Key Points• WT1 mRNA-electroporated DCs can prevent or delay relapse in 43% of patients with AML in remission after chemotherapy.• OS compares favorably with the new survival data from the Swedish Acute Leukemia Registry and correlates with molecular and WT1-specific CD8 1 T-cell responses.Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P 5 .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age £65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD8 1 T cells. Long-term OS was correlated with interferon-g 1 and tumor necrosis factor-a 1 WT1-specific responses in delayed-type hypersensitivity-infiltrating CD8 1 T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD8 1 T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224. (Blood. 2017;130(15):1713-1721

Transmission of ColE1/pMB1-derived plasmids, such as pBR322, from Escherichia coli donor strains was shown to be an efficient way to introduce these plasmids into Agro- Warren et al. (1978) showed that the CoEl-encoded mob gene products are involved and that one or more of these mob gene products recognize a special ColE 1 sequence called the bom site. Transfer is then initiated from the origin of transfer at or near the bom site. This system of plasmid mobilization has evolved in several colicin-producing plasmids. Mob and bom are specific within plasmid families, so that, for example, mob and bom of ColE1 and its natural analogue, pMB1, are interchangeable. pBR322 has the pMB1 bom site and can, therefore, be transmitted when the ColE1 mob functions are provided in trans (Finnegan and Sherratt, 1982). Here we report that the ColE1 -type mobilization is extendable to other unrelated Gram-negative bacteria, such as A. tumefaciens.A method for site-specific mutagenesis of Ti plasmids was developed, taking advantage of the efficient transmission from E. coli to A. tumefaciens of pBR322 clones containing mutant pTiC58 fragments, and of the fact that these pBR322 clones cannot replicate in A. tumefaciens. Stable exconjugants to Agrobacterium are therefore only obtained if transfer is followed by co-integration of the mutant clone and acceptor Ti plasmid. Full exchange of mutant and target Ti fragment, resulting from a second recombination, is obtained by screening for the appropriate combination of selectable markers.

This article discusses the range of manifestations of tuberculosis (TB) of the abdomen, including involvement of the gastrointestinal tract, the peritoneum, mesentery, omentum, abdominal lymph nodes, solid abdominal organs, the genital system and the abdominal aorta. Abdominal TB is a diagnostic challenge, particularly when pulmonary TB is absent. It may mimic many other abdominal diseases, both clinically and radiologically. An early correct diagnosis, however, is important in order to ensure proper treatment and a favorable outcome. Modern imaging is a cornerstone in the early diagnosis of abdominal TB and may prevent unnecessary morbidity and mortality. Generally, CT appears to be the imaging modality of choice in the detection and assessment of abdominal tuberculosis, other than gastrointestinal TB. Barium studies remain superior for demonstrating mucosal intestinal lesions. Ultrasound may be used for follow-up to monitor therapy response. The diagnosis of abdominal TB should be considered if suggestive imaging findings are found in patients with a high index of suspicion.

Accurate radiographic diagnosis is a cornerstone of the clinical management and outcome prediction of the head-injured patient. New technological advances, such as multi-detector computed tomography (MDCT) scanning and diffusion-weighted magnetic resonance imaging (MRI) have influenced imaging strategy. In this article we review the impact of these developments on the neuroradiological diagnosis of acute head injury. In the acute phase, multi-detector CT has supplanted plain X-ray films of the skull as the initial imaging study of choice. MRI, including fluid-attenuated inversion recovery, gradient echo T2* and diffusion-weighted sequences, is useful in determining the severity of acute brain tissue injury and may help to predict outcome. The role of MRI in showing diffuse axonal injuries is emphasized. We review the different patterns of primary and secondary extra-axial and intra-axial traumatic brain lesions and integrate new insights. Assessment of intracranial hypertension and cerebral herniation are of major clinical importance in patient management. We discuss the issue of pediatric brain trauma and stress the importance of MRI in non-accidental injury. In summary, new developments in imaging technology have advanced our understanding of the pathophysiology of brain trauma and contribute to improving the survival of patients with craniocerebral injuries.

Evaluation of the intracranial circulation provides valuable information in the diagnosis and prognosis of various intracranial abnormalities and may influence patient management. Technical advances in magnetic resonance angiography (MRA) have improved the accuracy of this technique in various clinical situations, such as aneurysms, arterial and venous steno-occlusive diseases, vascular malformations, inflammatory arterial diseases, preoperative assessment of the patency of dural sinuses, and congenital vascular abnormalities. In many centers, MRA has replaced conventional digital subtraction angiography in screening for intracranial vascular disease, because of its non-invasive and non-ionizing character. Several MRA techniques have been developed for the imaging of the intracranial vascular system, such as time-of-flight MRA (TOF MRA), phase-contrast MRA (PC MRA), and more recently contrast-enhanced MRA (CE MRA). In the evaluation of steno-occlusive disease, the three-dimensional (3D) TOF-MRA technique is recommended for arterial evaluation, and the 2D TOF or 2D PC-MRA technique for venous evaluation. For the evaluation of aneurysms and arteriovenous malformations (AVMs), we recommend the 3D CE-MRA technique, especially dynamic sequences in case of AVM. In this review, the technical aspects, limitations, and optimization of these MRA techniques will be discussed together with their indications in intracranial disease.

No abstract

Because it may cause paralysis, injury to the spine is one of the most feared traumas, and spinal cord injury is a major cause of disability. In the USA approximately 10,000 traumatic cervical spine fractures and 4000 traumatic thoracolumbar fractures are diagnosed each year. Although the number of individuals sustaining paralysis is far less than those with moderate or severe brain injury, the socioeconomic costs are significant. Since most of the spinal trauma patients survive their injuries, almost one out of 1000 inhabitants in the USA are currently being cared for partial or complete paralysis. Little controversy exists regarding the need for accurate and emergent imaging assessment of the traumatized spine in order to evaluate spinal stability and integrity of neural elements. Because clinicians fear missing occult spine injuries, they obtain radiographs for nearly all patients who present with blunt trauma. We are influenced on one side by fear of litigation and the possible devastating medical, psychologic and financial consequences of cervical spine injury, and on the other side by pressure to reduce health care costs. A set of clinical and/or anamnestic criteria, however, can be very useful in identifying patients who have an extremely low probability of injury and who consequently have no need for imaging studies. Multidetector (or multislice) computed tomography (MDCT) is the preferred primary imaging modality in blunt spinal trauma patients who do need imaging. Not only is CT more accurate in diagnosing spinal injury, it also reduces imaging time and patient manipulation. Evidence-based research has established that MDCT improves patient outcome and saves money in comparison to plain film. This review discusses the use, advantages and disadvantages of the different imaging techniques used in spinal trauma patients and the criteria used in selecting patients who do not need imaging. Finally an overview of different types of spinal injuries is given.

No abstract