The epidemiology of Clostridium difficile infection in patients with cancer

Introduction: Clostridium difficile infection (CDI) is a significant cause of healthcare-associated diarrhoea, and the emergence of endemic strains resulting in poorer outcomes is recognised worldwide. Patients with cancer are a specific high-risk group for development of infection.

Areas covered: In this review, modifiable and non-modifiable risk factors for CDI in adult patients with haematological malignancy or solid tumours are evaluated. In particular, the contribution of antimicrobial exposure, hospitalisation and gastric acid suppression to risk of CDI are discussed. Recent advances in CDI treatment are outlined, namely faecal microbiota transplantation and fidaxomicin therapy for severe/refractory infection in cancer populations. Outcomes of CDI, including mortality are presented, together with the need for valid severity rating tools customised for cancer populations.

Expert commentary: Future areas for research include the prognostic value of C. difficile colonisation in cancer patients and the potential impact of dedicated antimicrobial stewardship programs in reducing the burden of CDI in cancer units.     

Arterial concentration of 99mTc-sestamibi at rest, during peak exercise and after dipyridamole infusion

Tracers for myocardial perfusion imaging during stress should not only have high cardiac uptake but they should also have a fast blood clearance to prevent myocardial tracer uptake after the ischaemic stimulus. The present study characterize the early phase of the arterial (99m)Tc-sestamibi (MIBI) time-activity curve after venous bolus injection at rest, during peak exercise and after dipyridamole infusion. We included 11 patients undergoing angioplasty for one-vessel disease (rest study) and 20 patients evaluated for the detection of haemodynamic significant coronary stenoses by (99m)Tc-sestamibi single photon emission computed tomography (SPECT) using either bicycle exercise testing (10 patients) or standard dipyridamole testing (10 patients). Arterial blood samples of 1 ml were taken from the left femoral artery (rest study) or the right radial artery (exercise and dipyridamole studies) every 5 s during the first 5 min postinjection. In the exercise and the dipyridamole studies blood sampling were extended to include blood samples every 5 min 5-30 min postinjection. Peak MIBI concentration was lower and decrease in concentration slower after tracer injection during exercise than during dipyridamole stress testing. This may cause an underestimation of perfusion defects during exercise because of MIBI uptake after the ischaemic stimulus. The implications of the study not only refer to the choice of stress modality when using MIBI. This study also underlines the importance of considering early blood clearance in addition to regional myocardial tracerkinetic aspects such as myocardial extraction fraction when new tracers are introduced.     

Cardiac CT for Guiding Mitral Valve Interventions

Purpose of Review

The purpose of this paper is to review the current role of contrast-enhanced cardiac computed tomography (CT) in the peri-procedural planning of mitral valve (MV) repair.

Recent Findings

Cardiac CT is increasingly implemented in the peri-interventional management of patients undergoing MV repair or MV replacement due to its widespread availability and its ability to provide detailed information on the complex cardiac and valvular anatomy.

Summary

The complex anatomy of the MV challenges the management of minimally invasive MV repair with respect to device sizing and procedural planning. Advances in CT have enabled cardiac CT to provide critical information for the pre-procedural planning and post-procedural follow-up of MV repair. Therefore, it represents a key element in the improvement of the post-procedural outcome, the efficiency of implanted devices, and the prevention as well as advanced diagnostics of post-procedural complications. However, particular expertise is required to select adequate imaging protocols, perform comprehensive post-processing features, and to achieve specific quantitative image evaluation.

     

Cardiopulmonary resuscitation-associated major liver injury

AIM: To evaluate the frequency, presentation, treatment and outcome of cardiopulmonary resuscitation-associated major liver injury in patients after non-traumatic in- or out-of-hospital cardiac arrest. MATERIALS AND METHODS: Retrospective analysis of a cardiac arrest registry in a tertiary care hospital emergency department. We reviewed patients charts, laboratory data, diagnostic imaging studies and autoptic findings. RESULTS: Within 14.5 years, major liver injury (rupture/laceration, haemorrhage/haematoma) was found in 15 of 2558 cardiac arrest victims (0.6%). Eleven were male (73%), median age was 58 (IQR 53-67). In seven, resuscitation was started out-of-hospital. In 9 of the 15 patients, liver injury was correctly diagnosed intra vitam. In 5, haematocrit level was low on admission, in 8 haematocrit dropped significantly during observation; haemostasis was compromised in 13 patients, 4 of them receiving thrombolytic therapy. Bedside abdominal sonography showed free intra-peritoneal fluid in 8 of 9 cases examined. In 11 patients, we found liver rupture/laceration, in 4 liver haemorrhage/haematoma. The site of injury was the left liver lobe in 11, six underwent emergent surgery. Two of 15 patients survived to 6 months in good neurological condition, 1 after emergency surgery. No patient died from bleeding due to liver injury. CONCLUSION: Our single centre observation confirms that resuscitation-associated major liver injury is infrequent and shows that most patients had compromised haemostasis. Low or dropping haematocrit should trigger suspicion. Bedside sonography reveals intra-peritoneal fluid or liver injury. A conservative therapeutic approach or emergency surgery may be warranted. Major liver injury alone scarcely appears to influence overall outcome.     

CCR6, a CC Chemokine Receptor that Interacts with Macrophage Inflammatory Protein 3α and Is Highly Expressed in Human Dendritic Cells

Dendritic cells initiate immune responses by ferrying antigen from the tissues to the lymphoid organs for presentation to lymphocytes. Little is known about the molecular mechanisms underlying this migratory behavior. We have identified a chemokine receptor which appears to be selectively expressed in human dendritic cells derived from CD34⁺ cord blood precursors, but not in dendritic cells derived from peripheral blood monocytes. When stably expressed as a recombinant protein in a variety of host cell backgrounds, the receptor shows a strong interaction with only one chemokine among 25 tested: the recently reported CC chemokine macrophage inflammatory protein 3α. Thus, we have designated this receptor as the CC chemokine receptor 6. The cloning and characterization of a dendritic cell CC chemokine receptor suggests a role for chemokines in the control of the migration of dendritic cells and the regulation of dendritic cell function in immunity and infection.     

A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells.

The transduction of primary T cells to express chimeric T cell receptors (cTCR) for redirected targeting of tumor cells is an attractive strategy for generating tumor-specific T cells for adoptive therapy. However, tumor cells rarely provide costimulatory signals and hence cTCRs that transmit just a CD3zeta signal can only initiate target cell killing and interferon-gamma release and fail to induce full activation. Although incorporation of a CD28 component results in IL-2 release and limited proliferation, T cell activation remains incomplete. OX40 transmits a potent and prolonged T cell activation signal and is crucial for maintaining an immunological response. We hypothesize that the CD28-OX40-CD3zeta tripartite cytoplasmic domain will provide a full complement of activation, proliferation, and survival signals for enhanced anti-tumor activity.