Ocular manifestations of severe familial hypercholesterolemia.

Background: To study ocular manifestations of patients with severe familial hypercholesterolemia (FH). Methods: In this population-based case-control study, patients suffering from severe familial hypercholesterolemia from the Lebanese Familial Hypercholesterolemia Registry, along with age and gender-matched healthy controls were recruited. All participants underwent a comprehensive eye examination, and patients underwent fluorescein angiography as well. Logistic regression models were used to identify any association between patients with severe familial hypercholesterolemia and abnormal eye findings, while adjusting for hypertension and pack-year smoking. The main outcome measure of this study was the development of ocular vascular abnormalities. Results: 28 patients and 28 controls were recruited. Patients with severe familial hypercholesterolemia had significantly greater odds of developing corneal arcus and xanthelasmas than the control group (p < 0.001). Retinal vascular abnormalities (plaques) were exclusively and more significantly present in patients with familial hypercholesterolemia (18 %). Similarly, retinal arteriosclerosis was exclusively and significantly more prevalent in the familial hypercholesterolemia group (p < 0.001, adjusted odds ratio 6.8). Stratification by LDL levels and genotypes did not show any significant change in the prevalence of any ocular finding. Conclusion: In addition to the well-established increase in incidence of corneal arcus and xanthelasmas, severe familial hypercholesterolemia patients have more prevalent retinal vascular abnormalities that include vascular plaques and arteriosclerosis.

Intrapancreatic common hepatic artery in pancreatoduodenectomy: a technical note on how to deal with this exceedingly rare arterial variation.

Arterial variations in the liver's blood supply play a pivotal role in the success of pancreatoduodenectomy (PD), impacting both its technical execution and oncological outcomes. Among these variations, a common hepatic artery arising from the superior mesenteric artery (SMA) occurs in about 3% of cases. An exceptionally rare variation is the intrapancreatic common hepatic artery (IPCHA). Preserving or reconstructing the IPCHA is vital during PD to prevent liver and biliary necrosis. Particularly for cases of pancreatic cancer with high rates of intrapancreatic perineural spread, preserving IPCHA without compromising radicality presents challenges. We present a detailed report of the technique used for PD in the presence of IPCHA. Surgical technique details include a pylorus-preserving PD with the Cattell-Braasch maneuver, an artery-first approach, and meticulous dissection using "cold" scissors. We emphasize the importance of strategic surgical planning based on high-quality imaging studies, underscoring the need for pancreatic surgeons to be proficient in managing variations in visceral vessels. In conclusion, this case underscores the significance of navigating rare arterial variations in liver supply during PD, highlighting the necessity for meticulous surgical planning and execution.

Spontaneous Coronary Artery Dissection (SCAD) from an Interventionalist Perspective.

PURPOSE OF REVIEW: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome (ACS), particularly among women < 50 years of age. Here, we aim to review the pathogenesis of SCAD, discuss SCAD as an initial manifestation of systemic arterial disease, and highlight invasive strategies as well as unique challenges in the care of women with SCAD. RECENT FINDINGS: A paradigm shift has occurred in the care of SCAD patients in the past decade as recommendations for conservative management have become widespread. Invasive interventions are reserved for patients with hemodynamic compromise or active ischemia due to increased periprocedural complications and failure rates. Certain patient populations have been identified for larger territory infarcts and proximal disease including patients with known connective tissue disease, premenopausal women, and patients with pregnancy-associated SCAD (P-SCAD). Current recommended management of SCAD is conservative. Despite a growing awareness of SCAD and its known association with systemic arteriopathies in women, evidence-based data remains scarce. Future studies focused on identifying genetic factors, optimal medical therapy after SCAD, and techniques to minimize interventional complications are needed.

The Role of Natural Extracts in the Management of Infantile Hemangiomas and Vascular Tumors.

Hemangiomas are vascular tumors resulting from the proliferation of endothelial-like cells; they are the most common childhood tumors, affecting approximately 5-10% of newborns and infants. Besides hemangiomas, which are definitely benign tumors despite their overgrowth potential, there are other vascular tumors like hemangioendotheliomas, which may display intermediate characteristics between benign hemangiomas and highly malignant angiosarcomas. Standard therapy may be constricted by serious adverse effects, high cost, or traumatic influence. Diet is a major resource for health preservation, disease prevention, and treatment. The therapeutic property of edible berries, marine products, or medicinal plants have long been known and used in traditional medicine; a plant-based nutrition can prevent the development and progression of diseases associated with extensive neo-vascularization. The purpose of our review is to highlight those natural treatments that hemangioma and vascular tumor patients can receive in the future, both for their benefit and that of their families. We performed the review according to the Preferred Reporting Items for Systematic Reviews and Metanalysis Statement. We used the Web of Science, PubMed, and EMBASE engines for the study, and searched for the association of hemangioma with naturopathic treatment/plant extract/plants in published articles. We found that natural extracts from plants and fruits are cost-effective and safe treatments for hemangiomas and vascular tumors, as well as for other forms of cancer. In any case, more in vitro and in vivo studies are needed to confirm the proposed signaling pathways in tumors and validate the improvement parameters after natural products administration. The era of molecularly targeted therapy and personalized medicine is approaching and naturally occurring substances are very useful tools for tumor treatment and prevention. Plant extract substances have strong specificity and pertinence, are non- toxic and have few side effects, and may become an emerging cancer treatment.

Cerebrovascular Abnormalities in Adults Born SGA at 12 Years After Growth Hormone Cessation Compared to Controls.

CONTEXT: Increased cerebrovascular morbidity was reported in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood compared to the general population. However, previous studies did not have an appropriate control group, which is a major limitation. OBJECTIVE: To study cerebrovascular abnormalities (aneurysms, previous intracerebral hemorrhages and microbleeds) using magnetic resonance imaging (MRI) in adults born SGA at 12 years after cessation of childhood GH treatment (SGA-GH) compared to appropriate controls. METHODS: In this single-center, prospective study, brain MRIs were performed between May 2016 and December 2020 on a 3T MRI system. MRI images were scored by 2 neuroradiologists who were blinded to patient groupings. Participants included adults born SGA previously treated with GH and 3 untreated control groups: adults born SGA with persistent short stature (SGA-S), adults born SGA with spontaneous catch-up growth to a normal height (SGA-CU) and adults born appropriate for gestational age with a normal height (AGA). The intervention was long-term GH treatment during childhood and the main outcome measure was cerebrovascular abnormalities. RESULTS: A total of 301 adults were investigated. Aneurysms were found in 6 adults: 3 (3.6%) SGA-GH, 1 (2.9%) SGA-S and 2 (2.2%) AGA adults, without differences between SGA-GH adults and the controls. Previous intracerebral hemorrhages were only found in 2 SGA-S adults (4.8%). Microbleeds were found in 17 adults: 4 (4.3%) SGA-GH, 4 (9.5%) SGA-S, 3 (4.3%) SGA-CU and 6 (6.3%) AGA adults, without differences between SGA-GH adults and the controls. CONCLUSION: Our findings suggest that SGA-GH adults at 12 years after GH cessation have no increased prevalence of cerebrovascular abnormalities compared to appropriate controls. Further research is needed to confirm our findings.

Advancement in Understanding Diabetic Retinopathy: A Comprehensive Review.

Diabetic retinopathy (DR) is a significant global health concern, with its prevalence and severity increasing alongside the rising incidence of diabetes. DR is a leading cause of vision impairment among working-age adults, resulting in substantial economic and healthcare burdens. This article explores the epidemiology and pathophysiology of DR, highlighting the global variation in its prevalence and the associated systemic risk factors. It delves into the complex relationship between glycemic control, duration of diabetes, and medication use in the context of DR development and progression. The review also discusses current screening methods and their implications, emphasizing the need for efficient and scalable approaches. Furthermore, it investigates the various treatment strategies available for DR, including laser photocoagulation, vitreous body excision, and anti-vascular endothelial growth factor (VEGF) therapy, while underlining their limitations and potential side effects. In conclusion, this article underscores the urgency of developing novel preventive and therapeutic approaches for DR. It highlights the potential role of cytokines and growth factors as treatment targets and emphasizes the importance of glycemic control and management of systemic risk factors in mitigating the impact of this vision-threatening complication of diabetes. The article serves as a comprehensive resource for understanding the challenges posed by DR and the need for innovative strategies to address this growing public health concern.

Right hepatic artery anomalies in pancreatoduodenectomy-a risk for arterial resection but not for postoperative outcomes.

Background: Pancreatoduodenectomy (PD) is a complex surgical procedure known for its significant morbidity rates, and the presence of an aberrant hepatic artery (AHA) introduces additional challenges. The impact of AHA on post-PD outcomes has been a subject of conflicting findings in the medical literature. This study aimed to investigate how variations in hepatic arterial anatomy influence intra-operative variables and postoperative morbidity. Methods: A retrospective analysis was conducted on 113 PD cases. Patients with variant hepatic arterial anatomy (n=38) were categorized as Group 1, while those without vascular abnormalities comprised Group 2. Perioperative and postoperative outcomes were examined. Results: Patients in Groups 1 and 2 exhibited similar characteristics, and no notable differences in surgical complications were observed. There was, however, a noticeable trend towards a higher incidence of postpancreatectomy hemorrhage (PPH) in Group 1 (31.6% vs. 20.0%; P=0.17). Furthermore, a statistically significant increase in the rate of arterial resections was noted in patients with vascular anomalies (10.5% vs. 1.33%; P=0.02). Conclusions: The prevalence of vascular abnormalities in the hepatic arterial circulation is more frequent than initially anticipated. These anomalies present additional complexities to the already intricate PD procedure, leading to a heightened necessity for arterial resection, albeit without any discernible impact on postoperative complications.

The Association between Vascular Abnormalities and Glaucoma-What Comes First?

Glaucoma is a leading cause of irreversible blindness worldwide. While intraocular pressure (IOP) presents a major risk factor, the underlying pathophysiology still remains largely unclear. The correlation between vascular abnormalities and glaucoma has been deliberated for decades. Evidence for a role played by vascular factors in the pathogenesis of glaucomatous neurodegeneration has already been postulated. In addition, the fact that glaucoma causes both structural and functional changes to retinal blood vessels has been described. This review aims to investigate the published evidence concerning the relationship between vascular abnormalities and glaucoma, and to provide an overview of the "chicken or egg" dilemma in glaucoma. In this study, several biomarkers of glaucoma progression from a vascular perspective, including endothelin-1 (ET-1), nitric oxide, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs), were identified and subsequently assessed for their potential as pharmacological intervention targets.

Insights into Novel Choroidal and Retinal Clinical Signs in Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a rare inherited neurocutaneous disorder with a major impact on the skin, nervous system and eyes. The ocular diagnostic hallmarks of this disease include iris Lisch nodules, ocular and eyelid neurofibromas, eyelid café-au-lait spots and optic pathway gliomas (OPGs). In the last years, new manifestations have been identified in the ocular district in NF1 including choroidal abnormalities (CAs), hyperpigmented spots (HSs) and retinal vascular abnormalities (RVAs). Recent advances in multi-modality imaging in ophthalmology have allowed for the improved characterization of these clinical signs. Accordingly, CAs, easily detectable as bright patchy nodules on near-infrared imaging, have recently been added to the revised diagnostic criteria for NF1 due to their high specificity and sensitivity. Furthermore, subclinical alterations of the visual pathways, regardless of the presence of OPGs, have been recently described in NF1, with a primary role of neurofibromin in the myelination process. In this paper, we reviewed the latest progress in the understanding of choroidal and retinal abnormalities in NF1 patients. The clinical significance of the recently revised diagnostic criteria for NF1 is discussed along with new updates in molecular diagnosis. New insights into NF1-related neuro-ophthalmic manifestations are also provided based on electrophysiological and optical coherence tomography (OCT) studies.

The genetics of portal hypertension: Recent developments and the road ahead.

Portal hypertension (PH), defined as a pathological increase in the portal vein pressure, has different aetiologies and causes. Intrahepatic PH is mostly secondary to the presence of underlying liver disease leading to cirrhosis, characterized by parenchymal changes with deregulated accumulation of extracellular matrix and vascular abnormalities; liver sinusoidal endothelial cells and hepatic stellate cells are key players in PH progression, able to influence each other. However, PH may also develop independently of parenchymal damage, as occur in portosinusoidal vascular disorder (PSVD), a group of clinical and histological entities characterized by portal vasculature dysfunctions. In this particular group of disorders, the pathophysiology of PH is still poorly understood. In the last years, several genetic studies, based on genome-wide association studies or whole-exome sequencing analysis, have highlighted the importance of genetic heritability in PH pathogenesis, both in cirrhotic and non-cirrhotic cases. The common PNPLA3 p.I148M variant, one of the main determinants of the susceptibility to steatotic liver disease, has also been associated with decompensation in patients with PH. Genetic variations at loci influencing coagulation, mainly the ABO locus, may directly contribute to the pathogenesis of PH. Rare genetic variants have been associated with familiar cases of progressive PSVD. In this review, we summarize the recent knowledges on genetic variants predisposing to PH development, contributing to better understand the role of genetic factors in PH pathogenesis.

A somatic splice-site variant in PIK3R1 in a patient with vascular overgrowth and low immunoglobulin levels: A case report.

BACKGROUND: The PI3K/AKT pathway, extensively studied in cancer, is vital for regulating cell metabolism, differentiation, and proliferation. Pathogenic variants in the PIK3R1 gene, which encodes three regulatory units of class IA PI3Ks, have been found in affected tissue of individuals with vascular lesions. These variants predominantly occur in the iSH2 domain, disrupting inhibitory contacts with the catalytic unit and leading to PI3K activation. Germline variants in this gene are also linked to an immunological condition called Activated PI3K delta syndrome type 2 (APDS2). METHODS: This is a case report and literature review. Clinical data were retrieved from medical records. RESULTS: A male patient presented with extensive vascular malformation covering over 90% of his body, along with complete 2-3 toe syndactyly, suggesting a vascular malformation syndrome called PROS. Low levels of IgA and IgG were detected. The patient achieved his developmental milestones and had above-average weight, height, and head circumference. Exome sequencing of skin and blood DNA revealed a de novo variant in PIK3R1 (c.1746-2A>G, p.?) in 9% of the patient's blood cells and 25% of cultured fibroblasts. Initially, classified as a variant of uncertain significance, this variant was later confirmed to be the cause. CONCLUSIONS: This is the first intronic SNV in a canonical splice site within iSH2 described, highlighting the importance of iSH2 in the regulation of the PI3K/AKT pathway and its involvement in the development of vascular overgrowth and antibody deficiency.

Gastrointestinal bleeding in von Willebrand patients: special diagnostic and management considerations.

INTRODUCTION: Severe and recurrent gastrointestinal (GI) bleeding caused by angiodysplasia is a significant problem in patients with von Willebrand disease (VWD) and in those with acquired von Willebrand syndrome (AVWS). At present, angiodysplasia-related GI bleeding is often refractory to standard treatment including replacement therapy with von Willebrand factor (VWF) concentrates and continues to remain a major challenge and cause of significant morbidity in patients despite advances in diagnostics and therapeutics. AREAS COVERED: This paper reviews the available literature on GI bleeding in VWD patients, examines the molecular mechanisms implicated in angiodysplasia-related GI bleeding, and summarizes existing strategies in the management of bleeding GI angiodysplasia in patients with VWF abnormalities. Suggestions are made for further research directions. EXPERT OPINION: Bleeding from angiodysplasia poses a significant challenge for individuals with abnormal VWF. Diagnosis remains a challenge and may require multiple radiologic and endoscopic investigations. Additionally, there is a need for enhanced understanding at a molecular level to identify effective therapies. Future studies of VWF replacement therapies using newer formulations as well as other adjunctive treatments to prevent and treat bleeding will hopefully improve care.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. It is caused by problems with von Willebrand factor (VWF), a protein in blood that helps stop bleeding. People with VWD either have low levels of VWF or VWF that does not work properly. The disease causes bleeding symptoms in 1 in 1000 individuals. Three main types of VWD exist. Depending on the type, people can have minimal symptoms or serious bleeding that needs hospital care.Patients with severe VWD may often experience repeated bleeding from the gastrointestinal tract. This is usually due to the formation of abnormal fragile vessels (malformations) called angiodysplasia, which have been linked to the absence or abnormal function of VWF. These fragile vessels are very difficult to find and diagnose. At present, available treatments for angiodysplasia, including long-term VWF replacement therapy, are not very effective. As a result, VWD patients with angiodysplasia have a poor quality of life.More research is needed to better evaluate current treatments and explore the contribution of abnormal VWF in the development of angiogenesis and angiodysplasia in VWD which may reveal new targets for treatment.

Drainage Tube Placement for the Management of Rebleeding After Vascular Embolization in a Patient With Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF-1), a hereditary disease caused by a mutation of a gene on chromosome 17q11.2, is associated with manifestations in several organs. Although infrequent, vascular abnormalities are a complication of NF-1, and they are the second most common cause of death in patients with NF-1. Repairing the nutrient artery and achieving hemostasis are difficult once the artery has failed, thereby resulting in poor treatment outcomes. Herein, we report a case of a patient with NF-1 who presented with an enormous cervical hematoma caused by bleeding from a branch of the external carotid artery. Vascular embolization was performed initially; however, rebleeding from the embolized site occurred. Following the removal of the hematoma, drainage tube placement was effective in preventing micro-bleeding. Thus, drainage tube placement may be an effective treatment option in patients with rebleeding.

SARS-CoV-2 Infection: A Clinical and Histopathological Study in Pregnancy.

During pregnancy, SARS-CoV-2 infection is associated with several adverse outcomes, including an increased risk of pre-eclampsia, preterm delivery, hypertensive disorders, gestational diabetes, and fetal growth restriction related to the development of placenta vascular abnormalities. We analyzed human placenta from full-term, uncomplicated pregnancies with SARS-CoV-2 infection during the first, second, or third trimesters of gestation. We studied, by the immunohistochemistry technique, the expression of CD34 and podoplanin (PDPN) as markers of vasculogenesis to find any differences. As secondary outcomes, we correlated maternal symptoms with placental histological alterations, including fibrin deposits, lymphocyte infiltration in the villi, edema, and thrombi. Our results showed a PDPN expression around the villous stroma as a plexiform network around the villous nucleus of fetal vessels; significant down-regulation was observed in the villous stroma of women infected during the third trimester. CD34 showed no changes in expression levels. During SARS-CoV-2 infection, the most common maternal symptoms were fever, anosmia, ageusia and asthenia, and the majority were treated with paracetamol, corticosteroids and azithromycin. Patients that required multiple symptomatic treatments evidenced a large amount of fibrin deposition in the villi. Certainly, PDPN plays a key role in healthy placental vasculogenesis and thus in its proper physiology, and SARS-CoV-2 surely alters its normal expression. Further studies are necessary to understand what mechanisms are being altered to try to avoid possible complications for both the mother and fetus in terms of the contagions that will still occur.

Case Report with Systematic Literature Review on Vascular Complications of BCG Intravesical Therapy for Bladder Cancer.

(1) Background: Intravesical instillation of therapeutic Bacillus Calmette-Guerin (BCG) is the standard of treatment for non-muscular invasive bladder cancer. Although the exact immunomodulatory effects of BCG therapy in non-muscular invasive bladder cancer (NMIBC) are still unclear, it has been considered a safe and effective treatment with the largest to-date report of complications citing minimal side effects, none of which included arterial involvement; (2) Methods: A systematic literature review was performed using PubMed, Cochrane, Medline, and Google Scholar from database inception to March 2021. Only eligible studies reporting aneurysm formation in adult patients with a history of BCG immunotherapy and no previous vascular pathology were included; (3) Results: A systematic literature review was conducted, highlighting 17 reports suggestive of BCG-induced mycotic aneurysm development. We added a case of a 78-year-old male, 30 months after last BCG-instillation, with a mycotic abdominal aneurysm yielding Mycobacterium tuberculosis with pyrazinamide resistance culture.; (4) Conclusions: Concluding results suggest a higher incidence of vascular complications from BCG intravesical therapy in the treatment of non-muscular invasive bladder cancer than previously reported. Recommendations are made to emphasize further research of this immunotherapy complication to facilitate the creation of guidelines for diagnosis and management of these patients.

Imaging evaluation of a persistent left superior vena cava and its importance in electrophysiologic procedures.

Accurate characterization of thoracic vascular structures is essential to safe, efficient, and successful cardiac electrophysiologic procedures. Here we describe a case of persistent left superior vena cava incidentally discovered during an elective cryoablation of atrial fibrillation procedure to illustrate possible diagnostic modalities to identify vascular abnormalities.

Surgical resection of a thymoma developed in a case with isolated persistent left superior vena cava.

INTRODUCTION: Persistent left superior vena cava (PLSVC) is one of the most common vascular abnormalities in the chest. In approximately 10 % of cases, the right superior vena cava is missing, which is called isolated persistent left superior vena cava (IPLSVC). PRESENTATION OF CASE: The case is an 85 years-old female. An anterior mediastinal tumor was accidentally revealed when the patient was admitted after a traffic accident. As the tumor became larger within four months, a thymectomy was planned. The anterior mediastinal tumor was in front of the ascending aorta, which was close to the confluence of the left and right brachiocephalic veins in normal anatomy. However, in this case, the right superior vena cava was missing, and the right brachiocephalic vein flowed into the left superior vena cava by the chest computed tomography. Preoperative examinations found no accompanying cardiac abnormality. Robot-assisted thymectomy was performed. No tumor infiltration was observed in the right brachiocephalic vein. No abnormality was found in either phrenic nerve. The tumor could be safely resected, and her postoperative course was uneventful. The pathological diagnosis was a thymoma. DISCUSSION: A case of thymectomy with IPLSVC is quite rare. A careful observation of the preoperative computed tomography images helps to diagnose IPLSVC. Technically, thymectomy was not much different from normal, other than the reversed location of the veins. However, it should be noted that IPLSVC cases may have cardiac malformations. CONCLUSION: Thymectomy for thymoma with IPLSVC can be safely performed when the left and right veins are reversed.

Large Regenerative Nodules and Focal Nodular Hyperplasia-Like Lesions: Definition, Pathogenesis, and Imaging Findings.

Focal nodular hyperplasia-like (FNH-like) nodules are hepatocellular lesions with similar radiologic and pathologic features as typical FNH but occur within an abnormal liver. They arise due to alteration of hepatic vasculature at both the microscopic and macroscopic levels. Although these nodules are not thought to have malignant potential, their imaging features overlap with premalignant and malignant lesions including hepatocellular carcinoma (HCC) and arise in patients who may be at risk for HCC, posing a diagnostic and management dilemma. It is important to consider these benign entities when reviewing liver imaging of patients at risk for HCC to reduce unnecessary interventions.

A pediatric posterior neck venous malformation with an endocranial extension.

Venous malformations are frequently localized in the head and neck region. However, a cervical localization with an endocranial extension is rather a very uncommon occurrence. We present a case of a 4-year-old child who presented with a large posterior cervical mass evolving for a year, firm and painful at palpation. Imaging was required, revealing a posterior cervical mass with an extension to adjacent structures, a destruction of the occipital bone and an endocranial extension. A macrobiopsy of the mass showed numerous irregular vessels. A surgical treatment was performed due to the extension of the mass, the esthetic prejudice it caused and the uncertain diagnosis. Venous malformation diagnosis was confirmed by a histological examination of the resected piece. Surgical management was not associated with the mass recurrence in our case. Here, we aim at identifying the clinical and radiological features of venous malformations, and at describing the different therapeutic features of this condition.