications (major and minor) pre and post-TAVI procedure. In total, 264 patients were included. There were no significant differences in vascular complications (major and minor) between the two groups (13.6% in the MANTA group versus 21.2% in the PROSTAR group; p = 0.105), although there was a tendency to have fewer minor vascular complications in the Manta group (12.1% versus 20.5%; p = 0.067). Manta was associated with a lower rate of bleeding complications (3.8% versus 15.2%; p = 0.002), predominantly minor complications with fewer closure failures (4.5% versus 13.6%; p = 0.01), less use of covered stents (4.5% versus 12.9%; p = 0.016), and with no difference in the need for vascular surgery compared to the Prostar group (1.5% versus 2.3%; p = 0.652). On the other hand, Manta was associated with a higher rate of femoral stenosis (4.5% versus 0%; p = 0.013) without clinical significance (1.5% versus 0%; p = 0.156). The Manta and Prostar devices are equivalent in terms of vascular complications. The Manta, compared to the Prostar, is associated with fewer bleeding complications.

Pathogenesis and pathomorphology of distraction trauma in the framework of pre-trial investigations of cruelty to animals

The importance of identification and differential diagnosis of spinal injuries, in the case of polytrauma, the ability to distinguish the pathogenesis of various injuries are important and relevant both during clinical and during pathological examination of the animal’s body. The purpose of research is to provide veterinary practitioners and lawyers with strategies for identifying the cause (mechanism) of spinal cord injury and to assist triers of fact (decision-makers) in arriving at plausible and reasoned veterinary forensic conclusions. The research was performed using pathological and anatomical dissection and histological studies. It was established that damage to the cervical spinal cord due to traumatic bending of the neck was accompanied by partial or complete rupture of the intervertebral disc and destruction of the ligaments of the vertebrae. It was found that the hyperemia of the vessels of the meninges of the brain is the result of blood circulation disorders in the occipital artery and the caudal artery of the meninges, and mechanical damage to the integrity of the intervertebral discs or the destruction of the ligaments of the neck vertebrae led to various disorders of the innervation of various organs and systems of the body and ended the death of animals. It was proved that the distraction injury of the cervical spine led to the swelling of the medulla of the brain, haemorrhages of the caudalventral part of the brain substance. It was found that irritation of nervus vagus led to hyperemia of vessels of large (aorta and trunk of pulmonary artery) caliber, cranial mesenteric artery) caudal mesenteric artery and, accordingly, hyperemia of thoracic and abdominal organs. Application of research results will help in differentiation of various types of mechanical injuries of the spine (including differentiation from other pathological conditions of the body), determination of the area of the applied force vector

Abstract Number ‐ 43: Flow Diversion for Intracranial Aneurysms in Large Caliber Vessels: A Case Series

Introduction The safe and effective profile of flow diverters (FD) has allowed neuro‐interventionalists to consider them as a versatile tool for the treatment of aneurysms with different morphologies, locations, and characteristics. Optimal deployment with complete wall apposition affects FD performance. However, few devices are suitable for aneurysms in large caliber vessels. Herein, we aimed to describe the safety and efficacy of a large caliber (5 mm) FD for the treatment of intracranial aneurysms. Methods We performed a retrospective, multi‐center cohort study of adult patients in whom a 5 mm Surpass Streamline FD was implanted between 2018 and 2021 in the United States. Efficacy outcome was complete occlusion at final follow‐up. Safety outcomes were ischemic/hemorrhagic events and mortality up to 30 days following the procedure. Secondary safety was assessed by the rate of adjunctive devices/treatments to overcome technical complications and improve wall apposition. Results A total of 29 patients harboring 29 aneurysms were treated with 39 FDs (36 large‐diameter devices). Mean age was 57.8 ± 15.7 years. Aneurysm morphologies were saccular (n = 15), pseudoaneurysm (n = 7), fusiform (n = 6), and dissecting (n = 1). Locations were internal carotid artery (ICA) petro‐cavernous segment (n = 15), ICA paraophthalmic (n = 5), ICA cervical (n = 4), basilar artery (n = 3), and vertebral artery (n = 2). Aneurysm size mean was 11.4 ± 6.7 mm, and neck size mean 6.5 ± 3.9 mm. Proximal FD landing zone vessel diameter was 4.8 ± 1.3 mm and distal 4.5 ± 1.2 mm. At a mean final follow‐up of 12 ± 6 months, 18 (65%) aneurysms were completely occluded. Ischemic/hemorrhagic events occurred in 2 (7%), and 1 patient died during hospitalization. Balloon‐assisted angioplasty was performed in 19 (66%) cases, adjunctive stenting in 8 (28%), and coiling in 1 (3%). Patients who received an adjunctive device/treatment had an 82% (14/17) complete occlusion compared to 66% (4/6) in those who did not. Conclusions The use of large caliber FDs to treat complex intracranial aneurysms located in large‐diameter dysplastic vessels is technically feasible and safe. The use of adjunctive devices and techniques to achieve optimal wall apposition seems crucial to optimize treatment outcomes. Comparative studies with devices specially designed for this patient population might provide further insights into the best device selection.

Angioarchitecture of small retinoblastomas: the role of optical coherence tomography angiography

The study investigated the angioarchitecture of small retinoblastomas using OCTA. The study included 10 children with binocular retinoblastoma aged 2.7±0.5 months with small tumors of central localization (10 foci). The tumors were divided into 3 groups: group 1 (n=4) - tumor thickness 0.8±0.2 mm; group 2 (n=3) - 1.6±0.5 mm; group 3 (n=3) - 2.4±0.8 mm. OCTA was performed on Spectralis HRA+OCT (2460 scans in total). Vessels were identified in the superficial, deep and outer layers of the tumor on En Face images. Their average number was estimated by visualization of yellow pixels in the superficial layers on 10 sagittal sections. Statistical analysis was done using Microsoft Excel, Statistica 8.0. The Kruskal-Wallis H test was used for comparative analysis of independent variables with more than two samples. Retinal vessels with feeding anastomoses connecting them to multiple small tortuous tumor vessels in the superficial layers were identified in group 1. Number of yellow pixels - 16.5±0.5. In the deep layers - single chaotic vascular arcades. In flat small retinoblastomas the vascular component was not evaluated. In group 2 in the superficial layers of the tumor we found multiple geniculate vessels of large and small caliber anastomosing between themselves and the retinal vessels. Number of yellow pixels was 21±0.8. A few vessels were identified in the deep and outer layers. In group 3 we identified single convoluted vessels in the superficial layers with glow and quantity increasing in the deep layers. In the deep layers - emergence of a small number of vessels. The maximum number of multiple own tumor vessels was determined in the outer layers. Number of yellow pixels - 10±0.8. The obtained results confirm the possibility to preclinically identify the angioarchitecture of small retinoblastomas in order to determine the activity of tumor growth and serve as a marker of neoplasm regression in the future, after organ-preserving treatment.

Vascular decompression in the treatment of trigeminal neuralgia in dolichoectated vertebrobasilar artery

Dolichoectasia of vertebrobasilar artery is an uncommon and rare cause of trigeminal neuralgia. The article presents a case of successful treatment of a patient with trigeminal neuralgia caused by vertebrobasilar dolichoectasia. The technical complexity of the operation is due to the rigidity and tortuosity of a large-caliber vessel with perforating branches leading to the brain stem and limited space in the cerebellopontine angle. The implantation of Teflon wool in areas of neurovascular conflict is an effective surgical aid for complete elimination of trigeminal neuralgia while maintaining the anatomical integrity of the nerve structures and minimizing the risk to the patient.

Hypogastric artery ligation. Presentation of a case from the Teófilo Dávila General Hospital

Hemorrhage etymologically comes from the Latin haemorragia, from the Greek, αἱμορραγία composed of haima (blood) and regnymi (break), passed to Latin hemorrhage and later to Spanish, documenting it as emorragia in 1493. From a conceptual point of view, postpartum hemorrhage is defined as a blood loss greater than 500 ml in a vaginal delivery and greater than 1000 ml in a cesarean section, being among the leading causes of maternal death worldwide. The hypogastric artery is a large caliber vessel, responsible for the irrigation of a large area of ​​the pelvis and the organs located there. Hypogastric artery ligation is a surgical technique that was first described in 1894 with the aim of reducing gynecological and obstetric hemorrhage, since it endangers the life of the patient, increasing morbidity and mortality. This therapeutic surgical procedure should be taken into account as an effective method in the control of severe gynecological hemorrhages, where intraoperative complications are foreseeable with adequate knowledge of retroperitoneal anatomy.

Coronary Stenting in High Bleeding Risk Patients With Small Coronary Arteries Followed by One-Month Dual Antiplatelet Therapy: Onyx ONE Clear.

Small reference vessel diameters (RVDs) are a predictor of ischemic events after coronary stenting. Among patients at high bleeding risk (HBR) precluding long-term dual antiplatelet therapy (DAPT), those with small vessel disease (SVD) constitute an especially high-risk subgroup. Here, we evaluated the results of a durable-polymer, coronary zotarolimus-eluting stent (ZES) for the treatment of patients with SVD at HBR with 1-month DAPT. In the prospective, multicenter Onyx ONE (One-Month DAPT) Clear study, 1506 patients at HBR treated with a ZES that discontinued DAPT at 30 days were included. The clinical outcomes of patients undergoing treatment of lesions with an RVD of ≤2.5 mm (SVD group, as determined by the angiographic core laboratory) were compared with patients without SVD. The primary end point was the composite of cardiac death or myocardial infarction between 1 and 12 months. Small vessel diameter treatment was performed in 489 (32.5%) patients. Patients with SVD were more likely to be women, have undergone a previous percutaneous intervention, and have multivessel coronary artery disease than patients without SVD. There were no significant differences in lesion, device, or procedural success between the groups. The Kaplan-Meier rate estimate of the primary end point was 8.5% and 6.8% in patients with SVD and those without SVD, respectively (P = .425). No significant differences were found in any secondary end point. The Kaplan-Meier rate of stent thrombosis was 0.6% and 0.8% in patients with SVD and those without SVD, respectively (P = .50). Among patients at HBR treated with a ZES and 1-month DAPT, those with SVD had favorable 12-month ischemic and bleeding outcomes, which were comparable with those of patients with larger caliber vessels.

SARS-CoV-2 Associated Pulmonary Pathology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel entry in the betacoronaviridae group of coronaviruses. This is the second member of this group, and the third of the family overall to emerge in the last 20 years, which has caused significant health concerns due to the clinical severity and spread of the disease it causes—coronavirus disease identified in 2019 (COVID-19). While initially emerging as a respiratory disease, and while most cases experience symptoms predominantly from this system, SARS-CoV-2 has emerged as a multisystem pathogen. From a pathomorphological point of view, the severity of changes in the respiratory system can be summed up as diffuse alveolar damage—desquamation of the alveolar epithelium with exudative and proliferative changes—pulmonary hyaline membranes, Clara cell hyperplasia, squamous cell metaplasia, and fibrosis. The second most prominent way the disease affects the lung is through endotheliitis—damage to the endothelial cells of the pulmonary vasculature, predominantly affecting the medium and large caliber blood vessels that cause the well-established clinical phenomenon of thrombosis/thromboembolism of the pulmonary vasculature. As the spread of the disease continues with the emergence of new variants and the number of cases continues to grow, including a large percentage of recurrent cases, it is essential to remember that the viral effects are not only acute but, due to the proliferative phenomena, can produce chronic sequelae. Therefore, in the background of dwindling publication interest, it is critical to focus on the histopathological aspects of the pulmonary disease, with the goal of better understanding the effects of the virus on the organism and identifying probable future complications after infection.

Decellularized blood vessel development: Current state-of-the-art and future directions.

Vascular diseases contribute to intensive and irreversible damage, and current treatments include medications, rehabilitation, and surgical interventions. Often, these diseases require some form of vascular replacement therapy (VRT) to help patients overcome life-threatening conditions and traumatic injuries annually. Current VRTs rely on harvesting blood vessels from various regions of the body like the arms, legs, chest, and abdomen. However, these procedures also produce further complications like donor site morbidity. Such common comorbidities may lead to substantial pain, infections, decreased function, and additional reconstructive or cosmetic surgeries. Vascular tissue engineering technology promises to reduce or eliminate these issues, and the existing state-of-the-art approach is based on synthetic or natural polymer tubes aiming to mimic various types of blood vessel. Burgeoning decellularization techniques are considered as the most viable tissue engineering strategy to fill these gaps. This review discusses various approaches and the mechanisms behind decellularization techniques and outlines a simplified model for a replacement vascular unit. The current state-of-the-art method used to create decellularized vessel segments is identified. Also, perspectives on future directions to engineer small- (inner diameter >1 mm and <6 mm) to large-caliber (inner diameter >6 mm) vessel substitutes are presented.

Preclinical Large Vessel Occlusion Stroke Model: Capybaras ( Hydrochoerus hydrochoeris )

Background Existing preclinical large vessel occlusion stroke models have multiple limitations. We evaluated the capybara ( Hydrochoerus hydrochoeris ), the largest living rodent possessing sizable cerebral cortex with gyral complexity and large caliber vessels that share many intracranial vascular attributes as seen in humans, as a potential large vessel occlusion stroke model. Methods Conventional angiography was performed in an 18‐month‐old capybara. We (1) investigated the angiographic architecture, (2) evaluated the feasibility of microcatheter navigation and stent‐retriever deployment/retraction in the intracranial vessels and the associated arterial histological changes, (3) evaluated the leptomeningeal collateral pattern following transient large vessel occlusion stroke with coil occlusion, and (4) defined the infarct topography. Results The diagnostic portion of the conventional angiogram was uneventfully performed. Five passes of a 3 mm stent‐retriever were successfully performed in the right middle cerebral artery. Transient coil occlusion of the left carotid terminus/middle cerebral artery was then pursued for 45 minutes followed by coil removal. Finally, 5 passes of a 3 mm stent‐retriever were performed at the basilar artery with unchanged final angiography. The animal was euthanized 2.5 hours after extubation. The middle cerebral and basilar arteries were resected and histopathological sampling of their proximal, mid, and distal sections was pursued. In all vessel segments in which stent retriever devices were deployed, denudation and endothelial stripping of the intima (&lt;5% coverage) but preserved internal elastic lamina, media, and adventitia were observed. Subarachnoid hemorrhage was noted at the right Sylvian cistern. Brain histology revealed neuronal nuclear pyknosis in the left frontal cortex, left thalamus, and left hippocampal CA1 regions on hematoxilin and eosin. Luxol fast blue staining showed pallor and less conspicuous gray–white delineation, particularly in the frontal lobe. Conclusion We evaluated a novel preclinical model for thrombectomy. Capybara is a promising animal model for neurointervention. Further validation is warranted.

EGR2 Deletion Suppresses Anti-DsDNA Autoantibody and IL-17 Production in Autoimmune-Prone B6/lpr Mice: A Differential Immune Regulatory Role of EGR2 in B6/lpr Versus Normal B6 Mice.

Previous studies have reported that deletion of the transcription factor, early growth response protein 2 (EGR2), in normal C57BL/6 (B6) resulted in the development of lupus-like autoimmune disease. However, increased EGR2 expression has been noted in human and murine lupus, which challenges the notion of the autoimmune suppressive role of EGR2 in B6 mice. In this study, we derived both conditional EGR2-/-B6/lpr and EGR2-/-B6 mice to elucidate the immune and autoimmune regulatory roles of EGR2 in autoinflammation (B6/lpr) versus physiologically normal (B6) conditions. We found that conditional EGR2 deletion increased spleen weight, enhanced T cell activation and IFNγ production, and promoted germinal center B cells and LAG3+ regulatory T cells development in both B6/lpr and B6 mice. Nevertheless, EGR2 deletion also showed strikingly differential effects in these two strains on T lymphocyte subsets profile, Foxp3+ Tregs and plasma cell differentiation, anti-dsDNA autoantibodies and immunoglobulins production, and on the induction of IL-17 in in vitro activated splenocytes. Specifically, EGR2 deletion in B6/lpr mice significantly decreased serum levels of anti-dsDNA autoantibodies, total IgG, IgM, IgG1, and IgG2a with reduced plasma cells differentiation. Furthermore, EGR2 deletion in B6/lpr mice had no obvious effect on IgG immunocomplex deposition, medium caliber vessel, and glomeruli inflammation but increased complement C3 immunocomplex deposition and large caliber vessel inflammation in the kidneys. Importantly, we demonstrated that EGR2 deletion in B6/lpr mice significantly reduced pathogenic CD4-CD8-CD3+B220+ double negative T cells, which correlated with the reduced anti-dsDNA autoantibodies in serum and decreased IL-17 production in splenocytes of EGR2-/-B6/lpr mice. Together, our data strongly suggest that the role of EGR2 is complex. The immunoregulatory role of EGR2 varies at normal or autoinflammation conditions and should not be generalized in differential experimental settings.

The Medial Sural Artery Perforator Flap: A Historical Trek from Ignominious to “Workhorse”

Rather than just another “review,” this is intended to be an “overview” of the entire subject of the medial sural artery perforator (MSAP) flap as has been presented in the reconstructive literature from its inception in 2001 until the present, with any exceptions not purposefully overlooked. Unfortunately, the pertinent anatomy of the MSAP flap is always anomalous like most other perforator flaps, and perhaps even more variable. No schematic exists to facilitate the identification of a dominant musculocutaneous perforator about which to design the flap, so some adjunctive technology may be highly valuable for this task. However, if a relatively thin free flap is desirable for a small or moderate sized defect that requires a long pedicle with larger caliber vessels, the MSAP flap deserves consideration. Indeed, for many, this has replaced the radial forearm flap such as for partial tongue reconstruction. Most consider the donor site deformity, even if only a conspicuous scar on the calf, to be a contraindication. Yet certainly if used as a local flap for the knee, popliteal fossa, or proximal leg, or as a free flap for the ipsilateral lower extremity where a significant recipient site deformity already exists, can anyone really object that this is not a legitimate indication? As with any perforator flap, advantages and disadvantages exist, which must be carefully perused before a decision to use the MSAP flap is made. Perhaps not a “workhorse” flap for general use throughout the body, the MSAP flap in general may often be a valuable alternative.

Vascular implants - new aspects for in situ tissue engineering.

Conventional synthetic vascular grafts require ongoing anticoagulation, and autologous venous grafts are often not available in elderly patients. This review highlights the development of bioartificial vessels replacing brain‐dead donor‐ or animal‐deriving vessels with ongoing immune reactivity. The vision for such bio‐hybrids exists in a combination of biodegradable scaffolds and seeding with immune‐neutral cells, and here different cells sources such as autologous progenitor cells or stem cells are relevant. This kind of in situ tissue engineering depends on a suitable bioreactor system with elaborate monitoring systems, three‐dimensional (3D) visualization and a potential of cell conditioning into the direction of the targeted vascular cell phenotype. Necessary bioreactor tools for dynamic and pulsatile cultivation are described. In addition, a concept for design of vasa vasorum is outlined, that is needed for sustainable nutrition of the wall structure in large caliber vessels. For scaffold design and cell adhesion additives, different materials and technologies are discussed. 3D printing is introduced as a relatively new field with promising prospects, for example, to create complex geometries or micro‐structured surfaces for optimal cell adhesion and ingrowth in a standardized and custom designed procedure. Summarizing, a bio‐hybrid vascular prosthesis from a controlled biotechnological process is thus coming more and more into view. It has the potential to withstand strict approval requirements applied for advanced therapy medicinal products.

Study of angiogenesis in invasive breast carcinoma by morphometry and immunohistochemistry

BackgroundBreast cancer is the leading cause of cancer-related deaths in Asia and is emerging as the commonest female malignancy. Angiogenesis or neovascularization is important for the growth and spread of malignant tumors, and quantitative assessment of angiogenesis may prove valuable in prognostication. This study was undertaken to quantify and explore angiogenesis with immunohistochemistry with CD 34, CD 105, and vascular endothelial growth factor (VEGF), as well as morphometric analysis and correlate with the grades of the invasive breast carcinoma. MethodsAngiogenesis was assessed by morphometry and immunohistochemistry. Seventy cases of invasive ductal carcinoma (IDC) and twenty-five benign cases as controls were included in the study. Morphometry was performed on the CD34 and CD105 (Endoglin) stained representative histologic sections with the use of a computerized digital photomicrograph system using image analyzing software. Morphometric analysis and evaluation of vascular parameters, i.e. microvessel density (MVD), microvessel caliber (VC), and total microvessel boundary density (TVBD), were calculated. Semiquantitative assessment of angiogenesis of VEGF-stained sections was done by scoring. Immunohistochemical staining was correlated with the histological grade of the tumors. MVD, mean VC, TVBD with their mean values, SD, and range were calculated using Statistical Package for The Social Sciences (Version 20). One-way analysis of variance (ANOVA) with Tukey HSD was performed to assess the difference of the parameters for the groups. Spearman rank correlation coefficients ρ were calculated. ResultsThe vascular parameters were significantly more in malignant lesions as compared to benign lesions and showed differences with increasing grade. Grades of breast carcinoma showed a mild positive correlation with VEGF (ρ = 0.467), MVD-CD34 (ρ = 0.422) and VC-CD34 (ρ = 0.482); and moderate positive correlation with TVBD-CD34 (ρ = 0.615), VC-CD105 (ρ = 0.527), and TVBD-CD105 (ρ = 0.354). When these parameters were compared with each other for all four groups, VEGF showed a mild positive correlation with MVD-CD34 (ρ = 0.295), TVBD-CD34 (ρ = 0.339), and TVBD-CD105 ((ρ = 0.277). MVD-CD105 showed a mild positive correlation with MVD-CD34 TVBD-CD105 also showed a strong positive correlation with MVD-CD34. VC-CD105 showed a moderate positive correlation with VC-CD34. CD 105 stained fewer but larger caliber vessels. ConclusionsIn this study, vascular parameters showed significant differences in three grades of IDC with CD34. Differences were seen in vascular parameters stained with CD105 in three grades of IDC. Expression of VEGF also showed significant differences with positive correlations in the three grades of IDC. CD34 highlighted both old and newly formed microvessels. CD 105 stained fewer but larger caliber microvessels. VC-CD105 can be an extremely useful adjunct along with VEGF and CD34 to study angiogenesis of vessels in IDC.

Anaphylactic shock with pulmonary eosinophilic infiltration due to honeybee attack in a donkey: case report

ABSTRACT A case of a donkey attacked by Africanized honeybee is reported here with clinical signs of agitation, dehydration, congestion of the ocular mucous membranes, tongue edema, tachycardia and inspiratory dyspnea, and progression to death. At necropsy, diffuse, severe subcutaneous edema at face and cervical regions and severe diffuse pulmonary hyperemia with abundant edema without parenchymal collapse were observed. Microscopically, marked, diffuse deep dermis and panniculus carnosus edema and marked diffuse alveolar edema, with moderate population of eosinophils predominantly around larger caliber vessels were noted. The final diagnosis of anaphylactic shock was supported by history, clinical signs, and anatomic pathology findings. This is the first report of a honeybee attack with pulmonary eosinophilic infiltration in a mammal.

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders.

Toxins from Bothrops venoms targeting hemostasis are responsible for a broad range of clinical and biological syndromes including local and systemic bleeding, incoagulability, thrombotic microangiopathy and macrothrombosis. Beyond hemostais disorders, toxins are also involved in the pathogenesis of edema and in most complications such as hypovolemia, cardiovascular collapse, acute kidney injury, myonecrosis, compartmental syndrome and superinfection. These toxins can be classified as enzymatic proteins (snake venom metalloproteinases, snake venom serine proteases, phospholipases A2 and L-amino acid oxidases) and non-enzymatic proteins (desintegrins and C-type lectin proteins). Bleeding is due to a multifocal toxicity targeting vessels, platelets and coagulation factors. Vessel damage due to the degradation of basement membrane and the subsequent disruption of endothelial cell integrity under hydrostatic pressure and tangential shear stress is primarily responsible for bleeding. Hemorrhage is promoted by thrombocytopenia, platelet hypoaggregation, consumption coagulopathy and fibrin(ogen)olysis. Onset of thrombotic microangiopathy is probably due to the switch of endothelium to a prothrombotic phenotype with overexpression of tissue factor and other pro-aggregating biomarkers in association with activation of platelets and coagulation. Thrombosis involving large-caliber vessels in B. lanceolatus envenomation remains a unique entity, which exact pathophysiology remains poorly understood.

Image processing pipeline for the detection of blood flow through retinal vessels with subpixel accuracy in fundus images

Background and ObjectiveBlood flow detection through the retinal vessels is an essential step in diagnosing several eye diseases. It manifests itself as changes in vessel diameter in consecutive phases of blood flow. Previous studies focused mainly on determining retinal vessel diameter by the manual demarcation of vessel edges, which is time-consuming. As a result, only a few selected vessels were considered, which is not reliable. Such measurements are also prone to human errors and operator subjectivity, which additionally decreases their reliability. For these reasons, this paper proposes an automated pipeline to analyze the blood flow through retinal vessels. MethodsConvolutional neural networks were used for optic disc and vessel detection and full width at half maximum analysis used for vessel width assessment at the subpixel level. Measurements of the diameter were performed for five phases of the blood flow to all vessels at a particular distance derived from the optic disc size. We tested the approach on fundus images of five patients, with both eyes examined in each participant. The threshold for the detections of blood flow was when the retinal diameter vessel measurements were above the camera's resolution as compared among all 5 phases of blood flow. ResultsA total of 205 large caliber blood vessels were analyzed with blood flow detected in 18 retinal blood vessels. Conclusions Average vessel diameters derived from manual and automatic measurements differed on average by 4.96%. Average relative errors for single vessel measurements along the vessels range from 4.21 to 11.85%, with a global average at the level of 8%. Therefore, the measurements can be considered as accurate and in a high agreement between the expert and algorithm