Case report: Association between PTEN-gene variant and an aggressive case of multiple dAVFs.

Introduction: Mutations of the phosphatase and tensin homolog (PTEN) gene have been associated with a spectrum of disorders called PTEN hamartoma tumor syndrome, which predisposes the individual to develop various types of tumors and vascular anomalies. Its phenotypic spectrum includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome, autism spectrum disorders (ASD), some sporadic cancers, Lhermitte-Duclos disease (LDD), and various types of associated vascular anomalies. Clinical presentation: A previously healthy 27-year-old woman was experiencing visual scintillating scotomas and mild chronic headaches for the past 2 years. The initial computed tomographic (CT) and magnetic resonance imaging (MRI) scans did not reveal any abnormalities, but the possibility of pseudotumor cerebri was considered. Furthermore, a cerebral angiogram showed a posterior fossa dural arteriovenous fistula (dAVF), which was initially treated through embolization. However, in spite of proper treatment, this patient experienced multiple recurrent dAVFs in different locations, requiring multiple embolizations and surgeries. Despite exhibiting altered cerebral perfusion and hemodynamics, the patient did not display any significant symptoms until she experienced a sudden stroke resulting from deep venous thrombosis, which was not associated with any medical procedures or medication use. A comprehensive analysis was performed due to the aggressive nature of the dAVFs. Surprisingly, exome sequencing of a blood sample revealed a PTEN gene variant in chromosome 10, indicative of Cowden syndrome. However, no tumors or other vascular lesions were detected in other systems that would constitute Cowden syndrome. Conclusion: The rapid formation of multiple and complex dAVFs, coupled with not meeting the criteria for any other PTEN-related syndrome, unequivocally leads to the presentation of a novel phenotype of the PTEN germline variant.

Ultrasound-guided non-targeted liver core biopsy: comparison of the efficacy of two different core needle biopsy systems using an ex-vivo animal model and retrospective review of clinical experience.

PURPOSE: To compare the efficacy of two 18-gauge core needle biopsy systems, the Achieve® (Merit Medical) and the Marquee® (BD Bard), using an ex-vivo animal liver model and retrospective review of clinical experience. METHODS: Sixty ex-vivo liver biopsy samples were obtained using the Achieve® (n = 30) and the Marquee® (n = 30) needles. In addition, 20 liver biopsy samples from 20 patients obtained using the Achieve® (n = 10) and Marquee® (n = 10) were compared retrospectively. One pathologist, blinded to needle type, recorded total core length and the number of complete portal triads. Ex vivo measurements were compared using mixed effects linear, logistic, and ordinal regression. In vivo measurements were compared using Student's t-test. RESULTS: For the Achieve® and Marquee® needles, the mean(SD) total core length (mm) of ex vivo samples was 11.0(3.3) and 12.6(3.4), respectively (P = 0.069) and the adequacy rate was 23.3% and 50%, respectively (P = 0.04). Mean number of portal triads of ex vivo samples was 7.2(2.9) and 8.6(3.8), respectively (P = 0.13), and the adequacy rate was 73.3% and 83.3%, respectively (P = 0.32). For in vivo samples, the Achieve® and Marquee® needles demonstrates mean(SD) total core length (mm) of 24.6(7.1) and 32.0(4.6), respectively (P = 0.01), adequacy rate (P = 0.06). Mean number of portal triads was 14.9(4.8) and 19.6(4.1), respectively (P = 0.03), adequacy rate (P = 0.47). CONCLUSIONS: Slightly longer core biopsies were obtained with the Marquee® needle compared with the Achieve® needle. Early clinical experience demonstrates no significant difference in sample adequacy rates. Both needle types can be expected to provide adequate samples for pathologic assessment of liver tissue.

Endothelial Plasmalemma Vesicle-Associated Protein Regulates the Homeostasis of Splenic Immature B Cells and B-1 B Cells.

Plasmalemma vesicle-associated protein (Plvap) is an endothelial protein with roles in endothelial diaphragm formation and maintenance of basal vascular permeability. At the same time, Plvap has roles in immunity by facilitating leukocyte diapedesis at inflammatory sites and controlling peripheral lymph node morphogenesis and the entry of soluble Ags into lymph node conduits. Based on its postulated role in diapedesis, we have investigated the role of Plvap in hematopoiesis and show that deletion of Plvap results in a dramatic decrease of IgM+IgDlo B cells in both the spleen and the peritoneal cavity. Tissue-specific deletion of Plvap demonstrates that the defect is B cell extrinsic, because B cell and pan-hematopoietic Plvap deletion has no effect on IgM+IgDlo B cell numbers. Endothelial-specific deletion of Plvap in the embryo or at adult stage recapitulates the full Plvap knockout phenotype, whereas endothelial-specific reconstitution of Plvap under the Chd5 promoter rescues the IgM+IgDlo B cell phenotype. Taken together, these results show that Plvap expression in endothelial cells is important in the maintenance of IgM+ B cells in the spleen and peritoneal cavity.

Cerebrum-cervical arterial dissection in adults during sports and recreation / Dissecção arterial cérebro-cervical em adultos durante prática de esportes e recreação

Dissection of cervical arteries constitutes a medical emergency. Although relatively rarely, activities classified as sports and recreation may be a cause of arterial dissection independently of neck or head trauma. The purpose of the present paper was to present a series of cases of cerebrum-cervical arterial dissection in individuals during or soon after the practice of these sports activities. Methods Retrospective data on patients with arterial dissection related to sports and recreation. Results Forty-one cases were identified. The most frequently affected vessel was the vertebral artery. A large variety of activities had a temporal relationship to arterial dissection, and jogging was the most frequent of these. This is the largest case series in the literature. Conclusion Arterial dissection may be a complication from practicing sports.

A dissecção das artérias cervicais é uma emergência médica. Embora de forma relativamente rara, certas atividades descritas como esportes e recreação podem ser a causa de dissecção arterial independentemente de trauma de crânio ou cervical. O propósito do presente estudo é apresentar uma série de casos de dissecção de artérias cérebro-cervicais em indivíduos durante ou logo após a prática destas atividades desportivas. Métodos Dados retrospectivos de pacientes com dissecção arterial relacionada à prática de esportes e recreação. Resultados Quarenta e um casos foram identificados. A artéria mais frequentemente afetada foi a vertebral. Uma grande variedade de atividades teve relação temporal com a dissecção arterial, sendo a corrida a mais frequente delas. Esta é a maior série de casos da literatura. Conclusão Dissecção arterial pode ser uma complicação da prática de esportes.

Cerebrum-cervical arterial dissection in adults during sports and recreation.

UNLABELLED: Dissection of cervical arteries constitutes a medical emergency. Although relatively rarely, activities classified as sports and recreation may be a cause of arterial dissection independently of neck or head trauma. The purpose of the present paper was to present a series of cases of cerebrum-cervical arterial dissection in individuals during or soon after the practice of these sports activities. METHODS: Retrospective data on patients with arterial dissection related to sports and recreation. RESULTS: Forty-one cases were identified. The most frequently affected vessel was the vertebral artery. A large variety of activities had a temporal relationship to arterial dissection, and jogging was the most frequent of these. This is the largest case series in the literature. CONCLUSION: Arterial dissection may be a complication from practicing sports.

Safety and efficacy of the Gunther Tulip retrievable vena cava filter: midterm outcomes.

PURPOSE: To evaluate of the medium-term integrity, efficacy, and complication rate associated with the Gunther Tulip vena cava filter. METHODS: A retrospective study was performed of 369 consecutive patients who had infrarenal Gunther Tulip inferior vena cava filters placed over a 5-year period. The mean patient age was 61.8 years, and 59% were men. Venous thromboembolic disease and a contraindication to or complication of anticoagulation were the indications for filter placement in 86% of patients; 14% were placed for prophylaxis in patients with a mean of 2.3 risk factors. Follow-up was obtained by review of medical and radiologic records. RESULTS: Mean clinical follow-up was 780 days. New or recurrent pulmonary embolus occurred in 12 patients (3.3%). New or recurrent deep-vein thrombosis occurred in 53 patients (14.4%). There were no symptomatic fractures, migrations, or caval perforations. Imaging follow-up in 287 patients (77.8%) at a mean of 731 days revealed a single (0.3%) asymptomatic fracture, migration greater than 2 cm in 36 patients (12.5%), and no case of embolization. Of 122 patients with CT scans, asymptomatic perforations were identified in 53 patients (43.4%) at a mean 757 days. CONCLUSION: The Gunther Tulip filter was safe and effective at 2-year follow-up. Complication rates were similar to those reported for permanent inferior vena cava filters.

The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition.

Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels, and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival. Loss of diaphragms did not affect the fenestrae and transendothelial channels formation but disrupted the barrier function of fenestrated capillaries, causing a major leak of plasma proteins. This disruption results in early death of animals due to severe noninflammatory protein-losing enteropathy. Deletion of PV1 in endothelium, but not in the hematopoietic compartment, recapitulates the phenotype of global PV1 deletion, whereas endothelial reconstitution of PV1 rescues the phenotype. Taken together, these data provide genetic evidence for the critical role of the diaphragms in fenestrated capillaries in the maintenance of blood composition.

Caveolae, fenestrae and transendothelial channels retain PV1 on the surface of endothelial cells.

PV1 protein is an essential component of stomatal and fenestral diaphragms, which are formed at the plasma membrane of endothelial cells (ECs), on structures such as caveolae, fenestrae and transendothelial channels. Knockout of PV1 in mice results in in utero and perinatal mortality. To be able to interpret the complex PV1 knockout phenotype, it is critical to determine whether the formation of diaphragms is the only cellular role of PV1. We addressed this question by measuring the effect of complete and partial removal of structures capable of forming diaphragms on PV1 protein level. Removal of caveolae in mice by knocking out caveolin-1 or cavin-1 resulted in a dramatic reduction of PV1 protein level in lungs but not kidneys. The magnitude of PV1 reduction correlated with the abundance of structures capable of forming diaphragms in the microvasculature of these organs. The absence of caveolae in the lung ECs did not affect the transcription or translation of PV1, but it caused a sharp increase in PV1 protein internalization rate via a clathrin- and dynamin-independent pathway followed by degradation in lysosomes. Thus, PV1 is retained on the cell surface of ECs by structures capable of forming diaphragms, but undergoes rapid internalization and degradation in the absence of these structures, suggesting that formation of diaphragms is the only role of PV1.