ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma.

Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic and transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that, in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-coenzyme A (CoA) synthetase 2 (ACSS2) in the nucleus to couple high glucose metabolic flux with acetyl-histone H3 modification of neural crest (NC) lineage and glucose metabolism genes. Importantly, we show that acetaldehyde is a metabolite source for acetyl-histone H3 modification in an ALDH1A3-dependent manner, providing a physiologic function for this highly volatile and toxic metabolite. In a zebrafish melanoma residual disease model, an ALDH1-high subpopulation emerges following BRAF inhibitor treatment, and targeting these with an ALDH1 suicide inhibitor, nifuroxazide, delays or prevents BRAF inhibitor drug-resistant relapse. Our work reveals that the ALDH1A3-ACSS2 couple directly coordinates nuclear acetaldehyde-acetyl-CoA metabolism with specific chromatin-based gene regulation and represents a potential therapeutic vulnerability in melanoma.

The relationship between intraosseous catheter tip placement, flow rates, and infusion pressures in a high bone density cadaveric swine (Sus scrofa) model.

Background: Intraosseous (IO) infusion is a life-preserving technique when intravenous access is unobtainable. Successful IO infusion requires sufficiently high flow rates to preserve life but at low enough pressures to avoid complications. However, IO catheter tips are often misplaced, and the relative flow rates and pressures between IO catheter tips placed in medullary, trabecular, and cortical bone are not well described, which has important implications for clinical practice. Objectives: We developed the Zone Theory of IO Catheter Tip Placement based on bone density and proximity to the venous central sinus and then tested the influence of catheter tip placement locations on flow rates and pressures in a cadaveric swine model. Methods: Three cross-trained participants infused 500 mL of crystalloid fluid into cadaveric swine humerus and sternum (N = 210 trials total) using a push‒pull method with a 60 cm3 syringe. Computed tomography scans were scored by radiologists and categorized as zone 1 (medullary space), zone 2 (trabecular bone), or zone 3 (cortical bone) catheter tip placements. Differences between zones in flow rates, mean pressures, and peak pressures were assessed using analysis of variance and analysis of covariance to account for participant and site differences at the p < 0.05 threshold. Results: Zone 1 and zone 2 placements were essentially identical in flow rates, mean pressures, and peak pressures (each p > 0.05). Zone 1 and zone 2 placements were significantly higher in flow rates and lower in pressures than zone 3 placements (each p < 0.05 or less). Conclusion: Within the limitations of an unpressurized cadaveric swine model, the present findings suggest that IO catheter tip placements need not be perfect to acquire high flow rates at low pressures, only accurate enough to avoid the dense cortical bone of zone 3. Future research using in vivo animal and human models is needed to better define the clinical impact of IO catheter placement on infusion flow rates and pressures.

The Use of a Distal Radius Allograft for Severe Glenoid Bone Loss in the Setting of Revision Shoulder Arthroplasty: A Case Report.

CASE: A 71-year-old female patient presented with severe glenoid bone loss and deformity after 2 subsequent failed arthroplasty procedures because of baseplate failures. The patients then underwent a conversion from reverse shoulder arthroplasty to hemiarthroplasty, while using a distal radius allograft to augment the deformed glenoid. At the 2-year follow-up, the patient reported minimal pain and satisfactory outcomes. CONCLUSION: This case presents the distal radius as a potentially useful allograft option for augmenting severe glenoid bone loss in the setting of revision shoulder arthroplasty.

Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma.

PURPOSE: Ewing Sarcoma (ES), a rare cancer with a pathognomonic translocation resulting in the Ewing sarcoma gene (EWS)::FLI1 oncoprotein, has a poor prognosis in the relapsed/refractory (R/R) setting. Tokalas (TK)216 was designed to bind EWS::FLI1 proteins directly, disrupt protein-protein interactions, and inhibit transcription factor function. TK216 plus vincristine showed synergistic activity in preclinical tumor models. To our knowledge, we report the results of a first-in-class, first-in-human phase I/II trial of TK216 in R/R ES. PATIENTS AND METHODS: TK216 was administered intravenously as a continuous infusion to patients with R/R ES in 11 cohorts. The dosing duration of 7 days was later extended to 10, 14, and 28 days. Vincristine could be added on day 1 after cycle 2, per investigators' choice. The trial used a 3 + 3 design with an expansion cohort at the recommended phase II dose (RP2D). RESULTS: A total of 85 patients with a median age of 27 years (range, 11-77) were enrolled. The maximum tolerated dose for the 14-day infusion of TK216, 200 mg/m2 once daily, was determined in cohort 9 and selected as the RP2D. The median previous number of systemic therapies regimens was three (range, 1-10). The most frequent-related adverse events in patients treated at the RP2D included neutropenia (44.7%), anemia (29.4%), leukopenia (29.4%), febrile neutropenia (15.3%), thrombocytopenia (11.8%), and infections (17.6%). In cohorts 9 and 10, two patients had a complete response, one had a partial response, and 14 had stable disease; the 6-month progression-free survival was 11.9%. There were no responses among the eight patients in cohort 11. CONCLUSION: TK216 administered as 14-day continuous infusion with or without vincristine was well tolerated and showed limited activity at the RP2D in R/R ES.

Mechanical or Biological Prosthesis for Aortic Valve Replacement in Patients Aged 45 to 74 Years.

OBJECTIVE: The selection of valve prostheses for patients undergoing surgical aortic valve replacement (SAVR) remains controversial. In this study, we compared the long-term outcomes of patients undergoing aortic valve replacement with biological or mechanical aortic valve prostheses. METHODS: We evaluated late results among 5,762 patients aged 45-74 years who underwent biological or mechanical aortic valve replacement with or without concomitant coronary artery bypass from 1989 to 2019 at four medical centers. The Cox proportional hazards model was used to compare late survival; the age-dependent effect of prosthesis type on long-term survival was evaluated by an interaction term between age and prosthesis type. Incidences of stroke, major bleeding, and reoperation on the aortic valve following the index procedure were compared between prosthesis groups. RESULTS: Overall, 61% (n=3,508) of patients received a bioprosthesis. The 30-day mortality rate was 1.7% (n=58) in the bioprosthesis group and 1.5% (n=34) in the mechanical group (P=0.75). During a mean follow-up of 9.0 years, the adjusted risk of mortality was higher in the bioprosthesis group (HR=1.30, P<0.001). The long-term survival benefit associated with mechanical prosthesis persisted until 70 years of age. Bioprosthesis (vs mechanical prosthesis) was associated with a similar risk of stroke (P=0.20), lower risk of major bleeding (P<0.001), and higher risk of reoperation (P<0.001). CONCLUSIONS: Compared to bioprostheses, mechanical aortic valves are associated with a lower adjusted risk of long-term mortality in patients aged 70 years or younger. Patients <70 years old undergoing SAVR should be informed of the potential survival benefit of mechanical valve substitutes.

Assessing the Fractional Curve for Proper Management of Adult Degenerative Scoliosis.

Adult degenerative scoliosis (ADS) is a coronal plane deformity often accompanied by sagittal plane malalignment. Surgical correction may involve the major and/or distally-located fractional curves (FCs). Correction of the FC has been increasingly recognized as key to ameliorating radicular pain localized to the FC levels. The present study aims to summarize the literature on the rationale for FC correction in ADS. Three databases were systematically reviewed to identify all primary studies reporting the rationale for correcting the FC in ADS. Articles were included if they were English full-text studies with primary data from ADS ( ≥ 18 years old) patients. Seventy-four articles were identified, of which 12 were included after full-text review. Findings suggest FC correction with long-segment fusion terminating at L5 increases the risk of distal junctional degeneration as compared to constructs instrumenting the sacrum. Additionally, circumferential fusion offers greater FC correction, lower reoperation risk, and shorter construct length. Minimally invasive surgery (MIS) techniques may offer effective radiographic correction and improve leg pain associated with foraminal stenosis on the FC concavity, though experiences are limited. Open surgery may be necessary to achieve adequate correction of severe, highly rigid deformities. Current data support major curve correction in ASD where the FC concavity and truncal shift are concordant, suggesting that the FC contributes to the patient's overall deformity. Circumferential fusion and the use of kickstand rods can improve correction and enhance the stability and durability of long constructs. Last, MIS techniques show promise for milder deformities but require further investigation.

Socioeconomic disparities and the genomic landscape of gastric cancer.

The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden (P = 0.377) or microsatellite status (P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy.

Strain distribution in WS2 monolayers detected through polarization-resolved second harmonic generation.

Two-dimensional (2D) graphene and graphene-related materials (GRMs) show great promise for future electronic devices. GRMs exhibit distinct properties under the influence of the substrate that serves as support through uneven compression/ elongation of GRMs surface atoms. Strain in GRM monolayers is the most common feature that alters the interatomic distances and band structure, providing a new degree of freedom that allows regulation of their electronic properties and introducing the field of straintronics. Having an all-optical and minimally invasive detection tool that rapidly probes strain in large areas of GRM monolayers, would be of great importance in the research and development of novel 2D devices. Here, we use Polarization-resolved Second Harmonic Generation (P-SHG) optical imaging to identify strain distribution, induced in a single layer of WS2 placed on a pre-patterned Si/SiO2 substrate with cylindrical wells. By fitting the P-SHG data pixel-by-pixel, we produce spatially resolved images of the crystal armchair direction. In regions where the WS2 monolayer conforms to the pattern topography, a distinct cross-shaped pattern is evident in the armchair image owing to strain. The presence of strain in these regions is independently confirmed using a combination of atomic force microscopy and Raman mapping.

Longitudinal analysis of the lung proteome reveals persistent repair months after mild to moderate COVID-19.

In order to assess homeostatic mechanisms in the lung after COVID-19, changes in the protein signature of bronchoalveolar lavage from 45 patients with mild to moderate disease at three phases (acute, recovery, and convalescent) are evaluated over a year. During the acute phase, inflamed and uninflamed phenotypes are characterized by the expression of tissue repair and host defense response molecules. With recovery, inflammatory and fibrogenic mediators decline and clinical symptoms abate. However, at 9 months, quantified radiographic abnormalities resolve in the majority of patients, and yet compared to healthy persons, all showed ongoing activation of cellular repair processes and depression of the renin-kallikrein-kinin, coagulation, and complement systems. This dissociation of prolonged reparative processes from symptom and radiographic resolution suggests that occult ongoing disruption of the lung proteome is underrecognized and may be relevant to recovery from other serious viral pneumonias.

Plastic pollution and human pathogens: Towards a conceptual shift in risk management at bathing water and beach environments.

Emerging evidence indicates that micro- and macro-plastics present in water can support a diverse microbial community, including potential human pathogens (e.g., bacteria, viruses). This interaction raises important concerns surrounding the role and suitability of current bathing water regulations and associated pathogen exposure risk within beach environments. In response to this, we critically evaluated the available evidence on plastic-pathogen interactions and identified major gaps in knowledge. This review highlighted the need for a conceptual shift in risk management at public beaches recognising: (i) interconnected environmental risks, e.g., associations between microbial compliance parameters, potential pathogens and both contemporary and legacy plastic pollution; and (ii) an appreciation of risk of exposure to plastic co-pollutants for both water and waterside users. We present a decision-making framework to identify options to manage plastic-associated pathogen risks alongside short- and longer-term research priorities. This advance will help deliver improvements in managing plastic-associated pathogen risk, acknowledging that human exposure potential is not limited to only those who engage in water-based activity. We argue that adopting these recommendations will help create an integrated approach to managing and reducing human exposure to pathogens at bathing, recreational water and beach environments.

Mystery of the Muenke midface: spheno-occipital synchondrosis fusion and craniofacial skeletal patterns.

PURPOSE: The spheno-occipital synchondrosis (SOS) is an important site of endochondral ossification in the cranial base that closes prematurely in Apert, Crouzon, and Pfeiffer syndromes, which contributes to varying degrees of midface hypoplasia. The facial dysmorphology of Muenke syndrome, in contrast, is less severe with low rates of midface hypoplasia. We thus evaluated the timing of SOS fusion and cephalometric landmarks in patients with Muenke syndrome compared to normal controls. METHODS: Patients with Muenke syndrome who had at least one fine-cut head computed tomography scan performed from 2000 to 2020 were retrospectively reviewed. A case-control study was performed of patient scans and age- and sex-matched control scans. SOS fusion status was evaluated as open, partially closed, or closed. RESULTS: We included 28 patients and compared 77 patient scans with 77 control scans. Kaplan-Meier analysis demonstrated an insignificantly earlier timeline of SOS fusion in Muenke syndrome (p = 0.300). Mean sella-orbitale (SO) distance was shorter (44.0 ± 6.6 vs. 47.7 ± 6.7 mm, p < 0.001) and mean sella-nasion-Frankfort horizontal (SN-FH) angle was greater (12.1° ± 3.8° vs. 10.1° ± 3.2°, p < 0.001) in the Muenke group, whereas mean sella-nasion-A point (SNA) angle was similar and normal (81.1° ± 5.7° vs. 81.4° ± 4.7°, p = 0.762). CONCLUSION: Muenke syndrome is characterized by mild and often absent midfacial hypoplasia, with the exception of slight retropositioning of the infraorbital rim. Interestingly, SOS fusion patterns in these patients are not significantly different from age- and sex-matched controls despite an increased odds of fusion. It is possible that differences in timing of SOS fusion may manifest phenotypically at the infraorbital rim rather than at the maxilla.

Behaviourally assessed negative urgency is uniquely associated with binge-eating frequency.

OBJECTIVE: Binge eating appears to be associated with impulsivity, especially in response to negative affect (i.e., negative urgency). However, negative urgency is typically assessed via self-report, which captures only some aspects of urgency and may be subject to bias. Few studies have examined impulsivity following experimental manipulations of affect in binge-eating samples. METHOD: In the present study, individuals who engage in regular binge eating completed a behavioural impulsivity (go/no-go) task with high- and low-calorie food stimuli, once following negative affect induction and once following neutral affect induction. RESULTS: Greater behavioural impulsivity to high-calorie food cues while in a negative (and not a neutral) affective state was associated with more frequent binge-eating behaviour. Further, this behavioural measure of negative urgency uniquely accounted for variance in binge-eating frequency when controlling for self-reported negative urgency, suggesting that behavioural measures may be a useful complement to self-report measures. DISCUSSION: These findings provide novel and compelling evidence for the relationship between negative urgency and binge eating, highlighting negative urgency as a potentially important target for intervention.

Data to Care Pilot Program in Chicago: Experience, Outcomes, and Direction for the Future.

CONTEXT: Data to Care (D2C) involves sharing HIV surveillance data between health care facilities and health departments to improve continuity of care for people living with HIV (PLWH). The Chicago Department of Public Health (CDPH) initiated a D2C pilot program at the University of Chicago Medicine (UCM) from June 2016 to September 2019. OBJECTIVES: To describe the proportion of patients reported by UCM as not in care who were able to be matched to CDPH enhanced HIV/AIDS Reporting System (eHARS) and to report the individual-level factors associated with matching and viral suppression. DESIGN: Retrospective program evaluation. SETTING: UCM, an academic health care center that provides HIV care to adults via a Ryan White clinic on the south side of Chicago. PARTICIPANTS: Adult PLWH who had received care at UCM but did not have current documented HIV care visit(s). MAIN OUTCOME MEASURE: Proportion of matched patients; factors associated with matching and viral suppression. RESULTS: Overall, 72.4% (n = 813/1123) of patients reported by UCM were matched by CDPH to eHARS. Individuals aged 40 to 49 years (odds ratio [OR] = 1.99; 95% confidence interval [CI], 1.10-3.62), 50 to 59 years (OR = 2.47; 95% CI, 1.37-4.47), and 60 years or older (OR = 6.18; 95% CI, 3.18-12.32) were more likely to match in eHARS. People who lived outside of Chicago (OR = 0.09; 95% CI, 0.05-0.15) or with unknown zip codes (OR = 0.08; 95% CI, 0.05-0.12) were less likely to match. Men who have sex with men and persons older than 50 years were more likely to be virally suppressed. CONCLUSIONS: D2C is an evidence-based strategy for reengagement of PLWH; however, program implementation relies on successful data matching. We found that a large proportion of patients from UCM were not matched, particularly those who were younger or lived outside of Chicago. Additional research is needed to understand ways to improve data matching to facilitate reengagement in HIV care.

Adult Congenital Heart Disease Transplantation: Does Univentricle Physiology Impact Early Mortality?

BACKGROUND: With congenital heart disease patients increasingly living into adulthood, there is a growing population of adult congenital heart disease (ACHD) patients suffering from heart failure. Limited data exist evaluating heart transplant in this population. METHODS: Retrospective review was performed of ACHD patients undergoing heart transplantation 11/1990-1/2023. Kaplan-Meier, cumulative incidence accounting for competing risk of death, and subgroup analyses comparing those with biventricular (BiV) and univentricular (UniV) physiology were performed. Data are presented as median (interquartile range) or counts (%). RESULTS: 77 patients with a median age of 36 years (27, 45) were identified, including 57 (74%) BiV and 20 (26%) UniV. Preoperatively, UniV patients were more likely to have cirrhosis (9/20 [45.0%] vs 4/57 [7.0%], p<0.001) and protein losing enteropathy (4/20 [20.0%] vs 1/57 [1.8%], p=0.015). Multiorgan transplantation was performed in 23 patients (30%) and more frequently in UniV patients (10 [50%] vs. 13[23%], p=0.04). Operative mortality was 6.5%, 2/20 (10%) among UniV and 2/57 (4%) among BiV patients, p=0.276. Median clinical follow-up was 6.0 (1.4, 13.1) years. Survival tended to be lower among UniV patients compared to BiV patients, particularly within the first year (p=0.09), but was similar for survivors beyond one year. At 5 years, incidence of rejection was 28% (17%, 38%) and coronary allograft vasculopathy was 16% (7%, 24%). CONCLUSIONS: Underlying liver disease and need for heart/liver transplantation were significantly higher among UniV patients. Survival tended to be lower among UniV, particularly within the first year, but was similar for survivors beyond one year.

Single-base tiled screen unveils design principles of PspCas13b for potent and off-target-free RNA silencing.

The development of precise RNA-editing tools is essential for the advancement of RNA therapeutics. CRISPR (clustered regularly interspaced short palindromic repeats) PspCas13b is a programmable RNA nuclease predicted to offer superior specificity because of its 30-nucleotide spacer sequence. However, its design principles and its on-target, off-target and collateral activities remain poorly characterized. Here, we present single-base tiled screening and computational analyses that identify key design principles for potent and highly selective RNA recognition and cleavage in human cells. We show that the de novo design of spacers containing guanosine bases at precise positions can greatly enhance the catalytic activity of inefficient CRISPR RNAs (crRNAs). These validated design principles (integrated into an online tool, https://cas13target.azurewebsites.net/ ) can predict highly effective crRNAs with ~90% accuracy. Furthermore, the comprehensive spacer-target mutagenesis revealed that PspCas13b can tolerate only up to four mismatches and requires ~26-nucleotide base pairing with the target to activate its nuclease domains, highlighting its superior specificity compared to other RNA or DNA interference tools. On the basis of this targeting resolution, we predict an extremely low probability of PspCas13b having off-target effects on other cellular transcripts. Proteomic analysis validated this prediction and showed that, unlike other Cas13 orthologs, PspCas13b exhibits potent on-target activity and lacks collateral effects.

Cardiac rhabdomyoma: an uncommon culprit in sudden infant death.

Sudden death in infants remains a common and poorly understood cause of childhood mortality in the USA. Pediatric cardiac tumors, although rare, may underlie some cases of unexplained sudden infant death. Autopsy is a crucial diagnostic step in these cases, as both gross and microscopic examination of the heart may uncover occult cardiac tumors. Rhabdomyomas are the most common cardiac tumors in childhood and may result in arrythmia and sudden death. We present a case of sudden death in a healthy 5-month-old infant which initially appeared "SIDS-like" until thorough histological analysis revealed an underlying cardiac rhabdomyoma. The case is of particular importance in that the gross examination of the heart was considered completely normal, and the tumor only involved certain portions of the heart microscopically. Had a single random section of myocardium been the only heart section examined microscopically, the diagnosis might have been missed. This case emphasizes the importance of thorough microscopic examination in infant cases, especially in cases where the heart appears grossly normal.

Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner.

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD + can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD + precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known. Here we investigate the effect of long-term administration of NMN on the health, cancer burden, frailty and lifespan of male and female mice. Without increasing tumor counts or severity in any tissue, NMN treatment of males and females increased activity, maintained more youthful gene expression patterns, and reduced overall frailty. Reduced frailty with NMN treatment was associated with increases in levels of Anerotruncus colihominis, a gut bacterium associated with lower inflammation in mice and increased longevity in humans. NMN slowed the accumulation of adipose tissue later in life and improved metabolic health in male but not female mice, while in females but not males, NMN increased median lifespan by 8.5%, possible due to sex-specific effects of NMN on NAD + metabolism. Together, these data show that chronic NMN treatment delays frailty, alters the microbiome, improves male metabolic health, and increases female mouse lifespan, without increasing cancer burden. These results highlight the potential of NAD + boosters for treating age-related conditions and the importance of using both sexes for interventional lifespan studies.

Genomic sequences of Mycobacterium smegmatis A cluster phages LBerry, Pembroke, and Zolita.

LBerry, Pembroke, and Zolita are newly isolated bacteriophages that infect Mycobacterium smegmatis mc²155. Based on gene content similarity, LBerry and Pembroke are assigned to cluster A3, and Zolita is assigned to cluster A5. LBerry and Pembroke are 99% identical to Anaysia and Caviar, and Zolita is 99% identical to SydNat.

American Shoulder & Elbow Surgeons Perspectives on Political Advocacy.

BACKGROUND: Physician involvement in political advocacy has become increasingly important in recent years. This study aims to explore the types of involvement and barriers to involvement in political advocacy among American Shoulder and Elbow Surgeons (ASES) members, identify issues considered most important by ASES members, and assess demographic factors that might correlate with involvement in political advocacy efforts among ASES members. METHODS: This survey was conducted by the ASES Political Advocacy Committee over a two-week period in June 2021. The survey collected demographic information including sex, ethnicity, years in practice, practice type, political affiliation, and level of current involvement in political advocacy. Additional questions consisted of thoughts regarding current health care policy issues and the role of the American Academy of Orthopaedic Surgeons (AAOS)/ASES regarding such policy issues. RESULTS: We received 297 responses for a total response rate of 27%. Of those who responded, 24.6% identified as Democrat, 33% identified as Republican, and 42.4% identified as Independent. There was no difference in political affiliation between membership groups. Physician Reimbursement (82%), Medical Liability Reform (50%), and Physician Ownership (50%) were the most important issues identified among respondents. Physician Ownership, Physician Reimbursement and GME and Student Loan Reform were most important to those in early practice, while Quality and Research was most important to those with greater than 25 years of practice experience. CONCLUSION: There is strong agreement among surgeons regarding the most important political advocacy issues. The efforts of the AAOS and ASES should focus on these areas. Additionally, the vast majority of respondents felt that advocacy efforts had a positive impact on patients and surgeons.