The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?

Mesenchymal stromal cells (MSC) have emerged as promising cell therapies for multiple conditions based on demonstrations of their potent immunomodulatory and regenerative capacities in models of inflammatory disease. Understanding the effects of MSC on T cells has dominated the majority of work carried out in this field to date; recently, however, a number of studies have shown that the therapeutic effect of MSC requires the presence of macrophages. It is timely to review the mechanisms and manner by which MSC modulate macrophage populations in order to design more effective MSC therapies and clinical studies. A complex cross-talk exists through which MSC and macrophages communicate, a communication that is not controlled exclusively by MSC. Here, we examine the evidence that suggests that MSC not only respond to inflammatory macrophages and adjust their secretome accordingly, but also that macrophages respond to encounters with MSC, creating a feedback loop which contributes to the immune regulation observed following MSC therapy. Future studies examining the effects of MSC on macrophages should consider the antagonistic role that macrophages play in this exchange.

Three-dimensional magnetic resonance imaging analysis of hip morphology in the assessment of femoral acetabular impingement.

AIM: To determine a possible association between femoral-acetabular impingement (FAI) volume and the development of labral tear using a three-dimensional (3D) model reconstruction of the acetabulum and the femoral head. MATERIALS AND METHODS: Magnetic resonance arthrography images of the hip in 42 patients with pain and suspected labral tear were acquired using a 1.5T MRI machine. Using 3D analysis software, outlines of the acetabular cup and femoral head were drawn and 3D reconstruction obtained. To control for differences in patient size, ratios of acetabulum : femoral head volume (AFV) and acetabulum : femoral head surface area (AFA) were used for analysis. The association between volume of acetabulum : femoral head and FAI was investigated using ANOVA analysis. RESULTS: There were 19 men and 23 women with a mean age of 39 years (range 18-78 years). The average AFV was 0.64 (range 0.37-1.05, SD 0.16) and AFA was 0.73 (range 0.36-1.26, SD 0.23). Herniation pit was significantly associated with a small AFV. CONCLUSION: Femoral neck herniation pits are associated with a low AFV. Gross volume and surface area ratios do not appear to correlate with labral tears or cartilage loss. This technique will enable more advanced analysis of morphological variations associated with FAI.

Evaluation of optimised 3D turbo spin echo and gradient echo MR pulse sequences of the knee at 3T and 1.5T.

INTRODUCTION: To investigate the impact of parameter optimisation for novel three-dimensional 3D sequences at 1.5T and 3T on resultant image quality. METHODS: Following institutional review board approval and acquisition of informed consent, MR phantom and knee joint imaging on healthy volunteers (n = 16) was performed with 1.5 and 3T MRI scanners, respectively incorporating 8- and 15-channel phased array knee radiofrequency coils. The MR phantom and healthy volunteers were prospectively scanned over a six-week period. Acquired sequences included standard two-dimensional (2D) turbo spin echo (TSE) and novel three-dimensional (3D) TSE PDW (SPACE) both with and without fat-suppression, and T2∗W gradient echo (TrueFISP) sequences. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured for knee anatomical structures. Two musculoskeletal radiologists evaluated anatomical structure visualisation and image quality. Quantitative and qualitative findings were investigated for differences using Friedman tests. Inter- and intra-observer agreements were determined with κ statistics. RESULTS: Phantom and healthy volunteer images revealed higher SNR for sequences acquired at 3T (p-value <0.05). Generally, the qualitative findings ranked images acquired at 3T higher than corresponding images acquired at 1.5T (p < 0.05). 3D image data sets demonstrated less sensitivity to partial volume averaging artefact (PVA) compared to 2D sequences. Inter- and intra-observer agreements for evaluation across all sequences ranged from 0.61 to 0.79 and 0.71 to 0.92, respectively. CONCLUSION: Both 2D and 3D images demonstrated higher image quality at 3T than at 1.5T. Optimised 3D sequences performed better than the standard 2D PDW TSE sequence for contrast resolution between cartilage and joint fluid, with reduced PVA artefact. IMPLICATIONS FOR PRACTICE: With rapid advances in MRI scanner technology, including hardware and software, the optimisation of 3D MR pulse sequences to reduce scan time while maintaining image quality, will improve diagnostic accuracy and patient management in musculoskeletal MRI.

Comminuted fracture of the thoracic spine.

BACKGROUND: Road deaths fell initially after the introduction of the penalty points but despite this, the rate of spinal injuries remained unchanged. AIMS: We report a patient with a dramatic spinal injury, though without neurological deficit. We discuss the classification, management and economic impact of these injuries. METHODS: We describe the management of a patient with a comminuted thoracic spinal fracture without neurological injury. We conducted a literature review with regard to the availability of literature of the management of these injuries. RESULTS: This 17-year-old female was managed surgically and had a good functional outcome. There is no clear consensus in the published literature on the management of these injuries. CONCLUSIONS: Comminuted thoracic spinal factures are potentially devastating. Such a patient presents challenges in determining the appropriate treatment.

Pseudoaneurysm of the occipital artery: an unusual cause of persisting headache after minor head injury.

Post-traumatic pseudoaneurysms of the extracranial arteries in the scalp are uncommon sequelae of head injury. We report on a patient who presented four weeks after a minor head injury with a tender, pulsating and enlarging mass in the course of the left occipital artery. There was associated headache radiating to the vertex. Computed tomographic angiography confirmed the lesion to be a pseudoaneurysm of the occipital artery. The lump was resected with complete resolution of symptoms.

Actinomyces and an unidentified ameba associated with an intrauterine device.

PIP: A case report is presented of an asymptomatic 29-year-old Hawaiian patient with an IUD who had Actinomyces and an unidentified ameba in a Papanicolaou smear and in whom both organisms disappeared upon removal of the IUD. The patient presented for a routine pelvic examination as part of an employment physical. She denied any significant gastrointestinal or vaginal symptoms as well as any history of foreign travel. The patient reported that she had worn the same IUD for 9 years and that it had caused her no discomfort. A pelvic examination revealed a friable, papular cervix. The Papanicolaou smear revealed the presence of both amebae and colonies of Actinomyces. The findings were confirmed by the Armed Forces Institute of Pathology, which reported an intense, acute and chronic inflammatory reaction marked by the presence of amebae and Actinomyces species colonies. The patient returned 4 months later for a repeat pelvic examination and removal of her IUD. At that time a cervical smear showed only amebae. The patient was seen again 3 months following the IUD removal. She reported that her vaginal discharge had decreased. A repeat Papanicolaou smear was completely normal. Faulkner and Ory have reported a 5-fold increase of pelvic inflammatory disease among IUD users compared to nonusers. Among pelvic infections found to be associated with IUD users is genital actinomycosis. Many of these patients are asymptomatic with only cytologic evidence of Actinomyces, but these patients can progress to pelvic inflammation and abscess formation. Reports have recently described the presence of amebic trophozoites in IUD users. The main purpose in reporting this case is to alert the tropical medicine specialist to this entity. Amebic colonization appears to respond completely to IUD removal, and there is no need for additional medical or surgical treatment.^ieng