Impact of contrast agent injection duration on dynamic contrast‐enhanced MRI quantification in prostate cancer

The volume transfer constant K^trans, which describes the leakage of contrast agent (CA) from vasculature into tissue, is the most commonly reported quantitative parameter for dynamic contrast‐enhanced (DCE‐) MRI. However, the variation in reported K^trans values between studies from different institutes is large. One of the primary sources of uncertainty is quantification of the arterial input function (AIF). The aim of this study is to determine the influence of the CA injection duration on the AIF and tracer kinetic analysis (TKA) parameters (i.e. K^trans, k_ep and v_e). Thirty‐one patients with prostate cancer received two DCE‐MRI examinations with an injection duration of 5 s in the first examination and a prolonged injection duration in the second examination, varying between 7.5 s and 30 s. The DCE examination was carried out on a 3.0 T MRI scanner using a transversal T₁‐weighted 3D spoiled gradient echo sequence (300 s duration, dynamic scan time of 2.5 s). Data of 29 of the 31 were further analysed. AIFs were determined from the phase signal in the left and right femoral arteries. K^trans, k_ep and v_e were estimated with the standard Tofts model for regions of healthy peripheral zone and tumour tissue. We observed a significantly smaller peak height and increased width in the AIF for injection durations of 15 s and longer. However, we did not find significant differences in K^trans, k_ep or v_e for the studied injection durations. The study demonstrates that the TKA parameters K^trans, k_ep and v_e, measured in the prostate, do not show a significant change as a function of injection duration.     

Retrospective identification of a previously undetected clinical case of OXA-48-producing <Emphasis Type="Italic">K. pneumoniae</Emphasis> and <Emphasis Type="Italic">E. coli</Emphasis>: the importance of adequate detection guidelines

Introduction

The laboratory detection of OXA-48-carbapenemase-producing Enterobacteriaceae is difficult, as minimum inhibition concentrations for carbapenems are often below the clinical breakpoint. In 2011, the Dutch national guideline for the detection of highly resistant micro-organisms was issued, which includes recommendations on the use of carbapenem screening breakpoints for the detection of carbapenemase-producing Enterobacteriaceae.

Materials and Methods

During a validation study of the Check-MDR CT103 microarray (Check-Points, Wageningen, The Netherlands) in 2013, an OXA-48-like carbapenemase gen was identified in two isolates that were previously obtained from a patient with non-Hodgkin lymphoma in 2007. Whole-genome sequencing (WGS) and subsequent BLAST Ringe Image Generator (BRIG) analysis were performed to establish the presence of OXA-48 carbapenemase encoding plasmids and their similarity.

Results

This case report describes the first documented OXA-48-producing Klebsiella pneumonia (ST648) and Escherichia coli (ST866) in the Netherlands. A similar IncL/M plasmid was identified in both strains, suggesting within-patient horizontal transfer.

Conclusion

This case illustrates that OXA-48-carbapenemase-producing Enterobacteriaceae can be unnoticed without adequate laboratory detection procedures. Our observation stresses the importance of uniform and adequate laboratory methods for the timely and accurate detection of important antimicrobial resistance.

     

Perioperative factors determine outcome after surgery for severe acute pancreatitis

Introduction  

There is evidence that postponing surgery in critically ill patients with severe acute pancreatitis (SAP) leads to improved survival, but previous reports included patients with both sterile and infected pancreatic necrosis who were operated on for various indications and with different degrees of organ dysfunction at the moment of surgery, which might be an important bias. The objective of this study is to analyze the impact of timing of surgery and perioperative factors (severity of organ dysfunction and microbiological status of the necrosis) on mortality in intensive care unit (ICU) patients undergoing surgery for SAP.     

Relative adrenal insufficiency in patients with severe acute pancreatitis

Objective Inadequate cortisol levels and adrenal dysfunction may play a role in the pathophysiology of severe acute pancreatitis. This study aimed to analyse the incidence of relative adrenal insufficiency (RAI) in these patients, to identify factors associated with RAI and to describe how adrenal responsiveness affects outcome. Design Prospective observational multicenter study. Patients Twenty-five patients with severe acute pancreatitis. Interventions A short Synacthen test (SST) was performed within 5 days after admission to the hospital. The incidence of RAI, defined as an increment after SST of less than 9 μg/dl was the primary endpoint of the study. Serum cortisol was measured at baseline and at 30 and 60 min after administration of 250 μg adrenocorticotropic hormone. Measurements and results Median baseline cortisol level was 26.6 μg/dl, and increased to 43.2 μg/dl and 48.8 μg/dl after 30 min and 60 min respectively. RAI was found in 16% of all patients and in 27% of patients with organ dysfunction. Patients with RAI were more severely ill and had higher SOFA scores from days 4 to 7 after admission. All patients with RAI developed pancreatic necrosis, and all of them needed surgical intervention. Twenty-eight-day mortality was significantly higher in patients with RAI (75% vs. 5%, p = 0.007). Patients who died had a lower increment in cortisol levels after the SST than patients who survived. Conclusion RAI is frequent in patients with severe acute pancreatitis and organ dysfunction. It occurs in patients with more severe pancreatitis and is associated with increased mortality. An abstract of this work was presented at the 27th International Symposium on Intensive Care and Emergency Medicine (ISICEM) in Brussels, March 2007.     

Disturbances in Bone Largely Predict Aortic Calcification in an Alternative Rat Model Developed to Study Both Vascular and Bone Pathology in Chronic Kidney Disease

Because current rat models used to study chronic kidney disease (CKD)‐related vascular calcification show consistent but excessive vascular calcification and chaotic, immeasurable, bone mineralization due to excessive bone turnover, they are not suited to study the bone‐vascular axis in one and the same animal. Because vascular calcification and bone mineralization are closely related to each other, an animal model in which both pathologies can be studied concomitantly is highly needed. CKD‐related vascular calcification in rats was induced by a 0.25% adenine/low vitamin K diet. To follow vascular calcification and bone pathology over time, rats were killed at weeks 4, 8, 10, 11, and 12. Both static and dynamic bone parameters were measured. Vascular calcification was quantified by histomorphometry and measurement of the arterial calcium content. Stable, severe CKD was induced along with hyperphosphatemia, hypocalcemia as well as increased serum PTH and FGF23. Calcification in the aorta and peripheral arteries was present from week 8 of CKD onward. Four and 8 weeks after CKD, static and dynamic bone parameters were measurable in all animals, thereby presenting typical features of hyperparathyroid bone disease. Multiple regression analysis showed that the eroded perimeter and mineral apposition rate in the bone were strong predictors for aortic calcification. This rat model presents a stable CKD, moderate vascular calcification, and quantifiable bone pathology after 8 weeks of CKD and is the first model that lends itself to study these main complications simultaneously in CKD in mechanistic and intervention studies. © 2015 American Society for Bone and Mineral Research.     

Sleepiness phenomics: Modeling individual differences in subjective sleepiness profiles

The present study investigates individual differences in subjective sleepiness profiles during 36 h of sustained wakefulness in a modified constant routine protocol. Twenty-three volunteers (11 females), aged between 18 and 47 yrs (M age = 30.41, SD = 10.26) enrolled in the study. Subjective sleepiness ratings were collected every 2 h by means of visual analogue scales. Circadian rhythmicity was assessed by means of salivary cortisol. Subjective sleepiness data were analyzed using functional principal component analysis (fPCA). Our results show that approximately 80% of the variance is accounted for by three functional components. The first component explains 50.28% of the variance and is characterized by a profile of exclusively positive loadings, representing vertical shifts from the mean sleepiness profile. Scores on this component are positively related to self-reported habitual sleep times and mean slow wave activity (SWA) during wake. Positive scores on the second component (18.40% of the variance) are characterized by a higher than average peak-to-trough amplitude in subjective sleepiness profiles. Participants with higher than average scores on this component show a significantly higher amplitude in salivary cortisol profiles as opposed to participants with lower than average scores. Participants with positive scores on the third component (10.09% of the variance) show higher than average levels of subjective sleepiness during morning hours, a buildup of wake effort occurring later and more afternoon sleepiness after sleep deprivation than negative scorers. Peak levels of salivary cortisol occur significantly later in these participants. Taken together, our results suggest that component 1 represents tonic differences in sleepiness profiles primarily related to mechanisms of sleep homeostasis, component 2 to circadian amplitude differences and component 3 to diurnal preference. However, since the components are additions to a mean profile, each of the three components is likely to correspond to a mixture of multiple physiological parameters, rather than to a single process. The approach shows interesting potential for (1) revealing unidentified physiological processes, (2) testing existing assumptions about regulatory mechanisms at the basis of interindividual variability in sleepiness profiles and (3) the specification of sleepiness phenotypes on a quantitative basis.