Recombinant human activated protein C in the treatment of acute respiratory distress syndrome

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 noninvasive 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 The study was prematurely discontinued because rh-APC was withdrawn from the market.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 Registe

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

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

Measurement of 18F-FDG concentrations in blood samples: Comparison of direct calibration and standard solution methods

Objective: The purpose of this study was to compare the accuracy and reliability of 2 well counter methods for measuring the activity concentration of 18F-FDG in blood samples. Methods: Three to 5 blood samples from 154 patient studies were weighed and measured in a well counter. The 18F-FDG activity concentration was derived using, first, a direct calibration factor to convert measured well counter readings into activity concentration and, second, a comparison of measured counts with those of a specified standard solution. Results: The ratio between the activity concentration results of the 2 methods was 0.996 ± 0.033, indicating that the methods provided equal results. Conclusion: Because the standard solution method is more prone to human error, less reproducible, and more labor intensive, preference should be given to the direct calibration method

Course of impaired left ventricular function after acute myocardial infarction predicted with planar thallium-201 chloride and F18-fluorodeoxyglucose imaging

Planar rest myocardial thallium-201 chloride (201Tl)/F18-fluorodeoxyglucose (FDG) imaging has been shown to distinguish between viable and non-viable tissue. Twenty-five patients (60 ± 9 years) with acute myocardial infarction were studied using this technique within 6 ± 2 days (T1) after infarction and again after 42 ± 4 days (T6). Serial assessment of wall motion with 2D-echocardiography was performed to determine the predictive value of radionuclide indices for the course of impaired regional left ventricular function. No revascularization procedure was performed. Segmental 201Tl and FDG uptake was evaluated using circumferential profiles. Echocardiographic wall motion was scored as normal, hypokinetic or akinetic. Myocardial segments were considered non-viable if a match between 201Tl and FDG uptake was present, which is a concordant reduction in 201Tl and FDG uptake (Group A). Myocardial segments were considered viable if: a mismatch was present between 201Tl and FDG uptake which was defined as a segmental FDG uptake exceeding 201Tl uptake by ≤20% in a segment with reduced 201Tl uptake (Group B); a normal FDG uptake (≤75%) was present without a mismatch pattern in a segment with reduced 201Tl uptake (201Tl < 75% of peak activity) (Group C); a normal 201Tl uptake was present in the area of wall motion abnormality (Group D). Corresponding scintigraphic images obtained at T1 and T6 were compared. Results: 51 segments were normokinetic, 37 were hypokinetic and 26 were akinetic at T1. Of the 63 segments with wall motion abnormalities at T1, 18 regions showed a match (FDG-201Tl < 20%) (Group A). Regional function improved in only one (6%) of these segments. In 19 regions a mismatch was present (FDG-201Tl ≤ 20%) (Group B) of which three (16%) showed spontaneous improvement in function (p = NS vs. matched segments), although recovery varied considerably among patients. Regional function in two segments deteriorated. In 14 regions with reduced 201Tl uptake, DFG uptake was normal (Group C) of which five (36%) were improved after 6 weeks (p < 0.05 vs. match; p = NS vs. mismatched segments). Of the 12 segments with normal 201Tl uptake (Group D), seven (58%) showed improvement in function, whereas five (42%) did not show improvement (p < 0.05 vs. match). In addition, all scintigraphically selected viable segments were grouped (Group B + C + D) and compared with the non-viable segments (Group A). The predictive value of a positive viability test for spontaneous functional improvement was 33%. The predictive value of a negative viability test for lack of functional improvement was 94%. Conclusions: Absence of residual FDG uptake shortly after infarction is associated with irreversible injury, while preservation of metabolic activity identifies segments with variable outcome. Wall motion alone is not a good indicator for the presence of viable tissue. Planar 201Tl/FDG imaging allows early identification of viable but jeopardized tissue and may help select patients who will benefit from aggressive therapy to salvage endangered myocardium

Assessment of ICD eligibility in non-ischaemic cardiomyopathy patients:a position statement by the Task Force of the Dutch Society of Cardiology

International guidelines recommend implantation of an implantable cardioverter-defibrillator (ICD) in non-ischaemic cardiomyopathy (NICM) patients with a left ventricular ejection fraction (LVEF) below 35% despite optimal medical therapy and a life expectancy of more than 1 year with good functional status. We propose refinement of these recommendations in patients with NICM, with careful consideration of additional risk parameters for both arrhythmic and non-arrhythmic death. These additional parameters include late gadolinium enhancement on cardiac magnetic resonance imaging and genetic testing for high-risk genetic variants to further assess arrhythmic risk, and age, comorbidities and sex for assessment of non-arrhythmic mortality risk. Moreover, several risk modifiers should be taken into account, such as concomitant arrhythmias that may affect LVEF (atrial fibrillation, premature ventricular beats) and resynchronisation therapy. Even though currently no valid cut-off values have been established, the proposed approach provides a more careful consideration of risks that may result in withholding ICD implantation in patients with low arrhythmic risk and substantial non-arrhythmic mortality risk.</p

Feasibility of intraoperative detection of sentinel lymph nodes with 89-zirconium-labelled nanocolloidal albumin PET-CT and a handheld high-energy gamma probe

Background: PET/CT lymphoscintigraphy using 89Zr-nanocolloidal albumin has the potential to improve the preoperative identification of sentinel lymph nodes (SLNs), especially if located in the near proximity of the primary tumour. This study aims to demonstrate the feasibility of PET/CT lymphoscintigraphy followed by intraoperative detection of 89Zr-nanocolloidal albumin containing SLNs with the use of a handheld high-energy gamma probe. Methods: PET/CT lymphoscintigraphy was performed after peritumoural injection of 89Zr-nanocolloidal albumin in five patients with oral cavity carcinoma planned for surgical resection. SLN biopsy procedure was performed 18 h later. SLNs were detected using detailed information of PET/CT and the high-energy gamma probe. Results: In all patients, SLNs were identified on PET/CT lymphoscintigraphy. Intraoperative detection using the high-energy gamma probe was possible in 10 of 13 SLNs, at a short distance from the SLN. Conclusions: This study demonstrates that intraoperative detection of SLNs containing 89Zr-nanocolloidal albumin using a handheld high-energy gamma probe is feasible, but its clinical use and sensitivity seem to be limited. Trial registration: CCMO NL37222.092.11

Feasibility of intraoperative detection of sentinel lymph nodes with 89-zirconium-labelled nanocolloidal albumin PET-CT and a handheld high-energy gamma probe

BACKGROUND: PET/CT lymphoscintigraphy using89Zr-nanocolloidal albumin has the potential to improve the preoperative identification of sentinel lymph nodes (SLNs), especially if located in the near proximity of the primary tumour. This study aims to demonstrate the feasibility of PET/CT lymphoscintigraphy followed by intraoperative detection of89Zr-nanocolloidal albumin containing SLNs with the use of a handheld high-energy gamma probe. METHODS: PET/CT lymphoscintigraphy was performed after peritumoural injection of89Zr-nanocolloidal albumin in five patients with oral cavity carcinoma planned for surgical resection. SLN biopsy procedure was performed 18 h later. SLNs were detected using detailed information of PET/CT and the high-energy gamma probe. RESULTS: In all patients, SLNs were identified on PET/CT lymphoscintigraphy. Intraoperative detection using the high-energy gamma probe was possible in 10 of 13 SLNs, at a short distance from the SLN. CONCLUSIONS: This study demonstrates that intraoperative detection of SLNs containing89Zr-nanocolloidal albumin using a handheld high-energy gamma probe is feasible, but its clinical use and sensitivity seem to be limited. TRIAL REGISTRATION: CCMO NL37222.092.11

Predictive value of planar 18F-fluorodeoxyglucose imaging for cardiac events in patients after acute myocardial infarction

This long-term study examines the predictive value of planar myocardial 18F-fluorodeoxyglucose (FDG) imaging far cardiac events after acute myocardial infarction (AMI). From December 1989 to April 1991, 59 consecutive patients with AMI had undergone planar rest thallium-201 (TI-201)/FDG imaging far viability assessment; 53 (42 men) were included in this study. Mean fallow-up was 47 ± 15 months. Cardiac events were defined as cardiac- related death, reinfarction, late revascularization, and unstable angina pectoris. A mismatch pattern was defined as a FDG uptake exceeding TI-201 uptake by ≤20%. A concordant reduction in flow and metabolism was defined as a match. In the mismatch group (n = 39) were 19 events versus 1 event in the match group (n = 14) (p <0.009). In the mismatch group were 5 cardiac deaths, 3 reinfarctions, 7 late revascularizations, and 4 patients had unstable angina pectoris. There was 1 cardiac death in the match group. The event- free rote estimated using Kaplan Meier curves for patients with and without a mismatch was significantly different (p = 0.018). The relative risk for patients with a mismatch far developing a future cardiac event was estimated at 7.8 versus patients with a match. Thus, planar myocardial FDG imaging shortly after AMI has important prognostic significance far prediction of future cardiac events. Patients with a mismatch shortly after AMI have a high risk for future cardiac events on medical therapy