Daniel Rinewalt

Development and validation of a plasma biomarker panel for discerning clinical significance of indeterminate pulmonary nodules.

Introduction: The recent findings of the National Lung Screening Trial showed 24.2% of individuals at high risk for lung cancer having one or more indeterminate nodules detected by low-dose computed tomography–based screening, 96.4% of which were eventually confirmed as false positives. These positive scans necessitate additional diagnostic procedures to establish a definitive diagnosis that adds cost and risk to the paradigm. A plasma test able to assign benign versus malignant pathology in high-risk patients would be an invaluable tool to complement low-dose computed tomography–based screening and promote its rapid implementation. Methods: We evaluated 17 biomarkers, previously shown to have value in detecting lung cancer, against a discovery cohort, comprising benign (n = 67) cases and lung cancer (n = 69) cases. A Random Forest method based analysis was used to identify the optimal biomarker panel for assigning disease status, which was then validated against a cohort from the Mayo Clinic, comprising patients with benign (n = 61) or malignant (n = 20) indeterminate lung nodules. Results: Our discovery efforts produced a seven-analyte plasma biomarker panel consisting of interleukin 6 (IL-6), IL-10, IL-1ra, sIL-2R&agr;, stromal cell-derived factor-1&agr;+&bgr;, tumor necrosis factor &agr;, and macrophage inflammatory protein 1 &agr;. The sensitivity and specificity of our panel in our validation cohort is 95.0% and 23.3%, respectively. The validated negative predictive value of our panel was 93.8%. Conclusion: We developed a seven-analyte plasma biomarker panel able to identify benign nodules, otherwise deemed indeterminate, with a high degree of accuracy. This panel may have clinical utility in risk-stratifying screen-detected lung nodules, decrease unnecessary follow-up imaging or invasive procedures, and potentially avoid unnecessary morbidity, mortality, and health care costs.

The addition of hemiarch replacement to aortic root surgery does not affect safety

OBJECTIVES A hemiarch reconstruction, using deep hypothermic circulatory arrest, is the conventional approach for proximal aortic arch reconstruction, but it carries risks of neurologic events and coagulopathy. The addition of a hemiarch reconstruction to an aortic root replacement may prevent future aortic arch pathology. Outcomes of this approach at a tertiary care institution were examined to determine whether the addition of a hemiarch reconstruction to an aortic root replacement conferred any additional risk. METHODS A total of 384 patients underwent an aortic root replacement between April 2004 and June 2012. Of them, 177 (46%) had hemiarch replacement. Propensity score matching yielded 133 pairs of patients receiving hemiarch and non-hemiarch. RESULTS Sinus segment diameter was similar between groups; ascending aortic diameter was greater in the hemiarch group (median 50 vs 44 mm; P < .001). The hemiarch group had longer perfusion (median 186 vs 120.5 minutes; P < .001) and crossclamp times (median 140 vs 104 minutes; P < .001); median circulatory arrest was 13 minutes. There was no difference, hemiarch versus no hemiarch, in 30-day mortality (3.0% vs 1.5%; P = .41), stroke (2.3% vs 4.5%; P = .31), reoperation for bleeding (11% vs 10%; P = .84), or overall survival (5-year 88.0% [95% confidence interval, 81.9-94.0] vs 91.4% [95% confidence interval, 85.8-96.9], P = .24). CONCLUSIONS In this series, aortic root replacement ± hemiarch reconstruction had low mortality. Addition of hemiarch replacement extended perfusion times but not at the expense of safety. Hemiarch reconstruction should be performed when the aortic root aneurysm extends into the distal ascending aorta.

Comparison of outcomes and presentation in men-versus-women with bicuspid aortic valves undergoing aortic valve replacement.

Gender disparities in short- and long-term outcomes have been documented in cardiac and valvular heart surgery. However, there is a paucity of data regarding these differences in the bicuspid aortic valve (BAV) population. The aim of this study was to examine gender-specific differences in short- and long-term outcomes after surgical aortic valve (AV) replacement in patients with BAV. A retrospective analysis was performed in 628 consecutive patients with BAV who underwent AV surgery from April 2004 to December 2013. To reduce bias when comparing outcomes by gender, propensity score matching obtained on the basis of potential confounders was used. Women with BAV who underwent AV surgery presented with more advanced age (mean 60.7 ± 13.8 vs 56.3 ± 13.6 years, p <0.001) and less aortic regurgitation (29% vs 44%, p <0.001) and had a higher risk for in-hospital mortality (mean Ambler score 3.4 ± 4.4 vs 2.5 ± 4.0, p = 0.015). After propensity score matching, women received more blood products postoperatively (48% vs 34%, p = 0.028) and had more prolonged postoperative lengths of stay (median 5 days [interquartile range 5 to 7] vs 5 days [interquartile range 4 to 6], p = 0.027). Operative, discharge, and 30-day mortality and overall survival were not significantly different. In conclusion, women with BAV who underwent AV surgery were older, presented with less aortic regurgitation, and had increased co-morbidities, lending higher operative risk. Although women received more blood products and had significantly longer lengths of stay, short- and long-term outcomes were similar.

Effect of aortic aneurysm replacement on outcomes after bicuspid aortic valve surgery: Validation of contemporary guidelines

OBJECTIVE Bicuspid aortic valve (BAV) disease is associated with aortic dilatation and aneurysm (AN) formation. The American College of Cardiology/American Heart Association (ACC/AHA) 2006 guidelines recommend replacement of the ascending aorta for an aortic diameter (AD)> 45 mm in patients undergoing aortic valve replacement (AVR). We evaluated the outcomes of AVR and AVR with aortic replacement (AVR/AN). METHODS We retrospectively reviewed (2004-2011) the data from 456 patients with BAV and compared the morbidity and mortality between the AVR and AVR/AN groups and 3 subgroups: AVR with an AD<45 mm; AVR/AN with an AD of 45 to 49 mm; and AVR/AN with an AD of ≥50 mm. Propensity score matching was used to reduce bias. RESULTS Of the 456 patients, 250 (55%) underwent AVR and 206 (45%) AVR/AN, with 98% compliance with the current guidelines. The overall 30-day mortality was 0.9%. The AVR AD<45-mm group had adjusted short- and medium-term survival similar to that of the AVR/AN AD 45- to 49-mm and AVR/AN AD≥50-mm groups, with a 30-day mortality of 0.8%, 0%, and 1.9%, respectively (P=.41). The propensity score-matched AVR/AN AD≥50-mm group had significantly greater rates of reintubation than either the AVR AD<45-mm (P=.012) or AVR/AN AD 45- to 49-mm (P=.04) group and greater rates of prolonged ventilation (P=.022) than the AVR AD<45-mm group. No significant differences were found in reoperation or myocardial infarction among the subgroups. CONCLUSIONS In patients with undergoing AVR, no increase was seen in morbidity or mortality when adding aortic replacement with an AD of 45 to 49 mm, in accordance with the 2006 ACC/AHA guidelines, although the AVR/AN AD≥50-mm group had a greater risk of respiratory complications. Our findings indicate that compliance with the ACC/AHA guidelines is safe in select centers.

Evaluation of a novel laparoscopic simulation laboratory curriculum

BACKGROUND Simulation training may be an invaluable tool in training and assessing surgeons. Questions remain regarding its true impact on acquisition of laparoscopic skills and their transferability to the operating room. METHODS Twenty general surgery residents completed 5 exercises: bean drop/rope drill, foam cutting/endoloop, checkerboard, endostitch, and suturing/intracorporeal knot. After baseline scoring, residents had 3 weeks to practice before re-testing. Statistical analysis of objective and subjective scores included the signed rank test or paired t-test, the Kruskal-Walis test, the McNemar test, and the Global Operative Assessment of Laparoscopic Skills (GOALS). P < .05 was considered significant. RESULTS Five postgraduate year (PGY) 4 and 15 PGY 1-3 residents completed the curriculum. When compared with baseline, overall scores improved (P < .05) in all categories except for the bean drop/rope drill, which improved on objectively measured tasks only (dropped beads and beads threaded). The foam cutting/endoloop task was mastered by a majority of trainees at baseline leaving no room for improvement. CONCLUSION The results of this study reinforce that simulation leads to improvement in laparoscopic skills and that our curriculum is a valid educational tool. Further studies are needed to validate whether this results in improved skills in the operating room.

From unicuspid to quadricuspid: the impact of aortic valve morphology on 3D hemodynamics

Background The purpose of this study was to assess the impact of aortic valve morphology on aortic 3D blood flow dynamics and wall shear stress (WSS) in normal and a wide range of congenitally altered aortic valves ranging from unicuspid to quadricuspid morphology. Methods In-vivo aortic 3D hemodynamics were evaluated by MRI in 17 patients with unicuspid (n=3), bicuspid (n=9, 3 true bicuspid, 3 right-left (RL) coronary leaflet fusion, and 3 right-non (RN) coronary leaflet fusion), trileaflet (n=3), and quadricuspid aortic valves (n=2). Valve morphology and dynamics were assessed using 2D CINE MRI. Aortic blood flow was measured using ECG and respiration synchronized 4D flow MRI with full volumetric coverage of the aorta. Data analysis included co-registered visualization of aortic valve morphology with systolic 3D blood flow and grading of valve-specific aortic out-flow patterns. The influence of valve geometry on aortic hemodynamics was quantified by calculation of valve flow angle and segmental distribution of ascending aorta WSS. Results All congenitally altered valves showed marked flow derangement, elevated velocity jets along the aortic wall and distinct flow impingement locations. While all RLBAV valves were associated with flow jets directed towards the right anterior aortic wall, RN-fusion and unicuspid valves showed jet patterns towards the right-posterior wall. Quantitative analysis revealed higher flow angles for unicuspid, true BAV, RN-BAV, RL-BAV, and quadricuspid

A Subjective Assessment of Medical Student Perceptions on Animal Models in Medical Education

BACKGROUND There remains increasing societal pressure to limit the use of animals in medical education. The purpose of this study was to explore the subjective perceptions that medical students exposed to an animal model curriculum feel about the laboratory and its continued use. METHODS A 6-month prospective study was performed during the medical college core surgical clerkship. Medical students participated in both a trainer-based simulation workshop (dry laboratory) and a live-tissue animal laboratory (wet laboratory) in addition to their operative experience. Students completed a 23-question Likert survey at the end of the surgical clerkship. Data were compared using the chi-square test. RESULTS More students reported increased subjective stress levels in the wet laboratory (32.4%) compared with the dry laboratory (5.4%, p < 0.001). In addition, more students felt the wet laboratory (vs dry laboratory) prepared them for the anxiety (55.4% vs 24.3%, p < 0.001) and technical demands (67.6% vs 44.6%, p = 0.005) of the operating room. The majority of medical students (>90%) felt the wet laboratory was an important experience and should be continued. CONCLUSIONS The results of this study show a subjective benefit perceived by medical students when it comes to participation in an animal laboratory during their surgical clerkship. As such, over 90% of participating medical students feel the animal laboratory is important in medical education and should be continued in their surgical curriculum.

Higher clinical performance during a surgical clerkship is independently associated with matriculation of medical students into general surgery.

BACKGROUND The purpose of our study was to determine the predictive impact of individual academic measures for the matriculation of senior medical students into a general surgery residency. METHODS Academic records were evaluated for third-year medical students (n = 781) at a single institution between 2004 and 2011. Cohorts were defined by student matriculation into either a general surgery residency program (n = 58) or a non-general surgery residency program (n = 723). Multivariate logistic regression was performed to evaluate independently significant academic measures. RESULTS Clinical evaluation raw scores were predictive of general surgery matriculation (P = .014). In addition, multivariate modeling showed lower United States Medical Licensing Examination Step 1 scores to be independently associated with matriculation into general surgery (P = .007). CONCLUSIONS Superior clinical aptitude is independently associated with general surgical matriculation. This is in contrast to the negative correlation United States Medical Licensing Examination Step 1 scores have on general surgery matriculation. Recognizing this, surgical clerkship directors can offer opportunities for continued surgical education to students showing high clinical aptitude, increasing their likelihood of surgical matriculation.

Use of Historical Surgical Times to Predict Duration of Primary Aortic Valve Replacement

OBJECTIVES To test whether a model using a historical average of a surgeons surgical times for primary aortic valve replacements is a more accurate predictor of actual surgical times than solely relying on a surgeons estimate. DESIGN Retrospective review. SETTING Single university hospital that serves as a tertiary referral center. PARTICIPANTS All patients undergoing primary aortic valve replacement between October 2008 and September 2014. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Estimation biases, calculated as the difference between actual and predicted surgical time, were compared between the surgeon and the model, which included between 2 and 20 cases in the historical average. Kruskal-Wallis analysis of variance was used to compare all values. Pairwise comparisons were made using the Steel-Dwass test to determine whether using more cases in the model resulted in smaller estimation biases. Using the historical model reduced mean overestimation bias from 55.30 minutes to 0.90-to-4.67 minutes. No significant difference was seen based on the number of cases used. CONCLUSIONS An uncomplicated model can assist in providing comparatively unbiased estimations of surgical time for aortic valve replacements. The model can rely on a fewer number of cases (eg, 5) and does not benefit from including more cases (eg, 20).

The utility of mock oral examinations in preparation for the American Board of Surgery certifying examination.

BACKGROUND Determine the utility of mock oral examinations in preparation for the American Board of Surgery certifying examination (ABS CE). METHODS Between 2002 and 2012, blinded data were collected on 63 general surgery residents: 4th and 5th-year mock oral examination scores, first-time pass rates on ABS CE, and an online survey. RESULTS Fifty-seven residents took the 4th-year mock oral examination: 30 (52.6%) passed and 27 (47.4%) failed, with first-time ABS CE pass rates 93.3% and 81.5% (P = .238). Fifty-nine residents took the 5th-year mock oral examination: 28 (47.5%) passed and 31 (52.5%) failed, with first-time ABS CE pass rates 82.1% and 93.5% (P = .240). Thirty-eight responded to the online survey, 77.1% ranked mock oral examinations as very or extremely helpful with ABS CE preparation. CONCLUSIONS Although mock oral examinations and ABS CE passing rates do not directly correlate, residents perceive the mock oral examinations to be helpful.