Improvement in inpatient discharge planning for patients with alcohol use disorder with the implementation of a team-based multidisciplinary workflow.

BACKGROUND: Alcohol use disorder (AUD) is a major economic and healthcare burden in the United States. While there is evidence-based medication-assisted treatment (MAT) for AUD, few physicians implement these therapies on a regular basis. OBJECTIVE: To determine the impact of a pharmacy-guided AUD discharge planning workflow on the rate of MAT prescriptions and inpatient readmissions. METHODS: This was a single-centered pre-and-post intervention study over a 6-month period, with a 90-day pre-intervention period and a 90-day post-intervention period. The study included all patients over the age of 18 years admitted to a medicine or surgery floor bed who presented with alcohol withdrawal at any point during their hospital course. The intervention involved a pharmacy workflow, in which a list of patients admitted with alcohol withdrawal was automatically generated and referred to pharmacists, who then provided recommendations to the primary physician regarding prescriptions for naltrexone, acamprosate, and/or gabapentin. The patients were then contacted within 30 days after discharge for post-hospitalization follow-up. Our outcome measures were change in prescription rate of MATs, change in total and alcohol-related 90-day readmission rates, and change in total and alcohol-related 90-day emergency department (ED) visit rates. RESULTS: The pre-intervention period consisted of 49 patients and the post-intervention period consisted of 41 patients. Our workflow demonstrated a 195% increase in the prescription rate of MATs at discharge (p < 0.001), 61% reduction in 90-day total readmission rate (p < 0.05), 40% reduction in 90-day total ED visit rate (p = 0.09), 92% reduction in 90-day alcohol-related readmission rate (p < 0.05), and 88% reduction in 90-day alcohol-related ED visit rate (p < 0.05). CONCLUSIONS: Our intervention demonstrated that a pharmacy-based AUD discharge planning workflow has the potential to reduce inpatient readmissions and ED visits for patients with AUD, thus demonstrating improved patient outcomes with the potential to reduce healthcare costs.

Rates of price disclosure associated with the surgical treatment of early-stage breast cancer one year after implementation of federal regulations.

PURPOSE: Mastectomy, breast reconstruction (BR) and breast conserving therapy (BCT) are core components of the treatment paradigm for early-stage disease but are differentially associated with significant financial burdens. Given recent price transparency regulations, we sought to characterize rates of disclosure for breast cancer-related surgery, including mastectomy, BCT, and BR (oncoplastic reconstruction, implant, pedicled flap and free flap) and identify associated factors. METHODS: For this cross-sectional analysis, cost reports were obtained from the Turquoise Health price transparency platform for all U.S. hospitals meeting national accreditation standards for breast cancer care. The Healthcare Cost Report Information System was used to collect facility-specific data. Addresses were geocoded to identify hospital referral and census regions while data from CMS was also used to identify the geographic practice cost index. We leveraged a Poisson regression model and relevant Medicare billing codes to analyze factors associated with price disclosure and the availability of an OOP price estimator. RESULTS: Of 447 identified hospitals, 221 (49.4%) disclosed prices for mastectomy and 188 42.1%) disclosed prices for both mastectomy and some form of reconstruction including oncoplastic reduction (n = 184, 97.9%), implants (n = 187, 99.5%), pedicled flaps (n = 89, 47.3%), and free flaps (n = 81, 43.1%). Non-profit status and increased market competition were associated with price nondisclosure. 121 hospitals (27.1%) had an out-of-pocket price estimator that included at least one breast surgery. CONCLUSIONS: Most eligible hospitals did not disclose prices for breast cancer surgery. Distinct hospital characteristics were associated with price disclosure. Breast cancer patients face persistent difficulty in accessing costs.

Targeted Therapy for BRAF V600E Positive Pancreatic Adenocarcinoma: Two Case Reports.

BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) is a malignancy that typically portends a poor prognosis, with a median overall survival ranging from eight to twelve months in patients with metastatic disease. Novel modalities of therapy, primarily targeted therapy, are now considered for patients with targetable mutations, such as BRAF mutations based on next generation sequencing. BRAF mutations specifically within pancreatic adenocarcinoma remain rare with an incidence of approximately 3%. Previous research on BRAF mutated pancreatic adenocarcinoma is extremely scarce, limited primarily to case reports; therefore, little is known regarding this entity. CASE REPORT: We seek to contribute to prior literature with the presentation of two cases of patients with BRAF V600E + pancreatic adenocarcinoma, who did not have a favorable response to initial systemic chemotherapy and were both subsequently treated with targeted therapy (dabrafenib and trametinib). Each of the patients has sustained a favorable response and there is no evidence of progression thus far on dabrafenib and trametinib, highlighting the potential benefit of targeted therapy in these patients. CONCLUSION: These cases emphasize the importance of early next generation sequencing and the consideration of BRAF targeted treatment in this patient population, especially if a response to initial chemotherapy is not sustained.

Survival Benefit with Re-resection and Optimal Time to Re-resection in Gallbladder Cancer: a National Cancer Database Study.

PURPOSE: Gallbladder cancer is often diagnosed incidentally after cholecystectomy. Most patients will then undergo re-resection for potential residual disease; however, overall survival (OS) benefit data in this scenario is variable. This National Cancer Database analysis (NCDB) compared OS in patients with T1b-T3 gallbladder cancer who underwent re-resection and evaluated if time to resection impacts OS. METHODS: We reviewed the NCDB for patients who received initial cholecystectomy for gallbladder cancer and were subsequently eligible for re-resection based on tumor stage (T1b-T3 disease). Patients with re-resection were subdivided into four cohorts based on time to re-resection: 0-4 weeks, 5-8 weeks, 9-12 weeks, and > 12 weeks. We used a Cox proportional hazards ratio to identify factors associated with worse survival and logistic regression to evaluate characteristics associated with re-resection. OS was calculated using Kaplan Meier curves. RESULTS: A total of 791 (5.82%) patients received re-resection. Cox proportional hazards analysis showed a comorbidity score of 1 was associated with worse survival. Patients with higher comorbidity scores and treatment at comprehensive community, integrated, or academic cancer programs were less likely to undergo re-resection. Re-resection showed significantly improved OS [HR 0.87; 95 CI 0.77-0.98; p = 0.0203]. Improved survival was appreciated when re-resection was completed at 5-8 weeks [HR 0.67; CI 0.57-0.81], 9-12 weeks [HR 0.64; CI 0.52-0.79], or > 12 weeks [HR 0.61; CI 0.47-0.78] compared to 0-4 weeks. CONCLUSION: Optimal timing to re-resection in gallbladder cancer supports previous data showing benefit at > 4 weeks. However, there was no significant survival difference as to whether re-resection was completed at 5-8 weeks, 9-12 weeks, or > 12 weeks post initial cholecystectomy.

Primary Testicular Lymphoma: Single Center Experience.

BACKGROUND/AIM: Primary testicular lymphoma (PTL) is an exceedingly rare and aggressive form of non-Hodgkin's lymphoma; the most common subtype is diffuse large B-cell (DLBCL). Standard treatment includes orchiectomy, chemotherapy, central nervous system (CNS) prophylaxis, and prophylactic radiation to the contralateral testis. PTL can reoccur years after complete remission. Treatment to immune sanctuary sites, CNS and contralateral testis, is crucial in preventing relapse. There are limited data characterizing this entity and this study aimed to add to existing literature. PATIENTS AND METHODS: This descriptive retrospective study characterized twelve patients with PTL from years 2010-2021 at Allegheny Health Network. Their demographic data, prognostic factors, treatment regimens, and relapse sites (if any) were tabulated. The mean progression-free survival (PFS) was calculated to describe our experience in treating PTL. RESULTS: Twelve patients were diagnosed with PTL; 10/12 (83.33%) patients were diagnosed with ABC PTL-DLBCL. Median age of diagnosis was 67 years. Eight of the 12 (66.66%) were African American, 4/12 (33.33%) were Caucasian. At the time of diagnosis, 8/12 (66.66%) patients presented with an elevated lactate dehydrogenase (LDH) and 8/12 (66.66%) presented with a left testicular mass. Most were treated with R-CHOP (9/12), intrathecal methotrexate (IT-MTX) (10/12), and radiation to the contralateral testis (9/12). Three of the twelve (25%) patients relapsed. Median time to relapse was 8 months. Mean PFS was 50.417 months. CONCLUSION: We discuss our experience in treating PTL with RCHOP, IT-MTX, and irradiation to the contralateral testis and add to the limited pre-existing data that exist.

Reproducibility of laryngeal force sensor measurements.

OBJECTIVE: The laryngeal force sensor (LFS) measures force during suspension microlaryngoscopy (SML) procedures, and has been previously shown to predict postoperative complications. Reproducibility of its measurements has not been described. STUDY DESIGN: Prospective cohort study. SETTING: Academic medical center. METHODS: 291 adult patients had force data collected from 2017 to 2021 during various SML procedures. 94 patients had passive LFS monitoring (surgeon blinded to intraoperative recordings) and 197 had active LFS monitoring (surgeon able to see LFS recordings). 27 of these patients had repeat procedures, with unique LFS metrics for each procedure. The 27 patients were divided into three groups. Group 1 had passive use for both procedures, group 2 had passive use for the first procedure and active use for the second, and group 3 had active use for both procedures. Force metrics from the two procedures were compared with a paired samples t-test. RESULTS: For airway dilation procedures and cancer resection procedures, average force variances were significantly lower with active versus passive use of the LFS. Group 1-no significant changes in maximum force (procedure 1 = 163.8 N, procedure 2 = 133.8 N, p = 0.324) or average force (procedure 1 = 93.6 N, procedure 2 = 78.3 N, p = 0.617). Group 2-maximum force dropped by 35 % between procedures 1 (219.2 N) and 2 (142.5 N), p = 0.013. Average force dropped by 42.5 % between procedures 1 (147.2 N) and 2 (84.6 N), p = 0.007. Group 3-no significant changes in maximum force (procedure 1 = 158.6 N, procedure 2 = 158.2 N, p = 0.986) or average force (procedure 1 = 94.2, procedure 2 = 81.8, p = 0.419). CONCLUSIONS: LFS measurements were reproducible for similar procedures in the same patient when the type of LFS monitoring was not a confounder.

Association between patient-surgeon race and gender concordance and patient-reported outcomes following breast cancer surgery.

PURPOSE: Surgeon- and patient-related factors have been shown to influence patient experiences, quality of life (QoL), and surgical outcomes. We examined the association between patient-surgeon race and gender concordance with QoL after breast reconstruction. METHODS: We conducted a retrospective cross-sectional analysis of patients who underwent lumpectomy or mastectomy followed by breast reconstruction over a 3-year period. We created the following categories with respect to the race and gender of a patient-surgeon triad: no, intermediate, and perfect concordance. Multivariable regression was used to correlate postoperative global (SF-12) and condition-specific (BREAST-Q) QoL performance with patient-level covariates, gender and race concordance. RESULTS: We identified 375 patients with a mean (± SD) age of 57.6 ± 11.9 years, median (IQR) body mass index of 27.5 (24.0, 32.0), and median morbidity burden of 3 (2, 4). The majority of encounters were of intermediate concordance for gender (70%) and race (52%). Compared with gender-discordant triads, intermediate gender concordance was associated with higher SF-Mental scores (ß, 2.60; 95% CI, 0.21-4.99, p = 0.003). Perfect race concordance (35% of encounters) was associated with significantly higher adjusted SF-Physical scores (ß, 2.14; 95% CI, 0.50-4.22, p = 0.045) than the race-discordant group. There were no significant associations observed between race or gender concordance and BREAST-Q performance. CONCLUSION: Race-concordant relationships following breast cancer surgery were more likely to have improved global QoL. Perfect gender concordance was not associated with variation in QoL outcomes. Policy-level interventions are needed to facilitate personalized care and optimize breast cancer surgery outcomes.

Post-Mastectomy Tissue Expander Placement Followed by Radiation Therapy: A Cost-Effectiveness Analysis of Staged Autologous Versus Implant-Based Unilateral Reconstruction.

BACKGROUND: There is no preferred approach to breast reconstruction for patients with locally advanced breast cancer (LABC) who require post-mastectomy radiation therapy (PMRT). Staged implant and autologous reconstruction both have unique risks and benefits. No previous study has compared their cost-effectiveness with utility scores. METHODS: A literature review determined the probabilities and outcomes for mastectomy and staged implant or autologous reconstruction. Utility scores were used to calculate the quality-adjusted life years (QALYs) associated with successful surgery and postoperative complications. Medicare billing codes were used to assess costs. A decision analysis tree was constructed with rollback and incremental cost-effectiveness ratio (ICER) analyses. Sensitivity analyses were performed to validate results and account for uncertainty. RESULTS: Mastectomy with staged deep inferior epigastric perforator (DIEP) flap reconstruction is costlier ($14,104.80 vs $3216.93), but more effective (QALYs, 29.96 vs 24.87). This resulted in an ICER of 2141.00, favoring autologous reconstruction. One-way sensitivity analysis showed that autologous reconstruction was more cost-effective if less than $257,444.13. Monte Carlo analysis showed a confidence of 99.99% that DIEP flap reconstruction is more cost-effective. CONCLUSIONS: For patients with LABC who require PMRT, staged autologous reconstruction is significantly more cost-effective than reconstruction with implants. Despite the decreased morbidity, staged implant reconstruction has greater rates of complication.

Validation of the Neoadjuvant Rectal Cancer (NAR) Score for Prognostication Following Total Neoadjuvant Therapy (TNT) for Locally Advanced Rectal Cancer.

PURPOSE: The neoadjuvant rectal cancer (NAR) score is a prognostic tool for locally advanced rectal cancer (LARC) treated with total neoadjuvant therapy (TNT). It has been previously validated as an endpoint that predicts survival more accurately than pathologic complete response (pCR) and is the primary endpoint of the ongoing NRG-GI002 Phase II trial. Using the National Cancer Database (NCDB), we aimed to validate the NAR score's ability to predict survival in a large hospital-based dataset. METHODS: We queried the NCDB to identify locally advanced rectal cancer patients from 2004 to 2015 that received TNT followed by surgical resection. Overall survival (OS) was calculated using Kaplan-Meier curves evaluating NAR score and pCR separately. A multivariable Cox proportional hazards model was used to identify factors associated with survival. Multivariate regression was used to evaluate characteristics associated with a favorable (< 14.98) NAR score. RESULTS: From > 264,000 patients diagnosed with rectal adenocarcinoma in the NCDB, our final cohort yielded 209 patients with a median age of 62 years. Factors associated with worse survival included age > 62 years old (p = 0.04), lower income (p = 0.03), and unfavorable (≥ 14.98) NAR score (p = 0.04). On multivariate regression, tumors with perineural invasion and a higher comorbidity score (> 1) were less likely to have a favorable NAR response (p = 0.01 and p = 0.01). pCR was not associated with improved survival (p = 0.09). CONCLUSIONS: Our study validates the NAR score as a prognostic tool in patients receiving TNT for LARC. Tumors with perineural invasion and patients with a higher comorbidity score had worse NAR scores.

Is the Centralization of Complex Surgical Procedures an Unintended Spillover Effect of Global Capitation? - Insights from the Maryland Global Budget Revenue Program.

OBJECTIVE: To determine if global budget revenue (GBR) models incent the centralization of complex surgical care. SUMMARY BACKGROUND: In 2014, Maryland initiated a statewide GBR model. While prior research has shown improvements in cost and outcomes for surgical care post-GBR implementation, the mechanism remains unclear. METHODS: Utilizing state inpatient databases, we compared the proportion of adults undergoing elective complex surgeries (gastrectomy, pneumonectomy/lobectomy, proctectomies, and hip/knee revision) at high-concentration hospitals (HCHs) in Maryland and control states. Annual concentration, per procedure, was defined as hospital volume divided by state volume. HCHs were defined as hospitals with a concentration at least at the 75 th percentile in 2010. We estimated the difference-in-differences (DiD) of the probability of patients undergoing surgery at HCHs before and after GBR implementation. FINDINGS: Our sample included 122,882 surgeries. Following GBR implementation, all procedures were increasingly performed at HCHs in Maryland. States satisfied the parallel trends assumption for the centralization of gastrectomy and pneumonectomy/lobectomy. Post-GBR, patients were more likely to undergo gastrectomy (DiD: 5.5 p.p., 95% CI [2.2, 8.8]) and pneumonectomy/lobectomy (DiD: 12.4 p.p., 95% CI [10.0, 14.8]) at an HCH in Maryland compared with control states. For our hip/knee revision analyses, we assumed persistent counterfactuals and noted a positive DiD post-GBR implementation (DiD: 4.8 p.p., 95% CI [1.3, 8.2]). No conclusion could be drawn for proctectomy due to different pre-GBR trends. CONCLUSIONS: GBR implementation is associated with increased centralization for certain complex surgeries. Future research is needed to explore the impact of centralization on patient experience and access.

Prophylactic Anticoagulation in Patients With Pancreatic Adenocarcinoma: A Single Tertiary Care Center Retrospective QI Project.

BACKGROUND/AIM: A well-known complication of pancreatic adenocarcinoma (PDAC) is venous thromboembolism (VTE). The Khorana score is used as a tool to help determine the role of primary prophylaxis (PPx) in cancer patients with VTE. This study compared outcomes in PDAC patients who received primary PPx (anticoagulation) versus those who did not. PATIENTS AND METHODS: PDAC patients from 2017-2019 at Allegheny General Hospital were retrospectively reviewed. Descriptive statistics were presented via medians with interquartile ranges for continuous variables and percentages for categorical variables. Predictors of VTE development were determined using univariable and multivariable logistic regression models. T-tests and Chi-square tests were used to compare means and percentages, respectively. RESULTS: A total of 102 patients with full VTE PPx data were reviewed. At least one VTE event was identified in 29 patients (28.2%). A total of 4 out of these 29 patients (13.8%) were on PPx anticoagulation. Death secondary to VTE occurred in one patient without PPx. Two (2.0%) patients experienced bleeding events of those prescribed VTE PPx. On univariable analysis, stage IV disease, planned surgery, and unresectable disease were predictors of VTE development. On multivariate analysis, total pancreatectomy was a predictor of VTE development. There was no difference in average time to progression amongst patients who had developed VTE versus those who did not. CONCLUSION: The Khorana score for VTE PPx in PDAC patients in underutilized.

Deletion of Abi3/Gngt2 influences age-progressive amyloid ß and tau pathologies in distinctive ways.

BACKGROUND: The S209F variant of Abelson Interactor Protein 3 (ABI3) increases risk for Alzheimer's disease (AD), but little is known about its function in relation to AD pathogenesis. METHODS: Here, we use a mouse model that is deficient in Abi3 locus to study how the loss of function of Abi3 impacts two cardinal neuropathological hallmarks of AD-amyloid ß plaques and tau pathology. Our study employs extensive neuropathological and transcriptomic characterization using transgenic mouse models and adeno-associated virus-mediated gene targeting strategies. RESULTS: Analysis of bulk RNAseq data confirmed age-progressive increase in Abi3 levels in rodent models of AD-type amyloidosis and upregulation in AD patients relative to healthy controls. Using RNAscope in situ hybridization, we localized the cellular distribution of Abi3 in mouse and human brains, finding that Abi3 is expressed in both microglial and non-microglial cells. Next, we evaluated Abi3-/- mice and document that both Abi3 and its overlapping gene, Gngt2, are disrupted in these mice. Using multiple transcriptomic datasets, we show that expression of Abi3 and Gngt2 are tightly correlated in rodent models of AD and human brains, suggesting a tight co-expression relationship. RNAseq of the Abi3-Gngt2-/- mice revealed upregulation of Trem2, Plcg2, and Tyrobp, concomitant with induction of an AD-associated neurodegenerative signature, even in the absence of AD-typical neuropathology. In APP mice, loss of Abi3-Gngt2 resulted in a gene dose- and age-dependent reduction in Aß deposition. Additionally, in Abi3-Gngt2-/- mice, expression of a pro-aggregant form of human tau exacerbated tauopathy and astrocytosis. Further, using in vitro culture assays, we show that the AD-associated S209F mutation alters the extent of ABI3 phosphorylation. CONCLUSIONS: These data provide an important experimental framework for understanding the role of Abi3-Gngt2 function and early inflammatory gliosis in AD. Our studies also demonstrate that inflammatory gliosis could have opposing effects on amyloid and tau pathology, highlighting the unpredictability of targeting immune pathways in AD.

Acupuncture and Postoperative Pain Reduction.

PURPOSE OF REVIEW: Acupuncture is an analgesic technique that has long been utilized in Eastern medicine. In recent times, various acupuncture techniques have been used in integrated pain management approaches in Western medicine. It has even been adopted as an analgesic method in surgical patients. Currently, no review exists regarding various acupuncture techniques used in perioperative pain management and data describing the utility of these techniques. This paper synthesizes the latest literature regarding the role of acupuncture in perioperative pain management. The authors sought to describe various acupuncture modalities used to help manage surgical pain and synthesize the current body of literature to help readers make informed judgements on the topic. RECENT FINDINGS: Patients undergoing abdominal, spine/neuro, and gynecologic pelvic surgery generally benefit from acupuncture. Out of the various acupuncture techniques, electroacupuncture, transcutaneous electric acupoint stimulation, and traditional total body acupuncture seem to be most promising as adjuncts to multimodal perioperative analgesia. Benefits include improved analgesia and/or reduced narcotic requirements, decrease in PONV, and shorter time to return of bowel function. Acupuncture is a low-risk method that has the potential to enhance perioperative analgesia, decrease opioid requirement, and reduce unwanted side effects of anesthesia, surgery, and opioid administration such as nausea/vomiting. Given the variety of patient populations, various acupuncture techniques, and small patient populations for most current studies; it remains difficult to determine which acupuncture method would most benefit specific patients. Future studies with more robust sample sizes and prospective comparison on acupuncture technique would help better characterize acupuncture's role in perioperative pain management.

Association of computed tomography screening with lung cancer stage shift and survival in the United States: quasi-experimental study.

OBJECTIVE: To determine the effect of the introduction of low dose computed tomography screening in 2013 on lung cancer stage shift, survival, and disparities in the stage of lung cancer diagnosed in the United States. DESIGN: Quasi-experimental study using Joinpoint modeling, multivariable ordinal logistic regression, and multivariable Cox proportional hazards modeling. SETTING: US National Cancer Database and Surveillance Epidemiology End Results program database. PARTICIPANTS: Patients aged 45-80 years diagnosed as having non-small cell lung cancer (NSCLC) between 1 January 2010 and 31 December 2018. MAIN OUTCOME MEASURES: Annual per cent change in percentage of stage I NSCLC diagnosed among patients aged 45-54 (ineligible for screening) and 55-80 (potentially eligible for screening), median all cause survival, and incidence of NSCLC; multivariable adjusted odds ratios for year-to-year changes in likelihood of having earlier stages of disease at diagnosis and multivariable adjusted hazard ratios for changes in hazard of death before versus after introduction of screening. RESULTS: The percentage of stage I NSCLC diagnosed among patients aged 55-80 did not significantly increase from 2010 to 2013 (from 27.8% to 29.4%) and then increased at 3.9% (95% confidence interval 3.0% to 4.8%) per year from 2014 to 2018 (from 30.2% to 35.5%). In multivariable adjusted analysis, the increase in the odds per year of a patient having one lung cancer stage lower at diagnosis during the time period from 2014 to 2018 was 6.2% (multivariable adjusted odds ratio 1.062, 95% confidence interval 1.048 to 1.077; P<0.001) higher than the increase in the odds per year from 2010 to 2013. Similarly, the median all cause survival of patients aged 55-80 did not significantly increase from 2010 to 2013 (from 15.8 to 18.1 months), and then increased at 11.9% (8.9% to 15.0%) per year from 2014 to 2018 (from 19.7 to 28.2 months). In multivariable adjusted analysis, the hazard of death decreased significantly faster after 2014 compared with before 2014 (P<0.001). By 2018, stage I NSCLC was the predominant diagnosis among non-Hispanic white people and people living in the highest income or best educated regions. Non-white people and those living in lower income or less educated regions remained more likely to have stage IV disease at diagnosis. Increases in the detection of early stage disease in the US from 2014 to 2018 led to an estimated 10 100 averted deaths. CONCLUSIONS: A recent stage shift toward stage I NSCLC coincides with improved survival and the introduction of lung cancer screening. Non-white patients and those living in areas of greater deprivation had lower rates of stage I disease identified, highlighting the need for efforts to increase access to screening in the US.

Preparation and characterization of neutrally-buoyant oleosin-rich synthetic lipid droplets.

Lipid droplets also known as oil bodies are found in a variety of organisms and function as stores of high-energy metabolites. Recently, there has been interest in using lipid droplets for protein production and drug delivery. Artificial lipid droplets have been previously prepared, but their short lifetime in solution and inhomogeneity has severely limited their applicability. Herein we report an improved methodology for the production of synthetic lipid droplets that overcomes the aforementioned limitations. These advancements include: 1) development of a methodology for the expression and purification of high-levels of oleosin, a crucial lipid droplet component, 2) preparation of neutrally-buoyant synthetic lipid droplets, and 3) production of synthetic lipid droplets of a specific size. Together, these important enhancements will facilitate the advancement of lipid droplet science and its application in biotechnology.

Graduate Medical Education in Otolaryngology: Making Dollars and Sense of Reform.

Graduate medical education (GME) is funded by the Centers for Medicare and Medicaid Services through both direct and indirect payments. In recent years, stakeholders have raised concerns about the growth of spending on GME and distribution of payment among hospitals. Key stakeholders have proposed reforms to reduce GME funding such as adjustments to statutory payment formulas and absolute caps on annual payments per resident. Otolaryngology departmental leadership should understand the potential effects of proposed reforms, which could have significant implications for the short-term financial performance and the long-term specialty workforce. Although some hospitals and departments may elect to reduce resident salaries or eliminate positions in the face of GME funding cuts, this approach overlooks the substantial Medicare revenue contributed by resident care and high cost of alternative labor sources. Commitment to resident training is necessary to align both the margin and mission of otolaryngology departments and their sponsoring hospitals.

Outcomes among pediatric patients with cancer who are treated on trial versus off trial: A matched cohort study.

BACKGROUND: Approximately 50% of children with cancer in the United States who are aged <15 years receive primary treatment on a therapeutic clinical trial. To the authors' knowledge, it remains unknown whether trial enrollment has a clinical benefit compared with the best alternative standard therapy and/or off trial (ie, clinical trial effect). The authors conducted a retrospective matched cohort study to compare the morbidity and mortality of pediatric patients with cancer who are treated on a phase 3 clinical trial compared with those receiving standard therapy and/or off trial. METHODS: Subjects were aged birth to 19 years; were diagnosed between 2000 and 2010 with acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), rhabdomyosarcoma, or neuroblastoma; and had received initial treatment at the Children's Hospital of Philadelphia. On-trial and off-trial subjects were matched based on age, race, ethnicity, a diagnosis of Down syndrome (for patients with ALL or AML), prognostic risk level, date of diagnosis, and tumor type. RESULTS: A total of 428 participants were matched in 214 pairs (152 pairs for ALL, 24 pairs for AML, 32 pairs for rhabdomyosarcoma, and 6 pairs for neuroblastoma). The 5-year survival rate did not differ between those treated on trial versus those treated with standard therapy and/or off trial (86.9% vs 82.2%; P = .093). On-trial patients had a 32% lower odds of having worse (higher) mortality-morbidity composite scores, although this did not reach statistical significance (odds ratio, 0.68; 95% confidence interval, 0.45-1.03 [P = .070]). CONCLUSIONS: There was no statistically significant difference in outcomes noted between those patients treated on trial and those treated with standard therapy and/or off trial. However, in partial support of the clinical trial effect, the results of the current study indicate a trend toward more favorable outcomes in children treated on trial compared with those treated with standard therapy and/or off trial. These findings can support decision making regarding enrollment in pediatric phase 3 clinical trials.