Erin G. Brown

Placental Mesenchymal Stromal Cells Rescue Ambulation in Ovine Myelomeningocele

Myelomeningocele (MMC)—commonly known as spina bifida—is a congenital birth defect that causes lifelong paralysis, incontinence, musculoskeletal deformities, and severe cognitive disabilities. The recent landmark Management of Myelomeningocele Study (MOMS) demonstrated for the first time in humans that in utero surgical repair of the MMC defect improves lower limb motor function, suggesting a capacity for improved neurologic outcomes in this disorder. However, functional recovery was incomplete, and 58% of the treated children were unable to walk independently at 30 months of age. In the present study, we demonstrate that using early gestation human placenta‐derived mesenchymal stromal cells (PMSCs) to augment in utero repair of MMC results in significant and consistent improvement in neurologic function at birth in the rigorous fetal ovine model of MMC. In vitro, human PMSCs express characteristic MSC markers and trilineage differentiation potential. Protein array assays and enzyme‐linked immunosorbent assay show that PMSCs secrete a variety of immunomodulatory and angiogenic cytokines. Compared with adult bone marrow MSCs, PMSCs secrete significantly higher levels of brain‐derived neurotrophic factor and hepatocyte growth factor, both of which have known neuroprotective capabilities. In vivo, functional and histopathologic analysis demonstrated that human PMSCs mediate a significant, clinically relevant improvement in motor function in MMC lambs and increase the preservation of large neurons within the spinal cord. These preclinical results in the well‐established fetal ovine model of MMC provide promising early support for translating in utero stem cell therapy for MMC into clinical application for patients.

Hospital readmissions: necessary evil or preventable target for quality improvement.

Objectives:To evaluate readmission rates and associated factors to identify potentially preventable readmissions. Background:The decision to penalize hospitals for readmissions is compelling health care systems to develop processes to minimize readmissions. Research to identify preventable readmissions is critical to achieve these goals. Methods:We performed a retrospective review of University HealthSystem Consortium database for cancer patients hospitalized from January 2010 to September 2013. Outcome measures were 7-, 14-, and 30-day readmission rates and readmission diagnoses. Hospital and disease characteristics were evaluated to evaluate relationships with readmission. Results:A total of 2,517,886 patients were hospitalized for cancer treatment. Readmission rates at 7, 14, and 30 days were 2.2%, 3.7%, and 5.6%, respectively. Despite concern that premature hospital discharge may be associated with increased readmissions, a shorter initial length of stay predicted lower readmission rates. Furthermore, high-volume centers and designated cancer centers had higher readmission rates. Evaluating institutional data (N = 2517 patients) demonstrated that factors associated with higher readmission rates include discharge from a medical service, site of malignancy, and emergency primary admission. When examining readmission within 7 days for surgical services, the most common readmission diagnoses were infectious causes (46.3%), nausea/vomiting/dehydration (26.8%), and pain (6.1%). Conclusions:A minority of patients after hospitalization for cancer-related therapy are readmitted with potentially preventable conditions such as nausea, vomiting, dehydration, and pain. However, most factors associated with readmission cannot be modified. In addition, high-volume centers and designated cancer centers have higher readmission rates, which may indicate that readmission rates may not be an appropriate marker for quality improvement.

Multi-institutional practice patterns and outcomes in uncomplicated gastroschisis: A report from the University of California Fetal Consortium (UCfC)

BACKGROUND/PURPOSE Gastroschisis is a resource-intensive birth defect without consensus regarding optimal surgical and medical management. We sought to determine best-practice guidelines by examining differences in multi-institutional practices and outcomes. METHODS Site-specific practice patterns were queried, and infant-maternal chart review was retrospectively performed for gastroschisis infants treated at 5 UCfC institutions (2007-2012). The primary outcome was length of stay. Univariate analysis was done to assess variation practices and outcomes by site. Multivariate models were constructed with site as an instrumental variable and with sites grouped by silo practice pattern adjusting for confounding factors. RESULTS Of 191 gastroschisis infants, 164 infants were uncomplicated. Among uncomplicated patients, there were no deaths and only one case of necrotizing enterocolitis. Bivariate analysis revealed significant differences in practices and outcomes by site. Despite wide variations in practice patterns, there were no major differences in outcome among sites or by silo practice, after adjusting for confounding factors. CONCLUSIONS Wide variability exists in institutional practice patterns for infants with gastroschisis, but poor outcomes were not associated with expeditious silo or primary closure, avoidance of routine paralysis, or limited central line and antibiotic durations. Development of clinical pathways incorporating these practices may help standardize care and reduce health care costs.

In utero repair of myelomeningocele with autologous amniotic membrane in the fetal lamb model

BACKGROUND Despite advances in prenatal repair, myelomeningocele (MMC) still produces devastating neurologic deficits. The amniotic membranes (AM) are a biologically active tissue that has been used anecdotally for human fetal MMC repair. This study evaluated the use of autologous AM compared to skin closure in an established fetal MMC model. METHODS Seven fetal lambs underwent surgical creation of MMC at gestational age of 75days followed by in utero repair at gestational age of 100days. Lambs were repaired with an autologous AM patch followed by skin closure (n=4) or skin closure alone (n=3). Gross necropsy and histopathology of the spinal cords were performed at term to assess neuronal preservation at the lesion. RESULTS An increase in preserved motor neurons and a larger area of spinal cord tissue were seen in AM-repaired lambs, as was decreased wound healing of the overlying skin. Loss of nearly all spinal cord tissue with limited motor neuron preservation was seen in skin only-repaired lambs. CONCLUSIONS AM-repaired lambs showed increased protection of spinal cord tissue compared to skin only-repaired lambs, but the overlying skin failed to close in AM-repaired lambs. These results suggest a potential role for AM in fetal MMC repair that warrants further study.

Preoperative CA 19-9 kinetics as a prognostic variable in radiographically resectable pancreatic adenocarcinoma

Serial levels of CA 19‐9 are correlated with treatment response and survival; however, little is known about CA 19‐9 kinetics in the absence of therapy. We hypothesize that preoperative CA 19‐9 kinetics predict rate of resectability as well as survival.

Outcomes of Pancreaticoduodenectomy Where Should We Focus Our Efforts on Improving Outcomes

IMPORTANCE Changes in health care reimbursement policy have led to an era in which hospitals are motivated to improve quality of care while simultaneously reducing costs. Research demonstrating the most efficient means to target costs may have a positive effect on patient quality of life and the overburdened health care system. OBJECTIVE To evaluate the effect of hospital length of stay (LOS) and the occurrence of postoperative complications on total charges in patients undergoing elective pancreaticoduodenectomy. DESIGN, SETTING, AND PATIENTS We performed a retrospective review of 89 cases identified in an institutional database of patients who underwent elective pancreaticoduodenectomy at an academic tertiary care center from December 1, 2007, through May 31, 2012. MAIN OUTCOMES AND MEASURES Occurrence of postoperative and inpatient complications, LOS, incidence of readmission within 60 days of discharge, and hospital charges from initial postoperative hospitalization. Linear regression analysis was performed comparing LOS with hospital charges. RESULTS Thirty-four of 89 patients (38%) developed postoperative complications. Mean and median LOSs were 12 and 8 days, respectively. The LOS was significantly related to postoperative complications. Of the 34 patients who developed complications, the mean LOS was 19 days compared with 7 days for those patients not developing complications (P < .001). Only 2 of 55 patients (4%) without complications were readmitted to the hospital, whereas 13 of 34 patients (38%) with complications required readmission. Perioperative hospital charges were significantly related to LOS (R² = 0.840, R = 0.917). For those patients without complications, linear regression demonstrated a daily hospital charge of

Pregnancy-Related Attrition in General Surgery

11,612 (R² = 0.923, R = 0.961). However, for those patients with complications, the optimal relationship between LOS and hospital charges was exponential (R² = 0.832). CONCLUSIONS AND RELEVANCE Prolonged LOS is associated with increased total charges, but given the exponential increase in charges, the complication itself has an effect on increased charges above and beyond that of a prolonged hospitalization. The drive to reduce LOS after pancreaticoduodenectomy has minimal effect on overall charges to the patient. Efforts should be directed instead at reducing complications because this has a much more significant effect on financial outcomes.

Pediatric surgical readmissions: Are they truly preventable?☆

IMPORTANCE Residency attrition rates remain a great challenge for general surgery training programs. Despite the increasing acceptance of pregnancy during training, 1 common perception is that women who become pregnant are at increased risk of leaving surgery programs. OBJECTIVE To determine whether child rearing increases the risk of attrition from general surgery residency. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of all categorical general surgery residents in a single academic general surgery residency program over a 10-year period. All categorical general surgery residents matriculated from July 1, 1999, until July 1, 2009. MAIN OUTCOMES AND MEASURES Voluntary attrition rate, involuntary attrition rate, and incidence of child rearing among residents. RESULTS Eighty-five residents matched into categorical general surgery postgraduate year 1 spots from July 1, 1999, to July 1, 2009. Of the total residents, 49 (58%) were men while 36 (42%) were women. Attrition in the program was 18.8% (16 of 85). Seven (44%) of the residents who left the program were women; this was 19% of all female residents in the program. This was not significantly different from the proportion of men who left the program (P = .90). A higher percentage of women (57%) left after their intern year compared with men (22%). Furthermore, men had the highest rate of attrition during research (33%) while no women left during research years. Among the 85 residents, 9 women reported a total of 10 pregnancies and 16 men reported raising 21 children (1 woman and 1 man left the program). The proportion of child rearing was higher in those who did not leave the program but this did not reach significance (P = .10). Neither age (odds ratio, 1.0; 95% CI, 0.8-1.4), sex (odds ratio, 1.0; 95% CI, 0.2-3.6), nor incidence of child rearing during training (odds ratio, 1.0; 95% CI, 0.1-9.6) were associated with an increased risk of attrition. Residents with children born during training did not demonstrate fewer total case numbers (men, P = .40; women, P = .93) or board pass rates (men, P = .76; women, P = .50) compared with residents who did not have children during training. Women who had children during training were more likely to pursue fellowship (87.5%) than those who did not (66.7%)(P < .001). CONCLUSIONS AND RELEVANCE The current study demonstrated there was no association between female sex and attrition at our institution. Child rearing did not appear to be a risk factor for attrition in either men or women. Furthermore, child rearing did not negatively impact the quality of training based on case numbers and board pass rates. Despite prevalent stereotypes, child rearing did not cause women or men to leave the program.

Age Does Matter: A Pilot Comparison of Placenta-Derived Stromal Cells for in utero Repair of Myelomeningocele Using a Lamb Model

BACKGROUND/PURPOSE Reimbursement penalties for excess hospital readmissions have begun for the pediatric population. Therefore, research determining incidence and predictors is critical. METHODS A retrospective review of University HealthSystem Consortium database (N=258 hospitals; 2,723,621 patients) for pediatric patients (age 0-17years) hospitalized from 9/2011 to 3/2015 was performed. Outcome measures were 7-, 14-, and 30-day readmission rates. Hospital and patient characteristics were evaluated to identify predictors of readmission. RESULTS Readmission rates at 7, 14, and 30days were 2.1%, 3.1%, and 4.4%. For pediatric surgery patients (N=260,042), neither index hospitalization length of stay (LOS) nor presence of a complication predicted higher readmissions. Appendectomy was the most common procedure leading to readmission. Evaluating institutional data (N=5785), patients admitted for spine surgery, neurosurgery, transplant, or surgical oncology had higher readmission rates. Readmission diagnoses were most commonly infectious (37.2%) or for nausea/vomiting/dehydration (51.1%). Patients with chronic medical conditions comprised 55.8% of patients readmitted within 7days. 92.0% of patients requiring multiple rehospitalizations had comorbidities. CONCLUSIONS Readmission rates for pediatric patients are significantly lower than adults. Risk factors for adult readmissions do not predict pediatric readmissions. Readmission may be a misnomer for the pediatric surgical population, as most are related to chronic medical conditions and other nonmodifiable risk factors. LEVEL OF EVIDENCE Level IV.

Development of a locomotor rating scale for testing motor function in sheep.

Introduction: Fetal amniotic membranes (FM) have been shown to preserve spinal cord histology in the fetal sheep model of myelomeningocele (MMC). This study compares the effectiveness of placenta-derived mesenchymal stromal cells (PMSCs) from early-gestation versus term-gestation placenta to augment FM repair to improve distal motor function in a sheep model. Methods: Fetal lambs (n = 4) underwent surgical MMC creation followed by repair with FM patch with term-gestation PMSCs (n = 1), FM with early-gestation PMSCs (n = 1), FM only (n = 1), and skin closure only (n = 1). Histopathology and motor assessment was performed. Results: Histopathologic analysis demonstrated increased preservation of spinal cord architecture and large neurons in the lamb repaired with early-gestation cells compared to all others. Lambs repaired with skin closure only, FM alone, and term-gestation PMSCs exhibited extremely limited distal motor function; the lamb repaired with early-gestation PMSCs was capable of normal ambulation. Discussion: This pilot study is the first in vivo comparison of different gestational-age placenta-derived stromal cells for repair in the fetal sheep MMC model. The preservation of large neurons and markedly improved motor function in the lamb repaired with early-gestation cells suggest that early-gestation placental stromal cells may exhibit unique properties that augment in utero MMC repair to improve paralysis.