Introduction: In large-animal acute myocardial infarction (AMI) models, Wharton’s jelly (umbilical cord matrix) mesenchymal stem cells (WJMSCs) effectively promote angiogenesis and drive functional myocardial regeneration. Human data are lacking. Aim: To evaluate the feasibility and...
Background For transcoronary progenitor cells’ administration, injections under flow arrest (over-the-wire balloon technique, OTW) are used universally despite lack of evidence for being required for cell delivery or being effective in stimulating myocardial engraftment. Flow-mediated endothelial rolling is mandatory for subsequent cell adhesion and extravasation. Methods To optimize cell directing toward the coronary endothelium under maintained flow, the authors developed a cell-delivery side-holed perfusion catheter (PC). Thirty-four patients (36-69 years, 30 men) with primary stent-assisted angioplasty-treated anterior MI (peak TnI 151 [53-356]ng/dL, mean[range]) were randomly assigned to OTW or PC autologous 99Tc-extametazime-labeled bone marrow CD34+ cells (4.34 [0.92-7.54] × 106) administration at 6-14 days after pPCI (LVEF 37.1 [24-44]%). Myocardial perfusion (99mTc-MIBI) and labeled cells’ activity were evaluated (SPECT) at, respectively, 36-48 h prior to and 60 min after delivery. Results In contrast to OTW coronary occlusions, no intolerance or ventricular arrhythmia occurred with PC cells’ administration (P < .001). One hour after delivery, 4.86 [1.7-7.6]% and 5.05 [2.2-9.9]% activity was detected in the myocardium (OTW and PC, respectively, P = .84). Labeled cell activity was clearly limited to the (viable) peri-infarct zone in 88% patients, indicating that the infarct core zone may be largely inaccessible to transcoronary-administered cells. Conclusions Irrespective of the transcoronary delivery method, only ≈5% of native (i.e., non-engineered) CD34+ cells spontaneously home to the injured myocardium, and cell retention occurs preferentially in the viable peri-infarct zone. Although the efficacy of cell delivery is not increased with the perfusion method, by avoiding provoking ischemic episodes PC offers a rational alternative to the OTW delivery.
26 January 2013 in Medical Principles and Practice
Positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (FDG) has proven to be a valuable diagnostic modality in various diseases. Its accuracy has been improved with the hybrid PET/computed tomography (CT) technique because of precise anatomic location of areas of abnormal FDG accumulation. This integrated PET/CT modality has been widely adopted, particularly in oncology. This paper reviews the role of FDG-PET/CT imaging in breast cancer, non-small-cell lung cancer, colorectal cancer, head and neck cancer as well as lymphoma on the basis of recent key articles. Special attention is paid to preoperative diagnostic workup, evaluation of treatment response and survival prognosis. Experience from specialized centers indicates that there is strong evidence for the clinical effectiveness of FDG-PET/CT in staging, restaging and the prediction of response to therapy in the above-mentioned malignancies. It is concluded that this imaging modality contributes considerably to improved patient management and paves the way to personalize cancer treatment in a cost-effective way.
Rationale : New therapies for refractory angina are needed. Objective : Assessment of transendocardial delivery of bone marrow CD133 + cells in patients with refractory angina. Methods and Results : Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II–IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P =0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P =0.32; absolute changes of summed difference score: −1.38 [5.2] versus −0.73 [1.9], P =0.65; and total perfusion deficit: −1.33 [3.3] versus −2.19 [6.6], P =0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: −4.3 [11.3] versus 7.4 [11.8], P =0.02; end-diastolic volume: −9.1 [14.9] versus 7.4 [15.8], P =0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P =0.68), 4 (50% versus 33.3%; P =0.63), 6 (70% versus 50.0%; P =0.42), and 12 months (55.6% versus 81.8%; P =0.33) and use of nitrates after 12 months. Conclusion : Transendocardial CD133 + cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. Clinical Trial Registration : URL: http://www.clinicaltrials.gov . Unique identifier: NCT01660581.