Pre-operative radiomics model for prognostication in resectable pancreatic adenocarcinoma with external validation.

OBJECTIVES: In resectable pancreatic ductal adenocarcinoma (PDAC), few pre-operative prognostic biomarkers are available. Radiomics has demonstrated potential but lacks external validation. We aimed to develop and externally validate a pre-operative clinical-radiomic prognostic model. METHODS: Retrospective international, multi-center study in resectable PDAC. The training cohort included 352 patients (pre-operative CTs from five Canadian hospitals). Cox models incorporated (a) pre-operative clinical variables (clinical), (b) clinical plus CT-radiomics, and (c) post-operative TNM model, which served as the reference. Outcomes were overall (OS)/disease-free survival (DFS). Models were assessed in the validation cohort from Ireland (n = 215, CTs from 34 hospitals), using C-statistic, calibration, and decision curve analyses. RESULTS: The radiomic signature was predictive of OS/DFS in the validation cohort, with adjusted hazard ratios (HR) 2.87 (95% CI: 1.40-5.87, p < 0.001)/5.28 (95% CI 2.35-11.86, p < 0.001), respectively, along with age 1.02 (1.01-1.04, p = 0.01)/1.02 (1.00-1.04, p = 0.03). In the validation cohort, median OS was 22.9/37 months (p = 0.0092) and DFS 14.2/29.8 (p = 0.0023) for high-/low-risk groups and calibration was moderate (mean absolute errors 7%/13% for OS at 3/5 years). The clinical-radiomic model discrimination (C = 0.545, 95%: 0.543-0.546) was higher than the clinical model alone (C = 0.497, 95% CI 0.496-0.499, p < 0.001) or TNM (C = 0.525, 95% CI: 0.524-0.526, p < 0.001). Despite superior net benefit compared to the clinical model, the clinical-radiomic model was not clinically useful for most threshold probabilities. CONCLUSION: A multi-institutional pre-operative clinical-radiomic model for resectable PDAC prognostication demonstrated superior net benefit compared to a clinical model but limited clinical utility at external validation. This reflects inherent limitations of radiomics for PDAC prognostication, when deployed in real-world settings. KEY POINTS: • At external validation, a pre-operative clinical-radiomics prognostic model for pancreatic ductal adenocarcinoma (PDAC) outperformed pre-operative clinical variables alone or pathological TNM staging. • Discrimination and clinical utility of the clinical-radiomic model for treatment decisions remained low, likely due to heterogeneity of CT acquisition parameters. • Despite small improvements, prognosis in PDAC using state-of-the-art radiomics methodology remains challenging, mostly owing to its low discriminative ability. Future research should focus on standardization of CT protocols and acquisition parameters.

Gross primary production responses to warming, elevated CO2 , and irrigation: quantifying the drivers of ecosystem physiology in a semiarid grassland.

Determining whether the terrestrial biosphere will be a source or sink of carbon (C) under a future climate of elevated CO2 (eCO2 ) and warming requires accurate quantification of gross primary production (GPP), the largest flux of C in the global C cycle. We evaluated 6 years (2007-2012) of flux-derived GPP data from the Prairie Heating and CO2 Enrichment (PHACE) experiment, situated in a grassland in Wyoming, USA. The GPP data were used to calibrate a light response model whose basic formulation has been successfully used in a variety of ecosystems. The model was extended by modeling maximum photosynthetic rate (Amax ) and light-use efficiency (Q) as functions of soil water, air temperature, vapor pressure deficit, vegetation greenness, and nitrogen at current and antecedent (past) timescales. The model fits the observed GPP well (R2  = 0.79), which was confirmed by other model performance checks that compared different variants of the model (e.g. with and without antecedent effects). Stimulation of cumulative 6-year GPP by warming (29%, P = 0.02) and eCO2 (26%, P = 0.07) was primarily driven by enhanced C uptake during spring (129%, P = 0.001) and fall (124%, P = 0.001), respectively, which was consistent across years. Antecedent air temperature (Tairant ) and vapor pressure deficit (VPDant ) effects on Amax (over the past 3-4 days and 1-3 days, respectively) were the most significant predictors of temporal variability in GPP among most treatments. The importance of VPDant suggests that atmospheric drought is important for predicting GPP under current and future climate; we highlight the need for experimental studies to identify the mechanisms underlying such antecedent effects. Finally, posterior estimates of cumulative GPP under control and eCO2 treatments were tested as a benchmark against 12 terrestrial biosphere models (TBMs). The narrow uncertainties of these data-driven GPP estimates suggest that they could be useful semi-independent data streams for validating TBMs.

Challenging terrestrial biosphere models with data from the long-term multifactor Prairie Heating and CO2 Enrichment experiment.

Multifactor experiments are often advocated as important for advancing terrestrial biosphere models (TBMs), yet to date, such models have only been tested against single-factor experiments. We applied 10 TBMs to the multifactor Prairie Heating and CO2 Enrichment (PHACE) experiment in Wyoming, USA. Our goals were to investigate how multifactor experiments can be used to constrain models and to identify a road map for model improvement. We found models performed poorly in ambient conditions; there was a wide spread in simulated above-ground net primary productivity (range: 31-390 g C m-2  yr-1 ). Comparison with data highlighted model failures particularly with respect to carbon allocation, phenology, and the impact of water stress on phenology. Performance against the observations from single-factors treatments was also relatively poor. In addition, similar responses were predicted for different reasons across models: there were large differences among models in sensitivity to water stress and, among the N cycle models, N availability during the experiment. Models were also unable to capture observed treatment effects on phenology: they overestimated the effect of warming on leaf onset and did not allow CO2 -induced water savings to extend the growing season length. Observed interactive (CO2  × warming) treatment effects were subtle and contingent on water stress, phenology, and species composition. As the models did not correctly represent these processes under ambient and single-factor conditions, little extra information was gained by comparing model predictions against interactive responses. We outline a series of key areas in which this and future experiments could be used to improve model predictions of grassland responses to global change.

Antecedent moisture and temperature conditions modulate the response of ecosystem respiration to elevated CO2 and warming.

Terrestrial plant and soil respiration, or ecosystem respiration (Reco ), represents a major CO2 flux in the global carbon cycle. However, there is disagreement in how Reco will respond to future global changes, such as elevated atmosphere CO2 and warming. To address this, we synthesized six years (2007-2012) of Reco data from the Prairie Heating And CO2 Enrichment (PHACE) experiment. We applied a semi-mechanistic temperature-response model to simultaneously evaluate the response of Reco to three treatment factors (elevated CO2 , warming, and soil water manipulation) and their interactions with antecedent soil conditions [e.g., past soil water content (SWC) and temperature (SoilT)] and aboveground factors (e.g., vapor pressure deficit, photosynthetically active radiation, vegetation greenness). The model fits the observed Reco well (R2  = 0.77). We applied the model to estimate annual (March-October) Reco , which was stimulated under elevated CO2 in most years, likely due to the indirect effect of elevated CO2 on SWC. When aggregated from 2007 to 2012, total six-year Reco was stimulated by elevated CO2 singly (24%) or in combination with warming (28%). Warming had little effect on annual Reco under ambient CO2 , but stimulated it under elevated CO2 (32% across all years) when precipitation was high (e.g., 44% in 2009, a 'wet' year). Treatment-level differences in Reco can be partly attributed to the effects of antecedent SoilT and vegetation greenness on the apparent temperature sensitivity of Reco and to the effects of antecedent and current SWC and vegetation activity (greenness modulated by VPD) on Reco base rates. Thus, this study indicates that the incorporation of both antecedent environmental conditions and aboveground vegetation activity are critical to predicting Reco at multiple timescales (subdaily to annual) and under a future climate of elevated CO2 and warming.

C-arm cone-beam CT parenchymal blood volume imaging for transarterial chemoembolization of hepatocellular carcinoma: implications for treatment planning and response.

We report on the feasibility of C-arm cone-beam computed tomography (CBCT) parenchymal blood volume imaging (PBVI) performed immediately following transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) to assess the need for repeat treatment. Eighteen TACE procedures were included. A retrospective assessment was made for the presence or absence of residual disease requiring treatment on immediate post-TACE PBVI and on interval follow-up multidetector computed tomography (MDCT) or magnetic resonance imaging (MRI). In 9/18 cases, both PBVI and MDCT/MRI showed that no further treatment was required. In 6/18 cases, further treatment was required on both PBVI and MDCT/MRI. In three cases, PBVI showed that further treatment was not required but MDCT/MRI showed residual disease requiring repeat treatment. There were no cases with PBVI showing residual disease not detected on follow-up MDCT/MRI. The PBVI sensitivity for detecting disease requiring repeat TACE was 67% (95% confidence interval [CI] 30-93%), and specificity was 100% (95% CI 66-100%). The use of C-arm CBCT PBVI for the detection of residual viable tumor within a treated lesion immediately after TACE is feasible. It may allow repeat TACE to be planned without performing interval imaging with MDCT or MRI.

Decadal biomass increment in early secondary succession woody ecosystems is increased by CO2 enrichment.

Increasing atmospheric CO2 stimulates photosynthesis which can increase net primary production (NPP), but at longer timescales may not necessarily increase plant biomass. Here we analyse the four decade-long CO2-enrichment experiments in woody ecosystems that measured total NPP and biomass. CO2 enrichment increased biomass increment by 1.05 ± 0.26 kg C m-2 over a full decade, a 29.1 ± 11.7% stimulation of biomass gain in these early-secondary-succession temperate ecosystems. This response is predictable by combining the CO2 response of NPP (0.16 ± 0.03 kg C m-2 y-1) and the CO2-independent, linear slope between biomass increment and cumulative NPP (0.55 ± 0.17). An ensemble of terrestrial ecosystem models fail to predict both terms correctly. Allocation to wood was a driver of across-site, and across-model, response variability and together with CO2-independence of biomass retention highlights the value of understanding drivers of wood allocation under ambient conditions to correctly interpret and predict CO2 responses.

The Combined Impact of Surgical Team Education and Chlorhexidine 2% Alcohol on the Reduction of Surgical Site Infection following Cardiac Surgery.

BACKGROUND: The use of 2% chlorhexidine in 70% alcohol (CHG) has been associated with reduction in catheter-related bloodstream infections and surgical site infection (SSI) in general surgery. Also, improved awareness of best practice from the perspective of the operative team is likely to result in reductions in SSI rates. METHODS: This is an ambispective cohort study of patients undergoing elective cardiac surgery. Between January 2010 and December 2010, patients underwent surgical preparation using Alcohol Povidone Iodine (API). Between January 2011 and December 2011, the surgical team received education and switched to CHG for surgical preparation. Univariate analysis was performed to identify the impact of known risk factors for SSI. A logistic regression model was then fit to estimate the effect of education and CHG in the reduction of SSI in 2011, controlling for known SSI risk factors. RESULTS: There was a substantial reduction in overall SSI rate in 2011 following staff education and the introduction of CHG. The overall unadjusted SSI rate was 4.67% versus 2.08% (p<0.05) for 2010 and 2011 respectively. Using a logistic regression model, the combined effect of education and CHG in 2011 was a 63% reduction in SSI in cardiothoracic surgery (OR 0.37, 95% CI: 0.17-0.83, p=0.016), controlling for age, major co-morbidities, and SSI risk factors. CONCLUSIONS: Using CHG as pre-operative antiseptic in cardiothoracic surgery in a risk-adjusted cohort with education of the surgical team is associated with significantly lower SSI infection rates when compared with API. Emphasis must be placed on the multifactorial approach required to prevent postoperative wound infections.

Practical tips and tricks for assessing prosthetic valves and detecting paravalvular regurgitation using cardiac CT.

Paravalvular leaks are an uncommon but serious complication of prosthetic valves. Transthoracic echocardiography is used in the assessment of prosthetic valves but can be limited by acoustic shadowing from the prosthesis and poor acoustic windowing. Small case series have previously shown cardiac CT to have promising results in detecting paravalvular leaks. We assessed 32 valves in our institution on cardiac CT using echocardiography results as standard and developed methods for improved evaluation of prosthetic valves. These include optimizing prescan drug therapy for heart rate control, optimum window and center adjustments, and carefully selected image planes to best demonstrate the valve ring and valve annulus. Recognition of surgical material is also important to recognize. In this review, we provide a detailed description of these techniques with imaging examples of prosthetic valve evaluation using cardiac CT.