Occurrence and timing of withdrawal of life-sustaining measures in traumatic brain injury patients: a CENTER-TBI study

Funder: National Institute for Health Research (UK)Abstract: Background: In patients with severe brain injury, withdrawal of life-sustaining measures (WLSM) is common in intensive care units (ICU). WLSM constitutes a dilemma: instituting WLSM too early could result in death despite the possibility of an acceptable functional outcome, whereas delaying WLSM could unnecessarily burden patients, families, clinicians, and hospital resources. We aimed to describe the occurrence and timing of WLSM, and factors associated with timing of WLSM in European ICUs in patients with traumatic brain injury (TBI). Methods: The CENTER-TBI Study is a prospective multi-center cohort study. For the current study, patients with traumatic brain injury (TBI) admitted to the ICU and aged 16 or older were included. Occurrence and timing of WLSM were documented. For the analyses, we dichotomized timing of WLSM in early (< 72 h after injury) versus later (≥ 72 h after injury) based on recent guideline recommendations. We assessed factors associated with initiating WLSM early versus later, including geographic region, center, patient, injury, and treatment characteristics with univariable and multivariable (mixed effects) logistic regression. Results: A total of 2022 patients aged 16 or older were admitted to the ICU. ICU mortality was 13% (n = 267). Of these, 229 (86%) patients died after WLSM, and were included in the analyses. The occurrence of WLSM varied between regions ranging from 0% in Eastern Europe to 96% in Northern Europe. In 51% of the patients, WLSM was early. Patients in the early WLSM group had a lower maximum therapy intensity level (TIL) score than patients in the later WLSM group (median of 5 versus 10) The strongest independent variables associated with early WLSM were one unreactive pupil (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.3–12.4) or two unreactive pupils (OR 5.8, CI 2.6–13.1) compared to two reactive pupils, and an Injury Severity Score (ISS) if over 41 (OR per point above 41 = 1.1, CI 1.0–1.1). Timing of WLSM was not significantly associated with region or center. Conclusion: WLSM occurs early in half of the patients, mostly in patients with severe TBI affecting brainstem reflexes who were severely injured. We found no regional or center influences in timing of WLSM. Whether WLSM is always appropriate or may contribute to a self-fulfilling prophecy requires further research and argues for reluctance to institute WLSM early in case of any doubt on prognosis

A Boolean Dilemma:True or False Aneurysm?

A feared complication of acute myocardial infarction is the formation of a cardiac pseudoaneurysm. We report a case of a gargantuan, arrhythmogenic left-ventricular pseudoaneurysm with contradictory morphological characteristics. The integrative use of high-resolution 3-dimensional magnetic resonance imaging and computed tomography proved essential for the diagnostic discrimination and successful therapeutic intervention. (Level of Difficulty: Advanced.)

Histopathological Validation of Dark-Blood Late Gadolinium Enhancement MRI Without Additional Magnetization Preparation

BACKGROUND: Conventional bright‐blood late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI) often suffers from poor scar‐to‐blood contrast due to the bright blood pool adjacent to the enhanced scar tissue. Recently, a dark‐blood LGE method was developed which increases scar‐to‐blood contrast without using additional magnetization preparation. PURPOSE: We aim to histopathologically validate this dark‐blood LGE method in a porcine animal model with induced myocardial infarction (MI). STUDY TYPE: Prospective. ANIMAL MODEL: Thirteen female Yorkshire pigs. FIELD STRENGTH/SEQUENCE: 1.5 T, two‐dimensional phase‐sensitive inversion‐recovery radiofrequency‐spoiled turbo field‐echo. ASSESSMENT: MI was experimentally induced by transient coronary artery occlusion. At 1‐week and 7‐week post‐infarction, in‐vivo cardiac MRI was performed including conventional bright‐blood and novel dark‐blood LGE. Following the second MRI examination, the animals were sacrificed, and histopathology was obtained. Matching LGE slices and histopathology samples were selected based on anatomical landmarks. Independent observers, while blinded to other data, manually delineated the endocardial, epicardial, and infarct borders on either LGE images or histopathology samples. The percentage of infarcted left‐ventricular myocardium was calculated for both LGE methods on a per‐slice basis, and compared with histopathology as reference standard. Contrast‐to‐noise ratios were calculated for both LGE methods at 1‐week and 7‐week post‐infarction. STATISTICAL TESTS: Pearson's correlation coefficient and paired‐sample t‐tests were used. Significance was set at P < 0.05. RESULTS: A combined total of 24 matched LGE and histopathology slices were available for histopathological validation. Dark‐blood LGE demonstrated a high level of agreement compared to histopathology with no significant bias (−0.03%, P = 0.75). In contrast, bright‐blood LGE showed a significant bias of −1.57% (P = 0.03) with larger 95% limits of agreement than dark‐blood LGE. Image analysis demonstrated significantly higher scar‐to‐blood contrast for dark‐blood LGE compared to bright‐blood LGE, at both 1‐week and 7‐weeks post‐infarction. DATA CONCLUSION: Dark‐blood LGE without additional magnetization preparation provides superior visualization and quantification of ischemic scar compared to the current in vivo reference standard. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE:

Health Care Costs of Target Attainment for Beta-Lactam Antibiotics in Critically Ill Patients: A Retrospective Analysis of the EXPAT Study

BACKGROUND: Optimizing beta-lactam antibiotic treatment is a promising method to reduce the length of intensive care unit (ICU) stay and therefore reduce ICU costs. We used data from the EXPAT trial to determine whether beta-lactam antibiotic target attainment is a cost determinant in the ICU. METHODS: Patients included in the EXPAT trial were divided into target attainment and target nonattainment based on serum antibiotic levels. All hospital costs were extracted from the hospital administration system and categorized. RESULTS: In total, 79 patients were included in the analysis. Target attainment showed a trend toward higher total ICU costs (€44,600 versus €28,200, P = 0.103). This trend disappeared when correcting for ICU length of stay (€2680 versus €2700). Renal replacement therapy was the most important cost driver. CONCLUSIONS: Target attainment for beta-lactam antibiotics shows a trend toward higher total costs in ICU patients, which can be attributed to the high costs of a long stay in the ICU and renal replacement therapy

Integration of cardiac magnetic resonance imaging, electrocardiographic imaging, and coronary venous computed tomography angiography for guidance of left ventricular lead positioning

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Myocardial Scar Detection Using High-Resolution Free-Breathing 3D Dark-Blood and Standard Breath-Holding 2D Bright-Blood Late Gadolinium Enhancement MRI:A Comparison of Observer Confidence

Abstract:Objective:To compare observer confidence for myocardial scar detection using 3 different late gadolinium enhancement (LGE) data sets by 2 observers with different levels of experience.Materials and Methods:Forty-one consecutive patients, who were referred for 3D dark-blood LGE MRI before implantable cardioverter-defibrillator implantation or ablation therapy and who underwent 2D bright-blood LGE MRI within a time frame of 3 months, were prospectively included. From all 3D dark-blood LGE data sets, a stack of 2D short-axis slices was reconstructed. All acquired LGE data sets were anonymized and randomized and evaluated by 2 independent observers with different levels of experience in cardiovascular imaging (beginner and expert). Confidence in detection of ischemic scar, nonischemic scar, papillary muscle scar, and right ventricular scar for each LGE data set was scored using a using a 3-point Likert scale (1 = low, 2 = medium, or 3 = high). Observer confidence scores were compared using the Friedman omnibus test and Wilcoxon signed-rank post hoc test.Results:For the beginner observer, a significant difference in confidence regarding ischemic scar detection was observed in favor of reconstructed 2D dark-blood LGE compared with standard 2D bright-blood LGE (p = 0.030) while for the expert observer, no significant difference was found (p = 0.166). Similarly, for right ventricular scar detection, a significant difference in confidence was observed in favor of reconstructed 2D dark-blood LGE compared with standard 2D bright-blood LGE (p = 0.006) while for the expert observer, no significant difference was found (p = 0.662). Although not significantly different for other areas of interest, 3D dark-blood LGE and its derived 2D dark-blood LGE data set showed a tendency to score higher for all areas of interest at both experience levels.Conclusions:The combination of dark-blood LGE contrast and high isotropic voxels may contribute to increased observer confidence in myocardial scar detection, independent of observer's experience level but in particular for beginner observers

Steadily increasing inversion time improves blood suppression for free-breathing 3D late gadolinium enhancement MRI with optimized dark-blood contrast

Objectives Free-breathing 3-dimensional (3D) late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) techniques with high isotropic resolution and dark-blood contrast may optimize the delineation of myocardial scar patterns. The extended acquisition times required for such scans, however, are paralleled by a declining contrast agent concentration. Consequently, the optimal inversion time (TI) is continuously increasing. We hypothesize that a steadily increasing (dynamic) TI can compensate for this effect and can lead to improved blood nulling to optimize the dark-blood contrast. Materials and Methods Fifty consecutive patients with previous cardiac arrhythmias, scheduled for high-resolution 3D LGE MRI, were prospectively enrolled between October 2017 and February 2020. Free-breathing 3D dark-blood LGE MRI with high isotropic resolution (1.6 x 1.6 x 1.6 mm) was performed using a conventional fixed TI (n = 25) or a dynamic TI (n = 25). The average increase in blood nulling TI per minute was obtained from Look-Locker scans before and after the 3D acquisition in the first fixed TI group. This average increment in TI was used as input to calculate the dynamic increment of the initial blood nulling TI value as set in the second dynamic TI group. Regions of interest were drawn in the left ventricular blood pool to assess mean signal intensity as a measure for blood pool suppression. Overall image quality, observer confidence, and scar demarcation were scored on a 3-point scale. Results Three-dimensional dark-blood LGE data sets were successfully acquired in 46/50 patients (92%). The calculated average TI increase of 2.3 +/- 0.5 ms/min obtained in the first fixed TI group was incorporated in the second dynamic TI group and led to a significant decrease of 72% in the mean blood pool signal intensity compared with the fixed TI group (P < 0.001). Overall image quality (P = 0.02), observer confidence (P = 0.02), and scar demarcation (P = 0.01) significantly improved using a dynamic TI. Conclusions A steadily increasing dynamic TI improves blood pool suppression for optimized dark-blood contrast and increases observer confidence in free-breathing 3D dark-blood LGE MRI with high isotropic resolution

Imaging findings for response evaluation of ductal carcinoma in situ in breast cancer patients treated with neoadjuvant systemic therapy: a systematic review and meta-analysis

Objectives: In approximately 45% of invasive breast cancer (IBC) patients treated with neoadjuvant systemic therapy (NST), ductal carcinoma in situ (DCIS) is present. Recent studies suggest response of DCIS to NST. The aim of this systematic review and meta-analysis was to summarise and examine the current literature on imaging findings for different imaging modalities evaluating DCIS response to NST. More specifically, imaging findings of DCIS pre- and post-NST, and the effect of different pathological complete response (pCR) definitions, will be evaluated on mammography, breast MRI, and contrast-enhanced mammography (CEM). Methods: PubMed and Embase databases were searched for studies investigating NST response of IBC, including information on DCIS. Imaging findings and response evaluation of DCIS were assessed for mammography, breast MRI, and CEM. A meta-analysis was conducted per imaging modality to calculate pooled sensitivity and specificity for detecting residual disease between pCR definition no residual invasive disease (ypT0/is) and no residual invasive or in situ disease (ypT0). Results: Thirty-one studies were included. Calcifications on mammography are related to DCIS, but can persist despite complete response of DCIS. In 20 breast MRI studies, an average of 57% of residual DCIS showed enhancement. A meta-analysis of 17 breast MRI studies confirmed higher pooled sensitivity (0.86 versus 0.82) and lower pooled specificity (0.61 versus 0.68) for detection of residual disease when DCIS is considered pCR (ypT0/is). Three CEM studies suggest the potential benefit of simultaneous evaluation of calcifications and enhancement. Conclusions and Clinical Relevance: Calcifications on mammography can remain despite complete response of DCIS, and residual DCIS does not always show enhancement on breast MRI and CEM. Moreover, pCR definition effects diagnostic performance of breast MRI. Given the lack of evidence on imaging findings of response of the DCIS component to NST, further research is demanded. Key Points: • Ductal carcinoma in situ has shown to be responsive to neoadjuvant systemic therapy, but imaging studies mainly focus on response of the invasive tumour. • The 31 included studies demonstrate that after neoadjuvant systemic therapy, calcifications on mammography can remain despite complete response of DCIS and residual DCIS does not always show enhancement on MRI and contrast-enhanced mammography. • The definition of pCR has impact on the diagnostic performance of MRI in detecting residual disease,and when DCIS is considered pCR, pooled sensitivity was slightly higher and pooled specificity slightly lower.</p