Evaluation of novel candidate filtration markers from a global metabolomic discovery for glomerular filtration rate estimation.

Creatinine and cystatin-C are recommended for estimating glomerular filtration rate (eGFR) but accuracy is suboptimal. Here, using untargeted metabolomics data, we sought to identify candidate filtration markers for a new targeted assay using a novel approach based on their maximal joint association with measured GFR (mGFR) and with flexibility to consider their biological properties. We analyzed metabolites measured in seven diverse studies encompasing 2,851 participants on the Metabolon H4 platform that had Pearson correlations with log mGFR and used a stepwise approach to develop models to < -0.5 estimate mGFR with and without inclusion of creatinine that enabled selection of candidate markers. In total, 456 identified metabolites were present in all studies, and 36 had correlations with mGFR < -0.5. A total of 2,225 models were developed that included these metabolites; all with lower root mean square errors and smaller coefficients for demographic variables compared to estimates using untargeted creatinine. Seventeen metabolites were chosen, including 12 new candidate filtration markers. The selected metabolites had strong associations with mGFR and little dependence on demographic factors. Candidate metabolites were identified with maximal joint association with mGFR and minimal dependence on demographic variables across many varied clinical settings. These metabolites are excreted in urine and represent diverse metabolic pathways and tubular handling. Thus, our data can be used to select metabolites for a multi-analyte eGFR determination assay using mass spectrometry that potentially offers better accuracy and is less prone to non-GFR determinants than the current eGFR biomarkers.

The Effectiveness of a Mindfulness-Based Intervention Integrated with Physical Therapy (MIND-PT) for Postsurgical Rehabilitation After Lumbar Surgery: A Protocol for a Randomized Controlled Trial as Part of the Back Pain Consortium (BACPAC) Research Program.

BACKGROUND: Improving pain management for persons with chronic low back pain (LBP) undergoing surgery is an important consideration in improving patient-centered outcomes and reducing the risk of persistent opioid use after surgery. Nonpharmacological treatments, including physical therapy and mindfulness, are beneficial for nonsurgical LBP through complementary biopsychosocial mechanisms, but their integration and application for persons undergoing surgery for LBP have not been examined. This study (MIND-PT) is a multisite randomized trial that compares an enriched pain management (EPM) pathway that integrates physical therapy and mindfulness vs usual-care pain management (UC) for persons undergoing surgery for LBP. DESIGN: Participants from military treatment facilities will be enrolled before surgery and individually randomized to the EPM or UC pain management pathways. Participants assigned to EPM will receive presurgical biopsychosocial education and mindfulness instruction. After surgery, the EPM group will receive 10 sessions of physical therapy with integrated mindfulness techniques. Participants assigned to the UC group will receive usual pain management care after surgery. The primary outcome will be the pain impact, assessed with the Pain, Enjoyment, and General Activity (PEG) scale. Time to opioid discontinuation is the main secondary outcome. SUMMARY: This trial is part of the National Institutes of Health Helping to End Addiction Long-term (HEAL) initiative, which is focused on providing scientific solutions to the opioid crisis. The MIND-PT study will examine an innovative program combining nonpharmacological treatments designed to improve outcomes and reduce opioid overreliance in persons undergoing lumbar surgery.

Thromboelastography and Its Use in Pediatric Trauma Patients.

BACKGROUND/PURPOSE: Thromboelastography's (TEG's) use in pediatric trauma patients is not widely studied. Identifying clotting cascade defects can direct decision making regarding blood product transfusion. METHODS: We performed a single-center retrospective review of all level 1 pediatric trauma patients. Data collected included demographics, diagnoses, Injury Severity Score, intensive care unit length of stay (ICU LOS), mortality, TEG values, and blood products received. We identified TEG values associated with mortality, ICU LOS, and need for blood product transfusion. RESULTS: A total of 237 trauma 1 patients were identified. After exclusions, 148 patients were included for analysis. Most patients were below TEG transfusion cut points. Patients with elevated reaction time, K value, and fibrinolysis at 30 minutes had increased odds of mortality with odds ratios of 1.71 (95% confidence interval [CI], 1.22-2.40), 1.94 (95% CI, 1.23-3.05), and 1.15 (95% CI, 1.03-1.28), respectively. For ICU LOS, elevated reaction time, K value, and fibrinolysis at 30 minutes, α angle, and maximum amplitude demonstrated hazard ratios of 0.76 (95% CI, 0.65-0.88), 0.82 (95% CI, 0.64-1.0), 0.95 (95% CI, 0.88-0.99), 1.05 (95% CI, 1.02-1.08), and 1.04 (95% CI, 1.01-1.06), respectively. There was no association between TEG and blood product transfusion. CONCLUSIONS: Coagulopathic patients based on TEG had higher mortality. All TEG values, as they moved toward transfusion-trigger cut points, were associated with increased mortality.

Interadministrator Reliability of a Modified Instrumented Push and Release Test of Reactive Balance.

CONTEXT: Traditional assessments of reactive balance require sophisticated instrumentation to ensure objective, highly repeatable paradigms. This instrumentation is clinically impractical. The Push and Release test (P&R) is a well-validated clinical test that examines reactive balance, and the application of wearable inertial measurement units (IMU) enables sensitive and objective assessment of this clinically feasible test. The P&R relies on administrator experience and may be susceptible to interadministration reliability concerns. The purpose of this study was to evaluate the interadministrator reliability of objective outcomes from an instrumented, modified version of the P&R test. DESIGN: Crossover interadministrator design. METHODS: Twenty healthy adults (20-35 y) completed the P&R in 4 directions with 2 different administrators. Measures quantified using IMUs included step latency, step length, and time to stability. Lean angle (LA) at release was used as a measure of administration consistency. The intraclass correlation coefficient (ICC) estimate was used to assess interadministrator reliability in each direction. To determine consistency of LA within and across administrators, we calculated the SDs for each rater by direction and the interadministrator reliability of LA using ICC. RESULTS: Across individual directions, the ICC for agreement between raters ranged from .16 to .39 for step latency, from .52 to .62 for time to stability, and from .48 to .84 for step length. Summary metrics across all 4 directions produced higher ICC values. There was poor to moderate consistency in administration based on LA, but LA did not significantly affect any of the outcomes. CONCLUSION: The modified P&R yields moderate interadministrator reliability and high validity. Summary metrics over all 4 directions (the maximum step latency, the median time to stability, and the median step length) are likely more reliable than direction-specific scores. Variations in body size should also be considered when comparing populations.

Longitudinal Changes in Prorenin and Renin in the Chronic Renal Insufficiency Cohort.

INTRODUCTION: Prorenin, a precursor of renin, and renin play an important role in regulation of the renin-angiotensin system. More recently, receptor-bound prorenin has been shown to activate intracellular signaling pathways that mediate fibrosis, independent of angiotensin II. Prorenin and renin may thus be of physiologic significance in CKD, but their plasma concentrations have not been well characterized in CKD. METHODS: We evaluated distribution and longitudinal changes of prorenin and renin concentrations in the plasma samples collected at follow-up years 1, 2, 3, and 5 of the Chronic Renal Insufficiency Cohort (CRIC) study, an ongoing longitudinal observational study of 3,939 adults with CKD. Descriptive statistics and multivariable regression of log-transformed values were used to describe cross-sectional and longitudinal variation and associations with participant characteristics. RESULTS: A total of 3,361 CRIC participants had plasma available for analysis at year 1. The mean age (±standard deviation, SD) was 59 ± 11 years, and the mean estimated glomerular filtration rate (eGFR, ± SD) was 43 ± 17 mL/min per 1.73 m2. Median (interquartile range) values of plasma prorenin and renin at study entry were 4.4 (2.1, 8.8) ng/mL and 2.0 (0.8, 5.9) ng/dL, respectively. Prorenin and renin were positively correlated (Spearman correlation 0.51, p < 0.001) with each other. Women and non-Hispanic blacks had lower prorenin and renin values at year 1. Diabetes, lower eGFR, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and diuretics were associated with higher levels. Prorenin and renin decreased by a mean of 2 and 5% per year, respectively. Non-Hispanic black race and eGFR <30 mL/min/1.73 m2 at year 1 predicted a steeper decrease in prorenin and renin over time. In addition, each increase in urinary sodium excretion by 2 SDs at year 1 increased prorenin and renin levels by 4 and 5% per year, respectively. DISCUSSION/CONCLUSIONS: The cross-sectional clinical factors associated with prorenin and renin values were similar. Overall, both plasma prorenin and renin concentrations decreased over the years, particularly in those with severe CKD at study entry.

Blood Pressure Variability and Cardiovascular Outcomes in Patients With Prior Stroke: A Secondary Analysis of PRoFESS.

Background and Purpose- Every year in the United States, almost 185 000 ischemic strokes occur in patients with a prior stroke. Recurrent stroke has significantly higher morbidity and mortality. Among modifiable risk factors for recurrent stroke, hypertension is the most prevalent. Reducing systolic blood pressure is standard of care for secondary stroke prevention. Recent literature suggests that increased blood pressure variability (BPV) is associated with primary stroke, although studies have not convincingly shown that it is associated with recurrent stroke, which was the goal of this analysis. Methods- We conducted a secondary analysis of 17 916 patients in the PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial, which is the largest trial of patients with potential recurrent stroke. We calculated BPV and evaluated its effect on recurrent stroke (composite and stratified by ischemic or hemorrhagic stroke), major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure), and all-cause death. Results- Both systolic and diastolic BPV were associated with recurrent stroke, major cardiovascular events, and all-cause death. The association with stroke was significant for ischemic, but not hemorrhagic, stroke. For every 10-point increase in BPV (systolic SD, range =0-54.2), the hazard ratio for a recurrent ischemic stroke was 1.15 (95% CI, 1.02-1.32; P=0.02), for major cardiovascular events was 1.19 (95% CI, 1.09-1.31; P<0.001), and for all-cause death was 1.24 (95% CI, 1.10-1.39; P<0.001). Conclusions- Our study adds to the growing body of literature suggesting that BPV is an important and potentially modifiable risk factor for ischemic stroke, cardiovascular events, and all-cause death. Specifically, it is the first study to demonstrate that increased BPV is associated with recurrent ischemic stroke and that diastolic BPV can be as important as systolic BPV. Future work should focus on evaluating whether actively reducing BPV, using widely available and inexpensive antihypertensive medications, reduces the risk of cardiovascular disease.

Alternative waist-to-height ratios associated with risk biomarkers in youth with diabetes: comparative models in the SEARCH for Diabetes in Youth Study.

BACKGROUND/OBJECTIVES: The waist-to-height ratio (WHtR) estimates cardiometabolic risk in youth without need for growth charts by sex and age. Questions remain about whether waist circumference measured per protocol of the National Health and Nutrition Examination Survey (WNHAHtR) or World Health Organization (WWHOHtR) can better predict blood pressures and lipid parameters in youth. PARTICIPANTS/METHODS: WHtR was measured under both anthropometric protocols among participants in the SEARCH Study, who were recently diagnosed with diabetes (ages 5-19 years; N = 2 773). Biomarkers were documented concurrently with baseline anthropometry and again ~7 years later (ages 10-30 years; N = 1 712). For prediction of continuous biomarker outcomes, baseline WNHAHtR or WWHOHtR entered semiparametric regression models employing restricted cubic splines. To predict binary biomarkers (high-risk group defined as the most adverse quartile) linear WNHAHtR or WWHOHtR terms entered logistic models. Model covariates included demographic characteristics, pertinent medication use, and (for prospective predictions) the follow-up time since baseline. We used measures of model fit, including the adjusted-R2 and the area under the receiver operator curves (AUC) to compare WNHAHtR and WWHOHtR. RESULTS: For the concurrent biomarkers, the proportion of variation in each outcome explained by full regression models ranged from 23 to 46%; for the prospective biomarkers, the proportions varied from 11 to 30%. Nonlinear relationships were recognized with the lipid outcomes, both at baseline and at follow-up. In full logistic models, the AUCs ranged from 0.75 (diastolic pressure) to 0.85 (systolic pressure) at baseline, and from 0.69 (triglycerides) to 0.78 (systolic pressure) at the prospective follow-up. To predict baseline elevations of the triglycerides/HDL cholesterol ratio, the AUC was 0.816 for WWHOHtR compared with 0.810 for WNHAHtR (p = 0.003), but otherwise comparisons between alternative WHtR protocols were not significantly different. CONCLUSIONS: Among youth with recently diagnosed diabetes, measurements of WHtR by either waist circumference protocol similarly helped estimate current and prospective cardiometabolic risk biomarkers.

Trends in prevalence of cardiovascular risk factors from 2002 to 2012 among youth early in the course of type 1 and type 2 diabetes. The SEARCH for Diabetes in Youth Study.

BACKGROUND: Given diabetes is an important risk factor for cardiovascular disease (CVD), we examined temporal trends in CVD risk factors by comparing youth recently diagnosed with type 1 diabetes (T1D) and type 2 diabetes (T2D) from 2002 through 2012. METHODS: The SEARCH for Diabetes in Youth Study identified youth with diagnosed T1D (n = 3954) and T2D (n = 706) from 2002 to 2012. CVD risk factors were defined using the modified Adult Treatment Panel III criteria for metabolic syndrome: (a) hypertension; (b) high-density lipoprotein cholesterol ≤40 mg/dL; (c) triglycerides ≥110 mg/dL; and (d) waist circumference (WC) >90th percentile. Prevalence of CVD risk factors, stratified by diagnosis year and diabetes type, was reported. Univariate and multivariate logistic models and Poisson regression were fit to estimate the prevalence trends for CVD risk factors individually and in clusters (≥2 risk factors). RESULTS: The prevalence of ≥2 CVD risk factors was higher in youth with T2D than with T1D at each incident year, but the prevalence of ≥2 risk factors did not change across diagnosis years among T1D or T2D participants. The number of CVD risk factors did not change significantly in T1D participants, but increased at an annual rate of 1.38% in T2D participants. The prevalence of hypertension decreased in T1D participants, and high WC increased in T2D participants. CONCLUSION: The increase in number of CVD risk factors including large WC among youth with T2D suggests a need for early intervention to address these CVD risk factors. Further study is needed to examine longitudinal associations between diabetes and CVD.

Effects of Recent Concussion and Injury History on Instantaneous Relative Risk of Lower Extremity Injury in Division I Collegiate Athletes.

BACKGROUND: Growing evidence suggests that concussion increases the risk of lower extremity (LE) musculoskeletal injury. However, it is unclear to how the effect of concussion on LE injury risk may be influenced by previous injuries. This study sought to examine the association between concussion, previous LE injuries, and the risk LE injury to the same previously injured limb (ipsilateral) or the opposite limb (contralateral). METHODS: This retrospective study examined medical records from 110 concussed athletes and 110 matched controls for LE injuries in the 365 days before and after the concussion event. The effect of concussion on time to injury was assessed with a Cox proportional hazard model after adjusting for injury history. Fine and Gray subdistribution models assessed the cumulative risk of ipsilateral and contralateral injury by group. RESULTS: Concussion was associated with an increased instantaneous relative risk of LE injury when adjusting for LE injury history [hazard ratio (HR) = 1.67, 95% confidence interval (CI) = 1.11-2.53], agreeing with previous results. Among individuals who had a history of LE injuries before the concussion event, a nonsignificant yet moderate effect of concussion on the instantaneous relative risk of ipsilateral injuries was found after adjusting for the competing risk of contralateral injuries and censored values (HR = 1.85, 95% CI = 0.76-4.46). CONCLUSIONS: This study provides independent confirmation of previous studies, reporting an association between concussion and LE injury risk. Furthermore, this study suggests that future large-scale studies should consider the competing risk of ipsilateral, contralateral, and new injuries in populations with an injury history.

Use of Intravenous Acetaminophen in Postoperative Pain Management After Partial and Full Bony Impacted Third Molar Extractions: A Randomized Double-Blind Controlled Trial.

PURPOSE: Currently, there is a concern at the national level of the overuse of both prescription and nonprescription opioid use. The purpose of this study was to identify whether the use of the intravenous (IV) formulation of acetaminophen (Ofirmev; Mallinckrodt Pharmaceuticals, Staines-upon-Thames, United Kingdom) is an effective tool in the reduction of postoperative pain, with a secondary goal of reduction of postoperative narcotic use. MATERIALS AND METHODS: A total of 72 patients with previously diagnosed either partial bony or complete bony impacted third molars were selected with care to avoid long-acting local anesthetics or dissociative anesthetic agents. The patients' postoperative pain scores at 4 and 24 hours were collected via a verbal rating scale by the primary investigator. The exclusion criteria included administration of bupivacaine or ketamine, hepatic or renal impairment, pregnancy, or allergy to any of the normally administered sedation medications. RESULTS: At all postoperative increments (immediately, 4 hours, and 24 hours), there was no significant difference at P < .05 between scores for either the IV acetaminophen or placebo group. Although there was a recorded difference in reduction of pain at both 4 and 24 hours postoperatively, these were not statistically significant variables. CONCLUSIONS: The use of IV acetaminophen showed no statistically significant decrease in patient pain at either 4 or 24 hours postoperatively. Although there are not representative data suggesting the routine use of IV acetaminophen, on the basis of the abundance of literature on the treatment of pain for other procedures, this medication should not be discarded as ineffective.

Prognostic Factors and Significance of Gastrointestinal Leak After Cytoreductive Surgery (CRS) with Heated Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: Gastrointestinal leak (GIL) after cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC) is associated with significant morbidity and mortality. This study aimed to identify GIL prognostic factors and its impact on overall survival. METHODS: A retrospective analysis of a prospectively maintained database comprising 1270 CRS/HIPEC procedures was performed. Type of GIL, functional and resection status, morbidity, mortality, and survival were reviewed. RESULTS: Gastrointestinal leaks were identified in 8.7% (110/1270) of CRS/HIPEC procedures, including 53 anastomotic leaks (4.2%), 53 hollow viscus perforations (4.2%), and four leaks at unknown sites. The multivariate predictors of leak were Eastern Cooperative Oncology Group (ECOG) functional status (ECOG 1 vs. 0: odds ratio [OR] 2.12, p = 0.009; ECOG 2 vs. 0: OR 2.90, p = 0.004), and number of anastomoses (OR 5.34; p < 0.0001). The in-hospital mortality rate for the GIL cohort was 21.8% (24/110), with a 72% (80/110) reoperation rate. The leak cohort had a higher major morbidity rate (88.3 vs. 23.3%; p < 0.0001), a longer hospital stay (39.0 vs. 9.9 days; p < 0.0001), and a longer intensive care unit (ICU) stay (7.7 vs. 1.7 days; p = 0.0003). After surgical mortality was excluded, the overall survival periods for the leak and no-leak patients with complete cytoreduction were respectively 1.5 and 4.98 years (p = 0.0001). Clinically significant decreases in survival were observed for all primary malignancies. CONCLUSIONS: Gastrointestinal leak after CRS/HIPEC is a source of significant mortality, with a decrease in overall survival even after complete CRS. Preoperative functional status and number of anastomoses are predictors of leak for CRS/HIPEC patients.

Outcomes After Mastectomy and Lumpectomy in Elderly Patients with Early-Stage Breast Cancer.

INTRODUCTION: Survival in elderly patients undergoing mastectomy or lumpectomy has not been specifically analyzed. METHODS: Patients older than 70 years of age with clinical stage I invasive breast cancer, undergoing mastectomy or lumpectomy with or without radiation, and surveyed within 3 years of their diagnosis, were identified from the Surveillance, Epidemiology, and End Results and medicare health outcomes survey-linked dataset. The primary endpoint was breast cancer-specific survival (CSS). RESULTS: Of 1784 patients, 596 (33.4 %) underwent mastectomy, 918 (51.4 %) underwent lumpectomy with radiation, and 270 (15.1 %) underwent lumpectomy alone. Significant differences were noted in age, tumor size, American Joint Committee on Cancer (AJCC) stage, lymph node status (all p < 0.0001) and number of positive lymph nodes between the three groups (p = 0.003). On univariate analysis, CSS for patients undergoing lumpectomy with radiation [hazard ratio (HR) 0.61, 95 % confidence interval (CI) 0.43-0.85; p = 0.004] was superior to mastectomy. Older age (HR 1.3, 95 % CI 1.09-1.45; p = 0.002), two or more comorbidities (HR 1.57, 95 % CI 1.08-2.26; p = 0.02), inability to perform more than two activities of daily living (HR 1.61, 95 % CI 1.06-2.44; p = 0.03), larger tumor size (HR 2.36, 95 % CI 1.85-3.02; p < 0.0001), and positive lymph nodes (HR 2.83, 95 % CI 1.98-4.04; p < 0.0001) were associated with worse CSS. On multivariate analysis, larger tumor size (HR 1.89, 95 % CI 1.37-2.57; p < 0.0001) and positive lymph node status (HR 1.99, 95 % CI 1.36-2.9; p = 0.0004) independently predicted worse survival. CONCLUSIONS: Elderly patients with early-stage invasive breast cancer undergoing breast conservation have better CSS than those undergoing mastectomy. After adjusting for comorbidities and functional status, survival is dependent on tumor-specific variables. Determination of lymph node status remains important in staging elderly breast cancer patients.

Effect of epidural compared to patient-controlled intravenous analgesia on outcomes for patients undergoing liver resection for neoplastic disease.

BACKGROUND: Epidural analgesia is routinely used for postoperative pain control following abdominal surgeries, yet data regarding the safety and efficacy of epidural analgesia is controversial. METHODS: Pain-related and clinical perioperative data were extracted and correlated with baseline clinicopathologic data and method of analgesia (epidural vs. intravenous patient-controlled analgesia) in patients who underwent hepatectomy from 2012 to 2014. Chronic pain was defined by specific narcotic requirements preoperatively. RESULTS: Eighty-seven patients underwent hepatectomy with 60% having epidurals placed for postoperative pain control. Epidural patients underwent more major hepatectomies and open resections. Comparison of pain scores between both groups demonstrated no significant difference (all P > .05). A significantly lower proportion of TEA patients required additional IV pain medications than those with IVPCA (P < 0.001). There was no major effect of epidural analgesia on time to ambulation or complications (all P > 0.05). After adjusting for perioperative factors, and surgical extent and approach, no significant differences in fluids administered or length of stay were detected. CONCLUSIONS: Overall postoperative outcomes were not significantly different based on method of analgesia after adjusting for type and extent of hepatic resection. Though patients with epidurals underwent more extensive operations they required less additional IV pain medications than IVPCA patients.

Characteristics of hypertension in premature infants with and without chronic lung disease: a long-term multi-center study.

BACKGROUND: Many causes for neonatal hypertension in premature infants have been described; however in some cases no etiology can be attributed. Our objectives are to describe such cases of unexplained hypertension and to compare hypertensive infants with and without chronic lung disease (CLD). METHODS: We reviewed all cases of hypertension in premature infants referred from 18 hospitals over 16 years. Inclusion criteria were hypertension occurring at <6 months of age and birth at <37 weeks gestation; the main exclusion criterion was known secondary hypertension. Continuous variables were compared using analysis of variance. Nominal variables were compared using chi-square tests. RESULTS: A total of 97 infants met the inclusion criteria, of whom 37 had CLD. Among these infants, hypertension presented at a mean of 11.3 ± 3.2 chronological weeks of age and a postmenstrual age of 39.6 ± 3.6 weeks. Diagnostic testing was notable for plasma renin activity (PRA) being <11 ng/mL/h in 98% of hypertensive infants. Spironolactone was effective monotherapy in 51 of 56 cases of hypertension. Hypertension resolved in all infants, with an average treatment duration of 25 weeks. Significant differences between the two groups of infants were a 0.4 kg lower birthweight and a 2.5 weeks younger gestational age at birth in those with CLD (p < 0.01, p < 0.01, respectively). Hypertension presented in those with CLD 1.8 weeks later, but at the same postmenstrual age as those without CLD (p < 0.01, p = 0.45, respectively). CONCLUSION: Premature infants with unexplained hypertension, with and without CLD, presented at a postmenstrual age of 40 weeks with low PRA, transient time course, and a favorable response to spironolactone treatment.

Quality of life of older African American breast cancer survivors: a population-based study.

INTRODUCTION: Factors associated with lower health-related quality of life (HRQOL) among older African American (AA) breast cancer survivors (BCS) have not been elucidated. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare Health Outcome Survey linked dataset, all resected AA BCS over 65 were identified. Using the most recent survey after diagnosis, individuals with a VR12 physical (PCS) or mental (MCS) component score 10 points lower than the median were categorized as having poor HRQOL. Univariate and multivariate (MV) analyses identified predictors of poor HRQOL. RESULTS: Of 373 AA BCS (median age 74.6), median time from diagnosis to survey was 68.4 months with median follow-up of 138.6 months. Median PCS was 35.9 (IQR 28.5-44.5) with 76 (20.1%) reporting poor PCS. Median MCS was 50.6 (IQR 41.3-59.1) with 101 (27.1%) reporting poor MCS. Predictors of poor PCS included advanced age, larger tumor size, ≥2 comorbidities, inability to perform >2 of 6 activities of daily living (ADLs), modified/radical mastectomy, infiltrating lobular carcinoma, and stage III or IV disease (all p < 0.05). Comorbidities ≥2 and inability to perform >2 of 6 ADLs (p < 0.05) predicted poor MCS. Inability to perform >2 of 6 ADLs was the only independent predictor of poor PCS (OR 10.9, 95% CI 3.0-39.3; p < 0.001) and MCS (OR 7.6, 95% CI 4.3-13.3; p < 0.001). CONCLUSION: In elderly AA BCS, poor HRQOL was not associated with socioeconomic status or tumor-specific factors but rather impairment in ADLs. Physical and mental HRQOL in African American breast cancer survivors is not dependent on socioeconomic or tumor-related characteristics, but rather on inability to perform ADLs.

Counseling Practices for Fetal Hypoplastic Left Heart Syndrome.

While counseling parents of a fetus diagnosed with hypoplastic left heart syndrome (HLHS), pediatric cardiologists play a critical role in shaping a family's expectations for the months and years to come. However, techniques for the most effective counseling practices have not been studied, and significant variation among physicians is likely present. Web-based survey of pediatric cardiologists that perform fetal echocardiography using snowball sampling. 201 physicians responded (61% male, 81% from academic centers, and 95% from the U.S.), with an average experience of 12 years. The majority of respondents (73%) typically received initial referrals for HLHS between 20 and 24 weeks of gestation. Most physicians counsel families alone (54%), while others counsel with a nurse (35%), social worker (12%), and/or maternal-fetal medicine colleague (15%). Termination of pregnancy was discussed by 79% of respondents, although 15% did not know their state's legal limit for termination. While initial counseling sessions routinely described the typical earlier ramifications of HLHS, many long-term sequelae of the disease were not commonly discussed. Content of counseling was affected by region of the country, but not by practice setting, experience, or fetal volume. Respondents identified multiple barriers that limited their counseling practices. Our data suggest that current counseling practices often fail to cover important information. Perceived barriers to a full discourse on long-term sequelae of HLHS are common and may lead to a disconnect between reality and a family's understanding of the natural history of palliated HLHS. Opportunities to improve counseling practices exist, and there may be benefits to gain from more formal training.

Intern Boot Camp: Feasibility and impact of a 1-hour session to ensure graduating medical student competency in falls risk assessment.

The authors evaluated the feasibility of a 1-hour session to ensure competency in gait and falls risk assessment for medical students at their institution. The session included a history and exam with faculty and staff as standardized patients, gait recognition videos, and case evaluation for falls risk assessment and prevention. Student perceptions were evaluated using a retrospective pre-post survey, scored on a 5-point Likert-type scale. Wilcoxon signed-rank tests were used to assess change and Kruskal-Wallis tests were used to analyze differences by residency choice. A range of five to 11 faculty and staff certified 238 medical students during eight 1-hour sessions. Overall self-perception of competence in falls risk assessment and prevention improved (p ≤ .001), and did not differ by residency choice, both before and after the training program (p = .73 and p = .25). Feedback was positive. This session is a feasible way to teach and assess the competency for falls risk assessment with modest time commitment.

Cell line modeling to study biomarker panel in prostate cancer.

BACKGROUND: African-American men with prostate cancer (PCa) present with higher-grade and -stage tumors compared to Caucasians. While the disparity may result from multiple factors, a biological basis is often strongly suspected. Currently, few well-characterized experimental model systems are available to study the biological basis of racial disparity in PCa. We report a validated in vitro cell line model system that could be used for the purpose. METHODS: We assembled a PCa cell line model that included currently available African-American PCa cell lines and LNCaP (androgen-dependent) and C4-2 (castration-resistant) Caucasian PCa cells. The utility of the cell lines in studying the biological basis of variance in a malignant phenotype was explored using a multiplex biomarker panel consisting of proteins that have been proven to play a role in the progression of PCa. The panel expression was evaluated by Western blot and RT-PCR in cell lines and validated in human PCa tissues by RT-PCR. As proof-of-principle to demonstrate the utility of our model in functional studies, we performed MTS viability assays and molecular studies. RESULTS: The dysregulation of the multiplex biomarker panel in primary African-American cell line (E006AA) was similar to metastatic Caucasian cell lines, which would suggest that the cell line model could be used to study an inherent aggressive phenotype in African-American men with PCa. We had previously demonstrated that Protein kinase D1 (PKD1) is a novel kinase that is down regulated in advanced prostate cancer. We established the functional relevance by over expressing PKD1, which resulted in decreased proliferation and epithelial mesenchymal transition (EMT) in PCa cells. Moreover, we established the feasibility of studying the expression of the multiplex biomarker panel in archived human PCa tissue from African-Americans and Caucasians as a prelude to future translational studies. CONCLUSION: We have characterized a novel in vitro cell line model that could be used to study the biological basis of disparity in PCa between African-Americans and Caucasians.

Routine Admission to Intensive Care Unit After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy: Not Always a Requirement.

BACKGROUND: Routine postoperative intensive care unit (ICU) observation of patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is driven by historically reported morbidity and mortality data. The validity of this practice and the criteria for ICU admission have not been elucidated. METHODS: A prospectively maintained database of 1146 CRS/HIPEC procedures performed from December 1991 to 2014 was retrospectively analyzed. Patients with routine postoperative ICU admission were compared with patients sent directly to the surgical floor. To test the safety of non-ICU care practice, patients with less than 48 h ICU admission were compared with patients directly admitted to the floor. Demographics, primary tumor site, comorbidities, estimated blood loss (EBL), extent of CRS, Eastern Cooperative Oncology Group (ECOG) status, and overall survival were analyzed. RESULTS: Complete data were available for 1064 CRS/HIPEC procedures, of which 244 cases (22.93 %) did not require ICU admission. Multivariate logistic regression identified age [odds ratio (OR) 1.024; p = 0.02], EBL (OR 1.002; p < 0.0001), number of resected organs (OR 1.308; p = 0.01) and ECOG > 2 (OR 6.387; p = 0.003) as predictive variables of postoperative ICU admission. The cohort directly admitted to the floor demonstrated less minor grade I/II morbidity (29 vs. 47 %; p < 0.0001) and similar grade III/IV major morbidity (16.5 vs. 13.4 %; p = 0.3) than the patients admitted to the ICU for less than 48 h. CONCLUSIONS: ICU observation is not routinely required for all patients treated with CRS/HIPEC. Selective ICU admission based on ECOG status, nutritional status, age, EBL, and CRS extent is safe, with potential implications for hospitalization cost for these complex cases.

Stoma Creation and Reversal After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC) often includes stoma creation. We evaluated the indications, morbidity, and mortality associated with stoma creation and reversal after CRS/HIPEC. METHODS: Retrospective analysis of a prospective database of 1149 CRS-HIPEC procedures was performed. Patient demographics, type of malignancy, comorbidities, Clavien-graded morbidity, mortality, indications for stoma creation, and outcomes of subsequent reversal were abstracted. RESULTS: Sixteen percent (186/1149) of CRS/HIPEC procedures included stoma creation, whereas 1.1 % (11/963) of patients without initial stoma creation developed anastomotic leaks requiring stoma. Patients who required a stoma had worse preoperative performance status (ECOG 0/1: 77.2 vs. 86.1 %, p = 0.002), greater burden of disease (PCI 17.6 vs. 12.9, p < 0.0001), and were more likely to have R2 resections (74.5 vs. 48.8 %, p < 0.0001) than those without stoma creation. Stomas were intended to be permanent in 17.5 % (35/199). Of 164 patients with potentially reversible ostomies, only 26.2 % (43/164) underwent reversal. Disease progression (43/164, 26.2 %) and death (40/164, 24.3 %) most commonly precluded reversal. After reversal, 27.9 % (12/43) suffered a Clavien I/II morbidity, 27.9 % (12/43) suffered Clavien III/IV morbidity, and 30-day mortality was 4.7 % (2/43). Anastomotic leak occurred after 9 % (3/33) of ileostomy and 10 % (1/10) of colostomy reversals. CONCLUSIONS: Stomas are more common among CRS/HIPEC patients with a high burden of disease and poor functional status. Reversal is uncommon and is associated with significant major morbidity. Preoperative counseling for those with high disease burden and poor functional status should include the risk of permanent stoma.