A prospective study on the incidence of contrast-associated acute kidney injury after recanalization of chronic total coronary occlusions with contemporary interventional techniques.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a potential risk associated with the percutaneous coronary interventions (PCI) for chronic total coronary occlusions (CTO). This study should evaluate the incidence of CA-AKI in an era of advanced strategies of recanalization techniques and identify modifiable determinants. METHODS: We analysed 1924 consecutive CTO procedures in 1815 patients between 2012 and 2019. All patients were carefully monitored at least up to 48 h after a CTO procedure for changes in renal function. RESULTS: The incidence of CA-AKI was 5.6%, but there was no relation to the technical approach such as frequency of the retrograde technique, intravascular ultrasound or radial access. Procedures with CA-AKI had longer fluoroscopy times (37.6 vs 46.1 min; p = 0.005). The major determinants of CA-AKI were age, presence of diabetes and reduced ejection fraction, as well as chronic kidney disease stage ≥2, serum haemoglobin, and fluoroscopy time. Contrast volume or contrast volume/GFR ratio were not independent determinants of CA-AKI. Periprocedural perforations were more frequent in CA-AKI patients (11.3 vs 2.3%; p < 0.001), and in-hospital mortality was higher (2.8 vs 0.4%; p < 0.001). CONCLUSIONS: CA-AKI was associated with the risk of in-hospital adverse events. Established patient-related risk factors for CA-AKI (age, diabetes, preexisting chronic kidney disease, low ejection fraction) were confirmed in this study. In addition, the length of the procedure, coronary perforations and low preprocedural serum haemoglobin were risk factors that might be preventable in patients at high risk for CA-AKI.

Immunotherapy of B-cell non-Hodgkin lymphoma by targeting the chemokine receptor CXCR5 in a preclinical mouse model.

Bispecific antibodies are promising agents for immunotherapy. Here, we describe a quadroma-based trifunctional bispecific antibody binding the chemokine receptor CXCR5 and the T-cell antigen CD3 that efficiently prevents tumor growth in a mouse B-cell lymphoma model. CXCR5 regulates the tissue homeostasis of mature B cells and is highly expressed on B-cell non-Hodgkin and lymphocyte-predominant Hodgkin lymphoma, as well as on a subset of CD4(+) T cells known as follicular T-helper cells. In vitro, the bispecific CXCR5::CD3 antibody efficiently recruited effector T cells to CXCR5 expressing B cells and induced a co-stimulation-independent activation of CD8(+) and CD4(+) T cells as demonstrated by the de novo expression of CD25 and CD69, and secretion of the cytokines IFN-γ, TNF-α, IL-6 and IL-10 by peripheral blood mononuclear cells. Notably, at low antibody concentrations, CXCR5::CD3 displayed a significantly higher cytotoxic activity against autologous B cells than its parental antibodies or rituximab. In vivo imaging revealed that CXCR5::CD3 and its parental CXCR5 antibody efficiently prevent tumor growth in a xenograft model of B-cell lymphoma in mice and prolong their survival. Taken together, our results identify CXCR5 as a promising target for antibody-based therapies in the treatment of B-cell malignancies.

Anatomic and flow dynamic considerations for safe right axillary artery cannulation.

OBJECTIVES: Neuroprotection is of paramount interest in cardiac surgery. Right axillary artery cannulation is well established in aortic surgery because it significantly improves survival and outcome, but malperfusion of the right brain after direct cannulation has been reported. Anatomically, 4 vessel segments are potentially amenable for cannulation of the subclavian and axillary arteries. Clinical studies vary widely in dissection sites and cannulation techniques. We investigated critical flow dynamics in the right brain caused by arterial inflow after direct cannulation and specified cannulation positions that provide optimal cerebral perfusion. METHODS: Distances from the lateral margin of the axillary artery and the subclavian artery to the origin of the vertebral artery were measured in 14 human corpses by a flexible ruler. We calculated the hemodynamics within the vertebral artery, depending on different positions of the cannula tip, in a computer-calculated model. RESULTS: The mean distance from the axillary artery to the vertebral artery was 8.5 cm, and the mean distance from the subclavian artery to the vertebral artery was 6.7 cm. Computed flow calculations demonstrated reversed flow in the vertebral artery when the cannula tip was positioned too close to its orifice. To ensure safe supra-aortic flow, a cannula can be inserted securely up to 6.0 cm into the axillary artery and 4.2 cm into the subclavian artery. CONCLUSIONS: Direct cannulation of the right axillary artery can lead to cerebral malperfusion, caused by an obstruction of the vertebral artery's orifice by the arterial cannula or a subclavian steal phenomenon due to flow reversal. The safety of direct axillary artery cannulation can be improved by a well-considered dissecting site and insertion length of the cannula.