Patient Body Surface Research Articles

Patient-prosthesis mismatch and surgical aortic valve replacement outcomes: Retrospective analysis of single-center surgical data.

Patient-prosthesis mismatch (PPM) has been identified as a risk factor for mortality and reoperation in patients undergoing surgical aortic valve replacement (SAVR). We present a retrospective analysis of risk factors for PPM and the effects of PPM on early postoperative outcomes after SAVR. Chart review was conducted for patients (N = 3003) undergoing SAVR. PPM was calculated from valve reference orifice areas and patient body surface area. Logistic regression was used to analyze risk factors for PPM and develop a risk score from these results. Regression was also conducted to identify associations between projected PPM status and postoperative outcomes. Risk factors for PPM included female sex, higher body mass index (BMI), and use of the St. Jude Epic valve. Patients receiving St. Jude trifecta valves or mechanical valves were less likely to have predicted PPM. We developed a risk score using BMI, sex, and valve type, and retrospectively predicted PPM in our cohort. Mild PPM (odds ratio [OR] = 2.267), severe PPM (OR = 2.869), male sex (OR = 2.091), and younger age (OR = 0.940) were all predictors of SAVR reoperation, while aortic root replacement was associated with reduced reoperation rates (OR = 0.122). Severe PPM carried a risk of in-hospital mortality (OR = 3.599), and moderate PPM carried a smaller but significant risk (OR = 1.920). Other factors increasing postoperative morbidity and mortality included older age, renal failure, and diabetes. PPM could be retrospectively predicted in our cohort using a risk calculation from sex, BMI and valve type. We conclude that all degrees of PPM carry risk for mortality and reoperation.

Association of body surface area with fat mass, free fat mass and total weight in healthy individuals, and implications for the dosage of cytotoxic drugs.

In oncology, the dosage of anti-neoplastic drugs is generally adapted to the patient's body surface area (BSA). We investigated the potential differences between BSA and body weight (BW) in estimating the variability in body composition among individuals, especially older adults. The study population included 322 community-dwelling individuals with different age and sex: 45 adult men (AM, age 18-65 years), 86 older men (OM, age >65 years), 54 adult women (AW, age 18-65 years), and 137 older women (OW, age >65 years). For each participant, we estimated the body composition with dual-energy X-ray absorptiometry, and we calculated the BSA using the DuBois and DuBois formula. The strength of relationships between fat free mass (FFM) and fat mass (FM) with BSA, BW, and BMI were expressed as correlation (r) and determination coefficients (R2). Most of the included sample was normal weight (45.7%) or overweight (41.9%). FFM demonstrated a stronger association with BSA than with BW or BMI in all age/sex groups, with r ranging from 0.831 to 0.924 (p<0.001 for all) and R2 from 0.691 to 0.853. Conversely, BW and BMI were more strongly related to FM than BSA, especially in women. For such relationship, BW, in particular, showed r ranging from 0.793 to 0.924 (p<0.001 for all). This study suggests that BSA may be more appropriately used to estimate FFM, compared with BW. Instead, alternative parameters should be considered to estimate FM in patients at risk for adverse effects of lipophilic drugs, especially in older age.

Budgetary Impact of Bendamustine Ready-to-Dilute Products in Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma to a United States Infusion Facility.

BackgroundBendamustine hydrochloride (BND HCl) is indicated for first-line treatment of chronic lymphocytic leukemia (CLL) and rituximab-refractory indolent non-Hodgkin lymphoma (iNHL). There are two ready-to-dilute (RTD) formulations of BND HCl on the US market: a large-volume, long-duration infusion (BND-L) and a small-volume, short-duration infusion (BND-S). It is estimated that the shorter duration infusion could result in cost savings to infusion facilities.ObjectiveEstimate the one-year budget impact between BND-S and BND-L for use in the treatment of CLL and iNHL when all current BND-L utilization is replaced with BND-S, from the US infusion facility perspective.MethodsAn illustrative budget impact model estimated the change in costs associated with a projected increase from 50% to 100% market share for BND-S. The model included CLL and iNHL patient populations. Budgetary costs reflected facility expenditures on drug acquisition and administration based on recommended dosing for BND-S and BND-L. The base-case model assumptions and inputs were derived from scientific literature and publicly available resources. The total budget impact was calculated annually, along with the differences in per patient cost; one-way sensitivity analyses were conducted.ResultsPer-patient savings with BND-S use after the utilization shift were estimated at $2812.24 for CLL and $4769.01 for iNHL. Across both indications, the total annual incremental savings after the utilization shift were estimated at $452,209 for 250 CLL and iNHL patients in a 10,000-patient infusion facility, resulting in cost savings of $150.74 per BND HCI patient per month and $1808.84 per BND HCI patient per year. The model was sensitive to changes in proportion of patients receiving BND HCI infusions for CLL and iNHL, patient body surface area, and BND-S wholesale acquisition cost.ConclusionThis analysis estimated over $450,000 in annual savings for a 10,000-patient chemotherapy infusion facility following a utilization shift from 50% use of each RTD product to 100% use of BND-S in CLL and iNHL patients, driven by lower acquisition costs for BND-S and lower administration labor costs associated with rapid infusion.

Clinical Value of 3D-Printed Navigation Technology Combined with Neuroendoscopy for Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke with high morbidity and mortality. Rapid and massive bleeding may compress the brain tissue, causing space-occupying and pathological effects, such as reduced local cerebral blood flow, acidosis, and inflammatory and immune responses. Although the development of minimally invasive technique provides a new option for the treatment of ICH, their application is limited due to the difficulty in achieving accurate puncture localization under the guidance of the marks on CT. We selected 30 patients treated with neuroendoscopic surgery guided by 3D-printed navigation technology (experimental group) and 30 patients treated with neuroendoscopic surgery guided by hand-painted on the patient's body surface according to the marks on CT (control group). Our results showed that patients in the experimental group had a lower number of intraoperative punctures, shorter operation time, less intraoperative blood loss, higher hematoma clearance rate, and smaller volume of perihematomal edema than the patients in the control group. Moreover, patients in the experimental group had higher Glasgow Coma Scale score at discharge, shorter postoperative hospitalization time and ICU stay, and a lower rate of postoperative complications, despite the lack of statistically significant differences. In addition, no statistically significant differences were observed in mortality and Glasgow Outcome Scale score between the two groups. In conclusion, 3D-printed navigation technology used for the neuroendoscopic hematoma removal is a more reliable and less invasive approach in the treatment of ICH. This technique has great application prospects and deserves promotion in the future clinical practice.

Quantitative evaluation and comparison of coronary artery characteristics by 3D coronary volume reconstruction

Non-atherosclerotic abnormalities of vessel calibre, aneurysm and ectasia, are challenging to quantify and are often overlooked in qualitative reporting. Utilising a novel 3-dimensional (3D) quantitative coronary angiography (QCA) application, we have evaluated the characteristics of normal, diabetic and aneurysmal or ectatic coronary arteries. We selected 131 individuals under 50 years-of-age, who had undergone coronary angiography for suspected myocardial ischaemia between 1st January 2011 and 31st December 2015, at the Bristol Heart Institute, Bristol, UK. This included 42 patients with angiographically normal coronary arteries, 36 diabetic patients with unobstructed coronaries, and 53 patients with abnormal coronary dilatation (aneurysm and ectasia). A total of 1105 coronary segments were analysed using QAngio XA 3D (Research Edition, Medis medical imaging systems, Leiden, The Netherlands). The combined volume of the major coronary arteries was significantly different between each group (1240 ± 476 mm3 diabetic group, 1646 ± 391 mm3 normal group, and 2072 ± 687 mm3 abnormal group). Moreover, the combined coronary artery volumes correlated with patient body surface area (r = 0.483, p < 0.01). Inter-observer variability was assessed and intraclass correlation coefficient of the total coronary artery volume demonstrated a low variability of 3D QCA (r = 0.996, p < 0.001). Dedicated 3D QCA facilitates reproducible coronary artery volume estimation and allows discrimination of normal and diseased vessels.

Patient-specific computational flow modelling for assessing hemodynamic changes following fenestrated endovascular aneurysm repair

ObjectiveThis study aimed to develop an accessible patient-specific computational flow modelling pipeline for evaluating the hemodynamic performance of fenestrated endovascular aneurysm repair (fEVAR), with the hypothesis that computational flow modelling can detect aortic branch hemodynamic changes associated with fEVAR graft implantation. MethodsPatients who underwent fEVAR for juxtarenal aortic aneurysms with the Cook ZFEN were retrospectively selected. Using open-source SimVascular software, preoperative and postoperative visceral aortic anatomy was manually segmented from computed tomography angiograms. Three-dimensional geometric models were then discretized into tetrahedral finite element meshes. Patient-specific pulsatile in-flow conditions were derived from known supraceliac aortic flow waveforms and adjusted for patient body surface area, average resting heart rate, and blood pressure. Outlet boundary conditions consisted of three-element Windkessel models approximated from physiologic flow splits. Rigid wall flow simulations were then performed on preoperative and postoperative models with the same inflow and outflow conditions. We used SimVascular's incompressible Navier-Stokes solver to perform blood flow simulations on a cluster using 72 cores. ResultsPreoperative and postoperative flow simulations were performed for 10 patients undergoing fEVAR with a total of 30 target vessels (20 renal stents, 10 mesenteric scallops). Postoperative models required a higher mean number of mesh elements to reach mesh convergence (3.2 ± 1.8 × 106 vs 2.6 ± 1.1 × 106; P = .005) with a longer mean computational time (10.3 ± 6.3 hours vs 7.8 ± 3.5 hours; P = .04) compared with preoperative models. fEVAR was associated with small but statistically significant increases in mean peak proximal aortic arterial pressure (140.3 ± 11.0 mm Hg vs 136.9 ± 8.7 mm Hg; P = .02) and peak renal artery pressure (131.6 ± 14.8 mm Hg vs 128.9 ± 11.8 mm Hg; P = .04) compared with preoperative simulations. No differences were observed in peak pressure in the celiac, superior mesenteric, or distal aortic arteries (P = .17-.96). When measuring blood flow, the only observed difference was an increase in peak renal flow rate after fEVAR (17.5 ± 3.8 mL/s vs 16.9 ± 3.5 mL/s; P = .04). fEVAR was not associated with changes in the mean pressure or the mean flow rate in the celiac, superior mesenteric, or renal arteries (P = .06-.98). Stenting of the renal arteries did not induce significant changes time-averaged wall shear stress in the proximal renal artery (23.4 ± 8.1 dynes/cm2 vs 23.2 ± 8.4 dynes/cm2; P = .98) or distal renal artery (32.7 ± 13.9 dynes/cm2 vs 29.6 ± 11.8 dynes/cm2; P = .23). In addition, computational visualization of cross-sectional velocity profiles revealed low flow disturbances associated with protrusion of renal graft fabric into the aortic lumen. ConclusionsIn a pilot study involving a selective cohort of patients who underwent uncomplicated fEVAR, patient-specific flow modelling was a feasible method for assessing the hemodynamic performance of various two-vessel fenestrated device configurations and revealed subtle differences in computationally derived peak branch pressure and blood flow rates. Structural changes in aortic flow geometry after fEVAR do not seem to affect computationally estimated renovisceral branch perfusion or wall shear stress adversely. Additional studies with invasive angiography or phase contrast magnetic resonance imaging are required to clinically validate these findings. (JVS–Vascular Science 2021;2:53-69.) Clinical RelevanceUsing a computational flow modelling for assessing the hemodynamic performance of fenestrated endovascular aneurysm repair (fEVAR), this real-world, patient-specific study included 10 participants and found that structural changes in aortic flow geometry after fEVAR did not seem to adversely impact estimated renal or visceral branch perfusion metrics (eg, peak and mean arterial pressure and flow rates) or wall shear stress. These findings overall support the ongoing clinical use of commercially available fEVAR devices for repair of juxtarenal aortic aneurysms, and provides a computational framework for future evaluation of fEVAR configurations in a preoperative or postoperative settings.

Indications for transfusion of blood components

Indications for transfusion of blood components

Abstract 15302: Cardiac MRI Assessment of Cardiac Output Agrees With Simultaneous Fick Assessment in Pediatric Heart Transplant Patients

Introduction: Systemic cardiac output (Qs) and pulmonary blood flow (Qp) can be measured by cardiac magnetic resonance (CMR) and invasive oximetry, with studies showing good agreement between the two modalities. CMR-guided right heart catheterization (MR-RHC) collects simultaneous CMR and oximetry measurements permitting direct comparison. This study assessed agreement between CMR and Fick measurements of cardiac output in the pediatric heart transplant (HT) population. Methods: Twenty-three pediatric HT patients (body surface area range 0.6-2 m 2 ) with 53 MR-RHC between 2014 -2020 were reviewed. One outlier was excluded due to erroneous pulmonary vein saturation, leaving 52 MR-RHC for analysis. Measurements of un-indexed Qs and Qp from both CMR phase contrast and invasive oximetry using Fick were collected. Bland-Altman (BA) statistical and graphical analyses compared CMR versus Fick estimates of Qs and Qp. Results: BA limits of agreement (LOA) and corresponding concordance plot demonstrate good agreement between CMR and Fick (Figure 1). Panels A and B are the BA and concordance plots for Qs, respectively. Panels C and D are the BA and concordance plots for Qp, respectively. The 95% confidence interval LOA are -1.0 to +1.8 for Qs and -1.0 to +1.7 for Qp. Average bias and Lin correlation are similar for Qs and Qp at +0.36 L/min and 0.8, respectively. Conclusions: CMR and Fick measurements of Qs and Qp are similar in pediatric HT patients, with a tendency for slightly higher values by Fick estimates and similar LOA to previously published results. CMR acquired hemodynamics offer a radiation-free modality to reduce overall radiation exposure for pediatric HT patients.

Cael-101 Is Well-Tolerated in AL Amyloidosis Patients Receiving Concomitant Cyclophosphamide-Bortezomib-Dexamethasone (CyborD): A Phase 2 Dose-Finding Study (NCT04304144)

Immunoglobulin light Chain (AL) amyloidosis is the most common form of systemic amyloidosis, accounting for approximately 70% of the diagnosed cases in developed countries. There are no approved treatments for AL amyloidosis, and currently autologous stem cell transplants and/or chemotherapy targeted to eradicate the underlying plasma-cell dyscrasia (PCD) to stop the production of misfolded light chains are used. No therapies are available to remove existing amyloid deposits, improve and/or reverse organ dysfunction. CAEL-101 is a chimeric immunoglobulin G1 kappa isotype that reacts specifically with light chain fibrils, irrespective of their κ or λ isotype but, notably, not with the native forms. CAEL-101 was shown to bind to a cryptic epitope at the N-terminal of light chain proteins that adopt a non-native b-sheet structure, which is conserved in κ and λ mis-folded light chains. It is hypothesized that CAEL-101 will modify the disease course of AL amyloidosis by facilitating the removal of amyloid fibrils deposited in tissues. CAEL-101 was previously studied as monotherapy in an open label dose escalation Phase 1 study where it was shown to be safe, tolerable up to 500 mg/m2 and associated with an early organ response. No DLT were seen and the PK profile appeared not to reach linearity. The current multicenter, open-label, sequential cohort, dose-selection study of CAEL-101 in Mayo Stage I, II and IIIa AL amyloidosis patients was to define the safety and tolerability of CAEL-101 in combination with Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) as the standard of care (SOC) PCD therapy during a 27-day treatment period and to determine the recommended dose for the subsequent Phase 3 studies. Patients had measurable hematologic disease, as defined by at least one of:involved/uninvolved free light chain (FLC) difference (dFLC) &amp;gt; 5mg/dL orFLC &amp;gt;5mg/dL with abnormal ratio orserum protein electrophoresis (SPEP) m- spike &amp;gt; 0.5 g/dL Patients were seen in the clinic every week for 4 weeks to receive CAEL-101 2-HR IV infusions, and for safety and tolerability assessments. Subsequently, patients have been receiving CAEL-101 infusions approximately every other week. Actual dose was determined by patient body surface area in meters squared. When administered on the same day, CAEL-101 was administered first before CyBorD chemotherapy. The study employed a 3+3 dose escalation design, starting with a 500 mg/m2 dose. Patients were followed for dose-limiting toxicities (DLTs). The DLT observation period for the first cohort was through 14 days following the first infusion. For subsequent cohorts, this was through 27 days. At least 3 patients were enrolled in each dose cohort. Enrollment into a new cohort with the next higher dose of CAEL-101 did not begin until the DLT observation period had been completed for the last patient enrolled in the previous cohort, with further dosing cohorts at 750 and 1000 mg/m2. Safety assessment included vital signs, physical examinations, electrocardiograms (ECGs), clinical laboratory parameters (hematology, serum chemistry, urinalysis), and TEAEs. The pharmacokinetic (PK) profile of CAEL-101 was also assessed. The 13 patients averaging 65.2 years (range 47.6 to 79.6 years). The majority were male (76.9%), white (84.6%), and non-Hispanic (100%). Mayo staging I (7.7%), II (69.2%), and III (23.1%) reflected a wide range of disease severity in the patients enrolled. All patients were treated successfully through their 4th dose, the highest (1000 mg/m2) cohort enrolling 6 patients. No DLT was observed, and CAEL-101 was well-tolerated by all patients. The most common TEAEs were diarrhea and nausea (each 30.8%). Dose-normalized PK concentrations were best described by a linear two-compartment model, with terminal half-life of 28 days. This study demonstrated that CAEL-101 at doses up to 1000 mg/m2, given with CyBorD, was well-tolerated in the AL amyloidosis population. Two Phase 3 efficacy/safety studies, one enrolling Mayo Stage IIIa and the other Stage IIIb patients, have been initiated, and based on the findings from this Phase 2 study, the 1000 mg/m2 dose of CAEL-101 is being used for treatment in those studies. Figure 1 Disclosures Valent: Takeda Pharmaceuticals: Other: Teaching, Speakers Bureau; Celgene: Other: Teaching, Speakers Bureau; Amgen Inc.: Other: Teaching, Speakers Bureau. Silowsky:Caelum Biosciences: Current Employment, Current equity holder in private company. Kurman:Caelum Biosciences: Consultancy. Daniel:Caelum Biosciences: Current Employment, Current equity holder in private company. Jobes:Caelum Biosciences: Current Employment, Current equity holder in private company. Harnett:Caelum Biosciences: Consultancy, Current equity holder in private company. Ziola:Caelum Biosciences: Consultancy. Roviwong:Caelum Biosciences: Current Employment, Current equity holder in private company. Spector:Caelum Biosciences: Current Employment, Current equity holder in private company. Sobolov:Caelum Biosciences: Current Employment, Current equity holder in private company.

Experience using intravenous posaconazole in paediatric and young adult oncology patients.

Posaconazole exhibits broad-spectrum antifungal activity. An IV formulation became available in 2014. Few studies describing the use of this formulation exist in patients under the age of 18 years. This study describes our experience using IV posaconazole in paediatric and young adult cancer patients. This single-centre retrospective chart review evaluated patients who received IV posaconazole and had at least one posaconazole plasma concentration obtained after five or more days with a consistent dosage. Relationships between doses required to achieve a plasma concentration of ≥1 µg/mL and patient age, weight and body surface area (BSA) were evaluated. The clinical record was reviewed to identify descriptions of any adverse events. Twenty-five patients were analysed, with a median age of 10.5 years (range 1.9-22.9 years; 92% were <18 years). All patients were able to achieve a posaconazole plasma concentration ≥1 µg/mL during their treatment course. The daily mg/kg/day dose required to achieve the target concentration decreased significantly with increasing age of the patient (P = 0.018). Assessment of dosage based on BSA suggested a requirement of 225 mg/m2/day across all age groups <18 years. Adverse events documented in the clinical record were consistent with those described with the oral formulations. No CNS toxicities were observed with use of IV posaconazole. Concentrations ≥1 µg/mL are achievable and a BSA-based dosing approach may allow a consistent empirical dose for patients <18 years of age. Therapeutic drug monitoring is recommended to ensure patients achieve therapeutic concentrations.

High-Dose Methotrexate in Pediatric Acute Lymphoblastic Leukemia: Predictors of Delayed Clearance and the Effect of Increased Hydration Rate on Methotrexate Clearance.

ObjectivesHigh-dose methotrexate (HDMTX) is an important chemotherapeutic agent in the treatment of many cancers. Identification of the predictors of poor clearance during HDMTX infusions could advance the introduction of improved supportive care to prevent toxicities and reduce hospital length of stay. The purpose of this study was to identify relationships between patient physical characteristics and HDMTX clearance in the treatment of pediatric acute lymphoblastic leukemia (ALL). At our hospital, patients who have delayed methotrexate (MTX) clearance during a cycle of HDMTX receive an increased rate of hydration with subsequent cycles. This increase in hydration rate was examined for its potential to mitigate predictors of poor clearance and to prevent nephrotoxicity.MethodsThis study retrospectively examined the treatment records of 87 pediatric patients diagnosed with ALL who were treated on or according to Children’s Oncology Group (COG) protocols AALL0232, AALL0434, AALL1131, and AALL1231. Each patient received four cycles of HDMTX (5 g/m2 over 24 hours) at two-week intervals. Patients received either 125 ml/m2/hour (standard) or 200 ml/m2/hour (delayed clearance protocol) hydration before, with, and after each infusion. MTX levels taken at 24-, 42-, and 48-hour time points were used as an indirect measure of drug clearance. Two-tailed inference for ordinary least squares regression and both heteroskedastic and paired two-tailed t-tests were performed to identify physical characteristics associated with delayed MTX clearance and the effects of hydration rate on MTX clearance, respectively.ResultsPatient age and body surface area (BSA) were found to have statistically significant (p<0.05) positive associations with the serum MTX levels at 24, 42, and 48 hours in cycle 1. Age and BSA were significant only at the 24-hour time point in cycles 2 and 4. Weight alone was not associated with delayed MTX clearance. For patients who had delayed MTX clearance once and thus received the delayed clearance protocol in subsequent cycles, increasing the hydration rate from 125 to 200 ml/m2/hour was associated with a statistically significant decrease in average MTX levels as well as serum creatinine levels at the 24-, 42-, and 48-hour time points. Once patients with delayed clearance received the 200 ml/m2/hour rate of hydration, the history of prior poor clearance lost its predictive value for serum MTX levels and delayed clearance.ConclusionsThese results suggest that patient age and BSA are significant predictors of MTX clearance if all patients receive the same rate of hydration. Age and BSA affect the distribution phase of MTX kinetics, with downstream effects in the elimination phase. Increased hydration mitigates the effects of these physical characteristics on the elimination phase kinetics by improving renal elimination of MTX, causing a loss of significance of age and BSA as predictors of MTX levels in subsequent cycles at the 42- and 48-hour time points, but with less effect at 24 hours. Thus, hyperhydration regimens prior to cycle 1 of HDMTX could be considered for patients presenting with risk factors of advanced age or high BSA to avoid delayed clearance.

Patient-Specific Computational Flow Modelling for Assessing Hemodynamic Changes Following Fenestrated Endovascular Aneurysm Repair

Abstract Objective This study aimed to develop an accessible patient-specific computational flow modelling pipeline for evaluating the hemodynamic performance of fenestrated endovascular aneurysm repair (fEVAR), with the hypothesis that computational flow modelling can detect aortic branch hemodynamic changes associated with fEVAR graft implantation. Methods Patients who underwent fEVAR for juxtarenal aortic aneurysms with the Cook ZFEN were retrospectively selected. Using open-source SimVascular software, preoperative and postoperative visceral aortic anatomy was manually segmented from computed tomography angiograms. Three-dimensional geometric models were then discretized into tetrahedral finite element meshes. Patient-specific pulsatile in-flow conditions were derived from known supraceliac aortic flow waveforms and adjusted for patient body surface area, average resting heart rate, and blood pressure. Outlet boundary conditions consisted of three-element Windkessel models approximated from physiologic flow splits. Rigid wall flow simulations were then performed on preoperative and postoperative models with the same inflow and outflow conditions. We used SimVascular's incompressible Navier-Stokes solver to perform blood flow simulations on a cluster using 72 cores. Results Preoperative and postoperative flow simulations were performed for 10 patients undergoing fEVAR with a total of 30 target vessels (20 renal stents, 10 mesenteric scallops). Postoperative models required a higher mean number of mesh elements to reach mesh convergence (3.2 ± 1.8 × 106 vs 2.6 ± 1.1 × 106; P = .005) with a longer mean computational time (10.3 ± 6.3 hours vs 7.8 ± 3.5 hours; P = .04) compared with preoperative models. fEVAR was associated with small but statistically significant increases in mean peak proximal aortic arterial pressure (140.3 ± 11.0 mm Hg vs 136.9 ± 8.7 mm Hg; P = .02) and peak renal artery pressure (131.6 ± 14.8 mm Hg vs 128.9 ± 11.8 mm Hg; P = .04) compared with preoperative simulations. No differences were observed in peak pressure in the celiac, superior mesenteric, or distal aortic arteries (P = .17-.96). When measuring blood flow, the only observed difference was an increase in peak renal flow rate after fEVAR (17.5 ± 3.8 mL/s vs 16.9 ± 3.5 mL/s; P = .04). fEVAR was not associated with changes in the mean pressure or the mean flow rate in the celiac, superior mesenteric, or renal arteries (P = .06-.98). Stenting of the renal arteries did not induce significant changes time-averaged wall shear stress in the proximal renal artery (23.4 ± 8.1 dynes/cm2 vs 23.2 ± 8.4 dynes/cm2; P = .98) or distal renal artery (32.7 ± 13.9 dynes/cm2 vs 29.6 ± 11.8 dynes/cm2; P = .23). In addition, computational visualization of cross-sectional velocity profiles revealed low flow disturbances associated with protrusion of renal graft fabric into the aortic lumen. Conclusions In a pilot study involving a selective cohort of patients who underwent uncomplicated fEVAR, patient-specific flow modelling was a feasible method for assessing the hemodynamic performance of various two-vessel fenestrated device configurations and revealed subtle differences in computationally derived peak branch pressure and blood flow rates. Structural changes in aortic flow geometry after fEVAR do not seem to affect computationally estimated renovisceral branch perfusion or wall shear stress adversely. Additional studies with invasive angiography or phase contrast magnetic resonance imaging are required to clinically validate these findings. (JVS–Vascular Science 2021;▪:1-17.) Clinical Relevance Using a computational flow modelling for assessing the hemodynamic performance of fenestrated endovascular aneurysm repair (fEVAR), this real-world, patient-specific study included 10 participants and found that structural changes in aortic flow geometry after fEVAR did not seem to adversely impact estimated renal or visceral branch perfusion metrics (eg, peak and mean arterial pressure and flow rates) or wall shear stress. These findings overall support the ongoing clinical use of commercially available fEVAR devices for repair of juxtarenal aortic aneurysms, and provides a computational framework for future evaluation of fEVAR configurations in a preoperative or postoperative settings.

PCN61 US BUDGET IMPACT ANALYSIS OF BENDAMUSTINE READY-TO-DILUTE PRODUCTS IN CHRONIC LYMPHOCYTIC LEUKEMIA AND NON-HODGKIN LYMPHOMA

Bendamustine (BND) treats chronic lymphocytic leukemia (CLL) and indolent, rituximab-refractory B-cell non-Hodgkin lymphoma (iNHL). The budget impact of replacing BND large-volume, long-duration infusion (Belrapzo™; BND-L) formulation with BND small-volume, short-duration infusion (Bendeka®; BND-S) was analyzed. An illustrative budget impact model (BIM) was developed to estimate facility perspective changes in drug and administration labor costs associated with a hypothetical shift from 50%/50% BND-L/BND-S to exclusive BND-S use. Dosing and per-patient dose count (12 in CLL; 16 in iNHL) were based on product labeling and mean patient body surface area (BSA) of 1.8m2. Drug and diluent costs were derived from RED BOOK; administration labor costs were based on US Bureau of Labor Statistics data. Budget impact was estimated for a 10,000-patient facility, with 238 patients receiving BND for CLL or iNHL over one year. Univariate sensitivity analyses were conducted. Total estimated annual infusion facility incremental savings after utilization shift were $348,579, resulting in $1464.61 savings per-BND-patient-per year (PBPPY). Annual per-patient infusion labor costs per BND-S patient were $75.48 for CLL and $100.64 for INHL; BND-L costs were $226.44 and $603.84, respectively. The model was most sensitive to CLL patient count, BSA, and BND-S treatment cost. This BIM estimated annual savings of nearly $350,000 for 238 CLL and iNHL patients in an infusion facility following a utilization shift to 100% BND-S, driven primarily by lower administration labor costs associated with rapid infusion. With comparable drug acquisition costs, facilities see lower labor costs once payers reimburse drug costs. BND-S also provides a clinical advantage over BND-L with option to use 5% dextrose diluent; BND-S admixtures using 5% dextrose are stable at room temperature twice that of BND-L. Labor cost savings will be affected by number of sequential infusions in one day and infusion time reimbursement rates to facilities.

Psoas Muscle Area Serves as Prognostic Marker in Patients Receiving Left Ventricular Assist Device Implantation

Several risk scores and classifications are available to predict peri- and post-operative mortality of patients with end stage heart failure receiving Left Ventricular Assist Device (LVAD) implantation. The INTERMACS classification is most commonly used but recently assessment of sarcopenia has been suggested as additional predictor for post-operative outcome. Therefore, we evaluated whether or not psoas muscle area can serve as additional prognostic marker. A retrospective analysis on our patient cohort in the time span from January 2014 to April 2019 was performed. During that time period a total of 178 adult LVAD implantations were performed (Heart Ware n=42, HeartMate II n=4, HeartMate III n=61). Of those, 107 patients received an abdominal CT scan prior to surgery. Psoas mean area at level of the superior endplate of the third lumbar vertebra was measured axially corrected and correlated with patients body surface area, giving the indexed psoas mean area (PMAi). Patients then were divided in high or moderate muscle mass and low muscle mass in accordance to patient sex. Estimated survival calculated using the Kaplan-Meier-curve found a significant higher 30-day mortality in patients with low PMAi (log rank: 0.009). Whereas no differences were observed concerning in-hospital, 90-day and 1-year mortality. Lower muscle mass also had no impact on the length of ICU stay or necessity of temporary RVAD. Comparison of the distribution on the INTERMACS classification, revealed that patients with lower muscle mass had a higher probability to classify as INTERMACS level 1 or 2 (Level 1: 21% vs. 38.1%; Level 2: 14.8% vs. 23.8%). Patients with low PMAi in our cohort represented the sicker patients and had statistically significant higher short-term mortality. These findings suggest that PMAi can be used as an additional tool for risk stratification in patients undergoing LVAD implantation.

Effectiveness of combined antithrombin and thrombomodulin therapy on in-hospital mortality in mechanically ventilated septic patients with disseminated intravascular coagulation

Septic patients can develop disseminated intravascular coagulation (DIC), which is characterized by systemic blood coagulation and an increased risk of life-threatening haemorrhage. Although antithrombin (AT) and thrombomodulin (TM) combination anticoagulant therapy is frequently used to treat septic patients with DIC in Japan, its effectiveness in improving patient outcomes remains unclear. In this large-scale multicentre retrospective study of adult septic patients with DIC treated at Japanese hospitals between February 2010 and March 2016, we compared in-hospital mortality between AT monotherapy and AT + TM combination therapy. We performed logistic regression analysis with in-hospital mortality as the dependent variable and anticoagulant therapy as the main independent variable of interest. Covariates included patient demographics, disease severity, and body surface area. The AT group and AT + TM group comprised 1,017 patients from 352 hospitals and 1,205 patients from 349 hospitals, respectively. AT + TM combination therapy was not significantly associated with lower mortality when compared with AT monotherapy (odds ratio: 0.97, 95% confidence interval: 0.78–1.21; P = 0.81). AT + TM combination therapy was also not superior to AT monotherapy in reducing mechanical ventilation or hospitalization durations. Despite its widespread use for treating sepsis with DIC, AT + TM combination therapy is not more effective in improving prognoses than the simpler AT monotherapy.

Percent atheroma volume: Optimal variable to report whole-heart atherosclerotic plaque burden with coronary CTA, the PARADIGM study

Background and aimsDifferent methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three commonly used plaque burden definitions was least affected by differences in body surface area (BSA) and sex. MethodsThe PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who underwent serial CCTA >2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm3, (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAVnorm) in mm3 [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAVnorm were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed. ResultsThe study population comprised 1479 patients (age 60.7 ± 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11–13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAVnorm, but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAVnorm) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and TAVnorm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex. ConclusionsPAV was less affected by patient's body surface area then PV and TAVnorm and may be the preferred method to report coronary atherosclerotic burden.

Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?

To compare the uniformity and image quality between contrast media injection protocols adjusted for patient body weight (BW) versus body surface area (BSA) during coronary computed tomography (CT) angiography (CCTA). Consecutive patients (n=489) with suspected coronary artery disease were randomised prospectively to one of two CCTA protocols. In the BW protocol (n=245), patients received individualised iodine delivery rates (≤50 kg: 1 g/s; 51-60 kg: 1.2 g/s; 61-70 kg: 1.4 g/s; 71-80 kg: 1.6 g/s; 81-90 kg: 1.8 g/s; 91-100 kg: 2 g/s; >100 kg: 2.2 g/s). In the BSA protocol (n=244), patients received 9,600 mg iodine/m2 of contrast medium over 12 seconds. Attenuation and image noise were measured. Signal-to-noise ratio and contrast-to-noise ratio were calculated. Image quality was scored. Attenuation was assessed for correlation with BW and BSA using linear regression. There were no statistically significant differences in mean arterial attenuation (396.8±47.6 versus 395.8±42.2 HU, p=0.804; 95% confidence interval: -7 to 9), image noise (25.2±5.8 versus 25.5±5.4 HU; p=0.549), signal-to-noise ratio (16.7±4.4 versus 16.6±3.6; p=0.902), contrast-to-noise ratio (25.1±5.8 versus 25.8±7.4; p=0.258) or image quality scores (4.1±0.9 versus 4±0.9; p=0.770) between the BW and BSA protocols. There was no correlation between BW and aortic attenuation or between BSA and aortic attenuation (p=0.324 and 0.932, respectively). The average contrast media attenuation and image quality was comparable between BW-adjusted protocol and BSA-adjusted protocol.

Image Overlay Surgery Based on Augmented Reality: A Systematic Review.

Augmented Reality (AR) applied to surgical guidance is gaining relevance in clinical practice. AR-based image overlay surgery (i.e. the accurate overlay of patient-specific virtual images onto the body surface) helps surgeons to transfer image data produced during the planning of the surgery (e.g. the correct resection margins of tissue flaps) to the operating room, thus increasing accuracy and reducing surgery times. We systematically reviewed 76 studies published between 2004 and August 2018 to explore which existing tracking and registration methods and technologies allow healthcare professionals and researchers to develop and implement these systems in-house. Most studies used non-invasive markers to automatically track a patient's position, as well as customised algorithms, tracking libraries or software development kits (SDKs) to compute the registration between patient-specific 3D models and the patient's body surface. Few studies combined the use of holographic headsets, SDKs and user-friendly game engines, and described portable and wearable systems that combine tracking, registration, hands-free navigation and direct visibility of the surgical site. Most accuracy tests included a low number of subjects and/or measurements and did not normally explore how these systems affect surgery times and success rates. We highlight the need for more procedure-specific experiments with a sufficient number of subjects and measurements and including data about surgical outcomes and patients' recovery. Validation of systems combining the use of holographic headsets, SDKs and game engines is especially interesting as this approach facilitates an easy development of mobile AR applications and thus the implementation of AR-based image overlay surgery in clinical practice.

Should calculation of chemotherapy dosage for bowel cancer be based on body composition?

Dosage of chemotherapy for colon cancer is currently based on the patient's body surface area. Several studies have identified an association between low fat-free mass and chemotherapy toxicity among patients with metastatic colorectal cancer. This has been less widely studied for localised disease. This review aims to summarise studies that have investigated the association between clinical signs of disease-related malnutrition (low body mass index, weight loss and low muscle mass) and tolerance of chemotherapy in patients with localised colon cancer. We conducted a systematic search in PubMed with various synonyms of the terms 'colorectal cancer', 'adjuvant chemotherapy', 'nutritional status' and 'toxicity'. The search was concluded in May 2019. Of 553 articles, 39 were considered relevant and read in full text. Ten of these fulfilled the inclusion criteria for this review. Nine of the ten studies indicate an association between clinical signs of disease-related malnutrition and dose-limiting toxicity. The association appears to be especially pronounced in patients with low fat-free mass. The results support the hypothesis that there is an association between disease-related malnutrition and the prevalence of toxicity and modification of the course of adjuvant chemotherapy in patients with localised colon cancer. The potential benefits of basing chemotherapy dosage on body composition in addition to body surface area should be investigated in clinical trials.

A077 Incidence, Predictors and Prognostic Impact of Patient-Prosthesis Mismatch Following Transcatheter Aortic Valve Implantation

Patient-prosthesis mismatch (PPM) describes a state where the effective orifice area (EOA) of a valve prosthesis is too small relative to the patient's body surface area (BSA). We reviewed the incidence and prognostic impact of PPM following transcatheter aortic valve implantation (TAVI). A retrospective review of patients undergoing TAVI in the Auckland Region between October 2011 and December 2018 was performed. PPM was classified as severe (<0.65 cm2/m2), moderate (0.65-0.85 cm2/m2), or none (>0.85 cm2/m2) on post-TAVI echocardiography. Multivariable logistic regression analysis was used to determine independent predictors of PPM. One-year clinical outcomes were analysed. A total of 294 patients were included in this study (median age 81 years, interquartile range [IQR] 76 to 85 years], BSA 1.87m2, IQR 1.69 to 2.05m2). SAPIEN XT or S3 valves were used in 239 patients (81.3%) and 24 (8.2%) had valve-in-valve TAVI. Moderate and severe PPM were observed following TAVI in 42 (14.3%) and 26 (8.8%) patients respectively. In our multivariate analysis, larger BSA, smaller left ventricular outflow tract (LVOT) diameter and valve-in-valve procedures were identified as independent predictors of severe PPM. There was no significant difference in 30 day or 1-year mortality between PPM groups. Larger BSA, smaller LVOT diameter and valve-in-valve TAVI were predictors of moderate or severe PPM. PPM did not have a significant prognostic impact on mortality following TAVI, consistent with larger international registries.