The impact of sarcopenia on clinical outcomes in men with metastatic castrate-resistant prostate cancer.

INTRODUCTION: Sarcopenia is common in men with metastatic castrate-resistant prostate cancer (mCRPC) and has been largely assessed opportunistically through computed-tomography (CT) scans, excluding measures of muscle function. Therefore, the impact of a comprehensive assessment of sarcopenia on clinical outcomes in men with mCRPC is poorly understood. The objectives of this study were to comprehensively assess sarcopenia through CT scans and measures of muscle function and examine its impact on severe treatment toxicity, time to first emergency room (ER) visit, disease progression, and overall mortality in men initiating chemotherapy or androgen receptor-targeted axis (ARAT) therapy for mCRPC. METHODS: This was a secondary analysis of a prospective observational study of men with mCRPC at the Princess Margaret Cancer Centre between July 2015-May 2021. Participants were classified as sarcopenic if they had CT-based low muscle mass or low muscle density, a grip strength and gait speed score of <35.5kg and <0.8m/s, respectively, prior to treatment initiation. The impact of sarcopenia on severe treatment toxicity was assessed using multivariable logistic regression. Multivariable Cox regression models were used to determine the impact of sarcopenia on risk of visiting the ER, prostate-specific antigen progression, radiographic progression, and overall mortality. RESULTS: A total of 110 men (mean age: 74.6) were included in the analysis. At baseline, 30 (27.3%) were classified as sarcopenic. Sarcopenia was a significant predictor of severe toxicity (aOR = 6.26, 95%CI = 1.17-33.58, P = 0.032) and ER visits (aHR = 4.41, 95%CI = 1.26-15.43, p = 0.020) in men initiating ARAT but not in men initiating chemotherapy. Sarcopenia was also a predictor of radiographic progression (aHR = 2.39, 95%CI = 1.06-5.36, p = 0.035) and overall mortality (aHR = 2.44, 95%CI = 1.17-5.08, p = 0.018) regardless of treatment type. CONCLUSIONS: Baseline sarcopenia predicts radiographic progression and overall mortality in men with mCRPC regardless of the type of treatment and may also predict severe treatment toxicity and ER visits in men initiating ARAT.

Multisite Implementation of an American College of Surgeons Geriatric Surgery Quality Improvement Initiative.

BACKGROUND: The American College of Surgeons (ACS) Coalition for Quality in Geriatric Surgery (CQGS) identified standards of surgical care for the growing, vulnerable population of aging adults in the US. The aims of this study were to determine implementation feasibility for 30 selected standards, identify barriers and best practices in their implementation, and further refine these geriatric standards and verification process. STUDY DESIGN: The CQGS requested participation from hospitals involved in the ACS NSQIP Geriatric Surgery Pilot Project, previous CQGS feasibility analyses, and hospitals affiliated with a core development team member. Thirty standards were selected for implementation. After implementation, site visits were conducted, and postvisit surveys were distributed. RESULTS: Eight hospitals were chosen to participate. Program management (55%), immediate preoperative and intraoperative clinical care (62.5%), and postoperative clinical care (58%) had the highest mean percentage of "fully compliant" standards. Goals and decision-making (30%), preoperative optimization (28%), and transitions of care (12.5%) had the lowest mean percentage of fully compliant standards. Best practices and barriers to implementation were identified across 13 of the 30 standards. More than 80% of the institutions reported that participation changed the surgical care provided for older adults. CONCLUSIONS: This study represents the first national implementation assessment undertaken by the ACS for one of its quality programs. The CQGS pilot testing was able to demonstrate implementation feasibility for 30 standards, identify challenges and best practices, and further inform dissemination of the ACS Geriatric Surgery Verification Program.

Model-based meta-analysis of non-small cell lung cancer with standard of care PD-1 inhibitors and chemotherapy for early development decision making.

Single-arm cohorts/trials are often used in early phase oncology programs to support preliminary clinical activity assessments for investigational products, administered alone or in combination with standard of care (SOC) agents. Benchmarking clinical activity of those combinations against other treatments, including SOC, requires indirect comparisons against external trials, which presents challenges including cross-study differences in trial populations/other factors. To facilitate such nonrandomized comparisons, we developed a comprehensive model-based meta-analysis (MBMA) framework to quantitatively adjust for factors related to efficacy in metastatic non-small cell lung cancer (mNSCLC). Data were derived from 15 published studies assessing key programmed cell death protein-1 (PD-1) inhibitors pembrolizumab (n = 8) and nivolumab (n = 7), representing current SOC in mNSCLC. In the first stage, a mixed-effects logistic regression model for overall response rate (ORR) was developed accounting for effects of various population covariates on ORR. The ORR model results indicated an odds ratio (OR) of 1.02 for squamous versus non-squamous histology and OR of 1.20 for PD-ligand 1 tumor proportion score (TPS) per every 10% increase of TPS level. Next, a nonparametric mixed-effects model for overall survival (OS) was developed with ORR/other clinical covariates as input. Subsequently, MBMA simulations of relevant hypothetical scenarios involving single-arm trial design predicted OS hazard ratios as a function of ORR with matched patient characteristics. Findings from this MBMA and derived parameter estimates can be generally applied by the reader as a framework for interpreting efficacy data from early phase trials to support ORR-based go/no-go decisions and futility rules, illustrated through examples in this report.

National Comparison of Program Director Perceptions vs. Resident Reports of the Learning Environment and Well-Being.

OBJECTIVE: Our research objectives were to (1) assess the correlation between PD perceptions and their residents' reported experiences and (2) identify PD and program characteristics associated with alignment between PD perceptions and their residents' reports. DESIGN, SETTING, PARTICIPANTS: A survey was administered to US general surgery residents following the 2019 American Board of Surgery In-Training Examination (ABSITE) to study wellness (burnout, thoughts of attrition, and suicidality) and mistreatment (gender discrimination, sexual harassment, racial/ethnic/religious discrimination, bullying). General surgery program directors (PDs) were surveyed about the degree to which they perceived mistreatment and wellness within their programs. Concordance between PDs' perceptions and their residents' reports was assessed using Spearman correlations. Multivariable logistic regression models examined factors associated with alignment between PDs and residents. RESULTS: Of 6,126 residents training at SECOND Trial-enrolled programs, 5,240 (85.5%) responded to the ABSITE survey. All 212 PDs of programs enrolled in the SECOND Trial (100%) responded to the PD survey. Nationally, the proportion of PDs perceiving wellness issues was similar to the proportion of residents reporting them (e.g., 54.9% of PDs perceive that burnout is a problem vs. 40.1% of residents experience at least one burnout symptom weekly); however, the proportion of PDs perceiving mistreatment vastly underestimated the proportion of residents reporting it (e.g., 9.3% of all PDs perceive vs. 65.9% of all residents report bullying). Correlations between PDs' perceptions of problems within their program and their residents' reports were weak for racial/ethnic/religious discrimination (r = 0.176, p = 0.019), sexual harassment (r = 0.180, p = 0.019), burnout (r = 0.198, p = 0.007), and thoughts of attrition (r = 0.193, p = 0.007), and non-existent for gender discrimination, bullying, or suicidality. Multivariable regression models did not identify any program or PD characteristics that were consistently associated with improved resident-program director alignment. CONCLUSIONS: Resident and PD perceptions were generally disparate regarding mistreatment, burnout, thoughts of attrition, and suicidality. Reconciling this discrepancy is critical to enacting meaningful change to improve the learning environment and resident well-being.

Evaluating the Thematic Nature of Microaggression among Racial and Ethnic Minority Surgeons.

BACKGROUND: It is well documented that surgeons who identify as racial and ethnic minorities experience discrimination while navigating the surgical environment. There is evidence to suggest that the most prevalent form of discrimination experienced is microaggressions. This study sought to identify common microaggressions experienced in the surgical workplace by racial and ethnic minority surgeons with the use of a validated scale. METHODS: A one-time, deidentified survey was administered to surgeons who identified as a racial and ethnic minority via email. The survey included demographic questions and a shortened version of the Racial Microaggressions Scale, a validated 32-item scale developed to measure microaggressions in everyday life. Subscale means were calculated and compared using sample t-tests along with an analysis of variance. RESULTS: A total of 185 surgeons completed the survey with 166 included in the final analysis (97 male-identifying, 67 female-identifying). Significantly different microaggression experiences between race and ethnicity were found on the environmental (p < 0.001), foreigner/not belonging (p ≤ 0.001), low achieving/undesirable (p < 0.001), criminality (p < 0.001), and invisibility (p < 0.001) subscales with higher scores denoting more frequent experiences. Black and African American surgeons scored higher than Asian and Asian American and Hispanic and Latino surgeons on the low achieving/undesirable subscale (1.7 vs 0.9 and 1.2, respectively) and the invisibility subscale (1.5 vs 0.8 and 0.8, respectively). In addition, Asian and Asian American and Hispanic and Latino surgeons scored significantly higher on the foreigner/not belonging subscale compared with Black and African American surgeons (1.6 and 1.6 vs 0.9, respectively). CONCLUSIONS: The current study suggests that surgeons who identified as a racial and ethnic minority experience microaggressions in various ways. Understanding the specific experience of racial and ethnic minority surgeons is important as the surgical workplace strives to create more inclusive environments by acknowledging the lived experience of its diverse workforce.

Combined mechanical and oral antibiotic bowel preparation is associated with prolonged recurrence-free survival following surgery for colorectal cancer.

BACKGROUND AND OBJECTIVES: Recent studies suggest that bacteria influence the pathogenesis of primary colorectal cancer (CRC), yet their role in recurrence after resection is largely unknown. We have discovered that collagenase-producing bacteria promote cancer recurrence in mice, and that antibiotic bowel decontamination decreases colonization of these same organisms in humans. We hypothesized that preoperative combined mechanical and oral antibiotic bowel preparation would improve disease-free survival (DFS) in patients undergoing surgery for CRC. METHODS: We reviewed a cancer registry of patients treated for CRC at a tertiary center. Patients who received bowel preparation were compared to those that did not via a 1:1-propensity score matched for follow-up, age, sex, BMI, stage, location, chemoradiation, infection, anastomotic leak, and blood transfusion. RESULTS: One thousand two hundred and seventy-nine patients met inclusion criteria. Following propensity score matching, 264 patients receiving bowel prep were matched to 264 patients who did not. Kaplan-Meier estimates showed that patients who received bowel prep had a significantly improved 5-year DFS compared to those that did not (76.3% vs. 64.2%; p < .01). Cox regression demonstrated that bowel prep was associated with improved DFS (HR, 0.57; 95% CI, 0.37-0.89; p < .01). CONCLUSION: Combined mechanical and oral antibiotic bowel preparation is independently associated with improved recurrence-free survival in patients undergoing surgery for CRC.

Comprehensive Characterization of the General Surgery Residency Learning Environment and the Association With Resident Burnout.

OBJECTIVES: To characterize the learning environment (ie, workload, program efficiency, social support, organizational culture, meaning in work, and mistreatment) and evaluate associations with burnout in general surgery residents. BACKGROUND SUMMARY DATA: Burnout remains high among general surgery residents and has been linked to workplace exposures such as workload, discrimination, abuse, and harassment. Associations between other measures of the learning environment are poorly understood. METHODS: Following the 2019 American Board of Surgery In-Training Examination, a cross-sectional survey was administered to all US general surgery residents. The learning environment was characterized using an adapted Areas of Worklife survey instrument, and burnout was measured using an abbreviated Maslach Burnout Inventory. Associations between burnout and measures of the learning environment were assessed using multivariable logistic regression. RESULTS: Analysis included 5277 general surgery residents at 301 programs (85.6% response rate). Residents reported dissatisfaction with workload (n = 784, 14.9%), program efficiency and resources (n = 1392, 26.4%), social support and community (n = 1250, 23.7%), organizational culture and values (n = 853, 16.2%), meaning in work (n = 1253, 23.7%), and workplace mistreatment (n = 2661, 50.4%). The overall burnout rate was 43.0%, and residents were more likely to report burnout if they also identified problems with residency workload [adjusted odds ratio (aOR) 1.60, 95% confidence interval (CI) 1.31-1.94], efficiency (aOR 1.74; 95% CI 1.49-2.03), social support (aOR 1.37, 95% CI 1.15-1.64), organizational culture (aOR 1.64; 95% CI 1.39-1.93), meaning in work (aOR 1.87; 95% CI 1.56-2.25), or experienced workplace mistreatment (aOR 2.49; 95% CI 2.13-2.90). Substantial program-level variation was observed for all measures of the learning environment. CONCLUSIONS: Resident burnout is independently associated with multiple aspects of the learning environment, including workload, social support, meaning in work, and mistreatment. Efforts to help programs identify and address weaknesses in a targeted fashion may improve trainee burnout.

Creation of a COVID-19 Based Educational Curriculum: A Blueprint for Redesigning Surgical Education During Times of National Crisis.

Objective: To create a COVID-19 based educational curriculum for surgical residents. Background Data: The COVID-19 pandemic has resulted in disruptions to operative volume and clinical education for surgery residents. This has placed a greater importance on didactic education. However, in the face of pandemic-related uncertainty, focusing on a traditional educational curriculum may be a challenge for surgical residents. Methods: A dedicated resident educational team was created. This team identified specific surgical resident needs, evaluated institutional resources, created a curriculum and timeline, determined a feasible implementation format, and assessed resident opinions on the impact of the curriculum via anonymous survey. Results: A 1-month long COVID-19 based curriculum was developed, which covered (1) advanced critical care and resuscitation techniques pertinent to patients with COVID-19, (2) institutional physician experience in the COVID-units, (3) ethical dilemmas in resource management, (4) triaging of operative cases during the pandemic, and (5) published and ongoing COVID-19-related surgical research. In the postimplementation survey, a majority of residents reported that the curriculum helped improve their ability to take care of patients during the pandemic, provided an opportunity for questions, alleviated anxieties and concerns, and that they preferred the COVID-19 curriculum over traditional surgical topics. Conclusions: In the midst of national crisis and significant clinical disruption, real-time adjustments to surgical education can and should occur to address resident needs. The results of our study may serve as a blueprint for implementing rapid change to resident education in the future.

Development of a conceptual model for understanding the learning environment and surgical resident well-being.

BACKGROUND: Surgeon burnout is linked to poor outcomes for physicians and patients. Several conceptual models exist that describe drivers of physician wellness generally. No such model exists for surgical residents specifically. METHODS: A conceptual model for surgical resident well-being was adapted from published models with input gained iteratively from an interdisciplinary team. A survey was developed to measure residents' perceptions of their program. A confirmatory factor analysis (CFA) tested the fit of our proposed model construct. RESULTS: The conceptual model outlines eight domains that contribute to surgical resident well-being: Efficiency and Resources, Faculty Relationships and Engagement, Meaning in Work, Resident Camaraderie, Program Culture and Values, Work-Life Integration, Workload and Job Demands, and Mistreatment. CFA demonstrated acceptable fit of the proposed 8-domain model. CONCLUSION: Eight distinct domains of the learning environment influence surgical resident well-being. This conceptual model forms the basis for the SECOND Trial, a study designed to optimize the surgical training environment and promote well-being.

The American College of Surgeons Geriatric Surgery Verification Program and the Practicing Colorectal Surgeon.

The population is aging and older adults are increasingly undergoing surgery. Colorectal surgeons need to understand the risks inherent in the care of older adults and identify concrete ways to improve the quality of care for this vulnerable population. Goals for the practicing colorectal surgeon include: 1) introduce the American College of Surgeons' (ACS) Geriatric Surgery Verification (GSV) Program and understand the intersection with colorectal surgery, 2) examine the 30 evidence-based GSV standards and how they can achieve better outcomes after colorectal surgery, and 3) outline the value and benefits for colorectal surgeons of implementing such a program.

Evaluation of Postoperative Functional Health Status Decline Among Older Adults.

Importance: Functional outcomes have value for older adults who undergo surgical procedures. Preventing postoperative functional decline in this patient population necessitates the identification of the factors associated with this outcome and minimizing their implications. Objectives: To assess the prevalence of functional decline 30 days after a surgical procedure among older adults 80 years or older, examine the risk factors of this decline, and identify ways to minimize this decline by addressing its mutable factors. Design, Setting, and Participants: This retrospective cohort study used patient data from the Geriatric Surgery Pilot Project, a multi-institutional data registry of the American College of Surgeons National Surgical Quality Improvement Program. Inclusion criteria were patients 80 years or older who underwent a surgical procedure that required an inpatient stay at 1 of 23 hospitals enrolled in the Geriatric Surgery Pilot Project from January 1, 2015, to December 31, 2018, and had preoperative and postoperative functional health status data. Data analysis was performed from January 7, 2019, to December 2, 2019. Exposures: Adults 80 years or older who underwent an inpatient surgical procedure. Main Outcomes and Measures: The primary outcome was 30-day postoperative functional decline defined by a change in functional health status from admission or before the surgical procedure (ie, from independent to partially or totally dependent, or from partially dependent to totally dependent). Functional health status was measured by a patient's ability to perform activities of daily living. Secondary outcomes were hospital readmission and 30-day postoperative living location. Results: Of the 2013 patients analyzed in this study, 1128 were women (56.0%) and the mean (SD) age was 84.9 (3.9) years. Functional decline at 30 days after the surgical procedure was present in 406 patients (20.2%). Prevalence of this outcome increased with age, with 337 of 1751 patients aged 80 to 89 years (19.2%) experiencing decline compared with 69 of 262 patients 90 years or older (26.3%). In a risk-adjusted model, the geriatric-specific risk factors statistically significantly associated with this outcome included preoperative mobility aid use (odds ratio [OR] 1.76; 95% CI, 1.39-2.22; P < .001) and malnutrition (OR, 1.88; 95% CI, 1.04-3.43; P = .04) as well as postoperative delirium (OR, 2.20; 95% CI, 1.60-3.02; P < .001), pressure ulcer (OR, 1.83; 95% CI, 1.02-3.30; P = .04), and mobility aid at discharge (OR, 2.49; 95% CI, 1.72-3.59; P < .001). Among patients with a 30-day functional decline, 106 (26.1%) required hospital readmission and only 219 (53.9%) were living at home compared with 388 patients (95.6%) living at home before the procedure. Conclusions and Relevance: In this study, 1 in 5 older adults experienced a functional decline that persisted 30 days after a surgical procedure, an outcome that appeared to be associated with several geriatric-specific risk factors. Future trials are needed to evaluate whether the prevention or mitigation of these factors can decrease the rates of postoperative functional decline in this patient population.

Variation in Hospital Utilization of Minimally Invasive Distal Pancreatectomy for Localized Pancreatic Neoplasms.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) for localized neoplasms has been demonstrated to be feasible and safe. However, national adoption of the technique is poorly understood. Objectives of this study were to identify factors associated with use of minimally invasive distal pancreatectomy for localized neoplasms and assess hospital variation in MIDP utilization. METHODS: Retrospective cohort study of patients with pancreatic cysts, stage I pancreatic ductal adenocarcinoma, and stage I pancreatic neuroendocrine tumors undergoing distal pancreatectomy from the ACS NSQIP Pancreas Targeted Dataset. Factors associated with use of MIDP were identified using multivariable logistic regression and hospital-level variation was assessed. RESULTS: Analysis included 3,059 patients at 139 hospitals. Overall, 64.5% of patients underwent minimally invasive distal pancreatectomy. Patients were more likely to undergo MIDP if they had lower ASA classification (P = 0.004) or BMI ≥ 30 (P < 0.001) and less likely if they had pancreatic adenocarcinoma (P < 0.001). There was notable hospital variability in utilization (range 0 to 100% of cases). Hospital-level utilization of minimally invasive distal pancreatectomy did not appear to be driven by patient selection, as hierarchical analysis demonstrated that only 1.8% of observed hospital variation was attributable to measured patient selection factors. CONCLUSION: Utilization of MIDP for localized pancreatic neoplasms is highly variable. While some patient-level factors are associated with MIDP use, hospital adoption of MIDP appears to be the primary driver of utilization. Monitoring hospital-level use of MIDP may be a useful quality measure to monitor uptake of emerging techniques in pancreatic surgery.

Structure of the 30S ribosomal decoding complex at ambient temperature.

The ribosome translates nucleotide sequences of messenger RNA to proteins through selection of cognate transfer RNA according to the genetic code. To date, structural studies of ribosomal decoding complexes yielding high-resolution data have predominantly relied on experiments performed at cryogenic temperatures. New light sources like the X-ray free electron laser (XFEL) have enabled data collection from macromolecular crystals at ambient temperature. Here, we report an X-ray crystal structure of the Thermus thermophilus 30S ribosomal subunit decoding complex to 3.45 Å resolution using data obtained at ambient temperature at the Linac Coherent Light Source (LCLS). We find that this ambient-temperature structure is largely consistent with existing cryogenic-temperature crystal structures, with key residues of the decoding complex exhibiting similar conformations, including adenosine residues 1492 and 1493. Minor variations were observed, namely an alternate conformation of cytosine 1397 near the mRNA channel and the A-site. Our serial crystallography experiment illustrates the amenability of ribosomal microcrystals to routine structural studies at ambient temperature, thus overcoming a long-standing experimental limitation to structural studies of RNA and RNA-protein complexes at near-physiological temperatures.

Se-SAD serial femtosecond crystallography datasets from selenobiotinyl-streptavidin.

We provide a detailed description of selenobiotinyl-streptavidin (Se-B SA) co-crystal datasets recorded using the Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS) for selenium single-wavelength anomalous diffraction (Se-SAD) structure determination. Se-B SA was chosen as the model system for its high affinity between biotin and streptavidin where the sulfur atom in the biotin molecule (C10H16N2O3S) is substituted with selenium. The dataset was collected at three different transmissions (100, 50, and 10%) using a serial sample chamber setup which allows for two sample chambers, a front chamber and a back chamber, to operate simultaneously. Diffraction patterns from Se-B SA were recorded to a resolution of 1.9 Å. The dataset is publicly available through the Coherent X-ray Imaging Data Bank (CXIDB) and also on LCLS compute nodes as a resource for research and algorithm development.

The Hancock® Valved Conduit for Right Ventricular Outflow Tract Reconstruction in Sheep for Assessing New Devices.

BACKGROUND AND AIM OF THE STUDY: Xenograft conduits have been used successfully to repair congenital heart defects, but are prone to failure over time. Hence, in order to improve patient outcomes, better xenografts are being developed. When evaluating a conduit's performance and safety it must first be compared against a clinically available control in a large animal model. The study aim was to evaluate a clinically available xenograft conduit used in right ventricular outflow tract (RVOT) reconstruction in a sheep model. METHODS: RVOT reconstruction was performed in 13 adult and juvenile sheep, using the Medtronic Hancock® Bioprosthetic Valved Conduit (Hancock conduit). The method had previously been used on patients, and a newly modified variant termed 'RVOT Extraction' was employed to facilitate the surgical procedure. Animals were monitored over predetermined terms of 70 to 140 days. Serial transthoracic echocardiography, intracardiac pressure measurements and angiography were performed. On study completion the animals were euthanized and necropsies performed. RESULTS: Two animals died prior to their designated study term due to severe valvular stenosis and distal conduit narrowing, respectively. Thus, 11 animals survived the study term, with few or no complications. Generally, maximal and mean transvalvular pressure gradients across the implanted conduits were increased throughout the postoperative course. Among 11 full-term animals, seven conduits were patent with mild or no pseudointimal proliferation and with flexible leaflets maintaining the hemodynamic integrity of the valve. CONCLUSIONS: RVOT reconstruction using the Hancock conduit was shown to be successful in sheep, with durable and efficient performances. With its extensive clinical use in patients, and ability for long-term use in sheep (as described in the present study) it can be concluded that the Hancock conduit is an excellent control device for the evaluation of new xenografts in future preclinical studies.

Selenium single-wavelength anomalous diffraction de novo phasing using an X-ray-free electron laser.

Structural information about biological macromolecules near the atomic scale provides important insight into the functions of these molecules. To date, X-ray crystallography has been the predominant method used for macromolecular structure determination. However, challenges exist when solving structures with X-rays, including the phase problem and radiation damage. X-ray-free electron lasers (X-ray FELs) have enabled collection of diffraction information before the onset of radiation damage, yet the majority of structures solved at X-ray FELs have been phased using external information via molecular replacement. De novo phasing at X-ray FELs has proven challenging due in part to per-pulse variations in intensity and wavelength. Here we report the solution of a selenobiotinyl-streptavidin structure using phases obtained by the anomalous diffraction of selenium measured at a single wavelength (Se-SAD) at the Linac Coherent Light Source. Our results demonstrate Se-SAD, routinely employed at synchrotrons for novel structure determination, is now possible at X-ray FELs.

Carpentier-Edwards aortic pericardial bioprosthetic valve as a valid control in preclinical in vivo ovine studies.

To progress into clinical practice, a bioprosthetic heart valve must first pass through the preclinical evaluation phase. The International Standards Organization (ISO) recommends implantation of concurrent controls in any evaluation of a new or modified heart valve. A total of 8 adult sheep underwent aortic valve replacement, receiving either the CE Perimount Magna 3000 aortic pericardial bioprosthetic valve or the CE Perimount RSR aortic pericardial bioprosthetic valve, Model 2800. We performed serial blood sampling, echocardiography, angiography and necropsy after euthanasia. All 8 sheep survived until the end of their study term. Our 2-dimensional echocardiographic analysis showed a mean pressure gradient of 37.4±6.0mmHg at 14 days and 37.0±5.9mmHg at 90 days; mean cardiac output was 10.0±2.8l/min at 14 days and 9.6±1.6l/min at 90 days. Angiography before euthanasia showed a mean aortic transvalvular gradient of 32.3±15.3mmHg. At euthanasia, we saw no evidence of calcification in any of the valves. In our study, we found that both models of the CE bioprosthetic heart valve we tested proved to be valid controls, in the aortic position, in sheep-with no evidence of calcification. Most important, the valves we tested had a few model-related problems, allowing a clear determination of their suitability for introduction into a clinical trial. Investigators now have additional insight into the safety of these 2 models of valves and perhaps will be able to reduce the number of controls implanted.