Faculty Bibliography

OBJECTIVE:To estimate the rate of inpatient stay and the factors predicting inpatient status after robotic surgery for endometrial cancer following the change in the Medicare definition of "inpatient" to include hospitalization spanning 2 midnights. DESIGN/METHODS:Retrospective chart review (Canadian Task Force classification II-1). SETTING/METHODS:Academic hospital. PATIENTS/METHODS:All patients (n = 395) with endometrial cancer who underwent robotic surgical management between 2006 and 2010. INTERVENTION/METHODS:The outpatient stay group with hospitalization spanning 1 midnight was compared with the inpatient stay group with hospitalization spanning 2 midnights or longer through estimation of the adjusted relative risk (aRR) for various characteristics of interest. RESULTS:Ninety-six of 395 patients (24.3%) stayed at least 2 midnights and thus were deemed inpatients. Clinical factors associated with inpatient stay were increasing age, history of myocardial infarction (aRR, 2.0; 95% confidence interval [CI], 1.0-3.7), surgery start time at or after 12 noon (aRR, 1.7; 95% CI, 1.2-2.4), perioperative blood transfusion (aRR, 3.2; 95% CI, 2.3-4.5), and surgery performed in the year 2010 (aRR, 0.5; 95% CI, 0.3-0.7). Age ≥ 60 years was associated with at least a 2-fold adjusted risk of prolonged hospitalization. Body mass index, other medical comorbidities, operative duration, estimated blood loss, and performance of lymphadenectomy or additional surgical procedures were not identified as significant risk factors. CONCLUSION/CONCLUSIONS:Approximately 75% of the patients undergoing robotic surgery for endometrial cancer were discharged as outpatients. Recognition of factors predicting inpatient stay can improve hospital resource allocation and throughput in women undergoing robotic surgery for endometrial cancer.

Only a minority of patients with high risk lymphoma will be cured with autologous transplant, so maintenance with vorinostat, an oral agent with activity in relapsed lymphoma, was studied starting day + 60 for 21 consecutive days followed by a week off for up to 11 cycles. Twenty-three patients with lymphoma were treated. Ten patients completed the full 11-cycle treatment plan per protocol, four patients were removed due to progressive disease and seven withdrew or were removed from the study due to toxicities. Despite Prevnar vaccine administration every 2 months for three injections, the mean antibody concentration never reached protective levels (> 0.35 μg/mL). Fatigue and functional well-being measured by Brief Fatigue Inventory and Functional Assessment of Cancer Therapy-General improved significantly from cycle 1 to cycle 7, but depression scores from the Center for Epidemiologic Studies Depression scale did not change. Given the toxicities observed, this broad-spectrum deacetylase inhibitor at this schedule is not optimal for prolonged maintenance therapy.

BACKGROUND:Understanding the dynamics of the gut-brain axis has clinical implications for physical and mental health conditions, including obesity and anxiety. As such disorders have early life antecedents, it is of value to determine if associations between the gut microbiome and behavior are present in early life in humans. METHODS:We used next generation pyrosequencing to examine associations between the community structure of the gut microbiome and maternal ratings of child temperament in 77 children at 18-27months of age. It was hypothesized that children would differ in their gut microbial structure, as indicated by measures of alpha and beta diversity, based on their temperamental characteristics. RESULTS:Among both boys and girls, greater Surgency/Extraversion was associated greater phylogenetic diversity. In addition, among boys only, subscales loading on this composite scale were associated with differences in phylogenetic diversity, the Shannon Diversity index (SDI), beta diversity, and differences in abundances of Dialister, Rikenellaceae, Ruminococcaceae, and Parabacteroides. In girls only, higher Effortful Control was associated with a lower SDI score and differences in both beta diversity and Rikenellaceae were observed in relation to Fear. Some differences in dietary patterns were observed in relation to temperament, but these did not account for the observed differences in the microbiome. CONCLUSIONS:Differences in gut microbiome composition, including alpha diversity, beta diversity, and abundances of specific bacterial species, were observed in association with temperament in toddlers. This study was cross-sectional and observational and, therefore, does not permit determination of the causal direction of effects. However, if bidirectional brain-gut relationships are present in humans in early life, this may represent an opportunity for intervention relevant to physical as well as mental health disorders.

BACKGROUND:There remains a need for a quickly administered, stroke-specific, bedside measure of active wrist and finger movement for the expanding stroke population. The wrist stability and hand mobility scales of the upper extremity Fugl-Meyer Assessment (w/h UE FM) constitute a valid, reliable measure of paretic UE impairment in patients with active wrist and finger movement. OBJECTIVE:The aim of this study was to determine performance on the w/h UE FM in a stable cohort of survivors of stroke with only palpable movement in their paretic wrist flexors. DESIGN/METHODS:A single-center cohort study was conducted. METHOD/METHODS:Thirty-two individuals exhibiting stable, moderate upper extremity hemiparesis (15 male, 17 female; mean age=56.6 years, SD=10.1; mean time since stroke=4.6 years, SD=5.8) participated in the study, which was conducted at an outpatient rehabilitation clinic in the midwestern United States. The w/h UE FM and Action Research Arm Test (ARAT) were administered twice. Intraclass correlation coefficients (ICCs), Cronbach alpha, and ordinal alpha were computed to determine reliability, and Spearman rank correlation coefficients and Bland-Altman plots were computed to establish validity. RESULTS:Intraclass correlation coefficients for the w/h UE FM and ARAT were .95 and .99, respectively. The w/h UE FM intrarater reliability and internal consistency were greater than .80, and concurrent validity was greater than .70. This also was the first stroke rehabilitative study to apply ordinal alpha to examine internal consistency values, revealing w/h UE FM levels greater than .85. Concurrent validity findings were corroborated by Bland-Altman plots. CONCLUSIONS:It appears that the w/h UE FM is a promising tool to measure distal upper extremity movement in patients with little active paretic wrist and finger movement. This finding widens the segment of patients on whom the w/h UE FM can be effectively used and addresses a gap, as commonly used measures necessitate active distal upper extremity movement.

OBJECTIVES/OBJECTIVE:In addition to hysterectomy and bilateral salpingo-oophorectomy, comprehensive surgical staging for endometrial cancer includes pelvic and para-aortic lymphadenectomy. Clarifying and addressing the morbidity from these surgical procedures is imperative. The goal of this study was to assess the prevalence of lower extremity swelling after surgery for endometrial cancer. MATERIALS AND METHODS/METHODS:We performed a descriptive, cross-sectional survey study of women who underwent surgery for endometrial cancer at our institution from 2006 to 2008. Survey information included symptoms, management, and education regarding lymphedema. Demographic information such as race and education was collected in addition to clinical data such as body mass index and age. RESULTS:Of the 482 patients identified, 440 were determined eligible and 305 (69.3%) responded to the survey with information on lower limb swelling (LLS). Of the 108 (35%) responders who reported swelling, only 68 (22%) participants reported a diagnosis of lower limb lymphedema (LLL). The most commonly experienced symptoms among those who reported LLS were tightness, pain/tenderness, and heaviness. Among those with a diagnosis of LLL, most (60%) stated it affected their daily activities and noted exacerbating factors such as prolonged standing, heat, and walking. The most common therapies used to reduce symptoms included leg elevation (96%), compression stockings (65%), diuretics (46%), massage therapy (35%), and bandaging (25%). There was no association between LLS or LLL diagnosis and body mass index, age, race, and tobacco use. Only 8% of responders reported receiving preoperative education regarding risks for LLS and a desire for more comprehensive education was frequently noted. CONCLUSIONS:The patient-reported incidence of LLS occurred in approximately 35% of survey participants who underwent surgery for endometrial cancer. However, only 22% reported a diagnosis of LLL. Efforts to obtain the true incidence of LLL and to develop effective educational materials and programs to improve the management of lymphedema are warranted.

OBJECTIVE:To compare the efficacy of a regimen combining mental practice (MP) with overground training (OT) with the efficacy of a regimen consisting of OT only on gait velocity and lower extremity motor outcomes in individuals with chronic (>12mo postinjury), incomplete spinal cord injury (SCI). DESIGN/METHODS:Randomized, controlled, single-blinded study. SETTING/METHODS:Outpatient rehabilitation laboratories. PARTICIPANTS/METHODS:Subjects with chronic, incomplete SCI (N=18). INTERVENTIONS/METHODS:Subjects were randomly assigned to receive (1) OT only, occurring 3d/wk for 8 weeks; or (2) OT augmented by MP (MP + OT), during which randomly assigned subjects listened to an MP audio recording directly after OT sessions. MAIN OUTCOME MEASURES/METHODS:Subjects were administered a test of gait velocity as well as the Tinetti Performance Oriented Mobility Assessment, Spinal Cord Injury Independence Measure, and Satisfaction With Life Scale on 2 occasions before intervention, 1 week after intervention, and 12 weeks after intervention. RESULTS:A significant increase in gait velocity was exhibited across subjects at both 1 week posttherapy (P=.005) and at 12 weeks posttherapy (P=.006). However, no differences were seen in intervention response at either 1 or 12 weeks postintervention among subjects in the MP + OT group versus the OT-only group. CONCLUSIONS:OT was associated with significant gains in gait velocity, and these gains were not augmented by further addition of MP.

The use of propensity score methods to adjust for selection bias in observational studies has become increasingly popular in public health and medical research. A substantial portion of studies using propensity score adjustment treat the propensity score as a conventional regression predictor. Through a Monte Carlo simulation study, Austin and colleagues. investigated the bias associated with treatment effect estimation when the propensity score is used as a covariate in nonlinear regression models, such as logistic regression and Cox proportional hazards models. We show that the bias exists even in a linear regression model when the estimated propensity score is used and derive the explicit form of the bias. We also conduct an extensive simulation study to compare the performance of such covariate adjustment with propensity score stratification, propensity score matching, inverse probability of treatment weighted method, and nonparametric functional estimation using splines. The simulation scenarios are designed to reflect real data analysis practice. Instead of specifying a known parametric propensity score model, we generate the data by considering various degrees of overlap of the covariate distributions between treated and control groups. Propensity score matching excels when the treated group is contained within a larger control pool, while the model-based adjustment may have an edge when treated and control groups do not have too much overlap. Overall, adjusting for the propensity score through stratification or matching followed by regression or using splines, appears to be a good practical strategy.

The possibility that cytokine administration could enhance the antitumor effects of proteasome inhibition was explored. It was found that coadministration of bortezomib and interferon-α (IFN-α) induced synergistic apoptosis in human melanoma cell lines and prolonged survival in a murine model of melanoma. A phase I study was conducted to determine the tolerability and the maximum tolerated dose of bortezomib when administered in combination with IFN-α-2b to patients with metastatic melanoma. Patients were treated on a 5-week cycle. In week 1 of cycle 1, patients received 5 million U/m(2) IFN-α subcutaneously thrice weekly. During weeks 2-4 of cycle 1, bortezomib was administered intravenously weekly along with IFN-α thrice weekly. There was a treatment break during week 5. After cycle 1, bortezomib was administered in combination with IFN-α. Bortezomib was administered in escalating doses (1.0, 1.3, or 1.6 mg/m) to cohorts of 3 patients. Sixteen patients were treated (8 women, 8 men; median age 59 y). Common grade 3 toxicities included fatigue (5), vomiting (3), and diarrhea (3). Grade 4 toxicities included fatigue (3) and lymphopenia (1). The maximum tolerated dose for bortezomib was 1.3 mg/m(2). One patient had a partial response, and 7 had stable disease. Progression-free survival was 2.5 months, and overall survival was 10.3 months. Bortezomib administration did not augment the ability of IFN-α to induce phosphorylation of STAT1 in circulating immune cells; however, it did lead to reduced plasma levels of proangiogenic cytokines. The combination of bortezomib and IFN-α can be safely administered to melanoma patients.

Cardiac surgery associated acute kidney injury (CSA-AKI) is associated with poor outcomes including increased mortality, length of hospital stay (LOS) and cost. The incidence of acute kidney injury (AKI) is reported to be between 3 and 30% depending on the definition of AKI. We designed a multicenter randomized controlled trial to test our hypothesis that a perioperative infusion of sodium bicarbonate (SB) during cardiac surgery will attenuate the post-operative rise in creatinine indicating renal injury when compared to a perioperative infusion with normal saline. An interim analysis was performed after data was available on the first 120 participants. A similar number of patients in the two treatment groups developed AKI, defined as an increase in serum creatinine the first 48 h after surgery of 0.3 mg/dl or more. Specifically 14 patients (24%) who received sodium chloride (SC) and 17 patients (27%) who received SB were observed to develop AKI post-surgery, resulting in a relative risk of AKI of 1.1 (95% CI: 0.6-2.1, chi-square p-value = 0.68) for patients receiving SB compared to those who received SC. The data safety monitoring board for the trial recommended closing the study early as there was only a 12% probability that the null hypothesis would be rejected. We therefore concluded that a perioperative infusion of SB failed to attenuate the risk of CSA-AKI.