Bachelor of Science, University of Minnesota Twin Cities, Biology (2003)
Doctor of Medicine, Harvard University, MD (2009)
Residency, Stanford University Medical Center, General Surgery
My research focuses on identifying ways to improve both the quality and efficiency of existing surgical practices. This is accomplished through the use of clinical trials, cost-effectiveness modeling and dataset analysis.
To test the hypothesis that an exploratory proteomics analysis of urine proteins with subsequent development of validated urine biomarker panels would produce molecular classifiers for both the diagnosis and prognosis of infants with necrotizing enterocolitis (NEC).Urine samples were collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time of initial clinical concern for disease. The urine from 59 infants was used for candidate biomarker discovery by liquid chromatography/mass spectrometry. The remaining 60 samples were subject to enzyme-linked immunosorbent assay for quantitative biomarker validation.A panel of 7 biomarkers (alpha-2-macroglobulin-like protein 1, cluster of differentiation protein 14, cystatin 3, fibrinogen alpha chain, pigment epithelium-derived factor, retinol binding protein 4, and vasolin) was identified by liquid chromatography/mass spectrometry and subsequently validated by enzyme-linked immunosorbent assay. These proteins were consistently found to be either up- or down-regulated depending on the presence, absence, or severity of disease. Biomarker panel validation resulted in a receiver-operator characteristic area under the curve of 98.2% for NEC vs sepsis and an area under the curve of 98.4% for medical NEC vs surgical NEC.We identified 7 urine proteins capable of providing highly accurate diagnostic and prognostic information for infants with suspected NEC. This work represents a novel approach to improving the efficiency with which we diagnose early NEC and identify those at risk for developing severe, or surgical, disease.
View details for DOI 10.1016/j.jpeds.2013.10.091
View details for PubMedID 24433829
Early identification of patients at risk for developing pancreatic fistula (PF) after pancreaticoduodenectomy (PD) may facilitate prevention or treatment strategies aimed at reducing its associated morbidity.A retrospective review of 176 consecutive PD performed between 2006 and 2011 was conducted in order to analyze the association between the serum amylase on postoperative day 1 (POD1) and the development of PF.Serum amylase was recorded on POD1 in 146 of 176 PD cases (83.0 %). Twenty-seven patients (18.5 %) developed a postoperative PF: 6 type A, 19 type B, and 2 type C. Patients with a PF had a mean serum amylase on POD1 of 659 ± 581 compared to 246 ± 368 in those without a fistula (p < 0.001). On logistic regression, a serum amylase >140 U/L on POD1 was strongly associated with developing a PF (OR, 5.48; 95 % CI, 1.94-15.44). Sensitivity and specificity of a postoperative serum amylase >140 U/L was 81.5 and 55.5 %, respectively. Positive and negative predictive values were 29.3 and 93.0 %, respectively.An elevated serum amylase on POD1 may be used, in addition to other prognostic factors, to help stratify risk for developing PF following PD.
View details for DOI 10.1007/s11605-013-2293-3
View details for PubMedID 23903930
Necrotizing enterocolitis (NEC) is a major source of neonatal morbidity and mortality. Since there is no specific diagnostic test or risk of progression model available for NEC, the diagnosis and outcome prediction of NEC is made on clinical grounds. The objective in this study was to develop and validate new NEC scoring systems for automated staging and prognostic forecasting.A six-center consortium of university based pediatric teaching hospitals prospectively collected data on infants under suspicion of having NEC over a 7-year period. A database comprised of 520 infants was utilized to develop the NEC diagnostic and prognostic models by dividing the entire dataset into training and testing cohorts of demographically matched subjects. Developed on the training cohort and validated on the blind testing cohort, our multivariate analyses led to NEC scoring metrics integrating clinical data.MACHINE LEARNING USING CLINICAL AND LABORATORY RESULTS AT THE TIME OF CLINICAL PRESENTATION LED TO TWO NEC MODELS: (1) an automated diagnostic classification scheme; (2) a dynamic prognostic method for risk-stratifying patients into low, intermediate and high NEC scores to determine the risk for disease progression. We submit that dynamic risk stratification of infants with NEC will assist clinicians in determining the need for additional diagnostic testing and guide potential therapies in a dynamic manner.http://translationalmedicine.stanford.edu/cgi-bin/NEC/index.pl and smartphone application upon request.
View details for DOI 10.1371/journal.pone.0089860
View details for PubMedID 24587080
To assess the cost-effectiveness of diagnostic laparoscopy, computed tomography (CT), and magnetic resonance imaging (MRI) after indeterminate ultrasonography in pregnant women with suspected appendicitis.A decision-analytic model was developed to simulate appendicitis during pregnancy taking into consideration the health outcomes for both the pregnant women and developing fetuses. Strategies included diagnostic laparoscopy, CT, and MRI. Outcomes included positive appendectomy, negative appendectomy, maternal perioperative complications, preterm delivery, fetal loss, childhood cancer, lifetime costs, discounted life expectancy, and incremental cost-effectiveness ratios.Magnetic resonance imaging is the most cost-effective strategy, costing $6,767 per quality-adjusted life-year gained relative to CT, well below the generally accepted $50,000 per quality-adjusted life-year threshold. In a setting where MRI is unavailable, CT is cost-effective even when considering the increased risk of radiation-associated childhood cancer ($560 per quality-adjusted life-year gained relative to diagnostic laparoscopy). Unless the negative appendectomy rate is less than 1%, imaging of any type is more cost-effective than proceeding directly to diagnostic laparoscopy.Depending on imaging costs and resource availability, both CT and MRI are potentially cost-effective. The risk of radiation-associated childhood cancer from CT has little effect on population-level outcomes or cost-effectiveness but is a concern for individual patients. For pregnant women with suspected appendicitis, an extremely high level of clinical diagnostic certainty must be reached before proceeding to operation without preoperative imaging.
View details for DOI 10.1097/AOG.0b013e3182a4a085
View details for PubMedID 24084540
HYPOTHESIS In July 2011, surgical interns were prohibited from being on call from home by the new residency review committee guidelines on work hours. In support of the new Accreditation Council for Graduate Medical Education work-hour restrictions, we expected that a period of intern home call would correlate with increased rates of postoperative morbidity and mortality. DESIGN Prospective cohort. SETTING University-affiliated tertiary Veterans Affairs Medical Center. PATIENTS All patients identified in the Veterans Affairs National Surgical Quality Improvement Program database who underwent an operation performed by general, vascular, urologic, or cardiac surgery services between fiscal years (FYs) 1999 and 2010 were included. MAIN OUTCOME MEASURES During FYs 1999-2003, the first call for all patients went to an in-hospital intern. In the subsequent period (FYs 2004-2010), the first call went to an intern on home call. Thirty-day unadjusted morbidity and mortality rates and risk-adjusted observed to expected ratios were analyzed by univariate analysis and joinpoint regression, respectively. RESULTS Unadjusted overall morbidity rates decreased between 1999-2003 and 2004-2010 (12.14% to 10.19%, P = .003). The risk-adjusted morbidity observed to expected ratios decreased at a uniform annual percentage change of -6.03% (P < .001). Unadjusted overall mortality rates also decreased between the 2 periods (1.76% to 1.26%; P = .05). There was no significant change in the risk-adjusted mortality observed to expected ratios during the study. CONCLUSIONS The institution of an intern home call schedule was not associated with increased rates of postoperative morbidity or mortality.
View details for DOI 10.1001/jamasurg.2013.1063
View details for PubMedID 23715944
Necrotizing enterocolitis (NEC), a common cause of neonatal morbidity and mortality, is strongly associated with prematurity and typically occurs following initiation of enteral feeds. Mild NEC is adequately treated by cessation of enteral feeding, empiric antibiotics, and supportive care. Approximately 50% of affected infants will develop progressive intestinal necrosis requiring urgent operation. Several surgical techniques have been described, but there is no clear survival benefit for any single operative approach. While debate continues regarding the optimal surgical management for infants with severe NEC, future progress will likely depend on the development of improved diagnostic tools and preventive therapies.
View details for DOI 10.1016/j.clp.2012.12.011
View details for PubMedID 23415269
The vast majority of choledochal cysts occur as either saccular or diffuse fusiform dilatation of the extrahepatic bile duct. We describe the complete resection of a rare single intrahepatic choledochal cyst communicating with the extrahepatic biliary tree. While previous reports describe partial resection with enteral drainage, we performed a complete resection of this rare choledochal cyst.
View details for DOI 10.1016/j.jpedsurg.2012.12.016
View details for Web of Science ID 000316470100037
View details for PubMedID 23480926
Hospital readmission has attracted attention from policymakers as a measure of quality and a target for cost reduction. The aim of the study was to evaluate the frequency and patterns of rehospitalization after a pancreaticoduodenectomy (PD).The records of all patients undergoing a PD at an academic medical centre for malignant or benign diagnoses between January 2006 and September 2011 were retrospectively reviewed. The incidence, aetiology and predictors of subsequent readmission(s) were analysed.Of 257 consecutive patients who underwent a PD, 50 (19.7%) were readmitted within 30 days from discharge. Both the presence of any post-operative complication (P = 0.049) and discharge to a nursing/rehabilitation facility or to home with health care services (P = 0.018) were associated with readmission. The most common reasons for readmission were diet intolerance (36.0%), pancreatic fistula/abscess (26.0%) and superficial wound infection (8.0%). Nine (18.0%) readmissions had lengths of stay of 2 days or less and in four of those (8.0%) diagnostic evaluation was eventually negative.Approximately one-fifth of patients require hospital readmission within 30 days of discharge after a PD. A small fraction of these readmissions are short (2 days or less) and may be preventable or manageable in the outpatient setting.
View details for DOI 10.1111/j.1477-2574.2012.00563.x
View details for Web of Science ID 000313548400009
View details for PubMedID 23297725
Necrotising enterocolitis (NEC) is a major source of neonatal morbidity and mortality. The management of infants with NEC is currently complicated by our inability to accurately identify those at risk for progression of disease prior to the development of irreversible intestinal necrosis. We hypothesised that integrated analysis of clinical parameters in combination with urine peptide biomarkers would lead to improved prognostic accuracy in the NEC population.Infants under suspicion of having NEC (n=550) were prospectively enrolled from a consortium consisting of eight university-based paediatric teaching hospitals. Twenty-seven clinical parameters were used to construct a multivariate predictor of NEC progression. Liquid chromatography/mass spectrometry was used to profile the urine peptidomes from a subset of this population (n=65) to discover novel biomarkers of NEC progression. An ensemble model for the prediction of disease progression was then created using clinical and biomarker data.The use of clinical parameters alone resulted in a receiver-operator characteristic curve with an area under the curve of 0.817 and left 40.1% of all patients in an 'indeterminate' risk group. Three validated urine peptide biomarkers (fibrinogen peptides: FGA1826, FGA1883 and FGA2659) produced a receiver-operator characteristic area under the curve of 0.856. The integration of clinical parameters with urine biomarkers in an ensemble model resulted in the correct prediction of NEC outcomes in all cases tested.Ensemble modelling combining clinical parameters with biomarker analysis dramatically improves our ability to identify the population at risk for developing progressive NEC.
View details for DOI 10.1136/gutjnl-2013-305130
View details for PubMedID 24048736
Chest wall reconstruction in children is typically accomplished with either primary tissue repair or synthetic mesh prostheses. Primary tissue repair has been associated with high rates of scoliosis, whereas synthetic prostheses necessitate the placement of a permanent foreign body in growing children. This report describes the use of biologic mesh (Permacol; Covidien, Mansfield, MA) as an alternative to both tissue repair and synthetic prostheses in pediatric chest wall reconstruction.A retrospective chart review was performed identifying patients undergoing chest wall reconstruction with biologic mesh at our tertiary referral children's hospital between 2007 and 2011. Data collection included patient demographics, indication for chest wall resection, number of ribs resected, the administration of postoperative radiation, length of follow-up, postoperative complications, and the degree of spinal angulation (preoperatively and at most recent follow-up).Five patients (age, 9.0-21.7 years; mean, 15.4 years) underwent resection for primary chest wall malignancy followed by reconstruction with biologic mesh (Permacol) during the study period. There were no postoperative mesh-related complications, and none of the patients developed clinically significant scoliosis (follow-up, 1.1-2.6 years; mean 1.9 years).Biologic mesh offers a safe and dependable alternative to both primary tissue repair and synthetic mesh in pediatric patients undergoing chest wall reconstruction.
View details for DOI 10.1016/j.jpedsurg.2012.05.002
View details for Web of Science ID 000306523300039
View details for PubMedID 22813819
The proposed benefits of laparoscopic inguinal hernia repair in the pediatric population include less postoperative pain, smaller scars, and easier access to the contralateral groin. This is countered by slightly higher recurrence rates reported in some series. These differences are attributable to variation in the laparoscopic technique, surgeon experience, and certain anatomic features. We describe a modification of the laparoscopic-assisted transcutaneous hernia repair that achieves transfixation ligature of the hernia sac and that may further reduce recurrence.Institutional review board approval was obtained, and a retrospective chart review of all patients undergoing repair of symptomatic hernias using this new technique was carried out. Data collection included demographics, laterality of hernia, operative time, recurrence rate, and complications.Twenty-one patients (age 1-144 months) underwent hernia repair between October 2009 and October 2010 using a novel technique of transcutaneous transfixation ligature of the neck of the hernia sac. The mean operative time was 18 minutes (8-35 minutes). Follow-up was from 1 to 12 months. There was no intraoperative or postoperative complication and no recurrences to date.The technique described is a modification of the existing laparoscopic-assisted transcutaneous inguinal hernia repair that more closely approximates the criterion standard open repair. The technique addresses some prevailing concerns with the initially described method of transcutaneous repair, and short-term outcomes are positive. Long-term outcomes remain to be defined.
View details for DOI 10.1016/j.jpedsurg.2011.03.022
View details for Web of Science ID 000293950100040
View details for PubMedID 21843740
Surgical innovation involves the conceptualization, research, and translation of a novel idea into a viable procedure or device. The technological advancements made within the field of pediatric surgery over the last century have led to major improvements in patient care and outcomes. There has, however, been a parallel increase in the complexity of the regulatory bodies governing research and device implementation. This article briefly outlines the history of innovation in pediatric surgery, describes the existing regulatory bodies governing surgical research and device development (i.e., Department of Health and Human Services, Food and Drug Administration), and offers a set of guidelines for the pediatric surgeon planning to incorporate a new procedure or device into clinical practice.
View details for DOI 10.1089/lap.2010.0342
View details for Web of Science ID 000290557500017
View details for PubMedID 21443434
View details for PubMedID 21537230
Despite many advances in human embryonic stem cell (hESC) technology the ethical dilemma involving the destruction of a human embryo is one factor that has limited the development of hESC based clinical therapies. Two recent reports describing the production of pluripotent stem cells following the in vitro reprogramming of human somatic cells with certain defined factors illustrate one potential method of bypassing the ethical debate surrounding hESCs (Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007 Dec;318(5858):1917-1920; Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007 Nov;131(5): 861-872.). Other alternative methods include nuclear transfer, altered nuclear transfer, and parthenogenesis; each with its own set of advantages and disadvantages. This review discusses recent advances in these technologies with specific focus on the issues of embryo destruction, oocyte recovery, and the potential of each technology to produce large scale, patient specific cell transplantation therapies that would require little or no immunosuppression.
View details for DOI 10.1016/j.trre.2008.04.002
View details for PubMedID 18631882
Pancreatic development in mammals is controlled in part by the expression and function of numerous genes encoding transcription factors. Yet, how these regulate each other and their target genes is incompletely understood. Embryonic stem (ES) cells have recently been shown to be capable of differentiating into pancreatic progenitor cells and insulin-producing cells, representing a useful in vitro model system for studying pancreatic and islet development. To generate tools to study the relationships of transcription factors in pancreatic development we have established seven unique mouse ES cell lines with tetracycline-inducible expression of either Hnf4alpha, Hnf6, Nkx2.2, Nkx6.1, Pax4, Pdx1, and Ptf1a cDNAs. Each of the cell lines was characterized for induction of transgene expression after exposure to doxycycline (DOX) by quantitative real-time PCR and immunofluorescence microscopy. Transgene expression in the presence of DOX was at least 97-fold that seen in untreated cells. Immunofluorescent staining of DOX-treated cultures showed efficient (>95% of cells) transgene protein expression while showing <5% positive staining in uninduced cells. Each of the ES cell lines maintained their pluripotency as measured by teratoma formation. Furthermore, transgene expression can be efficiently achieved in vivo through DOX administration to mice. The establishment of ES cell lines with temporally controllable induction of critical pancreatic transcription factor genes provides a new set of tools that could be used to interrogate gene regulatory networks in pancreatic development and potentially generate greater numbers of beta cells from ES cells.
View details for Web of Science ID 000243752900019
View details for PubMedID 17253956
The latest generation of interactive cardiac magnetic resonance (MR) scanners has made cardiac interventions with real-time MRI possible. To date, cardiac MRI has been mostly applied to measure myocardial perfusion, viability, and regional function, but now the application of cardiac MRI can be extended to cardiovascular interventions. The purpose of this article is to illustrate the potential of MRI in stem cell therapy for cardiac restoration.We have applied MRI to (1) interactively target myocardial injections with a novel stem cell delivery catheter, and to compare gadolinium/blue dye injections to pathology; (2) assess myocardial perfusion with MR first pass imaging in an infarct model treated with stem cell therapy versus control animals; (3) measure regional functional changes using myocardial tissue tagging in the same animals.We were able to demonstrate the feasibility and safety of myocardial injections under MR fluoroscopy. The intramyocardial distribution of the blue dye at necropsy correlated well with the extent of gadolinium, as detected with a three-dimensional inversion recovery MR pulse sequence for late enhancement immediately after contrast injection. Preliminary results show that myocardial perfusion reserve and regional wall motion improved in the stem-cell-treated group, compared to a control group.These preliminary results suggest that (1) injections into the LV myocardium can be performed under real-time MRI guidance using a directed catheter approach, and (2) regional myocardial perfusion and function, measured with MRI, both improve after stem cell therapy. This ongoing study demonstrates the potential of MRI for image-guided interventions, combined with detailed evaluation of anatomy, function, perfusion, and viability.
View details for PubMedID 15009770