Citations

Abstract Funding Acknowledgements Type of funding sources: None. Background/introduction Morbidity and mortality associated with atherosclerotic cardiovascular diseases are prevalent in young patients. Meanwhile, traditional cardiovascular risk calculators underestimate disease risk in young adults. Purpose To characterize cardiometabolic risk factors and lipid levels in young adults with acute myocardial infarction. Setting: A multicenter, population-based analysis of patients diagnosed at our hospitals in Arizona, as well as our clinic health system spanning Minnesota and Wisconsin. Methods This is a retrospective cohort study including patients 18 to 50 years old diagnosed with acute myocardial infarction from October 1, 2015, to December 31, 2018. Parameters obtained included: Age, sex, ethnicity, body mass index, tobacco use, comorbid medical conditions, fasting blood glucose, hemoglobin A1c, lipid levels, and prescribed lipid-lowering therapy. Results Among 553 young patients diagnosed with acute myocardial infarction, the mean age at the time was 44.4 years, with men accounting for 69.1% of cases. The mean body mass index was 32.2 kg/m2. Hypertension, diabetes mellitus, and tobacco use were present in 64.7%, 25.9%, and 36.2% of patients. Insulin resistance, elevated triglycerides, and low HDL-C were present in 29.8%, 51.0%, and 62.8% of patients, respectively. Approximately 61.3% of patients within this cohort met World Health Organization criteria for diagnosis of metabolic syndrome. Mean LDL-C was 116 mg/dL and mean triglycerides were 190 mg/dL. Statin therapy was prescribed to 92 (16.6%) of patients prior to diagnosis of acute myocardial infarction, whereas 359 (67.3%) of patients met ACC/AHA criteria for lipid-lowering therapy. Within this subgroup receiving statin therapy, the mean serum LDL-C was 101 mg/dl, 26.1% had levels below 70 mg/dL, and 56.5% had LDL-C levels below 100 mg/dL. Thirty-four patients (6.1%) with LDL-C levels greater than 190 mg/dL, and 29 (85.3%) were not on lipid-lowering therapy. Conclusions and Relevance Multiple treatable risk factors were present in most young adults with acute myocardial infarction, including many with LDL-C levels below 100 mg/dL. Being overweight or obese was the most prevalent risk factor, while elevated non-HDL cholesterol was the most common lipid panel abnormality. In addition to known cardiometabolic risk factors, these findings build upon a growing body of evidence implicating triglyceride-rich lipoproteins in non-HDL and remnant cholesterol as an independent risk factor of ASCVD, which were common in this cohort of young patients presenting with myocardial infarction. In this cohort, lipid-lowering therapy was underutilized in young patients with known cardiometabolic risk factors, elevated estimated 10-year ASCVD risk, and individuals with phenotypic Familial Hypercholesterolemia.

Objective: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. Background and Aims: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. Methods: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA (CEACAM5) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. Results: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41–59%) and lower specificities (56–96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. Conclusions: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

Abstract Introduction Penile dysmorphophobia is common, with up to 20% of men reporting dissatisfaction with their genital size. The global market for Sexual Enhancement Supplements is estimated at $300 Million in the year 2020 and is projected to reach $608 Million by 2027 in the US alone. Evidence for efficacy is minimal, and purported claims are hyperbolic. Objective We sought to assess penile elongation internet offerings, quantify cost, ingredients, and risk and investigate scientific literature of product ingredients when available. Methods Three online marketplaces (Amazon, Google market, and Walmart) were queried for dietary supplements available without a prescription to improve penile size. Product labels were reviewed to compile penile size-related claims and active ingredients. The one-course (60-day) cost of treatment and consumer star rating were assessed. MEDLINE, Web of Science, and Google Scholar were queried with labeled ingredients to assess the scientific evidence from published and lay sources. Results A total of 84 dietary supplements claimed either increased penile length, girth, enhanced sexual performance, or a combination thereof. Of these 84 products, 90 ingredients were listed. The Mean 60-day cost was $52 (range of $12–$222). The median score by consumers in the markets with a possibility of star rating was 3.5 (range 2.4-4.2) with obvious repetitive and self-promotional tactics. Unsurprisingly, no scientific evidence supporting change in penile size was found for any products in our search. Actual described physiologic activity from active ingredients included were described as antidepressant, lipid and glucose lowering/metabolizing, blood pressure effecting, anti-inflammatory, renally protective, cognitive function effecting, antioxidant, and several ingredients weakly enhancing erectile activity. Renal failure, warnings against long-term use, heart problems, neuropathy, blood pressure effects, fertility toxicity, bleeding, liver disease, and numerous interactions with diabetes, blood thinning, immunosuppressant, and PDE5 medications were found for the ingredients. Conclusions Dietary supplements claiming to enhance penile size contained ingredients with conflicting or no scientific evidence to support their claims. Several ingredients were dangerous. Clinician awareness of these sham “solutions” and their continued mass consumption highlight the magnitude of misinformation, unrealistic expectations, shame, and enhancement desperation regarding penile size in the male public psyche. Disclosure No

Abstract Introduction Independently performed procedures by well-trained advanced practice providers (APP) facilitate access to specialized care. We sought to compare outcomes between physicians and APPs with intralesional collagenase clostridium histolyticum (CCH). Objective Compare outcomes of CCH injections based on injection provider. Outcomes included curvature improvement and adverse events. Methods Men receiving CCH between 2014-2021 at our institution by four physicians and four APPs were included in an IRB-approved database. CCH was delivered as a series of 8 injections per protocol. Patient demographics, procedural-related adverse events, and curvature changes were recorded. The “APP-ratio” is defined as percentage of total injections administered by an APP per patient. Results After excluding patients who did not complete the entire CCH course or return for final assessment, 150/406 patients were analyzed. Mean baseline penile curvature was 66.2° (SD 23). Mean absolute and percent improvements in curvature were 21.7° (SD 18) and 33% (SD 27). The mean APP ratio was 69%, and 133 patients (89%) had at least 25% of their injections performed by an APP. There was no significant difference (p=0.65, p=0.39) in absolute or relative curvature improvement based on the APP-ratio [Figure 1]. There was also no difference in adverse events (pain, swelling, and hematoma). Conclusions In our high-volume CCH practice, APPs achieve the same outcomes and safety compared to physicians. Greater training efforts expand access to care for patients with PD. Disclosure No

AbstractCardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

OBJECTIVE Clear diagnostic delineation is necessary for the development of a strong evidence base in lumbar spinal surgery. Experience with existing national databases suggests that International Classification of Diseases, Tenth Edition (ICD-10) coding is insufficient to support that need. The purpose of this study was to assess agreement between surgeon-specified diagnostic indication and hospital-reported ICD-10 codes for lumbar spine surgery. METHODS Data collection for the American Spine Registry (ASR) includes an option to denote the surgeon’s specific diagnostic indication for each procedure. For cases treated between January 2020 and March 2022, surgeon-delineated diagnosis was compared with the ICD-10 diagnosis generated by standard ASR electronic medical record data extraction. For decompression-only cases, the primary analysis focused on the etiology of neural compression as determined by the surgeon versus that determined on the basis of the related ICD-10 codes extracted from the ASR database. For lumbar fusion cases, the primary analysis compared structural pathology, which may have required fusion, as determined by the surgeon versus that determined on the basis of the extracted ICD-10 codes. This allowed for identification of agreement between surgeon delineation and extracted ICD-10 codes. RESULTS In 5926 decompression-only cases, agreement between the surgeon and ASR ICD-10 codes was 89% for spinal stenosis and 78% for lumbar disc herniation and/or radiculopathy. Both the surgeon and database indicated no structural pathology (i.e., none) suggesting the need for fusion in 88% of cases. In 5663 lumbar fusion cases, agreement was 76% for spondylolisthesis but poor for other diagnostic indications. CONCLUSIONS Agreement between surgeon-specified diagnostic indication and hospital-reported ICD-10 codes was best for patients who underwent decompression only. In the fusion cases, agreement with ICD-10 codes was best in the spondylolisthesis group (76%). In cases other than spondylolisthesis, agreement was poor due to multiple diagnoses or lack of an ICD-10 code that reflected the pathology. This study suggested that standard ICD-10 codes may be inadequate to clearly define the indications for decompression or fusion in patients with lumbar degenerative disease.

OBJECTIVE The Quality Outcomes Database (QOD) was established in 2012 by the NeuroPoint Alliance, a nonprofit organization supported by the American Association of Neurological Surgeons. Currently, the QOD has launched six different modules to cover a broad spectrum of neurosurgical practice—namely lumbar spine surgery, cervical spine surgery, brain tumor, stereotactic radiosurgery (SRS), functional neurosurgery for Parkinson’s disease, and cerebrovascular surgery. This investigation aims to summarize research efforts and evidence yielded through QOD research endeavors. METHODS The authors identified all publications from January 1, 2012, to February 18, 2023, that were produced by using data collected prospectively in a QOD module without a prespecified research purpose in the context of quality surveillance and improvement. Citations were compiled and presented along with comprehensive documentation of the main study objective and take-home message. RESULTS A total of 94 studies have been produced through QOD efforts during the past decade. QOD-derived literature has been predominantly dedicated to spinal surgical outcomes, with 59 and 22 studies focusing on lumbar and cervical spine surgery, respectively, and 6 studies focusing on both. More specifically, the QOD Study Group—a research collaborative between 16 high-enrolling sites—has yielded 24 studies on lumbar grade 1 spondylolisthesis and 13 studies on cervical spondylotic myelopathy, using two focused data sets with high data accuracy and long-term follow-up. The more recent neuro-oncological QOD efforts, i.e., the Tumor QOD and the SRS Quality Registry, have contributed 5 studies, providing insights into the real-world neuro-oncological practice and the role of patient-reported outcomes. CONCLUSIONS Prospective quality registries are an important resource for observational research, yielding clinical evidence to guide decision-making across neurosurgical subspecialties. Future directions of the QOD efforts include the development of research efforts within the neuro-oncological registries and the American Spine Registry—which has now replaced the inactive spinal modules of the QOD—and the focused research on high-grade lumbar spondylolisthesis and cervical radiculopathy.

IntroductionAdamantinoma‐like Ewing sarcoma (ALES) is a rare aggressive malignancy occasionally diagnosed in the thyroid gland. ALES shows basaloid cytomorphology, expresses keratins, p63, p40, frequently CD99, and harbours the t(11;22) EWSR1::FLI1 translocation. There is debate on whether ALES resembles more sarcoma or carcinoma.MethodsWe performed RNA sequencing from two ALES cases and compared findings with skeletal Ewing's sarcomas and nonneoplastic thyroid tissue. ALES was investigated by in situ hybridization (ISH) for high‐risk human papillomavirus (HPV) DNA and immunohistochemistry for the following antigens: keratin 7, keratin 20, keratin 5, keratins (AE1/AE3 and CAM5.2), CD45, CD20, CD5, CD99, chromogranin, synaptophysin, calcitonin, thyroglobulin, PAX8, TTF1, S100, p40, p63, p16, NUT, desmin, ER, FLI1, INI1, and myogenin.ResultsAn uncommon EWSR1::FLI transcript with retained EWSR1 exon 8 was detected in both ALES cases. Regulators of EWSR1::FLI1 splicing (HNRNPH1, SUPT6H, SF3B1) necessary for production of a functional fusion oncoprotein, as well as 53 genes (including TNNT1, NKX2.2) activated downstream to the EWSR1::FLI1 cascade, were overexpressed. Eighty‐six genes were uniquely overexpressed in ALES, most of which were related to squamous differentiation. Immunohistochemically, ALES strongly expressed keratins 5, AE1/AE3 and CAM5.2, p63, p40, p16, and focally CD99. INI1 was retained. The remaining immunostains and HPV DNA ISH were negative.ConclusionComparative transcriptomic profiling reveals overlapping features of ALES with skeletal Ewing's sarcoma and an epithelial carcinoma, as evidenced by immunohistochemical expression of keratin 5, p63, p40, CD99, the transcriptome profile, and detection of EWSR1::FLI1 fusion transcript by RNA sequencing.

Importance Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. Objective To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled. Exposures Amount and intensity of physical activity. Main Outcomes and Measures The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient’s exercise category. Results Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority. Conclusions and Relevance Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.

Anticipating and understanding cancers’ need for specific gene activities is key for novel therapeutic development. Here we utilized DepMap, a cancer gene dependency screen, to demonstrate that machine learning combined with network biology can produce robust algorithms that both predict what genes a cancer is dependent on and what network features coordinate such gene dependencies. Using network topology and biological annotations, we constructed four groups of novel engineered machine learning features that produced high accuracies when predicting binary gene dependencies. We found that in all examined cancer types, F1 scores were greater than 0.90, and model accuracy remained robust under multiple hyperparameter tests. We then deconstructed these models to identify tumor type-specific coordinators of gene dependency and identified that in certain cancers, such as thyroid and kidney, tumors’ dependencies are highly predicted by gene connectivity. In contrast, other histologies relied on pathway-based features such as lung, where gene dependencies were highly predictive by associations with cell death pathway genes. In sum, we show that biologically informed network features can be a valuable and robust addition to predictive pharmacology models while simultaneously providing mechanistic insights.