Steve Kwon

Abstract Boolean network is a modeling tool that describes a dynamic system with binary variables and their logical transition formulas. Recent studies in precision medicine use a Boolean network to discover critical genetic alterations that may lead to cancer or target genes for effective therapies to individuals. In this paper, we study a logical inference problem in a Boolean network to find all such critical genetic alterations in a minimal (parsimonious) way. We propose a bilevel integer programming model to find a single minimal genetic alteration. Using the bilevel integer programming model, we develop a branch and bound algorithm that effectively finds all of the minimal alterations. Through a computational study with eleven Boolean networks from the literature, we show that the proposed algorithm finds solutions much faster than the state-of-the-art algorithms in large data sets.

Approximately 2.4 million Americans are infected with hepatitis C virus (HCV) and persons born from 1945 through 1965 (i.e., baby boomers) account for nearly three-fourths of all HCV infections. The purpose of this study was to implement HCV screening for baby boomers presenting to a community hospital emergency department (ED) and to facilitate linkage to care. We developed a process within our electronic medical record system to screen patients for HCV testing eligibility, link eligible patients to laboratory orders, notify patients of HCV test results (via patient navigator), and track follow-up care. We tracked performance from February 2016 to December 2018. Sociodemographic compositions and linkage to care rates of all participants were evaluated. 14,927 patients from the birth cohort of 1945-1965 were screened for HCV. Of those tested, 555 (3.7%) had a positive HCV antibody test and 147 were HCV RNA positive patients (1.0%) demonstrating that only 27% of HCV antibody positive individuals were chronically infected. Males, black race and USA-born baby boomers had a higher prevalence of HCV antibody and viral load positivity (p<0.05). Initially, only 17.6% of patients were ultimately linked to care, which improved to over 94% after the implementation of patient navigation support. There is a need for HCV screening protocol in the community. The cost of implementing an HCV screening program must include information technology and a team of care coordinators to improve screening rates and facilitate linkage to continual care using the four pillars framework.

This prospective cohort study sought to identify predictors of functional decline in patients aged 65 years or older who underwent major, nonemergent abdominal or thoracic surgery in our tertiary hospital from 2006 to 2008. We used the Stanford Health Assessment Questionnaire-Disability Index (HAQ-DI) to evaluate functional decline; a 0.1 or greater increase was used to indicate a clinically significant decline. The preoperative Duke Activity Status Index (DASI) and a physical function score (PFS), assessing gait speed, grip strength, balance, and standing speed, were evaluated as predictors of decline. We enrolled 215 patients (71.2 ± 5.2 years; 56.7% female); 204 completed follow-up HAQ assessments (71.1 ± 5.3 years; 57.8% female). A significant number of patients had functional decline out to 1 year. Postoperative HAQ-DI increases of 0.1 or greater occurred in 45.3 per cent at 1 month, 30.1 per cent at 3 months, and 28.3 per cent at 1 year. Preoperative DASI and PFS scores were not predictors of functional decline. Male sex at 1 month (odds ratio [OR], 3.05; 95% confidence interval [CI], 1.41 to 6.85); American Society of Anesthesiologists class (OR, 3.41; 95% CI, 1.31 to 8.86), smoking (OR, 3.15; 95% CI, 1.27 to 7.85), and length of stay (OR, 1.09; 95% CI, 1.01 to 1.16) at 3 months; and cancer diagnosis at 1 year (OR, 2.6; 95% CI, 1.14 to 5.96) were associated with functional decline.

... Errol C. MD, FAAP; Chou, Sharon H. BS; Kwon, Steve BS. Article Outline. Collapse Box Author Information. From the Department of Pediatrics, University of Illinois, College of Medicine at Rockford, Rockford, IL. Reprints: Errol C. Baptist, MD, FAAP, 461 North Mulford Road, Suite ...

The Fontan operation has successfully prolonged the lives of patients born with single-ventricle physiology. A long-term consequence of post-Fontan elevation in systemic venous pressure and low cardiac output is chronic liver inflammation and cirrhosis, which lead to an increased risk of hepatocellular carcinoma (HCC). Surgical management of patients with post-Fontan physiology and HCC is challenging, as the requirement for adequate preload in order to sustain cardiac output conflicts with the low central venous pressure (CVP) that minimizes blood loss during hepatectomy. Consequently, liver resection is rarely performed, and most reports describe nonsurgical treatments for locoregional control of the tumors in these patients. Here, we present a multidisciplinary approach to a successful surgical resection of a HCC in a patient with Fontan physiology.

This prospective cohort study sought to identify predictors of functional decline in patients aged 65 years or older who underwent major, nonemergent abdominal or thoracic surgery in our tertiary hospital from 2006 to 2008. We used the Stanford Health Assessment Questionnaire-Disability Index (HAQ-DI) to evaluate functional decline; a 0.1 or greater increase was used to indicate a clinically significant decline. The preoperative Duke Activity Status Index (DASI) and a physical function score (PFS), assessing gait speed, grip strength, balance, and standing speed, were evaluated as predictors of decline. We enrolled 215 patients (71.2 ± 5.2 years; 56.7% female); 204 completed follow-up HAQ assessments (71.1 ± 5.3 years; 57.8% female). A significant number of patients had functional decline out to 1 year. Postoperative HAQ-DI increases of 0.1 or greater occurred in 45.3 per cent at 1 month, 30.1 per cent at 3 months, and 28.3 per cent at 1 year. Preoperative DASI and PFS scores were n...

There are increasing efforts towards improving the quality and safety of surgical care while decreasing the costs. In Washington state, there has been a regional and unique approach to surgical quality improvement. The development of the Surgical Care and Outcomes Assessment Program (SCOAP) was first described 5 years ago. SCOAP is a peer-to-peer collaborative that engages surgeons to determine the many process of care metrics that go into a "perfect" operation, track on risk adjusted outcomes that are specific to a given operation, and create interventions to correct under performance in both the use of these process measures and outcomes. SCOAP is a thematic departure from report card oriented QI. SCOAP builds off the collaboration and trust of the surgical community and strives for quality improvement by having peers change behaviors of one another. We provide, here, the progress of the SCOAP initiative and highlight its achievements and challenges.

There is limited evidence to characterize the burden of unmet need of surgical diseases in low- and middle-income countries. The purpose of this study was to determine rate of deaths attributable to a surgical condition and reasons for not seeking surgical care in Sierra Leone. The Surgeons OverSeas Assessment of Surgical Need (SOSAS) is a survey tool developed collaboratively to be used for cross-sectional data collection of the prevalence of surgical conditions in any country. A population-weighted cluster-sample household survey was conducted throughout Sierra Leone in 2012 using the SOSAS survey tool. Total of 1,840 households (11,870 individuals) were sampled, yielding a 98.3 % response rate. Overall, there were 709 total deaths reported (6.0 %). The mean age at death was 36.4 ± 30.1 years: 330 (46.6 %) were female. Most deaths occurred at home (58.1 % vs. 34.1 % in hospitals). Of the 709 deaths, 237 (33.4 %) were associated with conditions included in our predefined surgical disease category. Abdominal distension/pain was the most commonly associated surgical condition (13.9 %) followed by perinatal bleeding/illness (6.0 %). Among the 237 with surgical conditions, 51 (21.9 %) did not seek medical care, most commonly because of a lack of money (35.3 %) or inability to provide timely care (37.3 %). A large proportion of deaths in Sierra Leone was associated with surgical conditions, the majority of which did not undergo surgical intervention. Our results indicate that to remove barriers to effective surgical care in Sierra Leone policymakers should first focus on relieving financial burdens and increasing access to timely surgical care.

Significant gaps exist in the provision of surgical care in low- and middle-income countries (LMICs). The purpose of this study was to develop a metric to monitor surgical capacity in LMICs. The World Health Organization developed a survey called the Tool for Situational Analysis to Assess Emergency and Essential Surgical Care. Using this tool, we developed a surgical capacity scoring index and assessed its usefulness with data from Sierra Leone, Liberia, and the Solomon Islands. There were data from 10 hospitals in Sierra Leone, 16 hospitals in Liberia, and 9 hospitals in the Solomon Islands. The levels of surgical capacity were created using our scoring index based on a possible 100 points: level 1 for hospitals with <50 points, level 2 with 50-70 points, level 3 with 70-80 points, and level 4 with >80 points. In Sierra Leone, 44% of the hospitals had a surgical capacity rating of level 1, 50% level 2, and 10% level 3. In Liberia, 37.5% of the hospitals had a surgical capacity rating of level 1, 56.3% level 2, and only one hospital level 3. For Sierra Leone and Liberia, two factors--infrastructure and personnel--had the greatest deficits. In the Solomon Islands, 44.4% of the hospitals had their surgical capacity rated at level 1, 22.2% at level 2, 11.1% at level 3, and 22.2% at level 4. Pending pilot testing for reliability and validity, it appears that a systematic hospital surgical capacity index can identify areas for improvement and provide an objective measure for monitoring changes over time.

Journal of the American College of Surgeons, Volume 211, Issue 3, Pages S96-S97, September 2010, Authors:David R. Flum, MD, MPH, FACS; Steve Kwon, MD; Kara MacLeod, MD; Bruce Wang, MD; Rafael Alfonso, MD; Louis P. Garrison, MD; Sean D. Sullivan, MD. ...

Phosphatidylinositide 3-kinase (PI3K) is deregulated in many human tumor types, including primary liver malignancies. The kinase v-akt murine thymoma viral oncogene homolog 1 (Akt) and mammalian target of rapamycin complex (mTORC1) are effectors of PI3K that promote cell growth and survival, but their individual roles in tumorigenesis are not well defined. In livers of albumin (Alb)-Cre mice, we selectively deleted tuberous sclerosis (Tsc)1, a negative regulator of Ras homolog enriched in brain and mTORC1, along with Phosphatase and tensin homolog (Pten), a negative regulator of PI3K. Tumor tissues were characterized by histologic and biochemical analyses. The Tsc1fl/fl;AlbCre, Ptenfl/fl;AlbCre, and Tsc1fl/fl;Ptenfl/fl;AlbCre mice developed liver tumors that differed in size, number, and histologic features. Livers of Tsc1fl/fl;AlbCre mice did not develop steatosis; tumors arose later than in the other strains of mice and were predominantly hepatocellular carcinomas. Livers of the Ptenfl/fl;AlbCre mice developed steatosis and most of the tumors that formed were intrahepatic cholangiocarcinomas. Livers of Tsc1fl/fl;Ptenfl/fl;AlbCre formed large numbers of tumors, of mixed histologies, with the earliest onset of any strain, indicating that loss of Tsc1 and Pten have synergistic effects on tumorigenesis. In these mice, the combination of rapamycin and MK2206 was more effective in reducing liver cell proliferation and inducing cell death than either reagent alone. Tumor differentiation correlated with Akt and mTORC1 activities; the ratio of Akt:mTORC1 activity was high throughout the course of intrahepatic cholangiocarcinomas development and low during hepatocellular carcinoma development. Compared with surrounding nontumor liver tissue, tumors from all 3 strains had increased activities of Akt, mTORC1, and mitogen-activated protein kinase and overexpressed fibroblast growth factor receptor 1. Inhibition of fibroblast growth factor receptor 1 in Tsc1-null mice suppressed Akt and mitogen-activated protein kinase activities in tumor cells. Based on analyses of knockout mice, mTORC1 and Akt have different yet synergistic effects during the development of liver tumors in mice.

Although infrequent, metastases from primary cu-taneous squamous cell carcinoma (SCC) do oc-cur, with reported rates ranging from 0.3% to 16%.1-3 Parotid nodes, followed by cervical nodes, are com-monly the initial site of metastasis arising from primary SCC of the head ...

Studies suggest that computed tomography and ultrasonography can effectively diagnose and rule out appendicitis, safely reducing negative appendectomies (NAs); however, some within the surgical community remain reluctant to add imaging to clinical evaluation of patients with suspected appendicitis. The Surgical Care and Outcomes Assessment Program (SCOAP) is a physician-led quality initiative that monitors performance by benchmarking processes of care and outcomes. Since 2006, accurate diagnosis of appendicitis has been a priority for SCOAP. The objective of this study was to evaluate the association between imaging and NA in the general community. Data were collected prospectively for consecutive appendectomy patients (age > 15 years) at nearly 60 hospitals. SCOAP data are obtained directly from clinical records, including radiological, operative, and pathological reports. Multivariate logistic regression models were used to examine the association between imaging and NA. Tests for trends over time were also conducted. Among 19,327 patients (47.9% female) who underwent appendectomy, 5.4% had NA. Among patients who were imaged, frequency of NA was 4.5%, whereas among those who were not imaged, it was 15.4% (P < 0.001). This association was consistent for men (3% vs 10%, P < 0.001) and for women of reproductive age (6.9% vs 24.7%, P < 0.001). In a multivariate model adjusted for age, sex, and white blood cell count, odds of NA for patients not imaged were 3.7 times the odds for those who received imaging (95% CI: 3.0-4.4). Among SCOAP hospitals, use of imaging increased and NA decreased significantly over time; frequency of perforation was unchanged. Patients who were not imaged during workup for suspected appendicitis had more than 3 times the odds of NA as those who were imaged. Routine imaging in the evaluation of patients suspected to have appendicitis can safely reduce unnecessary operations. Programs such as SCOAP improve care through peer-led, benchmarked practice change.

To determine the impact of the Centers for Medicare and Medicaid Services' (CMS) bariatric surgery national coverage decision (NCD) on the use, safety, and cost of care CMS beneficiaries. In February 2006, the CMS issued a NCD restricting reimbursement for bariatric surgery to accredited centers and including coverage for laparoscopic adjustable gastric band (LAGB). A pre/postinterrupted time-series cohort study using nationwide Medicare data (2004-2008) evaluating rates of bariatric procedures/100,000 enrollees, 90-day mortality, readmission rate and payments. Forty-seven thousand thirty patients underwent procedures at 928 sites pre-NCD and 662 post-NCD. The procedure rate/100,000 patients dropped after the NCD to 17.8 (from 21.9 in 2005) increasing to 23.8 and 29.1 in 2007 and 2008, respectively. Open roux-en-y gastric bypass (ORYGB) and laparoscopic roux-en-y gastric bypass (LRYGB) were common pre-NCD (56.0% ORYGB, 35.5% LRYGB) changing post-NCD with LAGB inclusion (12.8% ORYGB, 48.7% LRYGB, 36.7% LAGB). 90-day mortality pre-NCD was 1.5% (1.8% ORYGB, 1.1% LRYGB) and post-NCD was 0.7% (1.7% ORYGB, 0.8% LRYGB, 0.3% LAGB; P < 0.001). The 90-day rates of readmission decreased post-NCD (19.9% to 15.4%), reoperation (3.2% to 2.1%) and payments ($24,363 to $19,746; P for all <0.001). Differences in outcome and cost were largely explained by a shift in procedure type and patient characteristics. The NCD was associated with a temporary reduction in procedure rate and a shift in types of procedures and patients undergoing bariatric surgery. It was associated with a significant decrease in the risk of death, complications, readmissions, and per patient payments.