Precise control of osteogenesis for craniofacial defect repair: the role of direct osteoprogenitor contact in BMP-2-based bioprinting.

BACKGROUND: Success with bone morphogenetic protein-2 (BMP-2) has been widely reported in the osseous reconstruction of large calvarial defects. These efforts have required enormous doses of BMP-2 and are not sufficiently refined to facilitate the detail-oriented repair required for intricate craniofacial structures. We have previously shown that inkjet-based bioprinting technologies allow for precisely customized low-dose protein patterns to induce spatially regulated osteogenesis. Here, we investigate the importance of direct contact between bioprinted BMP-2 and the dura mater (a source of osteoprogenitors) in mediating calvarial healing. METHODS: Five-millimeter osseous defects were trephinated in mouse parietal bones (N=8). Circular acellular dermal matrix (ADM) implants were prepared such that 1 semicircle of 1 face per implant was printed with BMP-2 bio-ink. These implants were then placed ink-toward (N=3) or ink-away (N=5) from the underlying dura mater. After 4 weeks, osteogenesis was assessed in each of the 4 possible positions (BMP-2-printed area toward dura, BMP-2-printed area away from dura, unprinted area toward dura, and unprinted area away from dura) by faxitron. RESULTS: The BMP-2-printed portion of the ADM generated bone covering an average of 66.5% of its surface area when it was face-down (printed surface directly abutting dura mater). By comparison, the BMP-2-printed portion of the ADM generated bone covering an average of only 21.3% of its surface area when it was face-up (printed surface away from dura). Similarly, the unprinted portion of the ADM generated an average of only 18.6% osseous coverage when face-down and 18.4% when face-up. CONCLUSIONS: We have previously shown that inkjet-based bioprinting has the potential to significantly enhance the role of regenerative therapies in craniofacial surgery. This technology affords the precise control of osteogenesis necessary to reconstruct this region's intricate anatomical architecture. In the present study, we demonstrate that direct apposition of BMP-2-printed ADM to a source of osteoprogenitor cells (in this case dura mater) is necessary for bio-ink-directed osteogenesis to occur. These results have important implications for the design of more complex bioprinted osseous structures.

Complete heart block as a herald sign for cardiac lymphoma.

A previously well 48-year-old man presented with presyncope and was found to be in complete heart block. Blood tests, echocardiography and coronary angiography were reported as normal, and a dual chamber permanent pacemaker was inserted. Six months later he re-presented with breathlessness. His chest X-ray showed cardiomegaly and echocardiography revealed a 4.4 cm pericardial effusion. A CT thorax revealed a mass originating from the intra-atrial septum, extending into the right atrium and ventricle. There were multiple pulmonary lesions suspected to be metastases. Histology demonstrated high-grade B-cell lymphoma. He was treated with eight cycles of R-CHOP chemotherapy and showed good radiological and clinical improvement. Post-treatment echocardiography found severe left ventricular dysfunction with an ejection fraction of <20%. Heart failure medical therapy was optimised and the pacemaker was upgraded to a resynchronisation device. A repeat scan 6 months post device upgrade showed an improvement in ejection fraction to 45%-50%.

A randomized trial of rescue angioplasty versus a conservative approach for failed fibrinolysis in ST-segment elevation myocardial infarction: the Middlesbrough Early Revascularization to Limit INfarction (MERLIN) trial.

OBJECTIVES: We sought to compare emergency coronary angiography with or without rescue percutaneous coronary intervention (PCI) with conservative treatment in patients with failed fibrinolysis complicating ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Most patients with STEMI receive fibrinolytic therapy and aspirin. The management of failed fibrinolysis is unclear. METHODS: A total of 307 patients with STEMI and failed fibrinolysis were randomized to emergency coronary angiography with or without rescue PCI or conservative treatment. RESULTS: Thirty-day all-cause mortality was similar in the rescue and conservative groups (9.8% vs. 11%, p = 0.7, risk difference [RD] 1.2%, 95% confidence interval [CI] -5.8 to 8.3). The composite secondary end point of death/re-infarction/stroke/subsequent revascularization/heart failure occurred less frequently in the rescue group (37.3% vs. 50%, p = 0.02, RD 12.7%, 95% CI 1.6 to 23.5), driven by less subsequent revascularization (6.5% vs. 20.1%, p < 0.01, RD 13.6%, 95% CI 6.2 to 21.4). Re-infarction and clinical heart failure were less common in the rescue group (7.2% vs. 10.4%, p = 0.3, RD 3.2%, 95% CI -3.3 to 9.9; and 24.2% vs. 29.2%, p = 0.3, RD 5.7%, 95% CI -4.3 to 15.6, respectively). Strokes and transfusions were more common in the rescue group (4.6% vs. 0.6%, p = 0.03, RD 3.9%, 95% CI 0.5 to 8.6; and 11.1% vs. 1.3%, p < 0.001, RD 9.8%, 95% CI 4.9 to 19.9, respectively). Left ventricular function at 30 days was the same in the two groups. CONCLUSIONS: Rescue angioplasty did not improve survival by 30 days, but improved event-free survival, almost completely due to a reduction in subsequent revascularization. Rescue angioplasty was associated with more strokes and more transfusions and did not result in preservation of left ventricular systolic function at 30 days.

A randomized prospective trial of ioxaglate 320 (Hexabrix) vs. iodixanol 320 (Visipaque) in patients undergoing percutaneous coronary intervention.

We performed a randomized, prospective, double blind trial comparing the use of the ionic dimer contrast agent ioxaglate 320 (Hexabrix) with the nonionic dimer contrast agent iodixanol 320 (Visipaque) in 618 patients undergoing percutaneous coronary intervention (PCI) for stable or unstable coronary artery syndromes. The aim was to determine whether the different anticoagulant and antiplatelet properties of these two contrast agents resulted in a significant difference in the incidence of a combined endpoint comprising the major complications of PCI. Procedural success rates were marginally higher in the Visipaque group compared to the Hexabrix group, although this did not reach statistical significance (96.7% vs. 93.9%; P = 0.09). There was a borderline statistically significant higher requirement for bailout stenting in the Visipaque group compared to the Hexabrix group (6.8% vs. 3.2%; P = 0.05), although this was not a predefined endpoint. The incidence of the combined primary endpoint of failed catheter laboratory outcome/requirement for bailout stenting/requirement for abciximab/myocardial infarction/death before hospital discharge was higher in the Visipaque group compared to the Hexabrix group (17.9% vs. 14.8%), although this did not reach statistical significance (P = 0.29). When subgroup analysis was performed, the incidence of the combined endpoint in patients with stable coronary artery disease randomized to receive either Visipaque or Hexabrix was identical (13.7%). In patients with an acute coronary syndrome, there was a trend toward a reduced incidence of the combined endpoint in the Hexabrix compared to the Visipaque group, although this did not reach statistical significance (17.2% vs. 24.8%; P = 0.17). More adverse reactions occurred in the Hexabrix group compared to the Visipaque group (8.7% vs. 4.9%; P = 0.06). We conclude that there is no clear advantage with the use of an ionic contrast agent in a large population of patients undergoing PCI for both stable and unstable coronary artery disease. Although the study was underpowered to detect significant differences with the use of either agent when patients with either stable or unstable coronary disease were studied, it is highly unlikely that the ionicity of the contrast agent confers any advantage for patients with stable coronary disease. There remains a possibility that ionic agents do have advantages for patients with unstable coronary artery disease undergoing PCI, although a larger study than ours would be required to confirm or refute this.