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Healthcare delivery is heterogenous; the reasons for this are numerous and complex. Patient-specific factors including geography, income, insurance status, age, and gender have been shown to bias surgical outcomes. Utilizing a prospectively collected all-payer database, we aim to evaluate the influence of socioeconomic factors on mortality and length of stay (LOS) after common cardiac surgical procedures.We utilized the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for the year 2019. We included patients undergoing coronary artery bypass grafting (CABG), aortic valve replacement (AVR), transcatheter aortic valve replacement (TAVR), and combined AVR/CABG using the 10th revision of the International Classification of Diseases procedure codes. AVR and CABG were combined into a separate cohort as this was felt to represent a different pathology than isolated valvular or coronary arterial disease. Baseline demographics were summarized. Multivariable regression was performed within each procedure group to model the odds of in-hospital mortality and hospital LOS with age, sex, insurance, zip-code median household income, and location as predictors.Baseline patient characteristics including gender, income, geography, and payer status were similar between CABG, AVR, and AVR/CABG. TAVR patients had a higher proportion of female sex and Medicare as the primary payer, with an overall greater age. Multivariable Cox proportional hazards regression found that higher income was strongly associated with decreased LOS following AVR and CABG, and moderately associated in TAVR and AVR/CABG. Private insurance was associated with a decreased LOS in patients undergoing CABG, AVR, TAVR, and AVR/CABG. Female sex and increased age were associated with increased odds of mortality in TAVR, CABG, and AVR/CABG. Private insurance was associated with a decreased odds of mortality in patients undergoing AVR.These findings reveal significant disparities in patient outcomes after routine cardiac operations that are associated with socioeconomic status. Patients who did not have private insurance or had lower incomes were found to be at risk for increased LOS. Women were at a higher risk of mortality for several operations, a finding which has been previously described elsewhere. Private insurance conveyed a decreased odds of mortality in patients undergoing AVR. This data set serves to highlight differences in healthcare outcomes based on a variety of socioeconomic, geographic, and other inherent factors. Additional research is needed to identify the mechanisms behind these disparities with the goal of providing equitable care to all patients.

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Fixed-dose and body mass index (BMI)–based enoxaparin regimens provide inadequate venous thromboembolism (VTE) prophylaxis for many trauma patients. The purpose of this study was to evaluate the effectiveness of a novel blood volume (BV)–based enoxaparin guideline vs a historical BMI-based guideline for VTE prophylaxis in trauma patients. Methods This was a retrospective pre/post study completed at a large academic level 1 trauma center. All adult trauma patients admitted from October through December 2019 and August through October 2020 who received prophylactic enoxaparin per guideline were included. The BV dosing was as follows: patients with a BV of 3 to 4.9 L received enoxaparin 30 mg every 12 hours, those with a BV of 5 to 6.9 L received 40 mg every 12 hours, and those with a BV of ≥7 L received 60 mg every 12 hours. The primary outcome was the percentage of patients who attained a target anti–factor Xa (anti-Xa) postdosing level at the first steady-state assessment (0.2 to 0.5 IU/mL). Results A total of 241 patients (99 for the BMI group and 142 for the BV group) were included. The study groups had a median age of 38 vs 42 years, a mean BMI of 27.4 vs 27.7 kg/m 2, and a mean BV of 5.1 vs 5.1 L, respectively. A total of 63 patients (62.6%) in the BMI group attained target anti-Xa levels compared to 115 patients (81%) in the BV group (P = 0.008). In multivariate regression, the BV-based guideline was the only variable associated with attainment of target anti-Xa levels (adjusted odds ratio, 2.02; P = 0.01). Clinically relevant bleeding and VTE rates were similar between the groups. Conclusion Dosing prophylactic enoxaparin using a BV-based dosing guideline significantly increased attainment of target anti-Xa levels.

The demographic composition of modern radiation therapy (RT) clinical trials is incompletely studied. Understanding and minimizing disparities in clinical trials is critical to ensure health equity and the generalizability of research findings.Clinicaltrials.gov was searched to identify RT clinical trials that occurred from 1996 to 2019. A total of 1242 trials were reviewed for patient characteristics. The demographic composition of the studies was summarized by the frequency and percentage of patients by race, gender, and ethnicity. The racial composition of the study population was compared with the 2018 US Census using a 1-sample χA total of 122 trials met the inclusion criteria, and 121 of these (99.1%) reported race. Trial subgroups included 63 trials in the United States (51.6%), 9 proton therapy trials (7.4%), 34 RT toxicity mitigation or prevention trials (27.9%), 24 trials for female cancer (19.7%), and 17 trials for male cancer (13.9%). US clinical trials overall, US RT toxicity mitigation or prevention trials, US trials for female cancer, and US trials for male cancer had significantly different racial compositions compared with the 2018 US Census data (P.001 for all). Compared with all clinical trials, those for proton therapy had the largest magnitude of significantly lower enrollment of participants who identified their race as Black, Asian, or other (P.001).This study characterized the racial composition of prospective RT clinical trials in a modern cohort. The racial population represented across multiple categories in the United States differed significantly from US census data and was most pronounced in trials evaluating proton therapy. This is a benchmark study for future efforts to characterize and balance the participation of underrepresented populations in RT clinical trials.

Warfarin has been used as an anticoagulant by millions of patients due to its effectiveness, availability, and low cost. Evidence on the safe extension of international normalized ratio (INR) testing frequency remains an area of interest, especially during the recent COVID-19 pandemic. The purpose of this study is to safely extend INR testing intervals in patients throughout a multisite, system-wide anticoagulation clinic. Updates were made to the pharmacist’s collaborative practice agreement (CPA) and nurse protocol to optimize practice and allow INR testing interval extension up to a maximum of 8-weeks. The primary outcome was the change in duration between INR tests (INR testing interval) measured before and after providing staff education on clinic updates. The mean duration between INR tests (SD) was 23.69 days (11.29) in the pre-intervention period and 25.58 days (13.91) in the post-intervention period. During the COVID-19 pandemic (post2), intervals were extended further to 27.81 days (14.96), demonstrating a statistically significant increase in INR testing interval from pre-intervention to post-intervention and to post2 (p 60% for the clinic population.

Background: Temporary mechanical circulatory support (tMCS) devices are used for patients with severe cardiac or respiratory failure; however, these patients are at high risk for clotting and bleeding. The best method to monitor heparin in these patients has not been established. Objective: To determine the risks for bleeding and clotting while monitoring heparin with either anti-Xa or activated clotting time (ACT) in tMCS patients. Methods: A retrospective cohort study was conducted on tMCS patients who received heparin adjusted according to an anti-Xa or ACT protocol. The primary outcome was incidence of major bleeding. Pertinent secondary outcomes were individual components of the primary outcome, clotting events, and time to therapeutic range. Results: There were 103 patients included in the study: 53 in the ACT group and 50 in the anti-Xa group. Overall, there were 30 (56.6%) patients with major bleeding in the ACT group, compared with 16 (32%) patients in the anti-Xa group ( P = 0.017). An anti-Xa–based protocol was associated with a decreased hazard of major bleeding (hazard ratio = 0.388 [0.215-0.701]; P = 0.002) in the univariate analysis. In the multivariable analysis, an anti-Xa protocol remained associated with a significantly lower hazard of bleeding. Findings were similar when broken down into more discrete subgroups of the entire cohort, extracorporeal membrane oxygenation life support (ECMO), and non-ECMO groups. Conclusion and Relevance: Anti-Xa monitoring was associated with a lower hazard of bleeding during tMCS compared to an ACT-based protocol. Further studies should evaluate if anti-Xa monitoring should be preferentially used in tMCS.

BACKGROUND: Donor ethnicity is a prognosticator in organ transplant. However, the impact of donor/recipient race-matching is unclear. We hypothesized that there would be increased survival in donor-recipient race-matched organ recipients due to genetic and physiologic similarities. METHODS: The UNOS database from 1999-2018 was queried for all solid organ transplantations including heart, lung, liver, kidney, and pancreas transplants. Data was sorted by donor and recipient race into matched and unmatched categories for Caucasian, African-American, and Hispanic transplant recipients. After controlling for potential confounders via inverse propensity of treatment weighting, post-transplant patient and graft survival were compared between race matched and unmatched donor groups for each organ. RESULTS: Race-matched Caucasian recipients experienced 1-3% improvement in mortality across most timepoints in lung, liver, and pancreas transplants while Hispanics did not benefit. Matched African-American recipients experienced 4-6% improvement in patient and graft survival in liver transplant but had 7-9% worse survival rates at 5 years in lung and pancreas transplants. CONCLUSIONS: Race-matching does not influence patient outcomes enough to factor into organ transplant offers. African-American liver transplant recipients benefited the most. Matching was detrimental to African-American lung and pancreas transplant recipients indicating there may be other factors influencing the outcomes of these transplants.

Background: The optimal dosing for enoxaparin venous thromboembolism (VTE) prophylaxis in low-weight trauma patients is unknown. Estimated blood volume (EBV) has shown promise as a dose modifier. Objective: To characterize the association of enoxaparin dose per EBV with the prevalence of VTE and bleeding in low-weight trauma patients. Methods: This was a retrospective study of trauma patients admitted over a 4-year period. Included patients were adults weighing Results: A total of 189 patients were included. Statistical comparisons for VTE were not performed because of low prevalence. The dose of enoxaparin per EBV was not statistically different between patients who did and did not bleed in all analyses. Doses per BMI and TBW were also not statistically different between the groups. In patients weighing Conclusion and Relevance: No significant associations between enoxaparin dose per EBV, BMI, or TBW and bleeding were noted in the study. Future analyses of EBV and other dose modifiers should consider inclusion of patients weighing

The chaperone protein SmgGDS promotes cell-cycle progression and tumorigenesis in human breast and nonsmall cell lung cancer. Splice variants of SmgGDS, named SmgGDS-607 and SmgGDS-558, facilitate the activation of oncogenic members of the Ras and Rho families of small GTPases through membrane trafficking via regulation of the prenylation pathway. SmgGDS-607 interacts with newly synthesized preprenylated small GTPases, while SmgGDS-558 interacts with prenylated small GTPases. We determined that cancer cells have a high ratio of SmgGDS-607:SmgGDS-558 (607:558 ratio), and this elevated ratio is associated with reduced survival of breast cancer patients. These discoveries suggest that targeting SmgGDS splicing to lower the 607:558 ratio may be an effective strategy to inhibit the malignant phenotype generated by small GTPases. Here we report the development of a splice-switching oligonucleotide, named SSO Ex5, that lowers the 607:558 ratio by altering exon 5 inclusion in SmgGDS pre-mRNA (messenger RNA). Our results indicate that SSO Ex5 suppresses the prenylation of multiple small GTPases in the Ras, Rho, and Rab families and inhibits ERK activity, resulting in endoplasmic reticulum (ER) stress, the unfolded protein response, and ultimately apoptotic cell death in breast and lung cancer cell lines. Furthermore, intraperitoneal (i.p.) delivery of SSO Ex5 in MMTV-PyMT mice redirects SmgGDS splicing in the mammary gland and slows tumorigenesis in this aggressive model of breast cancer. Taken together, our results suggest that the high 607:558 ratio is required for optimal small GTPase prenylation, and validate this innovative approach of targeting SmgGDS splicing to diminish malignancy in breast and lung cancer.

The surgical treatment of mitral disease in pediatrics is challenging. Managing diversity in patient anatomy, growth, and the need for long-term anticoagulation requires trade-offs between imperfect solutions. We sought to assess our approach to pediatric mitral valve surgery and identify predictors associated with mortality and recurrent mitral disease. The medical records, echocardiograms, and operative reports of all patients who underwent surgical intervention on the mitral valve from January 2000 to April 2016 were reviewed. A total of 143 patients underwent mitral valve surgery, 64 of which were neonates or infants (ages 10-355 days) and 79 of which were children (ages 1-17.8 years). Neonates and infants had a higher preoperative New York Heart Association heart failure classification in comparison to children (P0.001) with a less severe degree of mitral valve insufficiency (P = 0.007). Postoperative outcomes for primary repair patients (n = 133) demonstrated significant differences in recurrence of mitral valve disease, with 38% of neonates/infants and 21% of children affected (P = 0.028). Five-year rates of mortality or transplant were 22% (8%, 33%) in neonates and infants compared to 4% (0%, 10%) in children, P = 0.013. Mitral valve surgery in neonates and infants is particularly high risk and is associated with higher rate of recurrence and reintervention early. However, if successful early, mitral valve repair in neonates and infants can result in a durable freedom from reintervention that parallels freedom from reintervention in older children undergoing repair. Further understanding of mechanisms of failure and better matching of anatomic substrate to strategy is needed.

Non-alcoholic steatohepatitis (NASH) is a rapidly growing liver disease. The chemoattractant chemerin is abundant in hepatocytes, and hepatocyte expressed prochemerin protected from NASH. Prochemerin is inactive and different active isoforms have been described. Here, the effect of hepatocyte expressed muChem-156, a highly active murine chemerin isoform, was studied in the methionine–choline deficient dietary model of NASH. Mice overexpressing muChem-156 had higher hepatic chemerin protein. Serum chemerin levels and the capability of serum to activate the chemerin receptors was unchanged showing that the liver did not release active chemerin. Notably, activation of the chemerin receptors by hepatic vein blood did not increase in parallel to total chemerin protein in patients with liver cirrhosis. In experimental NASH, muChem-156 had no effect on liver lipids. Accordingly, overexpression of active chemerin in hepatocytes or treatment of hepatocytes with recombinant chemerin did not affect cellular triglyceride and cholesterol levels. Importantly, overexpression of muChem-156 in the murine liver did not change the hepatic expression of inflammatory and profibrotic genes. The downstream targets of chemerin such as p38 kinase were neither activated in the liver of muChem-156 producing mice nor in HepG2, Huh7 and Hepa1-6 cells overexpressing this isoform. Recombinant chemerin had no effect on global gene expression of primary human hepatocytes and hepatic stellate cells within 24 h of incubation. Phosphorylation of p38 kinase was, however, increased upon short-time incubation of HepG2 cells with chemerin. These findings show that muChem-156 overexpression in hepatocytes does not protect from liver steatosis and inflammation.

Patient engagement, adaptation and self-management play a critical role in improving Health Related Quality of Life (HRQOL) and reducing health care utilization in chronic disorders. There is no data on the level of patient engagement in patients with cyclic vomiting syndrome (CVS); we thus sought to determine their level of engagement and its association with clinical covariates. The Patient Activation Measure (PAM-13), a validated tool that measures the degree of patient engagement in their health was administered prospectively to patients with CVS. Data on demographics, health care utilization, and HRQOL (using the NIH PROMIS 10) were obtained. Patients were stratified into low engagement (PAM 1 & 2) and high engagement (PAM 3 & 4). The Fisher’s exact test and Wilcoxon rank-sum tests were used to identifying significant differences between the groups. Of 96 patients, 45% of patients had low levels of patient engagement. On multivariate analysis, low patient engagement was significantly associated with an increased number of CVS hospitalizations in the past year (aOR 1.26 [1.07, 1.54] p = .010), lower mental HRQOL scores (aOR 0.88 [0.78, 0.97] p = .022), current tobacco use (aOR 4.85 [1.24, 22.74] p = .031), and patients who were newly established in a specialized CVS clinic (aOR 44.40 [5.38, 70.02] p = .002). Almost half of CVS patients demonstrate poor patient engagement, which is associated with poor outcomes. Identifying these patients and treatment in a specialized CVS center can potentially improve HRQOL, reduce health care utilization and improve overall healthcare outcomes.

783 Background: Duodenal adenocarcinomas (DA) and ampullary adenocarcinoma (AA) are rare, comprising less than 1% of all gastrointestinal cancers. Optimal treatment sequencing strategies for patients with localized DA and AA have not been prospectively validated. We analyzed the clinical outcomes of patients with localized DA and AA treated with curative intent, multimodality therapy based on treatment sequencing – upfront surgery versus neoadjuvant therapy. Methods: Our institutional database was interrogated to identify adult patients with localized DA and AA diagnosed between January 2000 to December 2019. Adjusted survival analyses were performed to compare outcomes of patients that received neoadjuvant therapy (NAT - concurrent chemo-radiation +/-induction chemotherapy) versus upfront surgery (+/- adjuvant chemotherapy). Survival time was calculated from date of diagnosis to either death (overall survival; OS) or relapse/death (relapse free survival; RFS). Log-rank test and multiple Cox proportional hazards regression were performed to compare survival between treatment groups and adjust for relevant variables. Results: We identified 79 patients – 32 (41%) with DA and 47 (59%) with AA; Median age at diagnosis was 67. Forty two patients (53%) were male. Sixty-two patients underwent surgery – 27 (43.6%) patients with DA and 35 patients (56.4%) with AA. Among patients with DA, 18 (67%) were treated with upfront surgery, while 9 (33%) were treated with NAT. Among patients with AA, 32 (91%) were treated with upfront surgery while 3 (9%) were treated with NAT. Lymph node (LN) positivity rate in DA and AA patients treated with upfront surgery was 15% and 46% respectively, compared to 50% and 0% respectively, in patients treated with NAT (p = 0.26, p > 0.99 respectively). DA patients treated with upfront surgery had a median relapse free survival (mRFS) of 3.8 years compared to 1.4 years for those treated with NAT (p = 0.370). The median overall survival m(OS) was not reached (NR) for DA patients treated with upfront surgery (4 years +) or NAT (2.6 years +) p = 0.875). AA patients treated with upfront surgery had a median RFS of 4.7 years compared to NR for patients treated with NAT (p = 0.117) while the mOS of AA patients treated with upfront surgery and NAT were 5.9 years and NR respectively (p = 0.158). Conclusions: Among DA patients, there was no difference in outcome based on sequence of treatment delivery – NAT versus upfront surgery. DA patients with more aggressive clinical phenotype were likely treated with NAT, hence similar outcomes in both groups should prompt consideration of NAT for all patients with DA. Role of NAT in AA is not clear considering the small sample size.

Background Dysregulated lipid metabolism is critically involved in the development of hepatocellular carcinoma (HCC). The respective metabolic pathways affected in HCC can be identified using suitable experimental models. Mice injected with diethylnitrosamine (DEN) and fed a normal chow develop HCC. For the analysis of the pathophysiology of HCC in this model a comprehensive lipidomic analysis was performed. Methods Lipids were measured in tumor and non-tumorous tissues by direct flow injection analysis. Proteins with a role in lipid metabolism were analysed by immunoblot. Mann-Whitney U-test or paired Student´s t-test were used for data analysis. Results Intra-tumor lipid deposition is a characteristic of HCCs, and di- and triglycerides accumulated in the tumor tissues of the mice. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha, lipoprotein lipase and hepatic lipase protein were low in the tumors whereas proteins involved in de novo lipogenesis were not changed. Higher rates of de novo lipogenesis cause a shift towards saturated acyl chains, which did not occur in the murine HCC model. Besides, LDL-receptor protein and cholesteryl ester levels were higher in the murine HCC tissues. Ceramides are cytotoxic lipids and are low in human HCCs. Notably, ceramide levels increased in the murine tumors, and the simultaneous decline of sphingomyelins suggests that sphingomyelinases were involved herein. DEN is well described to induce the tumor suppressor protein p53 in the liver, and p53 was additionally upregulated in the tumors. Conclusions Ceramides mediate the anti-cancer effects of different chemotherapeutic drugs and restoration of ceramide levels was effective against HCC. High ceramide levels in the tumors makes the DEN injected mice an unsuitable model to study therapies targeting ceramide metabolism. This model is useful for investigating how tumors evade the cytotoxic effects of ceramides.

Objective To examine the factors affecting the transitions through treatment interventions after failure of non-surgical root canal treatment (NS-RCT). Methodology Insurance enrollment and claim information for enrollees of Delta Dental of Wisconsin (DDWI), USA were analyzed for 438,487 initial NS-RCT procedures to determine the effect of initial provider type and other covariates on additional treatments (no additional treatment, nonsurgical retreatment, surgical retreatment and extraction). A multi-state model was created using the “mstate” R package. Transitions between the four states identified by Code on Dental Procedures and Nomenclature were analyzed. Cox proportional Hazards regression stratified by transition type was used to estimate the effect of provider type on the risk of each transition, adjusting for covariates. Results The overall survival rates for all teeth that were treated by NS-RCT was 82.8% [95% CI 82.57%, 83.11%] at 10 years. Approximately, 7% of cases changed from the first state of initial NS-RCT during the 13-year study period with ultimately 0.9%, 0.4% and 5% of cases receiving non-surgical retreatment, surgical retreatment or extraction, respectively. Teeth are more likely to be retreated non-surgically than surgically, and to be extracted than retreated. In general, the probability of a tooth having non-surgical retreatment was higher if the initial provider was not an endodontist (Hazard Ratio (HR)=3.2). Molars were more likely to be non-surgically retreated (HR=2.0) or extracted (HR=2.8) when compared to anterior teeth. The probability of non-surgical retreatment (HR=0.93) or extraction (HR=0.50) was lower when a crown was placed within 90 days after NS-RCT. Conclusion Most teeth remained in the same state after treatment with no additional treatment transitions. When a transition occurred, it was more likely to be an extraction. Type of provider, age, location of the tooth, gender, and time to placement of final restoration significantly influence treatment transitions.

Despite the widespread belief that donor organ availability varies around holidays and seasons, there is little empirical data supporting this long-held belief. Variations in donor heart availability may be of interest to patients and clinicians. The UNOS/OPTN registry was queried for all heart donations from October 1987 through March 2017. Daily heart donation rates were modeled nationally using Poisson regression including splines for year and day of the year. Seasonality was assessed using a likelihood ratio test for the spine terms for day of the year. The holiday effect was assessed using conditional logistic regression. Seasonal plots suggest a significant, although modest, increase in organ availability during the summer months, except for region 1. The regions with the highest amplitude were region 7 (peak: June 21, amplitude: 16.63%) and region 6 (peak: July 5, amplitude: 11.29%). There was no significant difference in the odds of heart donation when comparing holidays vs. non-holidays using national data (odds ratio [95% CI]: 1.01 [0.98, 1.03], P = 0.560) or any regional subsets. There was no observable correlation between donor heart availability and holidays. However, a significant seasonality effect was observed with higher donation rates occurring during warmer months.

Introduction: Prior data suggest associations between hearing loss, cardiovascular (CV) risk factors, and CV disease. Whether specific hearing loss patterns, including a strial pattern associated with inner ear vascular disease, are associated with systemic endothelial dysfunction and carotid intima–media thickness (IMT) remains unclear. Methods: We evaluated participants without prevalent CVD in the Framingham Offspring Study who underwent formal audiogram testing and brachial and carotid artery ultrasounds. Audiograms were categorized as normal or as belonging to one of four abnormal patterns: cochlear-conductive, low-sloping, sensorineural, or strial. Endothelial function as measured by brachial artery flow-mediated dilation (FMDmm and FMD%). Internal and common intima–media thicknesses (icIMT and ccIMT, respectively) were compared between audiogram patterns. Results: We studied 1672 participants (mean age 59 years, 57.6% women). The prevalence of each hearing pattern was as follows: 43.7% normal; 20.3% cochlear-conductive; 20.3% sensorineural; 7.7% low-sloping; and 8.0% strial. Strial pattern hearing loss was nearly twice as prevalent ( p = 0.001) in those in the highest quartile of ccIMT and nearly 50% higher in those in the highest icIMT quartile ( p = 0.04). There were no statistically significant differences between the prevalence of the strial pattern comparing the lowest quartiles of FMDmm and FMD% with the upper three quartiles. Age- and sex-adjusted linear regression models did not show significant associations between the vascular measures and hearing patterns. Conclusion: Abnormal hearing patterns were not significantly associated with impaired brachial FMD and increased carotid IMT after adjusting for age and sex effects, which may reflect age and sex-related distributional differences based on hearing loss pattern.

Background The optimal vasoactive agent for management of patients with return of spontaneous circulation (ROSC) after cardiac arrest has not yet been identified. The Advanced Cardiac Life Support (ACLS) guidelines recommend initiation of either norepinephrine (NE), epinephrine (EPI), or dopamine (DA) to maintain adequate hemodynamics after ROSC is achieved. The goal of this study is to retrospectively assess the impact of initial vasopressor agent on incidence rate of rearrest, death, or need for additional vasopressor in post-cardiac arrest emergency department (ED) patients. Methods A retrospective review of electronic medical records was conducted at a tertiary care, academic medical center over a 32-month period. Inclusion criteria were any patient who received vasopressors in the ED after achieving ROSC from out-of-hospital cardiac arrest (OHCA), or in ED cardiac arrest. The incidence of the primary outcome was assessed during care within the ED, at six hours regardless of location (early resuscitation period), and throughout the entire hospitalization. Secondary outcomes included incidence of tachyarrhythmia while on vasopressor, type of additional therapy needed for refractory shock, and functional status at discharge as determined by discharge location (discharged home without assistance, or discharged to long term care facility, subacute rehabilitation, or assisted living). Results A total of 93 patients were included for analysis; 45 received NE, 42 EPI, and six DA. Due to small sample size, DA was excluded from reporting post hoc. Significantly more EPI patients met the primary outcome of refractory hypotension, rearrest, or death in the emergency department (EPI 21/42, 50% vs NE 10/45, 22.2%; p = 0.008). The incidence was no longer significantly different during the early resuscitation period of six hours (EPI 30/42, 71.4% vs NE 25/45, 55.6%; p = 0.182), or during the entire hospitalization (EPI 40/42, 95.2% vs NE 36/45, 80.0%; p = 0.051). Notably, the EPI group had higher rates of re-arrest prior to vasopressor initiation, potentially signaling more severe illness despite other prognostic variables being similarly distributed. In an adjusted regression model, which included adjustment for rearrest prior to vasopressor initiation, the odds of reaching the primary outcome in the ED were 3.94 [95%CI 1.38-12.2] (p = 0.013) times higher in the EPI group compared to NE treated patients. No difference in tachyarrhythmia or functional status at discharge was detected between groups. Conclusion These data suggest prospective study of initial vasopressors used for hemodynamic support after ROSC may be warranted. Rates of intra-emergency department refractory shock, rearrest, or death were higher amongst epinephrine treated patients compared to norepinephrine treated patients in this population. However, inability to control for potential confounding variables in retrospective studies limit the findings. These results are hypothesis generating and further study is warranted.

Objective In patients with primary aldosteronism, adrenal venous sampling (AVS) is performed to determine the presence of unilateral or bilateral adrenal disease. During AVS, verification of catheter positioning within the left adrenal vein (AV) and the right AV by comparison of AV and inferior vena cava (IVC) cortisol levels can be variable. The objective of this study was to determine the utility of AV epinephrine levels in assessing successful AV cannulation. Methods This was a single institution, retrospective review of patients who underwent AVS with cosyntropin stimulation for primary aldosteronism between 2009 and 2018. Successful cannulation of the AV was defined by an AV/IVC cortisol ratio selectivity index (SI) ≥3:1. Epinephrine thresholds to predict catheter placement in the AV were determined using logistic regression. The calculated epinephrine thresholds were compared with previously published thresholds. Results AVS was performed on 101 consecutive patients and, based on the SI, successful cannulation of the left AV and right AV occurred in 98 (97%) and 91(90%) patients, respectively. The calculated optimal epinephrine threshold to predict AV cannulation was 364 pg/mL (sensitivity, 92.1%; specificity, 94.6%) and the calculated optimal AV/IVC epinephrine ratio threshold was 27.4, (sensitivity, 92.1%; specificity, 91.3%). Among the 14 patients with failed AV cannulation, 3 patients would have been considered to have successful AVS using AV epinephrine levels >364 pg/mL and AV/IVC epinephrine ratio >27.4 thresholds. Conclusion Obtaining 2 right AV samples routinely as well as AV and IVC epinephrine levels during AVS could prevent unnecessary repeat AVS in patients with failed AV cannulation based on cortisol-based SI

Background Alvimopan has been shown to reduce length of stay after bowel resection. Use remains variable among institutions due to cost and efficacy concerns in laparoscopic surgery. Additionally, alvimopan’s effects have not been isolated from other medications within enhanced recovery protocols. The aim of this study was to distinguish the relationship between alvimopan use, length of stay, and cost in both open and laparoscopic segmental colectomies. Methods The Vizient dataset was queried to identify patients undergoing open and laparoscopic colectomies from 2015 to 2017. Patient demographics and treatment details were collected. Primary outcomes of interest included duration of stay and total direct costs. Results In the study, 12,727 patients met inclusion criteria and 3,358 (26.4%) received alvimopan. For both open and laparoscopic groups, alvimopan was associated with decreased length of stay in unadjusted (4.0 vs 6.0 days, P Conclusion Alvimopan use is associated with decreased length of stay for both open and laparoscopic colon resections, decreased cost in open procedures, and no cost difference for laparoscopic procedures.

Rib fractures are associated with increased mortality, particularly in the elderly. While opiate-based pain regimens remain the cornerstone of rib fracture management, issues related to opioids have driven research into alternative analgesics. Adjunctive ketamine use in lieu of opioids continues to increase but little evidence exists to support its efficacy or safety within the elderly trauma population.A prospective, randomized, double-blind placebo-controlled trial of elderly patients (age, ≥65 years) with three or more rib fractures admitted to a Level I trauma center was conducted. Exclusion criteria included Glasgow Coma Scale score less than 14, and chronic opiate use. Groups were randomized to either low-dose ketamine (LDK) at 2 μg·kg·min or an equivalent rate of 0.9% normal saline. The primary outcome was reduction in numeric pain scores (NPS). Secondary outcomes included oral morphine equivalent (OME) utilization, epidural rates, pulmonary complications, and adverse events.Thirty (50.8%) of 59 were randomized to the experimental arm. Groups were similar in makeup. Low-dose ketamine failed to reduce 24-hour NPS or OME totals. Subgroup analysis of 24 patients with Injury Severity Score greater than 15 demonstrated that LDK was associated with a reduction in OME utilization the first 24-hours (25.6 mg vs. 42.6 mg, p = 0.04) but at no other time points. No difference in other secondary outcomes or adverse events was noted.Low-dose ketamine failed to affect NPS or OME within the overall cohort, but a decrease in OME was observed in those with an Injury Severity Score greater than 15. Additional studies are necessary to confirm whether LDK benefits severely injured elderly patients.Therapeutic, level I.

Objective: Delays in specialized palliative care (PC) consultation in end-stage liver disease (ESLD) patients may be explained by clinician attitudes toward PC. Our aim is to assess the attitudes of hepatology and liver transplant (HLT) and PC clinicians toward PC consultation and consultant roles in ESLD patient care. Methods: Clinician members of HLT and PC professional societies were surveyed. Using a five-point Likert scale, they rated their comfort level toward various PC consultant roles and their agreement with triggers for and reasons to defer PC consultation. Change in attitudes toward PC consultation resulting from liver transplant (LT) eligibility was evaluated. Results: A total of 311 HLT (6.2%) and 379 PC (8.1%) clinicians completed the survey. The vast majority of HLT clinicians (>80%) were comfortable if PC consultants palliate symptoms, provide support, or facilitate advance care planning in LT-ineligible patients. LT eligibility reduced HLT clinician comfort toward all PC consultant roles, except supportive care. A vast majority of PC clinicians (>90%) were comfortable assuming all PC roles, except pain management without opioids (43-51%). About 80% of HLT clinicians agree with PC consultation in LT-ineligible patients with decompensated cirrhosis or hepatocellular carcinoma (HCC), compared to 20-30% if LT ineligible. Common justifications for deferring PC consultation included mild disease, LT eligibility, unavailability of PC specialists, and lack of addressable palliative issues. Conclusions: Barriers to specialized PC consultation in ESLD include HLT clinician discomfort with PC consultant roles, patients' LT eligibility, perception that PC is end-of-life care, unclear triggers for PC consultation, and concern about opioid-based pain palliation.

BackgroundEmerging data support a role for lipids in non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in humans. With experimental models such data can be challenged or validated. Mice fed a low-methionine, choline-deficient (LMCD) diet develop NASH and, when injected with diethylnitrosamine (DEN), HCC. Here, lipidomic analysis was used to elucidate whether the NASH and HCC associated lipid derangements resemble the lipid profile of the human disease.MethodsLipids were measured in the liver of mice fed a control or a LMCD diet for 16 weeks. DEN was injected at young age to initiate hepatocarcinogenesis. DEN treatment associated changes of the lipid composition and the tumor lipidome were evaluated.ResultsLMCD diet fed mice accumulated ceramides and triacylglycerols in the liver. Phospholipids enriched with monounsaturated fatty acids were also increased, whereas hepatic cholesterol levels remained unchanged in the LMCD model. Phosphatidylcholine and lysophosphatidylcholine concentrations declined in the liver of LMCD diet fed mice. The changes of most lipids associated with LMCD diet feeding were similar between water and DEN injected mice. Several polyunsaturated (PU) diacylglycerol species were already low in the liver of DEN injected mice fed the control diet. Tumors developed in the liver of LMCD diet fed mice injected with DEN. The tumor specific lipid profile, however, did not resemble the decrease of ceramides and PU phospholipids, which was consistently described in human HCC. Triacylglycerols declined in the cancer tissues, which is in accordance with a low expression of lipogenic enzymes in the tumors.ConclusionsThe LMCD model is suitable to study NASH associated lipid reprogramming. Hepatic lipid profile was modestly modified in the DEN injected mice suggesting a function of these derangements in carcinogenesis. Lipid composition of liver tumors did not resemble the human HCC lipidome, and most notably, lipogenesis and triacylglycerol levels were suppressed.

Simple Summary Hepatocellular carcinoma (HCC) is a frequent liver cancer and high expression of bioactive chemerin in hepatocytes was protective in experimental HCC models. The main risk factors for HCC are non-alcoholic fatty liver disease (NAFLD), hepatitis B and C infections. The current analysis showed that chemerin protein was induced in HCC tissues of NAFLD and hepatitis B infected patients. This upregulation was modest in patients with unknown disease etiology and not detected in hepatitis C infected patients. Protein levels of the chemerin receptor CMKLR1 strongly declined in the tumors of NAFLD patients and patients with unclear disease etiology but not in patients with viral infections. Our results demonstrate that the expression of chemerin in HCC is related to disease etiology and this could also apply to the role of chemerin in human HCC. In contrast to the present findings, chemerin was shown to be low in the HCC tissues of Asian patients with mostly viral disease etiology and this indicates ancestry-specific regulation of chemerin in HCC. Abstract Chemerin is protective in experimental models of hepatocellular carcinoma (HCC). Noteworthy, chemerin mRNA and protein were reduced in HCC tissues of Asian patients with mostly hepatitis B disease etiology. The current study nevertheless showed that chemerin protein was induced in tumor tissues of European HCC patients with non-alcoholic fatty liver disease (NAFLD) and patients with unclear disease etiology. A similar regulation was observed in hepatitis B virus (HBV), but not in hepatitis C virus (HCV), related HCC. The apparent discrepancy between the regulation of chemerin in HBV-HCC obtained from our study and recent reports led us to use the chemerin antibodies applied in the previous assays. These antibodies could not equally detect different chemerin isoforms, which were overexpressed in HepG2 cells. Higher chemerin protein in HCC was nevertheless confirmed by the use of all antibodies. Chemerin protein was low in Huh7 and PLC/PRF/5 cells whereas HepG2 and Hep3B cells had chemerin protein similar as primary human hepatocytes. Besides, the anti-tumor effects of retinoids in hepatocyte cell lines did not enclose upregulation of chemerin, which was initially discovered as a tazarotene induced protein in the skin. Finally, protein levels of the chemerin receptor, chemokine-like receptor 1 (CMKLR1), declined in non-viral, and tended to be lower in HBV-HCC tissues suggesting reduced chemerin activity in the tumors. To sum up, our work showed an opposite regulation of chemerin and CMKLR1 in NAFLD and HBV associated HCC. In HCV-HCC neither chemerin nor its receptor were changed in the tumor tissues. Current findings do not support a critical role of total chemerin protein levels in HCC of non-viral and viral etiology. Accordingly, tumor-localized chemerin protein was not associated with tumor-node-metastasis classification.

Objective To assess the prevalence of pediatric feeding disorder (PFD) in US children. Study design We conducted a retrospective cohort study of Medicaid Databases from Arizona (2009-2017) and Wisconsin (2005-2014) (public insurance databases) and The Truven Health Analytics MarketScan Commercial Claims and Encounters Database (2009-2015) (a nationwide private insurance database). Diagnoses and procedures were identified from inpatient and outpatient claims using the International Classification of Diseases (ICD)-9 and ICD-10 diagnostic codes and ICD and Current Procedural Terminology-4 procedure codes. Children with PFD were identified by presence of 1 or more PFD diagnosis and absence of any eating disorder diagnoses within a calendar year. Results We identified 126 002 and 367 256 children 5 years of age or younger with PFD with public and private insurance, respectively. Over a 5-year period (2009-2014) the prevalences of PFD in children with public insurance in Arizona and Wisconsin were 32.91 (95% CI, 32.61-33.20) and 34.73 (95% CI, 34.37-35.09) children per 1000 child-years, respectively. Similarly, the prevalence of PFD in private insurance carriers was 21.07 (95% CI, 21.00-21.14) children per 1000 child-years. The prevalence trends showed a significant linear increase in children within both insurance cohorts. In 2014, the annual prevalence of PFD was 1 in 23, 1 in 24, and 1 in 37 in children under 5 years in the publicly insured cohorts in Wisconsin, Arizona, and the privately insured cohort, respectively. Conclusions The prevalence of feeding disorders in the US rivals that of commonly diagnosed conditions such as eating disorders and autism.

Statisticians often face a dilemma, namely how to decide between choosing a parametric versus a nonparametric statistical model. Parametric statistical models can be asymptotically efficient if the model assumptions hold but biased under model misspecification. Nonparametric models, on the other hand, are often asymptotically unbiased but likely to be less efficient than parametric models if the parametric model is correctly specified. In this work, we propose a new estimator, which combines parametric and nonparametric estimators into a single estimating procedure. In contrast to previously suggested combined estimators, the new estimator ensures that it is asymptotically equivalent to the efficient parametric estimator if parametric assumptions hold. If the assumptions are violated, the combined estimator converges to the nonparametric estimator. The new combined estimator is illustrated with quantile regressions which estimate individualized prediction intervals. Through simulation studies, we explored the MSE of the proposed and competing estimators when data came from parametric distributions and, alternatively, when parametric assumptions were violated. The development of this approach was motivated by the real-data problem of predicting realistic hemoglobin A1C ranges in type 2 diabetes (T2DM) patients. A cross-validation confirmed that the proposed estimator shows better or similar prediction properties in comparison with several competing approaches.

Background There is currently limited data in the United States on the proportion of immunization doses given at pharmacies outside the influenza vaccine. This study aims to obtain baseline information on the percentage of vaccine doses administered at pharmacies in Wisconsin and to understand the immunization barriers for Wisconsin pharmacists, to inform interventions to increase immunization access at pharmacies. Methods Aggregated data from the Wisconsin Immunization Registry (WIR) was obtained for all vaccines administered at pharmacies to patients over the age of six from July 2017 through June 2018. In addition, a survey on attitudes towards and barriers to vaccination was sent to 2000 Wisconsin pharmacists with 236 respondents yielding a 12% response rate. Results WIR data demonstrates that zoster and influenza vaccines have the highest proportion of doses administered at pharmacies (39% and 20%, respectively). Human papillomavirus (HPV) vaccines have the lowest proportion of doses at 0.2%. Pharmacy survey shows that 86% provide immunizations. Most stock influenza vaccines (84%), whereas much fewer stock HPV vaccines (21%). The greatest immunization barriers for the pharmacy respondents include billing and reimbursement challenges and competing demands for staff. Conclusions Despite the barriers, community pharmacies have significant potential to address vaccination gaps. Physicians, patients, and legislative bodies are generally well-accepting of pharmacists as immunizers. Pharmacists, in order to be fully utilized as immunizers, must engage in active communication with patients and be willing to collaborate with physicians. Legislative policy and health insurance reimbursement reforms are also necessary to facilitate further pharmacist participation in immunization.

Alpha-syntrophin (SNTA) is a molecular adapter protein which is expressed in adipocytes. Knock-down of SNTA in 3T3-L1 preadipocytes increases cell proliferation, and differentiated adipocytes display small lipid droplets. These effects are both characteristics of healthy adipose tissue growth which is associated with metabolic improvements in obesity. To evaluate a role of SNTA in adipose tissue morphology and obesity associated metabolic dysfunction, SNTA deficient mice were fed a standard chow or a high fat diet. Mice deficient of SNTA had less fat mass and smaller adipocytes in obesity when compared to control animals. Accordingly, these animals did not develop liver steatosis and did not store excess triglycerides in skeletal muscle upon high fat diet feeding. SNTA-/- animals were protected from hyperinsulinemia and hepatic insulin resistance. Of note, body-weight, food uptake, and serum lipids were normal in the SNTA null mice. SNTA was induced in adipose tissues but not in the liver of diet induced obese and ob/ob mice. In human subcutaneous and visceral fat of seven patients SNTA was similarly expressed and was not associated with body mass index. Current data demonstrate beneficial effects of SNTA deficiency in obesity which is partly attributed to smaller adipocytes and reduced white adipose tissue mass. Higher SNTA protein in fat depots of obese mice may contribute to adipose tissue hypertrophy and ectopic lipid deposition which has to be confirmed in humans.

BACKGROUND Gallbladder cancer (GBC) is a lethal disease with high incidence among Hispanics. Overall survival (OS) among races/ethnicities has not been described using the most recent National Cancer Database. This study hypothesized that prognosis is worse for Hispanics compared to similar non-Hispanic populations. METHODS Patients with GBC were identified from the National Cancer Database and categorized as White, Black, Hispanic, and Other. Descriptive statistics, OS, and Cox regression were examined. RESULTS The study identified 12 952 patients. Median age was 71 years and 68.8% were female. The study characterized 69.8% White, 13.9% Black, 11.0% Hispanic, and 5.4% other patients. A 5-year OS curves differed, with survival highest in Hispanic patients (27% vs 23% Other, 18% White, and 17% Black, P