The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration

The transmembrane ligand ephrinB2 and its cognate Eph receptor tyrosine kinases are important regulators of vascular morphogenesis. EphrinB2 may have an active signaling role, resulting in bi-directional signal transduction downstream of both ephrinB2 and Eph receptors. To separate the ligand and receptor-like functions of ephrinB2 in mice, we replaced the endogenous gene by cDNAs encoding either carboxyterminally truncated (ephrinB2(DeltaC)) or, as a control, full-length ligand (ephrinB2(WT)). While homozygous ephrinB2(WT/WT) animals were viable and fertile, loss of the ephrinB2 cytoplasmic domain resulted in midgestation lethality similar to ephrinB2 null mutants (ephrinB2(KO)). The truncated ligand was sufficient to restore guidance of migrating cranial neural crest cells, but ephrinB2(DeltaC/DeltaC) embryos showed defects in vasculogenesis and angiogenesis very similar to those observed in ephrinB2(KO/KO) animals. Our results indicate distinct requirements of functions mediated by the ephrinB carboxyterminus for developmental processes in the vertebrate embryo.

Traumatic free wall and ventricular septal rupture - 'hybrid' management in a child

A 8-year-old boy showed a traumatic ventricular septal rupture following a blunt chest trauma, and was scheduled for elective catheter closure. Two weeks later, a follow-up echocardiogram revealed a pseudoaneurysm of the anterior wall of the left ventricle. Because of the apical location of the VSD, it was decided to proceed with transcatheter occlusion. After successful VSD closure, the patient was taken to the operation room for surgical repair of the left ventricular pseudoaneurysm. Symptoms and signs seen in patients with ventricular pseudoaneurysms appear to be discrete and variable, and a high clinical index of suspicion with a very close echocardiographic follow-up is strongly recommended after occurrence of a blunt cardiac trauma. The combined 'hybrid' approach of transcatheter closure of the intraventricular rupture followed by surgical closure of the pseudoaneurysm allows for a less invasive and efficient management of this rare combination of post-traumatic ventricular free wall and septal rupture in a child.

The value of conservative treatment in ruptures of the anterior cruciate ligament (ACL)

BACKGROUND: Thirty-eight of the 73 consecutive acute ruptures of the anterior cruciate ligament (ACL) proven by a magnetic resonance imaging scan (MRI) in skeletally mature patients (16-55 years old) were classified as suitable for primarily conservative treatment. Patient selection was performed using a preoperative screening protocol based on the structural damage, clinical symptoms, compliance, sportive activity, and the consent of a well-informed patient. METHODS: In 12 of the 38 treated patients, the conservative protocol showed a good to very good outcome, 2 patients had persistent giving-way and were considering ACL reconstruction, 14 patients had a secondary ACL reconstruction in our clinic (average 5.3 months after injury), 9 patients were operated on in other hospitals (average 13.3 months after injury), and 1 patient was lost to follow-up. RESULTS: All patients with successful conservative treatment were able to perform low-risk pivoting sports and two patients are practicing high-risk pivoting sports. The average International Knee Documentation Committee (IKDC) score was 92.5 (82.8-98.9); the subjective overall knee function was 93% (60% to 100%). Of the 12 patients with good and very good results, 6 continued playing the same sports at an unreduced intensity, 4 patients reduced their activities slightly, and 1 patient played more sports than before. CONCLUSIONS: Although the authors performed a preoperative screening to select patients suitable for conservative treatment, almost two-thirds of the primarily conservatively treated ACL ruptures needed an operative reconstruction in the long term. In one-third of the patients, conservative treatment led to a good or very good result. At the endpoint of the study only 12 (16%) of a total of 73 patients with acute injuries of the ACL had successful conservative treatment. Therefore, patients must be comprehensively instructed about the treatment program and the chances of success of conservative ACL treatment.

Clinical presentation of a traumatic cervical spine disc rupture in alpine sports: a case report

ABSTRACT: Isolated non-skeletal injuries of the cervical spine are rare and frequently missed. Different evaluation algorithms for C-spine injuries, such as the Canadian C-spine Rule have been proposed, however with strong emphasis on excluding osseous lesions. Discoligamentary injuries may be masked by unique clinical situations presenting to the emergency physician. We report on the case of a 28-year-old patient being admitted to our emergency department after a snowboarding accident, with an assumed hyperflexion injury of the cervical spine. During the initial clinical encounter the only clinical finding the patient demonstrated, was a burning sensation in the palms bilaterally. No neck pain could be elicited and the patient was not intoxicated and did not have distracting injuries. Since the patient described a fall prevention attempt with both arms, a peripheral nerve contusion was considered as a differential diagnosis. However, a high level of suspicion and the use of sophisticated imaging (MRI and CT) of the cervical spine, ultimately led to the diagnosis of a traumatic disc rupture at the C5/6 level. The patient was subsequently treated with a ventral microdiscectomy with cage interposition and ventral plate stabilization at the C5/C6 level and could be discharged home with clearly improving symptoms and without further complications.This case underlines how clinical presentation and extent of injury can differ and it furthermore points out, that injuries contracted during alpine snow sports need to be considered high velocity injuries, thus putting the patient at risk for cervical spine trauma. In these patients, especially when presenting with an unclear neurologic pattern, the emergency doctor needs to be alert and may have to interpret rigid guidelines according to the situation. The importance of correctly using CT and MRI according to both - standardized protocols and the patient's clinical presentation - is crucial for exclusion of C-spine trauma.

Thrombophilic risk factors in patients with cranial and spinal dural arteriovenous fistulae

OBJECTIVE: Numerous studies have reported the technical aspects and results of surgical and/or endovascular treatment of cranial dural arteriovenous fistulae (cDAVF) and spinal dural arteriovenous fistulae (sDAVF). Only a few of them have addressed the question of thrombophilic conditions, which may be relevant as pathogenetic factors or can increase the risk for venous thromboembolic events. Therefore, the objective of this study is to compare thrombophilic risk factors in patients with cDAVF and sDAVF with no history of trauma. METHODS: A total of 43 patients (25 with cDAVF and 18 with sDAVF) were included in this study. Blood samples were analyzed for G20210A mutation of the prothrombin gene and factor V Leiden mutation. In all patients, prothrombin time, international normalized ratio, fibrinogen, antithrombin, protein C and S activity, von Willebrand factor antigen, ristocetin cofactor activity, D-dimer, coagulation factor VIII activity, and tissue factor pathway inhibitor were determined. Screening was performed for the occurrence of lupus antiphospholipid and cardiolipin antibodies. RESULTS: The prevalence of G20210A mutation of the prothrombin gene was significantly higher in patients with cDAVF (n = 6) compared with patients with sDAVF (n = 0; P < 0.05, Fisher's exact test). A factor V Leiden mutation was found in 3 patients with sDAVF and in 1 patient with cDAVF (P = 0.29, Fisher's exact test). No significant difference was found for other parameters, except for fibrinogen, but decreased protein C activity was more frequent in patients with cDAVF compared with patients with sDAVF (4 versus 1). Decreased protein S activity was encountered in 3 patients (2 with sDAVF and 1 with cDAVF). Cardiolipin antibodies were found in 2 patients with cDAVF but in none with sDAVF, whereas only 1 patient with sDAVF had lupus antiphospholipid antibodies. CONCLUSION: In both groups of patients with dural arteriovenous fistulae, genetic thrombophilic abnormalities occurred in a higher percentage than in the general population. The differences of the genetic abnormalities may be involved in different pathophysiological mechanism(s) in the development of these distinct neurovascular entities.

The cranial bone window model: studying angiogenesis of primary and secondary bone tumors by intravital microscopy

The successful treatment of primary and secondary bone tumors in a huge number of cases remains one of the major unsolved challenges in modern medicine. Malignant primary bone tumor growth predominantly occurs in younger people, whereas older people predominantly suffer from secondary bone tumors since up to 85% of the most frequently occurring malignant solid tumors, such as lung, mammary, and prostate carcinomas, metastasize into the bone. It is well known that a tumor's course may be altered by its surrounding tissue. For this reason, reported here is the protocol for the surgical preparation of a cranial bone window in mice as well as the method to implant tumors in this bone window for further investigations of angiogenesis and other microcirculatory parameters in orthotopically growing primary or secondary bone tumors using intravital microscopy. Intravital microscopy represents an internationally accepted and sophisticated experimental method to study angiogenesis, microcirculation, and many other parameters in a wide variety of neoplastic and nonneoplastic tissues. Since most physiologic and pathophysiologic processes are active and dynamic events, one of the major strengths of chronic animal models using intravital microscopy is the possibility of monitoring the regions of interest in vivo continuously up to several weeks with high spatial and temporal resolution. In addition, after the termination of experiments, tissue samples can be excised easily and further examined by various in vitro methods such as histology, immunohistochemistry, and molecular biology.

Atraumatic splenic rupture in amyloidosis

BACKGROUND: Splenic involvement in amyloidosis is rather frequent (5-10%). An atraumatic rupture of the affected spleen is however an extremely rare event. We report on a patient with undiagnosed amyloidosis who underwent emergency splenectomy for atraumatic splenic rupture. METHODS: Review of the literature and identification of 31 patients, including our own case report, with atraumatic splenic rupture in amyloidosis. Analysis of the clinical presentation, the surgical management, the nomenclature and definition of predisposing factors of splenic rupture. RESULTS: We identified 15 women and 16 men (mean age 53.3 +/- 12.4 years; median 52, range: 27-82 years) with an atraumatic splenic rupture. Easy skin bruisability and factor X deficiency were detected in four (13%) and five patients (16%), respectively. The diagnosis of splenic rupture was made either by computed tomography (n = 12), ultrasound (n = 5), exploratory laparotomy (n = 9) or autopsy (n = 4). All patients underwent surgery (n = 27) or autopsy (n = 4). Amyloidosis was previously diagnosed in nine patients (29%). In the remaining 22 patients (71%), the atraumatic splenic rupture represented the initial manifestation of amyloidosis. Twenty-five patients (81%) suffered from primary (AL) and four patients (13%) from secondary amyloidosis (AA). In two patients, the type of amyloidosis was not specified. A moderate splenomegaly was a common feature (68%) and the characteristic intraoperative finding was an extended subcapsular hematoma with a limited parenchymal laceration (65%). In five patients with known amyloidosis, the atraumatic splenic rupture was closely associated with autologous stem-cell transplantation (ASCT) (16%). Three patients were suffering from multiple myeloma (10%). A biopsy-proven amyloidotic liver involvement was present in 14 patients (45%), which lead to atraumatic liver rupture in two patients. The splenic rupture related 30-day mortality was 26% (8/31). CONCLUSIONS: Atraumatic splenic rupture in amyloidosis is associated with a high 30-day mortality. It occurs predominantly in patients with previously undiagnosed amyloidosis. A moderate splenomegaly, coagulation abnormalities (easy skin bruisability, factor X deficiency) and treatment of amyloidosis with ASCT are considered predisposing factors for an atraumatic splenic rupture.

Systematic review of atraumatic splenic rupture

BACKGROUND: Atraumatic splenic rupture (ASR) is an ill defined clinicopathological entity. METHODS: The aim was to characterize aetiological and risk factors for ASR-related mortality in order to aid disease classification and treatment. A systematic literature review (1980-2008) was undertaken and logistic regression analysis employed. RESULTS: Some 632 publications reporting 845 patients were identified. The spleen was normal in 7.0 per cent (atraumatic-idiopathic rupture). One, two or three aetiological factors were found in 84.1, 8.2 and 0.7 per cent respectively (atraumatic-pathological rupture). Six major aetiological groups were defined: neoplastic (30.3 per cent), infectious (27.3 per cent), inflammatory, non-infectious (20.0 per cent), drug- and treatment-related (9.2 per cent) and mechanical (6.8 per cent) disorders, and normal spleen (6.4 per cent). Treatment comprised total splenectomy (84.1 per cent), organ-preserving surgery (1.2 per cent) or conservative measures (14.7 per cent). The ASR-related mortality rate was 12.2 per cent. Splenomegaly (P = 0.040), age above 40 years (P = 0.007) and neoplastic disorders (P = 0.008) were associated with increased ASR-related mortality on multivariable analysis. CONCLUSION: The condition can be classified simply into atraumatic-idiopathic (7.0 per cent) and atraumatic-pathological (93.0 per cent) splenic rupture. Splenomegaly, advanced age and neoplastic disorders are associated with increased ASR-related mortality.

Graft remodeling during growth following anterior cruciate ligament reconstruction in skeletally immature sheep

INTRODUCTION: Ruptures of the anterior cruciate ligament are being diagnosed with increasing frequency in skeletally immature individuals. It was our aim to investigate the graft remodelling process following an autologous, transphyseal reconstruction of the anterior cruciate ligament (ACL) in skeletally immature sheep. We hypothesized that the ligamentisation process in immature sheep is quicker and more complete when compared to adult sheep. MATERIALS AND METHODS: Skeletally immature sheep with an age of 4 months underwent a fully transphyseal ACL reconstruction using an autologous tendon. The animals were subsequently sacrificed at 3, 6, 12 and 24 weeks following surgery. Each group was characterised histomorphometrically, by immunostaining (VEGF, SMA), by transmission electron microscopy (TEM) and biomechanically (UFS Roboter). RESULTS: The histomorphometric analysis and presence of VEGF and SMA positive cells demonstrated a rapid return to a ligament like structure. The biomechanical analysis revealed an anteroposterior translation that was still increased even 6 months following surgery. CONCLUSION: As in adult sheep models, the remodeling of a soft tissue graft used for ACL reconstruction results in a biomechanically inferior substitute. However, the immature tissue seems to remodel faster and more complete when compared to adults.

Right ventricular rupture after lateral thoracotomy for removal of rib-associated telangiectatic osteosarcoma in a dog

OBJECTIVE: To describe a case of a focal right ventricular rupture following removal of a rib-associated telangiectatic osteosarcoma (TOS) in a dog. CASE SUMMARY: A 2-year-old spayed female mixed-breed dog, weighing 20 kg, was presented in compensated hypovolemic shock due to active bleeding into the thoracic cavity. The dog was stabilized with appropriate fluid administration. Subsequent computed tomographic examination revealed a large mineralized mass originating from the body of a rib and displacing the heart. Two days after surgical removal of this mass, focal right ventricular rupture occurred and the dog died. The mass was later identified as a TOS. NEW OR UNIQUE INFORMATION PROVIDED: Although hemothorax secondary to TOS has been described previously, this report describes for the first time, spontaneous focal right ventricular rupture as a rare complication of thoracotomy and rib resection for the removal of a rib-associated, intrathoracic TOS.

The silent loss of neuronavigation accuracy: a systematic retrospective analysis of factors influencing the mismatch of frameless stereotactic systems in cranial neurosurgery

BACKGROUND Neuronavigation has become an intrinsic part of preoperative surgical planning and surgical procedures. However, many surgeons have the impression that accuracy decreases during surgery. OBJECTIVE To quantify the decrease of neuronavigation accuracy and identify possible origins, we performed a retrospective quality-control study. METHODS Between April and July 2011, a neuronavigation system was used in conjunction with a specially prepared head holder in 55 consecutive patients. Two different neuronavigation systems were investigated separately. Coregistration was performed with laser-surface matching, paired-point matching using skin fiducials, anatomic landmarks, or bone screws. The initial target registration error (TRE1) was measured using the nasion as the anatomic landmark. Then, after draping and during surgery, the accuracy was checked at predefined procedural landmark steps (Mayfield measurement point and bone measurement point), and deviations were recorded. RESULTS After initial coregistration, the mean (SD) TRE1 was 2.9 (3.3) mm. The TRE1 was significantly dependent on patient positioning, lesion localization, type of neuroimaging, and coregistration method. The following procedures decreased neuronavigation accuracy: attachment of surgical drapes (DTRE2 = 2.7 [1.7] mm), skin retractor attachment (DTRE3 = 1.2 [1.0] mm), craniotomy (DTRE3 = 1.0 [1.4] mm), and Halo ring installation (DTRE3 = 0.5 [0.5] mm). Surgery duration was a significant factor also; the overall DTRE was 1.3 [1.5] mm after 30 minutes and increased to 4.4 [1.8] mm after 5.5 hours of surgery. CONCLUSION After registration, there is an ongoing loss of neuronavigation accuracy. The major factors were draping, attachment of skin retractors, and duration of surgery. Surgeons should be aware of this silent loss of accuracy when using neuronavigation.