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1.  Recombinant Human Activated Protein C in the Treatment of Acute Respiratory Distress Syndrome: A Randomized Clinical Trial 
PLoS ONE  2014;9(3):e90983.
Rationale
Pulmonary coagulopathy may play a pathogenetic role in acute respiratory distress syndrome (ARDS), by contributing to alveolocapillary inflammation and increased permeability. Recombinant human activated protein C (rh-APC) may inhibit this process and thereby improve patient outcome.
Methods
A prospective randomized, saline-controlled, single-blinded clinical trial was performed in the intensive care units of two university hospitals, and patients with ARDS were included within 24 h after meeting inclusion criteria.
Intervention
A 4-day course of intravenous rh-APC (24 mcg/kg/h) (n = 33) versus saline (n = 38).
Outcomes
The primary outcome parameter was the pulmonary leak index (PLI) of 67Gallium-transferrin as a measure of alveolocapillary permeability and secondary outcomes were disease severity scores and ventilator-free days, among others.
Results
Baseline characteristics were similar; in 87% of patients the PLI was above normal and in 90% mechanical or non-invasive ventilation was instituted at a median lung injury score of 2.5. There was no evidence that Rh-APC treatment affected the PLI or attenuated lung injury and sequential organ failure assessment scores. Mean ventilator-free days amounted to 14 (rh-APC) and 12 days (saline, P = 0.35). 28-day mortality was 6% in rh-APC- and 18% in saline-treated patients (P = 0.12). There was no difference in bleeding events. The study was prematurely discontinued because rh-APC was withdrawn from the market.
Conclusion
There is no evidence that treatment with intravenous rh-APC during 4 days for infectious or inflammatory ARDS ameliorates increased alveolocapillary permeability or the clinical course of ARDS patients. We cannot exclude underpowering.
Trial Registration
Nederlands Trial Register ISRCTN 52566874
doi:10.1371/journal.pone.0090983
PMCID: PMC3954619  PMID: 24632673
2.  Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin’s lymphoma using 89Zr-ibritumomab tiuxetan and PET 
Purpose
Positron emission tomography (PET) with 89Zr-ibritumomab tiuxetan can be used to monitor biodistribution of 90Y-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of 90Y-ibritumomab tiuxetan in humans on the basis of 89Zr-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of 90Y-ibritumomab tiuxetan influences biodistribution of 89Zr-ibritumomab tiuxetan and whether pre-therapy scout scans with 89Zr-ibritumomab tiuxetan can be used to predict biodistribution of 90Y-ibritumomab tiuxetan and the dose-limiting organ during therapy.
Methods
Seven patients with relapsed B-cell non-Hodgkin’s lymphoma scheduled for autologous stem cell transplantation underwent PET scans at 1, 72 and 144 h after injection of ~70 MBq 89Zr-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg 90Y-ibritumomab tiuxetan. Volumes of interest were drawn over liver, kidneys, lungs, spleen and tumours. Ibritumomab tiuxetan organ absorbed doses were calculated using OLINDA. Red marrow dosimetry was based on blood samples. Absorbed doses to tumours were calculated using exponential fits to the measured data.
Results
The highest 90Y absorbed dose was observed in liver (3.2 ± 1.8 mGy/MBq) and spleen (2.9 ± 0.7 mGy/MBq) followed by kidneys and lungs. The red marrow dose was 0.52 ± 0.04 mGy/MBq, and the effective dose was 0.87 ± 0.14 mSv/MBq. Tumour absorbed doses ranged from 8.6 to 28.6 mGy/MBq. Correlation between predicted pre-therapy and therapy organ absorbed doses as based on 89Zr-ibritumomab tiuxetan images was high (Pearson correlation coefficient r = 0.97). No significant difference between pre-therapy and therapy tumour absorbed doses was found, but correlation was lower (r = 0.75).
Conclusion
Biodistribution of 89Zr-ibritumomab tiuxetan is not influenced by simultaneous therapy with 90Y-ibritumomab tiuxetan, and 89Zr-ibritumomab tiuxetan scout scans can thus be used to predict biodistribution and dose-limiting organ during therapy. Absorbed doses to spleen were lower than those previously estimated using 111In-ibritumomab tiuxetan. The dose-limiting organ in patients undergoing stem cell transplantation is the liver.
doi:10.1007/s00259-011-2008-5
PMCID: PMC3276758  PMID: 22218876
Immuno-PET; Molecular imaging; Radioimmunotherapy; Ibritumomab tiuxetan; 89Zr; 90Y; Dosimetry; Lymphoma
3.  Observer Variation of 2-Deoxy-2-[F-18]fluoro-d-Glucose-Positron Emission Tomography in Mediastinal Staging of Non-Small Cell Lung Cancer as a Function of Experience, and its Potential Clinical Impact 
Molecular Imaging and Biology  2007;9(5):318-322.
Purpose
To test the extent of variation among nuclear medicine physicians with respect to staging non-small cell lung cancer with positron emission tomography (PET).
Procedures
Two groups of nuclear medicine physicians with different levels of PET experience reviewed 30 PET scans. They were requested to identify and localize suspicious mediastinal lymph nodes (MLN) using standardized algorithms. Results were compared between the two groups, between individuals, and with expert reading.
Results
Overall we found good interobserver agreement (kappa 0.65). Experience with PET translated into a better ability to localize MLN stations (68% vs. 51%, respectively), and experienced readers appeared to be more familiar with translating PET readings into clinically useful statements.
Conclusions
Although our results suggest that clinical experience with PET increases observers’ ability to read and interpret results from PET adequately, there is room for improvement. Experience with PET does not necessarily improve the accuracy of image interpretation.
doi:10.1007/s11307-007-0108-1
PMCID: PMC2039839  PMID: 17610119
FDG-PET scanning; Interobserver variation; Lung cancer; Experience; Mediastinal lymph node metastases
4.  Attenuation-Corrected vs. Nonattenuation-Corrected 2-Deoxy-2-[F-18]fluoro-d-glucose-Positron Emission Tomography in Oncology, A Systematic Review 
Molecular Imaging and Biology  2007;9(3):99-105.
Purpose
To perform a systematic review and meta-analysis to determine the diagnostic accuracy of attenuation-corrected (AC) vs. nonattenuation-corrected (NAC) 2-deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography (FDG-PET) in oncological patients.
Procedures
Following a comprehensive search of the literature, two reviewers independently assessed the methodological quality of eligible studies. The diagnostic value of AC was studied through its sensitivity/specificity compared to histology, and by comparing the relative lesion detection rate reported with NAC-PET vs. AC, for full-ring and dual-head coincidence PET (FR- and DH-PET, respectively).
Results
Twelve studies were included. For FR-PET, the pooled sensitivity/specificity on a patient basis was 64/97% for AC and 62/99% for NAC, respectively. Pooled lesion detection with NAC vs. AC was 98% [95% confidence interval (95% CI): 96–99%, n = 1,012 lesions] for FR-PET, and 88% (95% CI:81–94%, n = 288 lesions) for DH-PET.
Conclusions
Findings suggest similar sensitivity/specificity and lesion detection for NAC vs. AC FR-PET and significantly higher lesion detection for NAC vs. AC DH-PET.
doi:10.1007/s11307-007-0076-5
PMCID: PMC1915656  PMID: 17318671
Deoxyglucose (MeSH); Tomography, X-ray computed (MeSH); Tomography, emission-computed (MeSH); Neoplasms (MeSH); Human (MeSH); Systematic review (MeSH); Attenuation correction; Positron emission tomography

Results 1-4 (4)