Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony-stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells ...(MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man.
Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89+/-35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17+/-2.93 MNCCD34+/microL at baseline and 64.55+/-37.11 MNCCD34+/microL on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29+/-0.22 and 0.99+/-0.32 mm versus 0.49+/-0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 microg.kg(-1).min(-1)), wall motion score index showed improvement from 1.66+/-0.23 to 1.41+/-0.21 (P<0.004 versus control) and to 1.35+/-0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24+/-0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41+/-0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55+/-5 mm (P<0.002 versus control), and ejection fraction to 54+/-8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control).
G-CSF and mobilization of MNC(CD34+) after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.
Implantation of bone-marrow stem cells in the heart might be a new method to restore tissue viability after myocardial infarction. We injected up to 1.5×10
6 autologous AC133+ bone-marrow cells into ...the infarct border zone in six patients who had had a myocardial infarction and undergone coronary artery bypass grafting. 3–9 months after surgery, all patients were alive and well, global left-ventricular function was enhanced in four patients, and infarct tissue perfusion had improved strikingly in five patients. We believe that implantation of AC133+ stem cells to the heart is safe and might induce angiogenesis, thus improving perfusion of the infarcted myocardium.
These guidelines update the previous EANM 2009 guidelines on the diagnosis of pulmonary embolism (PE). Relevant new aspects are related to (a) quantification of PE and other ventilation/perfusion ...defects; (b) follow-up of patients with PE; (c) chronic PE; and (d) description of additional pulmonary physiological changes leading to diagnoses of left ventricular heart failure (HF), chronic obstructive pulmonary disease (COPD) and pneumonia. The diagnosis of PE should be reported when a mismatch of one segment or two subsegments is found. For ventilation, Technegas or krypton gas is preferred over diethylene triamine pentaacetic acid (DTPA) in patients with COPD. Tomographic imaging with V/P
SPECT
has higher sensitivity and specificity for PE compared with planar imaging. Absence of contraindications makes V/P
SPECT
an essential method for the diagnosis of PE. When V/P
SPECT
is combined with a low-dose CT, the specificity of the test can be further improved, especially in patients with other lung diseases. Pitfalls in V/P
SPECT
interpretation are discussed. In conclusion, V/P
SPECT
is strongly recommended as it accurately establishes the diagnosis of PE even in the presence of diseases like COPD, HF and pneumonia and has no contraindications.
Diagnosis of pulmonary embolism using V/P-SPECT may include the application of advanced image-processing techniques to identify V/P-mismatches. Aim of this study was to evaluate the benefit in ...clinical decision making in the diagnosis of pulmonary embolism.by whether adding to conventional reading a software that automatically calculates and visualizes the ventilation/perfusion-quotient pixel by pixel.
63 consecutive patients with a clinical suspicion of PE who underwent V/P-SPECT were included in this retrospective study. Images were randomly ordered both for standard as well as for software-assisted reading using V/P-quotients. Studies were read independently by 2 experienced and 2 inexperienced raters. Diagnostic performance and observer agreement of all readers and both reading methods were determined.
Expert observers consistently achieved a high diagnostic accuracy both in conventional as well as in software-assisted reporting (sensitivity: 0.94 vs. 0.94, specificity: 0.96 vs. 0.97, LR
: 17.32 vs. 28.86, LR
stayed constant at 0.06). For inexperienced readers, diagnostic performance improved: sensitivity raised from 0.74 to 0.85 and specificity from 0.86 to 0.95, LR
raised from 5.20 to 15.69, LR
decreased from 0.31 to 0.16. Inter-rater reliability (Fleiss' κ) improved from 0.63 to 0.86 by using V/P quotient.
Benefit from a software-tool that calculates V/P-ratio automatically is only small when used by experienced physicians If inexperienced readers use the software, the diagnostic accuracy increases. Images generated by automated calculation of V/P-mismatches are easy to read and their use might help to standardize and objectify interpretation of V/P-SPECT in the diagnosis of PE.
Peptide receptor radionuclide therapy is an effective treatment option for patients with well-differentiated somatostatin receptor-expressing neuroendocrine tumors. However, published data result ...mainly from retrospective monocentric studies. We initiated a multi-institutional, prospective, board-reviewed registry for patients treated with peptide receptor radionuclide therapy in Germany in 2009. In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297) and small intestine (80/297), whereas 56 were of unknown primary. Most tumors were well differentiated with median Ki67 proliferation rate of 5% (range 0.9-70%). Peptide receptor radionuclide therapy was performed using mainly yttrium-90 and/or lutetium-177 as radionuclides in 1-8 cycles. Mean overall survival was estimated at 213 months with follow-up between 1 and 230 months after initial diagnosis, and 87 months with follow-up between 1 and 92 months after start of peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with proliferation rate below 20%. Our results indicate that peptide receptor radionuclide therapy is an effective treatment for well- and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded as one of the primary treatment options for patients with somatostatin receptor-expressing neuroendocrine tumors.
The present study analyzes the improvement of the outcome of radioidine therapy in non-immunogenic hyperthyroidism by adapting the target dose to the 99mTc-pertechnetate thyroid uptake under ...suppression (TcTUs) prior to radioiodine therapy. The TcTUs is a substitute for the non-suppressible iodine turnover. The 89 patients presented with a basal thyrotropin level of < 0.1 mU/l, normal values for free triiodothyronine and thyroxine and with multifocal or disseminated thyroid autonomy. These terms describe the scintigraphic distribution pattern of autonomous iodine turnover. Thirty-two patients had a TcTUs between 1.6 and 3.2% (group A) and 57 had a TcTUs > 3.2% (group B). Fifty-five patients (three of group A and 52 of group B) were treated previously for overt hyperthyroidism with antithyroid drugs. Target doses of 150 and 200 Gy were used in both groups and 300 Gy in group B only. Six months after radioiodine therapy, a basal TSH level of > or = 0.5 mU/l as criterion of therapy success was observed in 94% of group A and in 54% of group B. Further differentiation of group B shows an increasing success rate with the target dose used: 45% after 150 Gy, 50% after 200 Gy and 90% after 300 Gy. In patients with a basal TSH level of < 0.5 mU/l after radioiodine therapy, the TcTUs was evaluated again.
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