Abnormal Vascular Structure Research Articles

Classification of childhood arterial ischemic stroke

The etiology of childhood arterial ischemic stroke is complex, and identifying the underlying cause is crucial for optimizing treatment and preventing recurrence. Currently, the classification methods for childhood arterial ischemic stroke are largely based on data from international studies, but a unified consensus have not yet been reached. This paper reviews the existing classification methods and their subtype definitions, and points out some doubts and ambiguities. On this basisi, combined with the data collected by Beijing Children's Hospital on Chinese children with arterial ischemic stroke, a new classification method (COIST) was proposed according to the etiology and pathogenesis, namely: inflammation (I), abnormal vascular structure (S), thrombophilia (T), heart disease (C), other identifiable causes (O), and uncertain causes; and various subtypes are listed. It is hoped that this new classification method can attract the attention and discussion of domestic colleagues, with the aim of further refinement, in order to help clinicians better understand and quickly identify the etiologies of childhood ischemic stroke.

Outcomes of "Over the Top" Anterior Cruciate Ligament Reconstruction Associated with a Lateral Extra-Articular Tenodesis in Children.

(1) Purpose: The incidence of anterior cruciate ligament (ACL) ruptures in children and adolescents has considerably increased during the last decades due to higher levels of competitive athletic activity, and early sport specialization and professionalization. Contemporary ACL reconstruction techniques have recently been subject to renewed interest in this population. The objective of this study is to report the short- and mid-term results of our physis-sparing ACL reconstruction technique using an "over the top" technique associated with a modified Lemaire procedure. (2) Methods: A retrospective series of 12 junior soccer players who presented to our clinic with a torn ACL between January 2019 and September 2021 was reviewed. The inclusion criteria were patients under 15 years with open tibial and femoral physes, with a stable contralateral knee, a minimum follow-up of 6 months, and a time frame from injury to surgery of <3 months. Patients with previous knee surgery, structural concomitant injuries, muscular, neurological, or vascular abnormalities, or hypersensitivity to metal alloys were excluded. The functional evaluation was performed using the International Knee Documentation Committee (IKDC) rating, Lysholm score, and Tegner activity level. Moreover, clinical and radiological assessments were also performed, including KT-1000 and knee X-rays. (3) Results: We identified 1 female and 11 male patients with ACL tears, with a mean age of 13.17 ± 0.9 months. Concomitant injuries include isolated vertical and bucket-handle tears of the medial meniscus, lateral meniscus tears, bilateral tear of both menisci. The mean follow-up time was 26 ± 12.6 months. The average IKDC, Lysholm and Tegner scores were 93.29 ± 11.04, 95.08 ± 13.2 and 9 ± 0.0 points, respectively. The average KT-1000 score of the participants was 0.96 ± 1.6 points. None of the included patients reported post-surgical complications or required additional surgeries. (4) Conclusions: Our novel ACL reconstruction with LET technique is a safe procedure that resulted in good clinical outcomes, lower failure rate and return to sports in skeletally immature patients.

PDGFRβ-Antagonistic Affibody-Mediated Tumor-Targeted Tumor Necrosis Factor-Alpha for Enhanced Radiotherapy in Lung Cancer.

The morbidity and mortality of lung cancer are still the highest among all malignant tumors. Radiotherapy plays an important role in clinical treatment of lung cancer. However, the effect of radiotherapy is not ideal due to the radiation resistance of tumor tissues. Abnormalities in tumor vascular structure and function affect blood perfusion, and oxygen transport is impeded, making tumor microenvironment hypoxic. Tumor hypoxia is the major cause of radiotherapy resistance. By promoting tumor vessel normalization and enhancing vascular transport function, tumor hypoxia can be relieved to reduce radiotherapy resistance and increase tumor radiotherapy sensitivity. In our previous study, a pericytes-targeted tumor necrosis factor alpha (named Z-TNFα) was first constructed and produced by genetically fusing the platelet-derived growth factor receptor β (PDGFRβ)-antagonistic affibody (ZPDGFRβ) to the TNFα, and the Z-TNFα induced normalization of tumor vessels and improved the delivery of doxorubicin, enhancing tumor chemotherapy. In this study, the tumor vessel normalization effect of Z-TNFα in lung cancer was further clarified. Moreover, the tumor hypoxia improvement and radiosensitizing effect of Z-TNFα were emphatically explored in vivo. Inspiringly, Z-TNFα specifically accumulated in Lewis lung carcinoma (LLC) tumor graft and relieved tumor hypoxia as well as inhibited HIF-1α expression. As expected, Z-TNFα significantly increased the effect of radiotherapy in mice bearing LLC tumor graft. In conclusion, these results demonstrated that Z-TNFα is also a promising radiosensitizer for lung cancer radiotherapy.

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.

TIPIC-al neck pain?

Transient perivascular inflammation of the carotid artery (TIPIC) is a benign unilateral self-limiting vascular condition that presents with neck pain, swelling, and increased pulsations just below and over the carotid bifurcation without structural vascular abnormality. TIPICs are frequently overlooked because they present with mild symptoms that resolve in a short period, both clinically and on imaging. Here, we present a case of a 32-year-old man who had neck pain for which ultrasound and magnetic resonance imaging was performed and later diagnosed with TIPIC syndrome on resolution of the symptoms.

Pediatric Vascular Anomalies: A Clinical and Radiological Perspective.

According to the International Society for the Study of Vascular Anomalies (ISSVA) classification, vascular anomalies include a diverse range of pathologies, classified as either vascular tumors or vascular malformations. This classification, last revised in 2018, aims to explain the biological basis of vascular lesions and help clinicians to manage the anomalies. In vascular tumors, there are proliferative changes of endothelial cells, while vascular malformations primarily consist of structural vascular abnormalities. Infantile hemangioma is the most common soft-tissue vascular tumor. Vascular malformations are an extensive group of malformations of the arterial, venous, and lymphatic systems, either in isolation or in combination. Radiological evaluation plays a key part in the management of pediatric patients with these entities. The understanding of sonography and magnetic resonance imaging findings entails its correlation with clinical findings at the time of scanning.

Testosterone Therapy in a Transgender Male Patient as a cause of Acute Ischemic Stroke (P2-5.011)

<h3>Objective:</h3> To share an intriguing case of a young transgender male patient receiving testosterone therapy who developed locked-in syndrome due to an acute ischemic stroke and to highlight potential risk factors for stroke in the LGBTQI+ community <h3>Background:</h3> There are many studies identifying risk factors for stroke in racially and ethnically diverse populations. However, there is little existing data for stroke risk factors in the LGBTQI+ community. Prior research has shown testosterone therapy in cis-gender men with initially low levels of testosterone increases the risk of stroke, especially in the first 2 years of use¹. While testosterone therapy has been shown to increase the risk of venous thrombosis, its role in arterial thrombosis is unclear². A proposed mechanism for thrombosis with testosterone replacement includes erythrocytosis, but the potential contribution of an independent pro-coagulant effect is yet to be determined³. <h3>Design/Methods:</h3> Literature review and case report. <h3>Results:</h3> An otherwise healthy 23-year-old transgender male on one year of testosterone therapy presented in an obtunded state. Examination revealed complete quadriplegia with sparing of vertical eye movements, consistent with locked-in syndrome. Imaging revealed complete occlusion of the basilar artery with distal reconstitution at the superior cerebellar arteries, and a large bilateral ischemic infarct of the pons. Computed tomography angiography did not demonstrate other large vessel disease or structural vascular abnormalities. Unfortunately, the patient was out of the time window for any acute stroke interventions. A hypercoagulable workup was performed but results were unrevealing and hematocrit was normal. Further investigation with transthoracic echocardiogram, transesophageal echocardiogram, and telemetry were negative for thrombus, patent foramen ovale, and atrial fibrillation. <h3>Conclusions:</h3> Acute ischemic stroke may be an under recognized complication of testosterone therapy in transgender males independent of degree of erythrocytosis. Further research is needed to establish a safety profile of testosterone therapy in this understudied population. <b>Disclosure:</b> Dr. Tan has nothing to disclose. Mrs. Kim Sing has nothing to disclose. Dr. Danziger has nothing to disclose. Mr. AW has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Avila has nothing to disclose. Dr. Alambyan has stock in Teleflex. Dr. Alambyan has stock in Natera. Dr. Alambyan has stock in Labcorp. Dr. Alambyan has stock in Veracyte. Dr. Alambyan has stock in Vicarious Surgical. Dr. Alambyan has stock in Unity Biotechnology. Dr. Alambyan has stock in Scynexis. Dr. Alambyan has stock in Stryker. Dr. Alambyan has stock in Eli Lilly. Dr. Alambyan has stock in DaVita. Dr. Alambyan has stock in Invitae. Dr. Alambyan has stock in Pfizer. Dr. Alambyan has stock in Bristol-Myers Squibb. Dr. Alambyan has stock in Johnson and Johnson. Dr. Alambyan has stock in Merck. Dr. Alambyan has stock in Medtronic. Dr. Alambyan has stock in AbbVie. The institution of Dr. Alambyan has received research support from Albert Einstein Healthcare Network. Dr. Mehdi has nothing to disclose. Dr. Gezalian has nothing to disclose. Dr. Ayodele has nothing to disclose. Dr. Toossi has nothing to disclose.

The Impact of Prenatal Diagnosis in the Evolution of Newborns with Congenital Heart Disease.

Congenital heart malformations are cardiac and/or vascular structural abnormalities that appear before birth, the majority of which can be detected prenatally. The latest data from the literature were reviewed, with reference to the degree of prenatal diagnosis regarding congenital heart malformations, as well as its impact on the preoperative evolution and implicitly on mortality. Studies with a significant number of enrolled patients were included in the research. Prenatal congenital heart malformations detection rates were different, depending on the period in which the study took place, the level of the medical center, as well as on the size of enrolled groups. Prenatal diagnosis in critical malformations such as hypoplastic left heart syndrome, transposition of great arteries and totally aberrant pulmonary venous drainage has proven its usefulness, allowing an early surgical intervention, thus ensuring improved neurological development, increasing the survival rate and decreasing the rate of subsequent complications. Sharing the experience and results obtained by each individual therapeutic center will definitely lead to drawing clear conclusions regarding the clinical contribution of congenital heart malformations prenatal detection.

Endovascular embolization and needle aspiration of a life-threatening cervical hematoma due to a neurofibromatosis type 1-associated arteriovenous fistula: illustrative case.

In cases of neurofibromatosis in which the bleeding source is considered strongly related to a neurofibroma, an open surgical approach could risk uncontrollable bleeding from the vascular wall infiltration by neurofibroma. The case of a neurofibromatosis type 1 (NF1)-associated arteriovenous fistula presenting with a life-threatening cervical hematoma that was successfully treated with alternative treatment is described. A 68-year-old woman diagnosed with NF1 presented with sudden onset of a spontaneous right cervical mass. Neck imaging on admission showed a massive subcutaneous hematoma with tracheal deviation and abnormal vascular structure in the hematoma. Digital subtraction angiography showed that an arteriovenous fistula (AVF) fed from a vertebral artery located within the hematoma cavity was the primary source of bleeding and feeding arteries from the occipital artery to the neurofibroma. Embolization of the cervical neurofibroma, as well as the AVF, was performed to reduce the secondary risk of bleeding, and was accomplished. After endovascular treatment, needle aspiration of the cervical hematoma was performed to reduce the mass effect. When performing open surgery via tissues with neurofibromatosis proliferation, uncontrollable bleeding can occur. Therefore, endovascular embolization and needle aspiration of the hematoma should be considered in this setting.

PS-C29-7: ASSOCIATION OF SERUM LEPTIN TO ADIPONECTIN RATIO AND CARDIOVASCULAR STRUCTURAL INDICES IN ESSENTIAL HYPERTENSIVE PATIENTS WITHOUT CHRONIC KIDNEY DISEASE

Objective: Dysregulated leptin and adiponectin profile is known to be associated with atherosclerotic disease. The evaluation of the leptin to adiponectin (L/A) ratio has been suggested as a powerful useful atherosclerotic index compared with adiponectin and leptin alone in patients with type 2 diabetes and obesity. In this study, we investigated the usefulness of L/A ratio for vascular structural abnormalities in essential hypertensive patients. Design and method: In 151 untreated essential hypertensive patients (86 males, average age 56 ± 12 years) without chronic kidney disease (urinary albumin excretion (UAE) less than 300 mg/g of creatinine and estimated glomerular filtration rate 60 mL/min/1.73m2 or more), blood sampling, 24-hour urine collection, and 24-hour blood pressure monitoring were performed. Intima-media thickness of carotid artery (IMT) and minimal forearm vascular resistance (MVR) (wall to lumen ratio in resistance vessel) were also measured by using ultrasonography and strain-gauge plethysmography, respectively. Results: L/A ratio was higher in men than in women (1.23 ± 1.56 vs 0.73 ± 0.87, p &lt; 0.05). There was no correlation between L/A ratio and systolic and diastolic blood pressure, and pulse rate. L/A ratio correlated positively with body mass index, triglyceride, hemoglobin A1c, HOMA-R and urinary C-peptide excretion (r = 0.57, 0.20, 0.20, 0.31, 0.27, p &lt; 0.05, respectively) and negatively with HDL-cholesterol (r = -0.24, p &lt; 0.05). In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p &lt; 0.05, respectively)In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p &lt; 0.05, respectively), whereas these indices did not associated with leptin and adiponectin individually. In multiple regression analysis, L/A ratio was an independent determinant for UAE, IMT and MVR. Conclusions: In patients with essential hypertension, L/A ratio was associated with obesity, abnormal glucose and lipid metabolism, increase in microalbuminuria, and arterial and arteriolar sclerosis. L/A ratio was considered as a useful indicator of vascular structural abnormalities in patients with essential hypertension.

Klotho promotes AMPK activity and maintains renal vascular integrity by regulating the YAP signaling pathway.

The development and formation of mammalian blood vessels are closely related to the regulation of signal transduction pathways. Klotho/AMPK and YAP/TAZ signaling pathways are closely related to angiogenesis, but the internal relationship between them is not clear. In this study, we found that Klotho heterozygous deletion mice (Klotho+/- mice) had obvious thickening of the renal vascular wall, obvious enlargement of vascular volume, and significant proliferation and pricking of vascular endothelial cells. Western blot showed that the expression levels of total YAP protein, p-YAP protein (Ser127 and Ser397), p-MOB1, MST1, LATS1, and SAV1 in renal vascular endothelial cells were significantly lower in Klotho+/- mice than in wild-type mice. Knockdown of endogenous Klotho in HUVECs accelerated their ability to divide and form vascular branches in the extracellular matrix. Meanwhile, the results of CO-IP western blot showed that the expression of LATS1 and p-LATS1 interacting with AMPK protein decreased significantly, and the ubiquitination level of YAP protein also decreased significantly in vascular endothelial cells of kidney tissue of Klotho+/- mice. Subsequently, continuous overexpression of exogenous Klotho protein in Klotho heterozygous deficient mice effectively reversed the abnormal renal vascular structure by weakening the expression of the YAP signal transduction pathway. Therefore, we confirmed that Klotho and AMPKα proteins were highly expressed in vascular endothelial cells of adult mouse tissues and organs; this resulted in a phosphorylation modification of YAP protein, closed the activity of the YAP/TAZ signal transduction pathway, and inhibited the growth and proliferation of vascular endothelial cells. When Klotho was absent, the phosphorylation modification of YAP protein by AMPKα was inhibited, resulting in the activation of the YAP/TAZ signal transduction pathway and finally inducing the excessive proliferation of vascular endothelial cells.

Akimba Proliferative Diabetic Retinopathy Model: Understanding Molecular Mechanism and Drug Screening for the Progression of Diabetic Retinopathy.

As the prevalence of diabetes has reached epidemic proportions worldwide, diabetic retinopathy incidence is increasing rapidly. An advanced diabetic retinopathy (DR) stage can lead to a sight-threatening form. There is growing evidence showing diabetes causes a range of metabolic changes that subsequently lead to pathological modifications in the retina and retinal blood vessels. To understand the complex mechanism of the pathophysiology of DR, a precise model is not readily available. By crossbreeding the Akita and Kimba strains, a suitable proliferative DR model was acquired. This new Akimba strain manifests marked hyperglycemia and vascular changes, which resemble the early and advanced stage of DR.Here, we describe the breeding method, colony screening for experiments, and imaging techniques widely used to investigate the DR progression in this model. We elaborate step-by-step protocols to set up and perform fundus, fluorescein angiography, optical coherence tomography, and optical coherence tomography-angiogram to study retinal structural changes and vascular abnormalities. In addition, we show a method to label the leukocytes with fluorescence and laser speckle flowgraphy to examine the inflammation in the retina and retinal vessel blood flow speed, respectively. Lastly, we describe electroretinogram to evaluate the functional aspect of the DR transformations.

Obesity, elevated levels of fasting plasma glucose and type 2 diabetes are associated with aortic stiffness.

Obesity and metabolic syndrome (MetS) are associated with structural and functional vascular abnormalities. MetS and its components may increase arterial stiffness and the risk of cardiovascular events. However, the relationship of MetS and its components, including obesity, with arterial stiffness is still not fully understood. In a group of 116 patients undergoing treatment for hypertension, we searched for the relationships between parameters of MetS and aortic stiffness expressed by pulse wave velocity (PWVAo). PWVAo was measured using an arteriograph working on the oscillometric principle, and pulse wave analysis (PWA) for noninvasive assessment of the parameters of central hemodynamics. From the cluster of parameters of MetS we found a significant association between body mass index (BMI) and aortic stiffness, and between fasting plasma glucose/type 2 diabetes (FPG/T2DM) and aortic stiffness. We did not find significant relationships between other components of MetS (HDL cholesterol and triglycerides) and aortic stiffness, based on the influence of hypolipidemic therapy. Arterial stiffness increased with age and was higher in females. Arterial stiffness was associated with age, sex, and MetS components (BMI and FPG/T2DM). Surprisingly, the parameters of dyslipidemia do not influence stiffness parameters, which can be explained by hypolipidemic therapy. The influence of hypolipidemic therapy should therefore be borne in mind when evaluating arterial tree function (Tab. 15, Ref. 62). Text in PDF www.elis.sk Keywords: obesity, fasting plasma glucose, type 2 diabetes, aortic stiffness, metabolic syndrome, arterial hypertension, cardiovascular risk.

The micro-pathological characteristics in cerebral arteriovenous malformations(cAVMs).

Rupture and hemorrhage is the most serious complication of cerebral arteriovenous malformation(cAVMs), and have a significant impact on quality of life. We investigated the hematoxylin and eosin staining and ultrastructural features of cAVMs and characterized the abnormal vascular structure of cAVMs. Light and electron microscopy were performed on a series of pathological specimens obtained from 12 patients with cAVMs who underwent surgical resection for the first time without radiosurgery or embolization therapy. In tunica intima, we found that the vascular endothelial cells of cAVMs were damaged, and the lysis of the cell body occurred in multiple regions. In tunica media, the arrangement of the elastic layer was disordered, and the thickness was uneven. Part of the structure of the elastic lamina was missing. The part of tunica adventitia was fractured and discontinuous. In addition, we also observed the phenomenon that different blood vessels share the same vascular wall. Macrophage phagocytosis and lymphocyte infiltration in the adventitial region of ruptured cAVMs. Abnormal lipid deposition in vascular endothelial cells and smooth muscle cells. The structural incompleteness of cAVMs may be an important cause of hemorrhage.

Hemorrhagic Stroke in Children and Adults With Sickle Cell Anemia: The Post-STOP Cohort.

Hemorrhagic stroke in young patients with sickle cell anemia remains poorly characterized. The Post-STOP (Stroke Prevention Trial in Sickle Cell Anemia) retrospective study collected follow-up data on STOP and STOP II clinical trial cohorts. From January 2012 to May 2014, a team of analysts abstracted data from medical records of prior participants (all with sickle cell anemia). Two vascular neurologists reviewed data to confirm hemorrhagic strokes defined as spontaneous intracerebral, subarachnoid, or intraventricular hemorrhage. Incidence rates were calculated using survival analysis techniques Results: Follow-up data were collected from 2850 of 3835 STOP or STOP II participants. Patients (51% male) were a median of 19.1 (interquartile range, 16.6-22.6) years old at the time of last known status. The overall hemorrhagic stroke incidence rate was 63 per 100 000 person-years (95% CI, 45-87). Stratified by age, the incidence rate per 100 000 person-years was 50 (95% CI, 34-75) for children and 134 (95% CI, 74-243) for adults >18 years. Vascular abnormalities (moyamoya arteriopathy, aneurysm or cavernous malformation) were identified in 18 of 35 patients with hemorrhagic stroke. The incidence rate of hemorrhagic stroke in patients with sickle cell anemia increases with age. Structural vascular abnormalities such as moyamoya arteriopathy and aneurysms are common etiologies for hemorrhage and screening may be warranted.

Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer's Disease.

Vascular dysfunction and structural abnormalities in Alzheimer’s disease (AD) are known to contribute to the progression of the pathology, and studies have tended to ignore the role of the vasculature in AD progression. We utilized the 3xTg-AD mouse model of AD to examine individual cerebral vessels and the cortical vascular network across the lifespan. Our vessel painting approach was used to label the entire cortical vasculature, followed by epifluorescence microscopy. The middle cerebral artery (MCA) tree was assessed with confocal microscopy, and a new method was developed to assess branching patterns as a measure of aging-related changes. We found that vascular remodeling was profoundly altered at 4–6 months of age, when the 3xTg-AD mouse is known to transition to cognitive impairment and Aβ deposition in both sexes. Analysis of vascular features (density, junctions, length) of the MCA territory highlighted sex-dependent differences across the 3xTg-AD mouse lifespan, with no alterations in branching patterns. Our current cerebrovascular angioarchitectural analyses demonstrate progressive alterations in individual cortical vessels, as well as in the vascular network of the cortex. These new findings advance our understanding of brain anatomy and physiology in the 3xTg-AD mouse, while potentially identifying unique diagnostic signatures of AD progression.

Bevacizumab combined with re-irradiation in recurrent glioblastoma.

BackgroundGlioblastoma is characterized by rich vasculature and abnormal vascular structure and function. Currently, there is no standard treatment for recurrent glioblastoma (rGBM). Bevacizumab (BEV) has established role of inhibiting neovascularization, alleviating hypoxia in the tumor area and activating the immune microenvironment. BEV may exert synergistic effects with re-irradiation (re-RT) to improve the tumor microenvironment for rGBM.PurposeThe purpose of this study was to evaluate the safety, tolerability, and efficacy of a combination of BEV and re-RT for rGBM treatment.MethodsIn this retrospective study, a total of 26 rGBM patients with surgical pathologically confirmed glioblastoma and at least one event of recurrence were enrolled. All patients were treated with re-RT in combination with BEV. BEV was administered until progression or serious adverse events.ResultsMedian follow-up was 21.9 months for all patients, whereas median progression-free survival (PFS) was 8.0 months (95% confidence interval [CI]: 6.5–9.5 months). In addition, the 6-month and 1-year PFS rates were 65.4% and 28.2%, respectively. The median overall survival (OS), 6-month OS rate, and 1-year OS rate were 13.6 months (95% CI: 10.2–17.0 months), 92.3%, and 67.5%, respectively. The patient showed good tolerance during the treatment with no grade > 3 grade side event and radiation necrosis occurrence rate of 0%. Combined treatment of gross total resection (GTR) before re-RT and concurrent temozolomide during re-RT was an independent prognostic factor that affected both OS and PFS in the whole cohort (OS: 0.067, 95% CI: 0.009–0.521, p = 0.010; PFS: 0.238, 95% CI: 0.076–0.744, p = 0.038).ConclusionIn this study, re-RT combined with concurrent and maintenance BEV treatment was safe, tolerable, and effective in rGBM patients. Moreover, GTR before re-RT and selective concurrent temozolomide could further improve patient PFS and OS.

Preeclampsia associated changes in volume density of fetoplacental vessels in Chinese women and mouse model of preeclampsia

Preeclampsia (PE) is associated with abnormal placental vascular structure. However, the volume density of fetoplacental vessels in PE remains unclear. Additionally, manually annotated CT angiography, which is widely used to analyze placental vessels, has issues regarding inaccuracy. Thus, computer-aided CT angiography for analyzing the volume density of fetoplacental vessels would facilitate the understanding of PE pathogenesis. We performed computer-aided CT angiography to compare differences in placentas among 17 women with PE and 34 normotensive women. The contrast ratio in CT angiography was significantly enhanced using a three-dimensional (3-D) Hessian matrix algorithm. The PE-like mouse model was established by administration of 125mg/kg/day NG-nitro-l-arginine methyl ester (l-NAME) for 10 days. The presence of endothelial marker CD31 was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The expression of angiogenic factors (PlGF, VEGFA, and sFlt1) in placentas was detected using qRT-PCR and western blotting. The volume density in fetoplacental vessels and CD31 expression were significantly reduced in women with PE and l-NAME-induced mice. Additionally, the downregulation of angiogenic factors (PlGF/VEGFA) and upregulation of an anti-angiogenic factor (sFlt1) were determined in a mouse model. Contrast-enhanced CT angiography with the aid of a 3-D Hessian matrix algorithm was performed. PE significantly affects the formation of vascular vessels, resulting in a lower volume density of fetoplacental vessels in humans and mice. This may be explained by the abnormal release of angiogenic factors during PE.

Pulmonary arterial hypertension in hereditary hemorrhagic telangiectasia associated with ACVRL1 mutation: a case report

IntroductionHereditary hemorrhagic telangiectasia is an autosomal dominant condition with an estimated prevalence of 1 in 5000. It is characterized by the presence of abnormalities of vascular structures, and may affect many organ systems, including the lungs, brain, spinal cord, gastrointestinal tract, and liver. A causative mutation is identified in approximately 97% of patients with definite hereditary hemorrhagic telangiectasia in one of three genes including a mutation in endoglin, a mutation in a locus mapped to chromosome 5, and an activin receptor-like kinase-1 (ACVRL1) mutation that is associated with an increased incidence of primary pulmonary hypertension. Pulmonary arterial hypertension is a rare (15–25 cases per million people) but severe vascular disorder. Heritable pulmonary arterial hypertension is associated with several gene mutations, with 75% having a mutation in the bone morphogenetic protein receptor 2 (BMPR2). However, the remaining 25% of patients have other associated genetic mutations including ACVLR1, which is also associated with hereditary hemorrhagic telangiectasia. Pulmonary arterial hypertension is a rare complication in patients with hereditary hemorrhagic telangiectasia (< 1% of the hereditary hemorrhagic telangiectasia population). We describe a case report with this rare occurrence.Case presentationA 70-year-old white/caucasian Irish male presented for screening for hereditary hemorrhagic telangiectasia due to a history of recurrent epistaxis (once/week) and a family history suggestive of pulmonary hypertension. Genetic testing confirmed an ACVRL1 mutation, while an echocardiogram and right heart catheterization confirmed pulmonary arterial hypertension. On examination, he had several mucocutaneous telangiectasia across his face. He was commenced on tadalafil and macitentan. However, this led to increased iron deficiency anemia and pedal edema. Selexipag was also added to his drug regime. He continues to require intermittent admissions for diuresis and blood transfusions.ConclusionThe association of hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension is rare (< 1%). Here we describe a case of hereditary hemorrhagic telangiectasia complicated with pulmonary arterial hypertension as a result of an ACVRL1 mutation. We also describe the clinical challenges of treating these two conditions together, as treatment options for pulmonary arterial hypertension tend to worsen hereditary hemorrhagic telangiectasia symptoms.

ISSVA Classification of Vascular Anomalies and Molecular Biology.

Vascular anomalies include various diseases, which are classified into two types according to the International Society for the Study of Vascular Anomalies (ISSVA) classification: vascular tumors with proliferative changes of endothelial cells, and vascular malformations primarily consisting of structural vascular abnormalities. The most recent ISSVA classifications, published in 2018, detail the causative genes involved in many lesions. Here, we summarize the latest findings on genetic abnormalities, with the presentation of the molecular pathology of vascular anomalies.