Interval changes in four-dimensional flow-derived in vivo hemodynamics stratify aortic growth in type B aortic dissection patients.

Aortic diameter growth in type B aortic dissection (TBAD) is associated with progressive aortic dilation, resulting in increased mortality in patients with both de novo TBAD (dnTBAD) and residual dissection after type A dissection repair (rTAAD). Preemptive thoracic endovascular aortic repair may improve mortality in patients with TBAD, although it is unclear which patients may benefit most from early intervention. In vivo hemodynamic assessment using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has been used to characterize TBAD patients with growing aortas. In this longitudinal study, we investigated whether changes over time in 4D flow-derived true and false lumen (TL and FL) hemodynamic parameters correlate with aortic growth rate, which is a marker of increased risk. We retrospectively identified TBAD patients with baseline and follow-up 4D flow CMR at least 120 days apart. Patients with TBAD intervention before baseline or between scans were excluded. 4D flow CMR data analysis included segmentation of the TL and FL, followed by voxel-wise calculation of TL and FL total kinetic energy (KE), maximum velocity (MV), mean forward flow (FF), and mean reverse flow (RF). Changes over time (Δ) were calculated for all hemodynamic parameters. Maximal diameter in the descending aorta was measured from magnetic resonance angiogram images acquired at the time of 4D flow. Aortic growth rate was defined as the change in diameter divided by baseline diameter and standardized to scan interval. Thirty-two patients met inclusion criteria (age: 56.9 ± 14.1 years, female: 13, n = 19 rTAAD, n = 13 dnTBAD). Mean follow-up time was 538 days (range: 135-1689). Baseline aortic diameter did not correlate with growth rate. In the entire cohort, Δ FL MV (Spearman's rho [rho] = 0.37, p = 0.04) and Δ FL RF (rho = 0.45, p = 0.01) correlated with growth rate. In rTAAD only, Δ FL MV (rho = 0.48, p = 0.04) and Δ FL RF (rho = 0.51, p = 0.03) correlated with growth rate, while in dnTBAD only, Δ TL KE (rho = 0.63, p = 0.02) and Δ TL MV (rho = 0.69, p = 0.01) correlated with growth rate. 4D flow-derived longitudinal hemodynamic changes correlate with aortic growth rate in TBAD and may provide additional prognostic value for risk stratification. 4D flow MRI could be integrated into existing imaging protocols to allow for the identification of TBAD patients who would benefit from preemptive surgical or endovascular intervention.

Engel J ，Kilinc O ，Weiss E ，Baraboo J ，Mehta C ，Hoel A ，Malaisrie SC ，Markl M ，Allen BD ... -  《-》

Four-dimensional flow cardiovascular magnetic resonance aortic cross-sectional pressure changes and their associations with flow patterns in health and ascending thoracic aortic aneurysm.

Ascending thoracic aortic aneurysm (ATAA) is a silent and threatening dilation of the ascending aorta (AscAo). Maximal aortic diameter which is currently used for ATAA patients management and surgery planning has been shown to inadequately characterize risk of dissection in a large proportion of patients. Our aim was to propose a comprehensive quantitative evaluation of aortic morphology and pressure-flow-wall associations from four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) data in healthy aging and in patients with ATAA. We studied 17 ATAA patients (64.7 ± 14.3 years, 5 females) along with 17 age- and sex-matched healthy controls (59.7 ± 13.3 years, 5 females) and 13 younger healthy subjects (33.5 ± 11.1 years, 4 females). All subjects underwent a CMR exam, including 4D flow and three-dimensional anatomical images of the aorta. This latter dataset was used for aortic morphology measurements, including AscAo maximal diameter (iDMAX) and volume, indexed to body surface area. 4D flow MRI data were used to estimate 1) cross-sectional local AscAo spatial (∆PS) and temporal (∆PT) pressure changes as well as the distance (∆DPS) and time duration (∆TPT) between local pressure peaks, 2) AscAo maximal wall shear stress (WSSMAX) at peak systole, and 3) AscAo flow vorticity amplitude (VMAX), duration (VFWHM), and eccentricity (VECC). Consistency of flow and pressure indices was demonstrated through their significant associations with AscAo iDMAX (WSSMAX:r = -0.49, p < 0.001; VECC:r = -0.29, p = 0.045; VFWHM:r = 0.48, p < 0.001; ∆DPS:r = 0.37, p = 0.010; ∆TPT:r = -0.52, p < 0.001) and indexed volume (WSSMAX:r = -0.63, VECC:r = -0.51, VFWHM:r = 0.53, ∆DPS:r = 0.54, ∆TPT:r = -0.63, p < 0.001 for all). Intra-AscAo cross-sectional pressure difference, ∆PS, was significantly and positively associated with both VMAX (r = 0.55, p = 0.002) and WSSMAX (r = 0.59, p < 0.001) in the 30 healthy subjects (48.3 ± 18.0 years). Associations remained significant after adjustment for iDMAX, age, and systolic blood pressure. Superimposition of ATAA patients to normal aging trends between ∆PS and WSSMAX as well as VMAX allowed identifying patients with substantially high pressure differences concomitant with AscAo dilation. Local variations in pressures within ascending aortic cross-sections derived from 4D flow MRI were associated with flow changes, as quantified by vorticity, and with stress exerted by blood on the aortic wall, as quantified by wall shear stress. Such flow-wall and pressure interactions might help for the identification of at-risk patients.

Bouaou K ，Dietenbeck T ，Soulat G ，Bargiotas I ，Houriez-Gombaud-Saintonge S ，De Cesare A ，Gencer U ，Giron A ，Jiménez E ，Messas E ，Lucor D ，Bollache E ，Mousseaux E ，Kachenoura N ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

Elwenspoek MM ，Thom H ，Sheppard AL ，Keeney E ，O'Donnell R ，Jackson J ，Roadevin C ，Dawson S ，Lane D ，Stubbs J ，Everitt H ，Watson JC ，Hay AD ，Gillett P ，Robins G ，Jones HE ，Mallett S ，Whiting PF ... -  《-》

Early three-dimensional growth in uncomplicated type B aortic dissection is associated with long-term outcomes.

Late adverse events (LAEs) are common among initially uncomplicated type B aortic dissection (uTBAD); however, identifying those patients at highest risk of LAEs remains a significant challenge. Early false lumen (FL) growth has been suggested to increase risk, but confident determination of growth is often hampered by error in two-dimensional clinical measurements. Semi-automated three-dimensional (3D) mapping of aortic growth, such as by vascular deformation mapping (VDM), can potentially overcome this limitation using computed tomography angiograms (CTA). We hypothesized that FL growth in the early pre-dissection phase by VDM can accurately predict LAEs. We performed a two-center retrospective study of patients with uTBAD, with paired CTAs in the acute (1-14 days) and subacute/early chronic (1-6 months) periods. VDM analysis was used to map 3D growth. Standard clinical CT measures (ie, aortic diameters, tear characteristics) were also collected. Multivariate analysis was conducted using a decision tree and Cox proportional hazards model. LAEs were defined as aneurysmal FL (>55 mm); rapid growth (>5 mm within 6 months); aorta-specific mortality, rupture, or re-dissection. A total of 107 (69% male) patients with uTBAD initially met inclusion criteria with a median follow-up of 7.3 years (interquartile range [IQR], 4.7-9.9 years). LAEs occurred in 72 patients (67%) at 2.5 years (IQR, 0.7-4.8 years) after the initial event. A multivariate decision tree model identified VDM growth (>2.1 mm) and baseline diameter (>42.7 mm) as optimal predictors of LAEs (area under the receiver operating characteristic curve = 0.94), achieving an 87% accuracy (sensitivity of 93%, specificity of 76%) after leave-one-out validation. Guideline reported high-risk features were not significantly different between groups. Early growth of the FL in uTBAD was the best tested indicator for LAEs and improves upon the current gold-standard of baseline diameter in selecting patients for early prophylactic thoracic endovascular aortic repair.

Marway PS ，Campello Jorge CA ，Tjahjadi N ，Baker TJ ，Mistelbauer G ，Baeumler K ，Hinostroza V ，Higashigaito K ，Mastrodicasa D ，Masotti M ，Nordsletten D ，Patel HJ ，Fleischmann D ，Burris NS ... -  《-》