Update and audit of the St George's classification algorithm of primary lymphatic anomalies: a clinical and molecular approach to diagnosis.

Primary lymphatic anomalies may present in a myriad of ways and are highly heterogenous. Careful consideration of the presentation can lead to an accurate clinical and/or molecular diagnosis which will assist with management. The most common presentation is lymphoedema, swelling resulting from failure of the peripheral lymphatic system. However, there may be internal lymphatic dysfunction, for example, chylous reflux, or lymphatic malformations, including the thorax or abdomen. A number of causal germline or postzygotic gene mutations have been discovered. Some through careful phenotyping and categorisation of the patients based on the St George's classification pathway/algorithm. The St George's classification algorithm is aimed at providing an accurate diagnosis for patients with lymphoedema based on age of onset, areas affected by swelling and associated clinical features. This has enabled the identification of new causative genes. This update brings the classification of primary lymphatic disorders in line with the International Society for the Study of Vascular Anomalies 2018 classification for vascular anomalies. The St George's algorithm considers combined vascular malformations and primary lymphatic anomalies. It divides the types of primary lymphatic anomalies into lymphatic malformations and primary lymphoedema. It further divides the primary lymphoedema into syndromic, generalised lymphatic dysplasia with internal/systemic involvement, congenital-onset lymphoedema and late-onset lymphoedema. An audit and update of the algorithm has revealed where new genes have been discovered and that a molecular diagnosis was possible in 26% of all patients overall and 41% of those tested.

Porto-sinusoidal vascular disease: proposal and description of a novel entity.

Portal hypertension in the absence of portal vein thrombosis and without cirrhosis, but with mild or moderate alterations of liver histology (eg, obliterative venopathy, nodular regenerative hyperplasia, or incomplete septal cirrhosis) is being increasingly recognised. Owing to the heterogeneity of causes and histological findings, a substantial number of terms have been used to describe such idiopathic non-cirrhotic portal hypertension. Patients with the same clinical and histological features exist, but without portal hypertension at the time of diagnosis. Therefore, improved criteria are needed to define this form of liver disease. Here, we propose the term porto-sinusoidal vascular disease, since all lesions found involve the portal venules or sinusoids. The definition of this entity is based on the characteristic absence of cirrhosis with or without signs of portal hypertension or histological lesions. The presence of known causes of liver disease does not rule out porto-sinusoidal vascular disease, but specific causes of vascular liver disease are excluded from its definition. The diagnosis of porto-sinusoidal vascular disease is based on liver biopsy and might include signs specific for portal hypertension with normal or mildly elevated liver stiffness values and no complete portal vein thrombosis. We provide simple diagnostic criteria, because agreement on a uniform nomenclature is an essential requirement for future collaborative studies.

Classification and ultrasound findings of vascular anomalies in pediatric age: the essential.

Proper nomenclature is a major obstacle in understanding and managing vascular anomalies. Often the same term is used for totally different types of lesions or, conversely, the same lesion may be labeled with different terms. Although in recent times there has been a greater understanding of the problems concerning vascular anomalies, episodes of improper use of terminology still remain. The aim of this article, starting from the most recent classification of vascular anomalies, is to provide a clinical and instrumental approach to identifying these lesions and to converge towards a clear and unambiguous terminology that must become univocal among the various operators to avoid diagnostic misunderstandings and therapeutic errors.

Vascular Surgery and Geriatric Patients.

As the population ages, surgical decision-making in vascular surgery has become more complex. Older patients may not have been offered vascular surgical intervention in the past because of prohibitive physiologic demands and poor health. Patients now have more aggressive management of vascular risk factors with medications, such as statin therapy, and less invasive endovascular or hybrid treatment options. Outcomes in elderly patients may not be comparable with younger patients for entities such as aortic aneurysm repair, carotid endarterectomy, or lower extremity revascularization. Despite this, desirable outcomes can be successfully achieved and should be offered to carefully selected elderly individuals.

[Evaluation of a Classification Model of Horizontal Vascular Lesions of the Vocal Folds]. / Evaluation eines Klassifikationsmodells horizontaler Gefäßveränderungen der Stimmlippen.

OBJECTIVE: There exists no valid classification of beginning vascular changes of the vocal folds. We tested an own classification model of visible beginning horizontal vascular changes. MATERIAL AND METHODS: 168 indirect endoscopic pictures (84 white light=WL and 84 Narrow Band Imaging=NBI) of vocal folds were presented to 3 different consultants for classification (graduation normal, slight, moderately, high-grade belonged to the vascular features ectasia, meander, convolute, frequency of the vessels, ramification, change in direction). The self-confidence was declared by the consultants with a numeric rating scale. RESULTS: A classification of beginning vascular changes of the vocal folds is possible, especially of ectasia, meander, convolute, frequency of the vessels, ramification, change in direction (p<0.0001). Significantly more vascular lesions can be detected by NBI than with white light endoscopy alone (p<0.0001). There are no significant differences (p=0.3529) in self-confidence of the classification. But it differs between the consultants highly significant (p<0.0001). The inexperienced classifier shows the highest growth in the learning curve. The intrarater- and interrater-variability differs only slightly between WL and NBI. CONCLUSIONS: Beginning horizontal changes of vocal fold vessels can be classified. Endoscopic NBI-pictures of the vocal folds demonstrate the beginning of vascular changes better compared to endoscopic white light pictures alone. The familiarity and expertise with the classification model and the endoscopic imaging technique affect the self-confidence of the evaluation.

Extrahepatic portal vein obstruction and portal vein thrombosis in special situations: Need for a new classification.

Extrahepatic portal vein obstruction is a vascular disorder of liver, which results in obstruction and cavernomatous transformation of portal vein with or without the involvement of intrahepatic portal vein, splenic vein, or superior mesenteric vein. Portal vein obstruction due to chronic liver disease, neoplasm, or postsurgery is a separate entity and is not the same as extrahepatic portal vein obstruction. Patients with extrahepatic portal vein obstruction are generally young and belong mostly to Asian countries. It is therefore very important to define portal vein thrombosis as acute or chronic from management point of view. Portal vein thrombosis in certain situations such as liver transplant and postsurgical/liver transplant period is an evolving area and needs extensive research. There is a need for a new classification, which includes all areas of the entity. In the current review, the most recent literature of extrahepatic portal vein obstruction is reviewed and summarized.

Relação entre biomarcadores inflamatórios, de adesão celular, de estresse oxidativo, de lesão endotelial, remodelamento tecidual e vascular e os diferentes estágios da doença venosa crônica primária (classes clínicas CEAP C0a, C2, C3, C4) / Relationship between biomarkers of inflammation, cell adhesion, oxidative stress, endothelial cell damage, vascular and tissue remodeling and the different stages of primary chronic venous disease (CEAP clinical classes C0a, C2, C3, C4)

A doença venosa crônica (DVC) é uma desordem complexa que compreende sinais e sintomas que variam das telangiectasias às úlceras ativas. A DVC é classificada de acordo com aspectos clínicos, etiológicos, anatômicos e fisiopatológicos (CEAP) em sete classes variando de C0 à C6. A principal causa da DVC é a hipertensão venosa que altera o fluxo venoso e, consequentemente, a força de cisalhamento que induz alterações fenotípicas nas células endoteliais que passam a expressar mediadores pró-inflamatórios e pró-trombóticos, que levam à adesão de leucócitos, ao aumento do estresse oxidativo, da permeabilidade vascular e do dano endotelial e ao remodelamento tecidual e vascular.Em virtude dos inúmeros mecanismos e da diversidade de moléculas envolvidas na patogênese e progressão da DVC, é essencial conhecer a interação entre elas e também saber quais são as moléculas (biomarcadores) que se correlacionam positivamente ou negativamente com a gravidade da doença. Foram avaliados os níveis de Interleucina-6 (IL-6), sL-selectina, sE-selectina, sP-selectina, molécula de adesão intercelular-1solúvel (sICAM-1), molécula de adesão das células vasculares-1 solúvel (sVCAM-1), ativador tecidual do plasminogênio (tPA), atividade do inibidor do ativador do plasminogênio-1 (PAI-1), trombomodulina solúvel (sTM), fator de von Willebrand (vWF), metaloproteinase de matriz (MMP)-2, MMP-3, MMP-9, inibidor tecidual das MMPs -1 (TIMP-1), angiopoietina-1 e -2, sTie-2 e s-Endoglina e fator de crescimento do endotélio vascular (VEGF) no sangue coletado da veia braquial de 173 mulheres com DVC primária divididas em grupos C2, C3, C4 e C4 menopausadas (C4m) e de 18 voluntárias saudáveis (grupo C0a). Foram também analisados os níveis urinários de ent-prostaglandina F2α nesses grupos. Não foram encontradas diferenças estatisticamente significativas com relação às concentrações sanguíneas e urinárias de sE-selectina, sP-selectina, sICAM-1, atividade de PAI-1, MMP-3, razão TIMP-1/MMP-3 ...

Chronic Venous Disease (CVD) is a complex disorder, which encompasses signs and symptoms that vary from telangiectasias to active ulcers. The CVD is classified according Clinical, Etiologic, Anatomical and Pathophysiological (CEAP) aspects into seven classes varying from C0 to C6. The main cause of CVD is venous hypertension, which alters venous flow and consequently, shear stress. Abnormal shear stress induces phenotypic changes in endothelial cells that start to express pro-inflammatory and pro-thrombotic mediators that lead to leukocyte adhesion, oxidative stress, increased vascular permeability and endothelial cell damage and tissue and vascular remodeling. Due to several mechanisms and the diversity of molecules involved in the pathogenesis and progression of CVD, is essential to know the interplay between them and which are the molecules (biomarkers) that correlate positively and negatively with the severity of the disease. We investigated the levels of interleukin-6 (IL-6), sL-selectin, sE-selectin, sP-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, soluble thrombomodulin (sTM), von Willebrand factor (vWf), matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, tissue inhibitor of metaloproteinases-1 (TIMP-1), angiopoietin-1 and -2, sTie-2, s-Endoglin, vascular endothelial growth factor (VEGF) in the blood taken from the brachial vein of 173 patients with primary CVD divided into C2, C3, C4 and menopaused C4 (C4m) groups and 18 healthy volunteers (C0a group).We also investigated the urinary levels of ent-prostaglandin F2α in these groups. There was no statistically significant difference between groups with respect to blood or urinary levels of sE-selectin, sP-selectin, sICAM-1, PAI-1 activity, MMP-3, TIMP-1/MMP-3 ratio, angiopoietin-2, angiopoietin-1/angiopoietin-2 ratio, s-Endoglin ...

An observational study into the management of arteriomegaly: a call for a revised classification system.

INTRODUCTION: Arteriomegaly is the diffuse ectasia of arteries with or without aneurysmal disease. Patients with arteriomegaly have a higher incidence of morbidity including limb loss compared to patients with other arteriopathies. The aim of this observational study was to review the management of these patients in our institution. METHODS: Radiologists and surgeons prospectively reviewed aortofemoral angiography. Patients with arteriomegaly were identified. Data relating to demographics, mode of presentation, risk factors, type of arteriomegaly, management and progression of disease were analysed. RESULTS: Arteriomegaly was identified in 1.3% of patients (n = 69) undergoing lower limb angiography in the study period. Of these, the majority (n = 67) were men. The mean age was 74 years (range: 60-89 years) and 76% were smokers. Co-morbidities included coronary artery disease (55%), diabetes mellitus (20%), hypertension (45%) and cerebrovascular events (6%). Forty-nine patients presented with critical limb ischaemia and eighteen patients were seen electively in the outpatients department with symptoms of intermittent claudication. Data were incomplete for two male patients and were therefore not included. At presentation, 22 patients were classified as Hollier type I, 5 were type II and 9 were type III. Thirty-one patients had arteriomegalic vessels but no aneurysmal disease. After a median follow-up duration of 76 months (range: 6-146 months), 34 patients progressed to type I, 2 to type II and 18 to type III. Thirteen remained without aneurysmal disease. Twenty-nine patients required angioplasty and twenty-eight required bypass surgery during this time. In total, 102 procedures were required for complicated disease. The limb salvage rate was 92%. Although 8 patients in our series died, the remaining 59 are under regular follow up. CONCLUSIONS: This study illustrates the progressive nature of arteriomegaly. Results of the management of these patients in our institution are similar to those in the literature. We suggest an additional fourth category to Hollier's classification that describes arteriomegalic disease without aneurysmal degeneration as this, too, deserves special management. Regular follow-up visits and early intervention for patients with arteriomegaly is advocated to reduce the high incidence of morbidity.

Comparison of the new ASCO classification with the TOAST classification in a population with acute ischemic stroke.

Precise analysis of stroke subtypes is important for clinical treatment decisions, the prognostic evaluation of patients, as well as defining stroke populations in clinical studies. The TOAST classification is the most widely used and approved form for etiologic subtyping. Increasing knowledge about stroke mechanisms and the introduction of new diagnostic techniques have supported the promotion of the new ASCO phenotypic classification, which aims to characterize patients using different grades of evidence for stroke subtypes. We prospectively assigned 103 consecutive patients from our stroke center for subtype classification using ASCO and TOAST. Clinical features and complementary investigations were recorded according to our standardized acute stroke care protocol. Evidence grade 1 with ASCO was assessed in 12.62% for large artery disease (A), 23.30% small-vessel disease (S), 36.89% cardiac source (C) and 1.94% another cause (O). Evidence grades 1-3 were identified in 60.19% A, 75.73% S, 49.51% C, and 3.88% O. A total of 68.93% of the patients were classified in more than one category, and only 3.88% remained completely undetermined. The κ value for inter-rater agreement was 0.92-1. Using TOAST, the distribution was 9.71% A, 23.30% S, 34.95% C, 1.94% O, and 30.10% undetermined. The ASCO classification showed a good concordance with TOAST. The inter-rater agreement was high. The comprehensive character of ASCO allows the recording of important additional information. This may be helpful for a specific treatment adaptation in each individual patient and creation of different etiological profiles in view of adapted clinical trials.

[Vascular calcification: types and mechanisms]. / Calcificación vascular: tipos y mecanismos.

Vascular calcification has traditionally been considered to be a passive process that was associated with advanced age, atherosclerosis, uncommon genetic diseases and some metabolic alterations such as diabetes mellitus and end-stage kidney failure. However, in the last years, vascular calcification has been proven to be an active and regulated process, similar to bone mineralisation, in which different bone-related proteins are involved. Recent results question the classic classification of vascular calcification into intimal and medial calcification, at least in capacitance arteries. Pro and anti-calcifying mechanisms play an active role in calcium deposition in vascular cells, making this area an active focus of research. The identification of therapeutic targets which can slow down the progression or even reverse vascular calcification could be an important step forward in the treatment of patients with chronic kidney disease.

[Molecular mechanisms of vascular calcification].

Vascular calcification is an active process similar to physiological mineralization of skeletal tissues. Not only apoptosis, cellular senescence, and osteochondrogenic transdifferentiation of vascular smooth muscle cells, but also degeneration and degradation of elastin may play an important role in its developmental process. Vascular calcification is induced by the interactions among various regulatory molecules for calcification in the progression of atherosclerosis or arteriosclerosis.

Revision of the venous clinical severity score: venous outcomes consensus statement: special communication of the American Venous Forum Ad Hoc Outcomes Working Group.

In response to the need for a disease severity measurement, the American Venous Forum committee on outcomes assessment developed the Venous Severity Scoring system in 2000. There are three components of this scoring system, the Venous Disability Score, the Venous Segmental Disease Score, and the Venous Clinical Severity Score (VCSS). The VCSS was developed from elements of the CEAP classification (clinical grade, etiology, anatomy, pathophysiology), which is the worldwide standard for describing the clinical features of chronic venous disease. However, as a descriptive instrument, the CEAP classification responds poorly to change. The VCSS was subsequently developed as an evaluative instrument that would be responsive to changes in disease severity over time and in response to treatment. Based on initial experiences with the VCSS, an international ad hoc working group of the American Venous Forum was charged with updating the instrument. This revision of the VCSS is focused on clarifying ambiguities, updating terminology, and simplifying application. The specific language of proven quality-of-life instruments was used to better address the issues of patients at the lower end of the venous disease spectrum. Periodic review and revision are necessary for generating more universal applicability and for comparing treatment outcomes in a meaningful way.

Clinical utility of susceptibility-weighted imaging in vascular diseases of the brain.

Susceptibility-weighted imaging (SWI) is a rapidly evolving technique that utilizes both the magnitude and phase information to obtain valuable information about susceptibility changes between tissues. SWI is very sensitive to the paramagnetic effects of deoxyhemoglobin. SWI plays an important role in the diagnostic evaluation and management of acute stroke. In addition, it also plays an important role in the imaging of patients with chronic arterial occlusion and in understanding the effects of chronic infarction, like incomplete infarction and cortical laminar necrosis. The hemodynamic status and oxygen extraction fraction can also be evaluated. SWI is useful in evaluating cerebral venous sinus thrombosis by demonstrating the hemorrhagic venous infarction and thrombus in the sinus and the cortical veins, as well as secondary phenomena like venous stasis in the form of engorged cortical and transmedullary veins and collateral slow flow. Low-flow vascular malformations that are not visualized well on conventional sequences are depicted in exquisite detail along with the venous components on SWI. SWI is used for evaluating cavernomas, developmental venous anomalies, telangiactasias, dural arteriovenous fistulas and the various components of arteriovenous malformations. It has also evolved as a noninvasive technique for evaluating various anomalies of the venous system without administering contrast. Vasculopathies and vasculitis are associated with cerebral microbleeds which are detected on SWI. On the basis of the additional information provided by SWI, it can be included in the routine brain imaging protocol.

Correlação entre classificação clínica ceap e qualidade de vida na doença venosa crônica / Relationship between quality of life and the ceap clinical classification in chronic venous disease

OBJETIVOS: Avaliar a qualidade de vida (QV) na doença venosa crônica (DVC) e analisar a relação entre QV e severidade da doença. MÉTODOS: Trata-se de um estudo transversal com uma amostra de conveniência de 50 pacientes com DVC diagnosticada. Os pacientes foram classificados quanto à severidade da DVC pela classificação clínica da Clinical manifestations, Etiologic factors, Anatomic distribuition of disease, Pathophysiologic findings (CEAP) e agrupados em: CEAP 1, 2, 3 (menos comprometidos clinicamente) e CEAP 4, 5, 6 (mais comprometidos clinicamente). A QV foi avaliada pelo questionário SF-36. Para comparação dos escores do SF-36 entre os grupos foi utilizado o teste Mann-Whitney U e para verificar associação entre QV e CEAP, o coeficiente de correlação de Spearman. Foi considerada diferença estatisticamente significativa p<0,05. O programa estatístico SPSS, versão 16.0 foi utilizado para as análises. RESULTADOS: 74 por cento da amostra eram mulheres e a média de idade foi significativamente maior (p<0,001) entre os indivíduos CEAP 4, 5, 6 (56,6±10,3) do que entre os CEAP 1, 2, 3 (40,6±10,7). Todos os domínios do Componente Saúde Física (CSF) do SF-36 apresentaram escores significativamente menores no grupo CEAP 4, 5, 6 (p<0,05), representando maior comprometimento físico e funcional. Apenas os domínios do CSF apresentaram correlação negativa e estatisticamente significativa com a CEAP. CONCLUSÕES: Os aspectos físicos e funcionais foram mais comprometidos, sobretudo nas formas mais graves da DVC. Estes achados podem contribuir para melhor compreensão dos efeitos da DVC na QV e melhor direcionamento das intervenções terapêuticas nessa população.

OBJECTIVES: To evaluate the quality of life (QOL) of patients with chronic venous disease (CVD) and to analyze the relationship between QOL and disease severity. METHODS: This was a cross-sectional study with a convenience sample of 50 participants with a diagnosis of CVD. The participants were classified according to disease severity using the CEAP clinical classification (Clinical manifestations, Etiological factors, Anatomical distribution of disease, Pathophysiological findings). They were then divided into two groups: CEAP 1, 2 and 3 (less clinically compromised) and CEAP 4, 5 and 6 (more clinically compromised). QOL was evaluated using the SF-36 questionnaire. The Mann-Whitney U test was used to compare the SF-36 scores between the groups. The Spearman correlation was used to evaluate the association between QOL and the CEAP. Differences were considered statistically significant with p < 0.05. The SPSS statistical software version 16.0 was used for the analyses. RESULTS: Seventy-four percent of the sample was female. The mean age was significantly higher (p<0.001) among participants classified as CEAP 4, 5 and 6 (56.6±10.3) than among those classified as CEAP 1, 2 and 3 (40.6±10.7). All the domains of the physical component of the SF-36 presented significantly lower scores in the CEAP 4, 5 and 6 group (p<0.05), thus showing greater physical and functional impairment. Only the domains of the physical component presented statistically significant negative correlations with the CEAP. CONCLUSIONS: The physical and functional characteristics were more impaired, especially in the more severe forms of CVD. These findings may contribute to a better understanding of the effects of CVD on QOL and better management of therapeutic interventions in this population.

Nonspecific interstitial pneumonia associated with collagen vascular disease: analysis of CT features to distinguish the various types.

OBJECTIVE: The purpose of this study was to analyze the CT findings of interstitial lung diseases that are associated with collagen vascular disease (CVD), with particular attention to nonspecific interstitial pneumonia (NSIP), and to examine whether it is possible to predict the clinical diagnosis of CVDs based on the CT findings alone. METHODS: CT scans of 49 patients with NSIP associated with CVD (15 males, 34 females; mean age, 55+/-10 years; age range, 25-76 years) were included in this retrospective study. All patients underwent a surgical biopsy. The clinical diagnosis comprised rheumatoid arthritis (RA) (n=15), systemic sclerosis (SSc) (n=8), polymyositis and dermatomyositis (PM/DM) (n=18), Sjögren's syndrome (SjS) (n=4), and mixed connective tissue disease (MCTD) (n=4). Each CT was reviewed by two independent observers who made a clinical diagnosis based on the CT findings alone. RESULTS: The observers made a correct diagnosis for 22 (45%) of the 49 patients. A correct diagnosis was made for: RA in 7 (47%) of 15 patients; SSc in 3 (38%) of 8 patients; PM/DM in 11 (61%) of 18 patients; SjS in 1 (25%) of 4 patients. None of the 4 MCTD cases was diagnosed. CONCLUSION: It is difficult to make a correct clinical diagnosis of the various types of CVDs based solely on CT findings. However, it is probable to make a reasonably accurate clinical diagnosis in cases that show the typical CT findings, especially for PM/DM patients.