Major adverse kidney events predict reduced survival in ventricular assist device supported patients.

AIMS: There is limited data describing major adverse kidney events (MAKE) in patients supported with ventricular assist devices (VAD). We aim to describe the association between MAKE and survival, risk factors for MAKE, and renal trajectory in VAD supported patients. METHODS AND RESULTS: We conducted a single-centre retrospective analysis of consecutive VAD implants between 2010 and 2019. Baseline demographics, biochemistry, and adverse events were collected for the duration of VAD support. MAKE was defined as the first event to occur of sustained drop (>50%) in estimated glomerular filtration rate (eGFR), progression to stage V chronic kidney disease, initiation or continuation of renal replacement therapy beyond implant admission or death on renal replacement therapy at any time. One-hundred and seventy-three patients were included, median age 56.8 years, 18.5% female, INTERMACS profile 1 or 2 in 75.1%. Thirty-seven patients experienced MAKE. On multivariate analysis, post-implant clinical right ventricular failure and the presence of chronic haemolysis, defined by the presence of schistocytes on blood film analysis, were significantly associated with increased risk of MAKE (adjusted odds ratio 9.88, P < 0.001 and adjusted odds ratio 3.33, P = 0.006, respectively). MAKE was associated with reduced survival (hazard ratio 4.80, P < 0.001). Patients who died or experienced MAKE did not demonstrate the expected transient 3-month improvement in eGFR, seen in other cohorts. CONCLUSIONS: MAKE significantly impacts survival. In our cohort, MAKE was predicted by post-implant right ventricular failure and chronic haemolysis. The lack of early eGFR improvement on VAD support may indicate higher risk for MAKE.

Value of Renal Histology in Predicting Cardiorenal Outcomes in Heart Transplant-listed Patients.

Cardiorenal syndrome (CRS) contributes significantly to morbidity and mortality in patients requiring mechanical circulatory support and transplantation. There are no validated markers to predict major adverse kidney events (MAKEs), for which simultaneous heart-kidney transplant (SHKT) could offer improved survival. We evaluate renal histology in predicting MAKEs in transplant-listed patients. Methods: We identified 18 patients with renal histology consistent with CRS from 655 consecutive heart transplant-listed patients between 2010 and 2019. Biopsies were analyzed for glomerular, tubular, interstitial, and arteriolar changes tallied to give a biopsy chronicity score. The primary outcome, MAKE, was a composite of death, need for renal replacement therapy (RRT), or estimated glomerular filtration rate decline >50%. These were evaluated at 2 time points: before and following the transplant. Secondary outcomes included the individual components of the composite outcomes and the need for short-term RRT following the transplant. Results: The mean age was 52.3 y, 22% were female. Five patients did not survive to transplant. One patient underwent successful SHKT. MAKE occurred in 8 of 18 before the transplant and in 8 of 13 following the transplant. Neither outcome was predicted by baseline biochemistry. The biopsy chronicity score was significantly higher in patients with MAKE before transplant (4.3 versus 1.7, P = 0.024) and numerically higher in patients requiring short-term RRT following transplant (3.2 versus 0.7, P = 0.075). Contrary to limited previous literature, interstitial fibrosis did not predict any outcome, whereas tubular atrophy and arteriosclerosis were associated with MAKE before transplant. Conclusions: A higher biopsy chronicity score was associated with adverse kidney endpoints, raising its potential utility over standard biochemistry in considering SHKT referral.

Effect of meal glycemic load and caffeine consumption on prolonged monotonous driving performance.

OBJECTIVE: Monotonous driving involves low levels of stimulation and high levels of repetition and is essentially an exercise in sustained attention and vigilance. The aim of this study was to determine the effects of consuming a high or low glycemic load meal on prolonged monotonous driving performance. The effect of consuming caffeine with a high glycemic load meal was also examined. METHOD: Ten healthy, non-diabetic participants (7 males, age 51±7yrs, mean±SD) completed a repeated measures investigation involving 3 experimental trials. On separate occasions, participants were provided one of three treatments prior to undertaking a 90min computer-based simulated drive. The 3 treatment conditions involved consuming: (1) a low glycemic load meal+placebo capsules (LGL), (2) a high glycemic load meal+placebo capsules (HGL) and (3) a high glycemic load meal+caffeine capsules (3mgkg-1 body weight) (CAF). Measures of driving performance included lateral (standard deviation of lane position (SDLP), average lane position (AVLP), total number of lane crossings (LC)) and longitudinal (average speed (AVSP) and standard deviation of speed (SDSP)) vehicle control parameters. Blood glucose levels, plasma caffeine concentrations and subjective ratings of sleepiness, alertness, mood, hunger and simulator sickness were also collected throughout each trial. RESULT: No difference in either lateral or longitudinal vehicle control parameters or subjective ratings were observed between HGL and LGL treatments. A significant reduction in SDLP (0.36±0.20m vs 0.41±0.19m, p=0.004) and LC (34.4±31.4 vs 56.7±31.5, p=0.018) was observed in the CAF trial compared to the HGL trial. However, no differences in AVLP, AVSP and SDSP or subjective ratings were detected between these two trials (p>0.05). CONCLUSION: Altering the glycemic load of a breakfast meal had no effect on measures of monotonous driving performance in non-diabetic adults. Individuals planning to undertake a prolonged monotonous drive following consumption of a morning meal may consider consuming caffeine as a means of improving vehicle control.

Dosimetric comparison of peripheral NSCLC SBRT using Acuros XB and AAA calculation algorithms.

There is a concern for dose calculation in highly heterogenous environments such as the thorax region. This study compares the quality of treatment plans of peripheral non-small cell lung cancer (NSCLC) stereotactic body radiation therapy (SBRT) using 2 calculation algorithms, namely, Eclipse Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB), for 3-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT). Four-dimensional computed tomography (4DCT) data from 20 anonymized patients were studied using Varian Eclipse planning system, AXB, and AAA version 10.0.28. A 3DCRT plan and a VMAT plan were generated using AAA and AXB with constant plan parameters for each patient. The prescription and dose constraints were benchmarked against Radiation Therapy Oncology Group (RTOG) 0915 protocol. Planning parameters of the plan were compared statistically using Mann-Whitney U tests. Results showed that 3DCRT and VMAT plans have a lower target coverage up to 8% when calculated using AXB as compared with AAA. The conformity index (CI) for AXB plans was 4.7% lower than AAA plans, but was closer to unity, which indicated better target conformity. AXB produced plans with global maximum doses which were, on average, 2% hotter than AAA plans. Both 3DCRT and VMAT plans were able to achieve D95%. VMAT plans were shown to be more conformal (CI = 1.01) and were at least 3.2% and 1.5% lower in terms of PTV maximum and mean dose, respectively. There was no statistically significant difference for doses received by organs at risk (OARs) regardless of calculation algorithms and treatment techniques. In general, the difference in tissue modeling for AXB and AAA algorithm is responsible for the dose distribution between the AXB and the AAA algorithms. The AXB VMAT plans could be used to benefit patients receiving peripheral NSCLC SBRT.

Dosimetric evaluation of inspiration and expiration breath-hold for intensity-modulated radiotherapy planning of non-small cell lung cancer.

The purpose of this study was to compare target coverage and lung tissue sparing between inspiration and expiration breath-hold intensity-modulated radiotherapy (IMRT) plans for patients with non-small cell lung cancer (NSCLC). In a prospective study, seven NSCLC patients gave written consent to undergo both moderate deep inspiration and end-expiration breath-hold computed tomography (CT), which were used to generate five-field IMRT plans. Dose was calculated with a scatter and an inhomogeneity correction algorithm. The percentage of the planning target volume (PTV) receiving 90% of the prescription dose (PTV(90)), the volume of total lung receiving >or=10 Gy (V(10)) and >or=20 Gy (V(20)) and the mean lung dose (MLD) were compared by the Student's paired t-test. Compared with the expiration plans, the mean +/- SD reductions for V(10), V(20) and MLD on the inspiration plans were 4.0 +/- 3.7% (p = 0.031), 2.5 +/- 2.3% (p = 0.028) and 1.1 +/- 0.7 Gy (p = 0.007), respectively. Conversely, a mean difference of 1.1 +/- 1.1% (p = 0.044) in PTV(90) was demonstrated in favour of expiration. When using IMRT, inspiration breath-hold can reduce the dose to normal lung tissue while expiration breath-hold can improve the target coverage. The improved lung sparing at inspiration may outweigh the modest improvements in target coverage at expiration.

Functional image-based radiotherapy planning for non-small cell lung cancer: A simulation study.

BACKGROUND AND PURPOSE: To investigate the incorporation of data from single-photon emission computed tomography (SPECT) or hyperpolarized helium-3 magnetic resonance imaging ((3)He-MRI) into intensity-modulated radiotherapy (IMRT) planning for non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Seven scenarios were simulated that represent cases of NSCLC with significant functional lung defects. Two independent IMRT plans were produced for each scenario; one to minimise total lung volume receiving >or=20Gy (V(20)), and the other to minimise only the functional lung volume receiving >or=20Gy (FV(20)). Dose-volume characteristics and a plan quality index related to planning target volume coverage by the 95% isodose (V(PTV95)/FV(20)) were compared between anatomical and functional plans using the Wilcoxon signed ranks test. RESULTS: Compared to anatomical IMRT plans, functional planning reduced FV(20) (median 2.7%, range 0.6-3.5%, p=0.02), and total lung V(20) (median 1.5%, 0.5-2.7%, p=0.02), with a small reduction in mean functional lung dose (median 0.4Gy, 0-0.7Gy, p=0.03). There were no significant differences in target volume coverage or organ-at-risk doses. Plan quality index was improved for functional plans (median increase 1.4, range 0-11.8, p=0.02). CONCLUSIONS: Statistically significant reductions in FV(20), V(20) and mean functional lung dose are possible when IMRT planning is supplemented by functional information derived from SPECT or (3)He-MRI.

Clinical implications of the anisotropic analytical algorithm for IMRT treatment planning and verification.

PURPOSE: To determine the implications of the use of the Anisotropic Analytical Algorithm (AAA) for the production and dosimetric verification of IMRT plans for treatments of the prostate, parotid, nasopharynx and lung. METHODS: 72 IMRT treatment plans produced using the Pencil Beam Convolution (PBC) algorithm were recalculated using the AAA and the dose distributions compared. Twenty-four of the plans were delivered to inhomogeneous phantoms and verification measurements made using a pinpoint ionisation chamber. The agreement between the AAA and measurement was determined. RESULTS: Small differences were seen in the prostate plans, with the AAA predicting slightly lower minimum PTV doses. In the parotid plans, there were small increases in the lens and contralateral parotid doses while the nasopharyngeal plans revealed a reduction in the volume of the PTV covered by the 95% isodose (the V(95%)) when the AAA was used. Large changes were seen in the lung plans, the AAA predicting reductions in the minimum PTV dose and large reductions in the V(95%). The AAA also predicted small increases in the mean dose to the normal lung and the V(20). In the verification measurements, all AAA calculations were within 3% or 3.5mm distance to agreement of the measured doses. CONCLUSIONS: The AAA should be used in preference to the PBC algorithm for treatments involving low density tissue but this may necessitate re-evaluation of plan acceptability criteria. Improvements to the Multi-Resolution Dose Calculation algorithm used in the inverse planning are required to reduce the convergence error in the presence of lung tissue. There was excellent agreement between the AAA and verification measurements for all sites.

Dosimetric verification of the anisotropic analytical algorithm for radiotherapy treatment planning.

BACKGROUND AND PURPOSE: To investigate the accuracy of photon dose calculations performed by the Anisotropic Analytical Algorithm, in homogeneous and inhomogeneous media and in simulated treatment plans. MATERIALS AND METHODS: Predicted dose distributions were compared with ionisation chamber and film measurements for a series of increasingly complex situations. Initially, simple and complex fields in a homogeneous medium were studied. The effect of inhomogeneities was investigated using a range of phantoms constructed of water, bone and lung substitute materials. Simulated treatment plans were then produced using a semi-anthropomorphic phantom and the delivered doses compared to the doses predicted by the Anisotropic Analytical Algorithm. RESULTS: In a homogeneous medium, agreement was found to be within 2% dose or 2mm dta in most instances. In the presence of heterogeneities, agreement was generally to within 2.5%. The simulated treatment plan measurements agreed to within 2.5% or 2mm. CONCLUSIONS: The accuracy of the algorithm was found to be satisfactory at 6 and 10MV both in homogeneous and inhomogeneous situations and in the simulated treatment plans. The algorithm was more accurate than the Pencil Beam Convolution model, particularly in the presence of low density heterogeneities.

The role of intensity-modulated radiotherapy in the treatment of parotid tumors.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment plans with three-dimensional conformal radiotherapy (3D-CRT) plans to investigate the suitability of IMRT for the treatment of tumors of the parotid gland. METHODS AND MATERIALS: One 3D-CRT treatment plan and 10 IMRT treatment plans with differing beam arrangements were produced for each of nine patient data sets. The plans were compared using regret analysis, dose conformity, dose to organs at risk, and uncomplicated tumor control probability (UTCP). RESULTS: The target dose was comparable in the 3D-CRT and IMRT plans, although improvements were seen when seven and nine IMRT fields were used. IMRT reduced the mean dose to the contralateral parotid gland and the maximum doses to the brain and the spinal cord, but increased the ipsilateral lens dose in some cases. Each IMRT arrangement produced a higher UTCP than the 3D-CRT plans; the largest absolute difference was 9.6%. CONCLUSIONS: IMRT is a suitable means for treating cancer of the parotid, and a five-field class solution is proposed. It produced substantial sparing of organs at risk and higher UTCPs than 3D-CRT and should enable dose escalation.