Lindsay E. Kuo

Early, H+-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates

Biased left-right asymmetry is a fascinating and medically important phenomenon. We provide molecular genetic and physiological characterization of a novel, conserved, early, biophysical event that is crucial for correct asymmetry: H+ flux. A pharmacological screen implicated the H+-pump H+-V-ATPase in Xenopus asymmetry, where it acts upstream of early asymmetric markers. Immunohistochemistry revealed an actin-dependent asymmetry of H+-V-ATPase subunits during the first three cleavages. H+-flux across plasma membranes is also asymmetric at the four- and eight-cell stages, and this asymmetry requires H+-V-ATPase activity. Abolishing the asymmetry in H+ flux, using a dominant-negative subunit of the H+-V-ATPase or an ectopic H+ pump, randomized embryonic situs without causing any other defects. To understand the mechanism of action of H+-V-ATPase, we isolated its two physiological functions, cytoplasmic pH and membrane voltage (Vmem) regulation. Varying either pH or Vmem, independently of direct manipulation of H+-V-ATPase, caused disruptions of normal asymmetry, suggesting roles for both functions. V-ATPase inhibition also abolished the normal early localization of serotonin, functionally linking these two early asymmetry pathways. The involvement of H+-V-ATPase in asymmetry is conserved to chick and zebrafish. Inhibition of the H+-V-ATPase induces heterotaxia in both species; in chick, H+-V-ATPase activity is upstream of Shh; in fish, it is upstream of Kupffers vesicle and Spaw expression. Our data implicate H+-V-ATPase activity in patterning the LR axis of vertebrates and reveal mechanisms upstream and downstream of its activity. We propose a pH- and Vmem-dependent model of the early physiology of LR patterning.

Bariatric Centers of Excellence: Effect of Centralization on Access to Care

BACKGROUND In 2006, the Centers for Medicare and Medicaid Services restricted coverage for bariatric procedures to designated high-volume Centers of Excellence. The effect of centralization of elective surgical procedures on the ability of patients to access surgery has not been studied previously. STUDY DESIGN Inpatient claims data from 2008 to 2011 from 2 high-volume surgical states were used. All patients older than 18 years undergoing a bariatric surgical procedure were included. The number of bariatric procedures and characteristics of patients undergoing bariatric surgery were examined in each year. Nonparametric tests for trend were performed to analyze time trends. Difference-in-difference analyses were performed to assess the rate of bariatric surgery in underserved Medicare patients compared with underserved patients with other payers. RESULTS The percentage of procedures performed at Centers of Excellence increased from 60.5% in 2008 to 73.1% in 2011 (p < 0.01). The proportion of Medicare patients receiving surgery at a Center of Excellence increased from 77.7% in 2008 to 88.1% in 2011 (p < 0.01). The proportion of bariatric surgery patients from underserved groups increased over time except among those residing in rural areas, for whom there was no change. Among patients from underserved populations, only black Medicare patients experienced an increase in bariatric surgery use when compared with non-Medicare patients. The travel distance for Medicare patients consistently exceeded travel distance for non-Medicare patients. However, travel distance for Medicare patients decreased slightly during the study period. CONCLUSIONS Despite the longer travel distance required for Medicare patients, centralization of bariatric surgery to Centers of Excellence did not result in impaired access to care. In fact, in this study, an improvement in access to bariatric surgery was seen and persisted among some underserved populations.

A Milestone-Based Evaluation System—The Cure for Grade Inflation?

PURPOSE Controversy exists over the optimal use of the Milestones in the process of resident evaluation and feedback. We sought to evaluate the performance of a Milestones-based feedback system in comparison to a traditional model. METHODS The traditional evaluation system (TES) consisted of a generic 16-item survey using a 5-point Likert scale ranging from 1 to 5, and a free-text comments section. The Milestones-based evaluation system (MBES) was launched in July 2014, ranging from 0 to 4. Individual milestones were mapped to rotations based on resident educational goals by postgraduate year (PGY). The MBES consisted of a survey with a maximum of 7 items, followed by a free-text comment section. Within each evaluation system, an overall composite score was calculated for each categorical general surgical resident. To scale the 2 systems for comparison, TES scores were adjusted downward by 1 point. Descriptive statistics were performed. Univariate analysis was performed with the Wilcoxon signed-rank test. A test for trend across PGY was used for the MBES only. RESULTS In the traditional system, the median score was 3.66 (range: 3.2-4.0). There was no meaningful difference in the median score by PGY. In the new system, the median score was 2.69 (range: 1.5-3.7, p < 0.01). The median score differed across PGY and increased by PGY of training (p < 0.01). There was an increase in differences between median scores by PGY. CONCLUSIONS On using the milestones to facilitate faculty evaluation of resident knowledge and skill, there was a trend in increasing score by PGY of training. In the MBES, scores could be used to better discriminate resident skill and knowledge levels and resulted in improved differentiation in scoring by PGY. The use of the milestones as a basis for evaluation enabled the program to provide more meaningful feedback to residents and represents an improvement in surgical education.

Reoperative parathyroidectomy: who is at risk and what is the risk?

BACKGROUND Persistent and recurrent hyperparathyroidism necessitate reoperation, which is associated with increased procedure-specific complication rates. The effect of reoperative parathyroidectomy on more generalized outcomes is poorly understood. We sought to determine patient, provider, and perioperative characteristics associated with reoperation, as well as to determine the associated risks. METHODS All patients receiving a parathyroidectomy in the American College of Surgeons National Surgical Quality Improvement Program database (2008-2011) were identified. Patients receiving initial parathyroidectomy were compared with those receiving reoperative parathyroidectomy. Descriptive statistics and univariate analyses were performed. Multivariate logistic regression models were developed for significant outcome measures. RESULTS Of 9114 parathyroidectomies performed, 8738 (95.9%) were initial and 376 (4.1%) were reoperative. The annual rate of reoperation was 3.6%-4.8%. Patients undergoing reoperative parathyroidectomy were more likely to be obese (48.5 versus 40.0%, P = 0.009) and American Society of Anesthesiologist class 3 (40.7 versus 30.3%, P = 0.001) than patients undergoing initial parathyroidectomy. There was no difference in gender, age, or race. Reoperations had a longer median operative time (101 minimum, interquartile range [IQR] [74-146] versus 76 [55-105], P <0.001) and a longer postoperative length of stay (median days until discharge 1, IQR [1-1] versus 1, IQR [0-1], P <0.001). No difference was found in the rates of mortality and common postoperative morbidity as measured in NSQIP. Patients undergoing reoperation were more likely to be readmitted within 30 d (12.7 versus 2.6%, P <0.001). After adjusting for confounders, reoperation continued to be significantly associated with readmission (odds ratio 3.82, confidence interval: 1.63-8.97; P = 0.002). CONCLUSIONS Obesity and an American Society of Anesthesiologist 3 classification are independently associated with reoperation. Readmission within 30 d is associated with reoperation and is a target for patient education and quality improvement after this procedure.

Failure-to-rescue after injury is associated with preventability: The results of mortality panel review of failure-to-rescue cases in trauma

Background. Failure‐to‐rescue is defined as the conditional probability of death after a complication, and the failure‐to‐rescue rate reflects a centers ability to successfully “rescue” patients after complications. The validity of the failure‐to‐rescue rate as a quality measure is dependent on the preventability of death and the appropriateness of this measure for use in the trauma population is untested. We sought to evaluate the relationship between preventability and failure‐to‐rescue in trauma. Methods. All adjudications from a mortality review panel at an academic level I trauma center from 2005–2015 were merged with registry data for the same time period. The preventability of each death was determined by panel consensus as part of peer review. Failure‐to‐rescue deaths were defined as those occurring after any registry‐defined complication. Univariate and multivariate logistic regression models between failure‐to‐rescue status and preventability were constructed and time to death was examined using survival time analyses. Results. Of 26,557 patients, 2,735 (10.5%) had a complication, of whom 359 died for a failure‐to‐rescue rate of 13.2%. Of failure‐to‐rescue deaths, 272 (75.6%) were judged to be non‐preventable, 65 (18.1%) were judged potentially preventable, and 22 (6.1%) were judged to be preventable by peer review. After adjusting for other patient factors, there remained a strong association between failure‐to‐rescue status and potentially preventable (odds ratio 2.32, 95% confidence interval, 1.47–3.66) and preventable (odds ratio 14.84, 95% confidence interval, 3.30–66.71) judgment. Conclusion. Despite a strong association between failure‐to‐rescue status and preventability adjudication, only a minority of deaths meeting the definition of failure to rescue were judged to be preventable or potentially preventable. Revision of the failure‐to‐rescue metric before use in trauma care benchmarking is warranted.

Variation in the Utilization of Minimally Invasive Surgical Operations.

Objective: The goal of this study was to examine regional variation in use of minimally invasive surgical (MIS) operations. Summary Background Data: Regional variation exists in performance of surgical operations. Variation in the use of MIS has not been studied. Methods: Five operations that are performed open or MIS were selected: cholecystectomy, appendectomy, colectomy, antireflux, and bariatric. A 3-state database from 2008 to 2011 was used; states were divided into hospital service areas (HSAs). For each operation, the percentage of MIS operations was calculated. HSAs with less than 50% or more than 150% of the MIS average were considered outliers. Population demographics, geography, and hospital and physician presence were compared between HSAs. Rates of performance by patient disease and the presence of MIS surgeons were also investigated. Results: MIS cholecystectomy was performed with low variation; MIS appendectomy, antireflux, and bariatric operations with medium variation; and MIS colectomy with high variation. With the exception of MIS colectomy, there were no differences in the patient demographics, geography, or disease types treated with an MIS approach between HSAs with low-, non-, or high utilization of MIS. There is no correlation between the number of MIS surgeons and the percentage of procedures performed MIS. Conclusions: Variation in utilization of MIS exists and differs by operation. Patient demographics, patient disease, and the ability to access care are associated only with variation in use of MIS for colectomy. For all other operations studied, these factors do not explain variation in MIS use. Further investigation is warranted to identify and eliminate causes of variation.

Management of Thyroid Nodular Disease: Current Cytopathology Classifications and Genetic Testing.

Preoperative diagnosis and operative planning for patients with thyroid nodules has improved over the last decade. The Bethesda criteria for cytopathologic classification of thyroid nodule aspirate has enhanced communication between pathologists and clinicians. Multiple genetic tests, including molecular markers and the Afirma gene expression classifier, have been developed and validated. The tests, along with clinical and radiologic information, are most useful in the setting of indeterminate cytology. The development of an updated diagnostic and treatment algorithm incorporating all available tests will help standardize the management of patients with nodular thyroid disease and reduce variation and inefficiencies in care.

Variation in the use of minimally invasive bariatric surgery

BACKGROUND Obesity is a significant public health problem in the United States. Despite the known benefits of bariatric surgery, most patients eligible for bariatric surgery do not receive it. Access to minimally invasive bariatric surgery (MIS), the surgical gold standard, may be a limitation. OBJECTIVES We investigated geographic variation in the utilization of laparoscopy for bariatric surgical procedures. METHODS We utilized a unique 3-state inpatient database. Adult patients receiving initial bariatric surgery were included. Patients were divided into hospital service areas (HSAs). Rates of MIS utilization in each HSA were calculated. HSAs were divided into quintiles of utilization. Patient and hospital characteristics were compared across quintiles. RESULTS Over the 5-year study period, 127,008 patients received bariatric surgery. MIS technology was available in all HSAs. MIS was performed in 88.4% of procedures and was performed in 70.6% of patients in the lowest quintile compared with 97.0% in the highest (P<.01). The use of laparoscopy across quintiles varied significantly by rural hospital status: All 7 rural hospitals were located in the lowest quintile of utilization. CONCLUSION Variation in the performance of MIS bariatric surgical procedures exists. These differences can likely be attributed to physician preference or patient population. Obesity rates are elevated in rural areas. The implementation of MIS bariatric surgery programs in rural areas may improve the treatment of obesity and downstream co-morbidities in these populations.

Comparing International and United States Undergraduate Medical Education and Surgical Outcomes Using a Refined Balance Matching Methodology.

Objective: The aim of this study is to compare surgical outcomes of international medical graduates (IMGs) and United States medical graduates (USMGs). Summary of Background Data: IMGs represent 15% of practicing surgeons in the United States (US), and their training pathways often differ substantially from USMGs. To date, differences in the clinical outcomes between the 2 cohorts have not been examined. Methods: Using a unique dataset linking AMA Physician Masterfile data with hospital discharge claims from Florida and New York (2008–2011), patients who underwent 1 of 32 general surgical operations were stratified by IMG and USMG surgeon status. Mortality, complications, and prolonged length of stay were compared between IMG and USMG surgeon status using optimal sparse network matching with balance. Results: We identified 972,718 operations performed by 4581 surgeons (72% USMG, 28% IMG). IMG and USMG surgeons differed significantly in demographic (age, gender) and baseline training (years of training, university affiliation of training hospital) characteristics. USMG surgeons performed complex procedures (13.7% vs 11.1%, P < 0.01) and practiced in urban settings (79.4% vs 75.6%, P < 0.01) more frequently, while IMG surgeons performed a higher volume of studied operations (50.7 ± 5.1 vs 57.8 ± 8.4, P < 0.01). In the matched cohort analysis of 396,810 patients treated by IMG and USMG surgeons, rates of mortality (USMG: 2.2%, IMG: 2.1%; P < 0.001), complications (USMG: 14.5%, IMG: 14.3%; P = 0.032), and prolonged length of stay (pLOS) (USMG: 22.7%, IMG: 22.8%; P = 0.352) were clinically equivalent. Conclusion: Despite considerable differences in educational background, surgical training characteristics, and practice patterns, IMG and USMG-surgeons deliver equivalent surgical care to the patients whom they treat.

A risk prediction model for mortality in the moribund general surgical patient.

INTRODUCTION Surgeons struggle to counsel families on the role of surgery and likelihood of survival in the moribund patient. We sought to develop a risk prediction model for postoperative inpatient death for the moribund surgical candidate. MATERIALS AND METHODS Using 2007-2012 American College of Surgeons National Surgical Quality Improvement Program data, we identified American Society of Anesthesiologists class 5 (moribund) patients. The sample was randomly divided into development and validation cohorts. In the development cohort, preoperative patient characteristics were evaluated. The primary outcome measure was in-hospital mortality. Factors significant in univariate analysis were entered into a multivariable model; points were assigned based on β coefficients. A scoring system was generated to predict inpatient mortality. Models were developed separately for operations performed within and after 24 hours of admission, and tested on the validation cohort. RESULTS A total of 3120 patients were included. In-hospital mortality was 50.6%. In multivariable analysis, patient characteristics associated with in-hospital mortality were age, functional status, recent dialysis, recent myocardial infarction, ventilator dependence, body mass index, and procedure type. The scoring system generated from this model accurately predicted in-hospital mortality for patients undergoing surgery within and after 24 hours. CONCLUSION A simple risk prediction model using readily available preoperative patient characteristics accurately predicts postoperative mortality in the moribund surgical patient. This scoring system can assist in decision making.