Anatomical Ablation of the Atrioventricular Node.

Background: Atrioventricular (AV) conduction ablation has been achieved by targeting the area of penetration of the conduction axis as defined by recording a His bundle potential. Ablation of the His bundle may reduce the possibility of a robust junctional escape rhythm. It was hypothesised that specific AV nodal ablation is feasible and safe. Methods: The anatomical position of the AV node in relation to the site of penetration of the conduction axis was identified as described in dissections and histological sections of human hearts. Radiofrequency (RF) ablation was accomplished based on the anatomical criteria. Results: Specific anatomical ablation of the AV node was attempted in 72 patients. Successful AV nodal ablation was accomplished in 63 patients (87.5%), following 60 minutes (IQR 50-70 minutes) of procedure time, 3.4 minutes (IQR 2.4-5.5 minutes) of fluoroscopy time, and delivery of 4 (IQR 3-6) RF lesions. An escape rhythm was present in 45 patients (71%), and the QRS complex was similar to that before ablation in all 45 patients. Atropine was administered in six patients after the 10-min waiting period and did not result in restoration of conduction. In nine patients, AV conduction could not be interrupted, and AV block was achieved with ablation of the His after delivery of 12 (IQR 8-15) RF lesions. No cases of sudden death were encountered, and all patients had persistent AV block during a median 10.5 months (IQR 5-14 months) of follow-up. Conclusion: Anatomical ablation of the AV node is feasible and safe, and results in an escape rhythm similar to that before ablation.

Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications.

Bicuspid aortic valve (BAV) is the most common congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that specific gene variants predispose to early-onset complications of BAV (EBAV). We analyzed whole-exome sequences (WESs) to identify rare coding variants that contribute to BAV disease in 215 EBAV-affected families. Predicted damaging variants in candidate genes with moderate or strong supportive evidence to cause developmental cardiac phenotypes were present in 107 EBAV-affected families (50% of total), including genes that cause BAV (9%) or heritable thoracic aortic disease (HTAD, 19%). After appropriate filtration, we also identified 129 variants in 54 candidate genes that are associated with autosomal-dominant congenital heart phenotypes, including recurrent deleterious variation of FBN2, MYH6, channelopathy genes, and type 1 and 5 collagen genes. These findings confirm our hypothesis that unique rare genetic variants drive early-onset presentations of BAV disease.

Leveraging Generative AI to Accelerate Biocuration of Medical Actions for Rare Disease.

BACKGROUND: Structured representations of clinical data can support computational analysis of individuals and cohorts, and ontologies representing disease entities and phenotypic abnormalities are now commonly used for translational research. The Medical Action Ontology (MAxO) provides a computational representation of treatments and other actions taken for the clinical management of patients. Currently, manual biocuration is used to assign MAxO terms to rare diseases, enabling clinical management of rare diseases to be described computationally for use in clinical decision support and mechanism discovery. However, it is challenging to scale manual curation to comprehensively capture information about medical actions for the more than 10,000 rare diseases. METHODS: We present AutoMAxO, a semi-automated workflow that leverages Large Language Models (LLMs) to streamline MAxO biocuration for rare diseases. AutoMAxO first uses LLMs to retrieve candidate curations from abstracts of relevant publications. Next, the candidate curations are matched to ontology terms from MAxO, Human Phenotype Ontology (HPO), and MONDO disease ontology via a combination of LLMs and post-processing techniques. Finally, the matched terms are presented in a structured form to a human curator for approval. RESULTS: We used this approach to process 4,918 unique medical abstracts and identified annotations for 21 rare genetic diseases, we extracted 18,631 candidate disease-treatment curations, 538 of which were confirmed and transferred to the MAxO annotation dataset. CONCLUSION: The results of this project underscore the potential of generative AI to accelerate precision medicine by enabling a robust and comprehensive curation of the primary literature to represent information about diseases and procedures in a structured fashion. Although we focused on MAxO in this project, similar approaches could be taken for other biomedical curation tasks.

CD81 fusion alters SARS-CoV-2 Spike trafficking.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic caused the biggest public health crises in recent history. Many expect future coronavirus introductions into the human population. Hence, it is essential to understand the basic biology of these viruses. In natural infection, the SARS-CoV-2 Spike (S) glycoprotein is co-expressed with all other viral proteins, which modify cellular compartments to maximize virion assembly. By comparison, most of S is degraded when the protein is expressed in isolation, as in current molecular vaccines. To probe the maturation pathway of S, we redirected its maturation by fusing S to the tetraspanin protein CD81. CD81 is a defining constituent of extracellular vesicles (EVs) or exosomes. EVs are generated in large numbers by all cells, extruded into blood and lymph, and transfer cargo between cells and systemically (estimated 1012 EVs per mL plasma). EVs, like platelets, can be transfused between unrelated donors. When fusing the proline-stabilized form of strain Delta S into the flexible, large extracellular loop of CD81 rather than being degraded in the lysosome, S was extruded into EVs. CD81-S fusion containing EVs were produced in large numbers and could be isolated to high purity. Purified CD81::S EVs bound ACE2, and S displayed on individual EV was observed by cryogenic electron microscopy (EM). The CD81::S-fusion EVs were non-toxic and elicited an anti-S trimer and anti-RBD antibody response in mice. This report shows a design path to maximize viral glycoprotein assembly and release without relying on the co-expression of potentially pathogenic nonstructural viral proteins. IMPORTANCE: The severe acute respiratory syndrome coronavirus 2 pandemic caused the biggest public health crises in recent history. To understand the maturation pathway of S, we fused S to the tetraspanin protein CD81. The resulting molecule is secreted in extracellular vesicles and induces antibodies in mice. This may be a general design path for viral glycoprotein vaccines.

Evaluation of the Diagnostic Accuracy of GPT-4 in Five Thousand Rare Disease Cases.

Large language models (LLM) have shown great promise in supporting differential diagnosis, but 23 available published studies on the diagnostic accuracy evaluated small cohorts (number of cases, 30-422, mean 104) and have evaluated LLM responses subjectively by manual curation (23/23 studies). The performance of LLMs for rare disease diagnosis has not been evaluated systematically. Here, we perform a rigorous and large-scale analysis of the performance of a GPT-4 in prioritizing candidate diagnoses, using the largest-ever cohort of rare disease patients. Our computational study used 5267 computational case reports from previously published data. Each case was formatted as a Global Alliance for Genomics and Health (GA4GH) phenopacket, in which clinical anomalies were represented as Human Phenotype Ontology (HPO) terms. We developed software to generate prompts from each phenopacket. Prompts were sent to Generative Pre-trained Transformer 4 (GPT-4), and the rank of the correct diagnosis, if present in the response, was recorded. The mean reciprocal rank of the correct diagnosis was 0.24 (with the reciprocal of the MRR corresponding to a rank of 4.2), and the correct diagnosis was placed in rank 1 in 19.2% of the cases, in the first 3 ranks in 28.6%, and in the first 10 ranks in 32.5%. Our study is the largest to be reported to date and provides a realistic estimate of the performance of GPT-4 in rare disease medicine.

Comparison of Five-Day vs. Fourteen-Day Incubation of Cultures for Diagnosis of Periprosthetic Joint Infection in Hip Arthroplasty.

Background: Periprosthetic joint infections (PJI) are among the most morbid complications in total hip arthroplasty (THA). The ideal incubation time, however, for intraoperative cultures for PJI diagnosis remains unclear. As such, the aim of this study was to determine if any differences existed in culture-positive rates and organism detection between five-day and fourteen-day cultures. Methods: This retrospective cohort study consisted of THA cases diagnosed with PJI performed between May 2014 and May 2020 at a single tertiary-care institution. Analyses compared five-day and fourteen-day cultures and carried out a pre-specified subgroup analysis by organism and PJI type. Results: A total of 147 surgeries were performed in 101 patients (57.1% females), of which 65% (n = 98) obtained five-day cultures and 34% (n = 49) obtained fourteen-day cultures. The positive culture rate was 67.3% (n = 99) with Staphylococcus aureus being the most common pathogen identified (n = 41 specimens, 41.4%). The positive culture rate was not significantly different between groups (66.3% five-day, 69.4% fourteen-day, p = 0.852). Fourteen-day cultures had a significantly longer time-to-positive culture (5.0 days) than five-day cultures (3.0 days, p < 0.001), a higher rate of fungi (5.6% vs. 0%), and a lower rate of Gram-negatives (4.5% vs. 18.7%, p = 0.016). Conclusions: Fourteen-day cultures did not increase the positivity rate, had higher rates of slow-growth pathogens, and had a longer time-to-positivization than five-day cultures. Prolonged culture holds may provide more thorough organism detection for PJI without increasing the diagnostic culture yield.

Asymmetric effects of hydroclimate extremes on eastern US tree growth: Implications on current demographic shifts and climate variability.

Forests around the world are experiencing changes due to climate variability and human land use. How these changes interact and influence the vulnerability of forests are not well understood. In the eastern United States, well-documented anthropogenic disturbances and land-use decisions, such as logging and fire suppression, have influenced forest species assemblages, leading to a demographic shift from forests dominated by xeric species to those dominated by mesic species. Contemporarily, the climate has changed and is expected to continue to warm and produce higher evaporative demand, imposing stronger drought stress on forest communities. Here, we use an extensive network of tree-ring records from common hardwood species across ~100 sites and ~1300 trees in the eastern United States to examine the magnitude of growth response to both wet and dry climate extremes. We find that growth reductions during drought exceed the positive growth response to pluvials. Mesic species such as Liriodendron tulipifera and Acer saccharum, which are becoming more dominant, are more sensitive to drought than more xeric species, such as oaks (Quercus) and hickory (Carya), especially at moderate and extreme drought intensities. Although more extreme droughts produce a larger annual growth reduction, mild droughts resulted in the largest cumulative growth decreases due to their higher frequency. When using global climate model projections, all scenarios show drought frequency increasing substantially (3-9 times more likely) by 2100. Thus, the ongoing demographic shift toward more mesic species in the eastern United States combined with drier conditions results in larger drought-induced growth declines, suggesting that drought will have an even larger impact on aboveground carbon uptake in the future in the eastern United States.

Looking to "Level the Field": A Qualitative Study of How Clinicians Operationalize Social Determinants in Critical Care.

INTRODUCTION: Current critical care practice does not integrate social determinants of health (SDOH) in systematic or standardized ways. Routine assessment of SDOH in the intensive care unit (ICU) may improve clinical decision-making, patient- and family-centered outcomes, and clinician well-being. Given the appropriateness and feasibility of SDOH assessment in the ICU is unknown, we aimed to understand how ICU clinicians think about and use SDOH. METHODS: We conducted semi-structured interviews with clinicians focused on barriers to and facilitators of assessing SDOH during critical illness and perceptions on screening for SDOH in the ICU. We used chart-stimulated recall to assist clinicians in reflecting on how SDOH applied to and was used in patients' care. After deidentifying interviews, we analyzed transcripts guided by a thematic analysis approach using a combination of inductive and deductive coding, the latter framed within the Centers for Disease Control SDOH Healthy People framework. RESULTS: We completed interviews with 30 clinicians, in a variety of professional roles. The majority of clinicians self-identified as men (17, 56.7%) of White race (25, 83.3%). Clinicians contextualize their use of SDOH within three frames of reference: 1) their own identity and experiences; 2) their relationships and communication with patients and caregivers; and 3) immediate structures of care around ICU patients including clinician advocacy, care transitions, and readmission. Clinicians identified that discussing SDOH could allow them to recognize bias faced by their patients, elucidate drivers of critical illness, and navigate communication with patients caregivers. Clinicians worried about ICU-specific factors impeding the discussion of SDOH including time contraints and acuity, high stakes and emotions, and negative anticipatory emotions. DISCUSSION: Clinicians gather SDOH during critical illness both to understand their patients' stories and provide individualized care, which may lead to better clinician satisfaction and patient- and family-centered care outcomes. Educational and operational efforts to increase SDOH assessment and use in critical care should also gather and integrate the perspectives of patients and caregivers regarding the collection and use of SDOH in the ICU.

Real-World Adherence and Discontinuation of Oral Antipsychotics and Associated Factors in a National Sample of US Medicare Beneficiaries with Schizophrenia.

Purpose: Little is known about adherence to and discontinuation of newly initiated oral antipsychotics (OAPs) as well as associated factors among Medicare beneficiaries with schizophrenia. This study aimed to examine rates of OAP adherence and discontinuation and associated factors in a national sample of fee-for-service Medicare beneficiaries with schizophrenia. Patients and Methods: This retrospective study used 100% fee-for-service Medicare claims data to identify adult beneficiaries with schizophrenia, initiating a new OAP between 01/01/2017 and 12/31/2019 (index date = date of new OAP prescription). Outcomes included adherence and discontinuation. Factors associated with adherence were assessed using logistic and linear regressions; Cox regressions were used to assess factors associated with discontinuation. Results: In our final sample of 46,452 Medicare beneficiaries with schizophrenia, 35.4% were adherent to their newly initiated OAP (mean [SD] PDC: 0.52 [0.37]) over 12 months after initiation. Most patients (79.4%) discontinued their new OAP (median [IQR] time to discontinuation: 3.6 (1.0, 9.9) months). Factors associated with lower odds of adherence included younger age (OR: 0.43; 95% CI: 0.40-0.47, p <0.001 for patients aged 18-35 relative to patients aged ≥65 years); non-White race (OR: 0.72; 95% CI: 0.69-0.75, p <0.001 relative to White patients); and evidence of prior schizophrenia-related hospitalization (OR: 0.80; 95% CI: 0.77-0.83, p <0.001 relative to patients without evidence of prior schizophrenia-related hospitalization). Similar associations were observed for discontinuation outcomes. Twice-daily dosing frequency was also associated with lower odds of adherence (odds ratio [OR]: 0.93; 95% CI: 0.89-0.97, p = 0.0014) and higher hazard of discontinuation (hazard ratio [HR]: 1.03; 95% CI: 1.00-1.05, p = 0.0244) relative to once-daily dosing frequency. Conclusion: We found high rates of non-adherence and discontinuation among Medicare beneficiaries initiated on currently available OAPs. We also identified risk factors that contribute to increased odds of medication non-adherence. By identifying at-risk patient populations, targeted interventions can be initiated to facilitate treatment continuity.

Plain Language Summary: Although half of patients with schizophrenia are covered by Medicare, little is known about how consistently they take their antipsychotic medications, which is a crucial part of successful treatment. We found that only 1/3 of Medicare beneficiaries consistently took their medications and nearly 80% discontinued treatment, often shortly after starting it. Younger patients, non-White patients, and patients who had to take pills multiple times per day were less likely to consistently take their medications.

Ethical Issues in Implementation Science: A Qualitative Interview Study of Participating Clinicians.

BACKGROUND: Implementation science presents ethical issues not well addressed by traditional research ethics frameworks. There is little empirical work examining how clinicians whose work is affected by implementation studies view these issues. Accordingly, we interviewed clinicians working at sites participating in an implementation study seeking to improve patient handoffs to the intensive care unit (ICU). METHODS: We performed semi-structured interviews with 32 clinicians working at sites participating in an implementation study aiming to improve patient handoffs from the operating room to the ICU. We analyzed the interviews using an iterative coding process following a conventional content analysis approach. RESULTS: Clinicians' greatest concern about involvement was possible damage to interpersonal relations with more senior clinicians. They were divided about whether informed consent from clinicians was necessary but were satisfied with the study's approach of sending out mass communications about the study. They did not think opting out of the implementation portion of the study was feasible but saw this inability to opt out as unproblematic because they equated the study with routine quality improvement. Those clinicians who helped launch the study at their sites recounted several different ways of doing so beyond simply facilitating access. CONCLUSIONS: The risks that clinicians identified stemmed more from their general status as employees than their specific work as clinicians. Implementation researchers should be attuned to the ethical ramifications of involving employees of varying ranks. Implementation researchers using hybrid designs should also be sensitive to the possibility that practitioners affected by a study will equate it with quality improvement and overlook its research component. Finally, the interactions that go into facilitating an implementation study are more various than the "gatekeeping" typically discussed by research ethicists. More research is needed on the ethics of the myriad interactions that are involved in making implementation studies happen.

Complete pathologic response in esophageal adenocarcinoma: does it make a difference?

Advancements in neoadjuvant regimens for esophageal adenocarcinoma have enabled some patients to achieve complete pathologic response at time of esophagectomy. There are currently limited data detailing this trend or the implications of complete pathologic response on survival. The National Cancer Database was used to identify 16,169 patients with esophageal adenocarcinoma that received trimodal therapy including esophagectomy between 2006 and 2020. Of these, 11.4% had complete pathologic response at esophagectomy. Patient factors, staging characteristics, and survival trends were evaluated. In patients diagnosed between 2016 and 2020, the rate of complete pathologic response was 17.5%. Female sex (OR 1.295, 95% CI 1.134-1.481, p = 0.0001), Black race (OR 1.729, 95% CI 1.362-2.196, p = 0.0002), Hispanic ethnicity (OR 1.418, 95% CI 1.073-1.875, p = 0.0141), and later era of diagnosis (2016-2020 OR 2.898, 95% CI 2.508-3.349, p < 0.0001) were independent predictors of complete pathologic response. Clinical stage II disease was associated with an increased probability of complete pathologic response (OR 1.492, 95% CI 1.19-1.871) while clinical stage III disease had a decreased probability of complete pathologic response (OR 0.762, 95% CI 0.621-0.936, p < 0.0001). Complete pathologic response conveyed a strong survival benefit, with a median survival of 86.4 months (95% CI 73.9-102.1) versus 30.7 months (95% CI 29.8-31.7, p < 0.0001) in those without complete pathologic response. Four-year median survival was also higher in those with complete pathologic response (63.3%, 95% CI 60.8-66.0% vs. 39.2%, 95% CI 38.4-40.1%, p < 0.0001). In summary, complete pathologic response is associated with a profound survival advantage in patients with esophageal adenocarcinoma. Such knowledge carries implications for patient counseling, prognostication, and surveillance and demonstrates a need for improved identification of complete clinical response prior to esophagectomy.

"Does an Additional Advanced Degree Influence Career Trajectory as a Shoulder and Elbow Surgeon?"

BACKGROUND: As orthopedic surgery becomes increasingly competitive, orthopedic surgeons are now pursuing advanced degrees more frequently to enhance their resumes or gain additional expertise. The specific impact of this additional training and education on a surgeon's career trajectory is not well defined. The purpose of this study was to understand the impact of an advanced degree on the academic career of orthopedic shoulder and elbow surgeons. METHODS: Orthopedic shoulder and elbow fellowship-trained surgeons were identified using the directory listed on the American Shoulder and Elbow Surgeons website. Demographics, education, and current professional roles were obtained. Research productivity was obtained using SCOPUS and Google Scholar. Advanced degrees were defined as those additional to the primary medical degree (Doctor of Medicine [MD] or Doctor of Osteopathic Medicine [DO]). Outcome measures collected included timing of advanced degree obtainment, current academic and leadership roles, leadership on journal editorial boards, and research productivity. Statistical analysis was performed using the chi-square test and Mann-Whitney U test to determine the association of advanced degrees on outcome measures. RESULTS: In total, 893 orthopedic shoulder and elbow surgeons were identified, of whom 129 had advanced degrees. Most common advanced degrees included Master of Science (MS/MSc; 43%), Master of Business Administration (MBA; 23%), and Doctor of Philosophy (PhD; 13%). The most common period of degree obtainment was before medical school (35%) with the least common times being after medical school/before residency (0.9%) and between residency and fellowship training (0.9%). Surgeons who held advanced degrees demonstrated greater research productivity, with a higher h-index (p < 0.001), a greater number of citations (p < 0.001), and more publications (p < 0.001). Of the 523 shoulder and elbow surgeons who worked at an academic institution, those holding advanced degrees were more likely to serve as orthopedic department chair (p < 0.001) and serve an editorial board position (< 0.001). CONCLUSION: This study found that having an advanced degree as an orthopedic shoulder and elbow surgeon was linked to higher research impact and productivity and an increased likelihood of becoming a department chair and holding an editorial position. These significant findings can help future trainees and department leadership in understanding the importance and impact of additional training on career trajectories for academic faculty.

Local Infiltration Analgesia Is Superior to Regional Nerve Blocks for Total Hip Arthroplasty: Less Falls, Better Mobility, and Same-Day Discharge.

Background: Multimodal analgesia in total hip arthroplasty (THA) provides better pain control, mobility, and reduced side effects compared to monotherapies. Local infiltration analgesia (LIA) and regional nerve blocks (RNBs) are commonly used throughout these protocols. This study aimed to compare these procedures as part of a multimodal analgesia protocol for patients undergoing THA. Materials and Methods: A retrospective review of 1100 consecutive elective primary THAs was performed in 996 patients between June 2018 and December 2021. The RNB consisted of a preoperative continuous femoral nerve catheter and single-shot obturator nerve block, and LIA consisted of the intraoperative infiltration of weight-based bupivacaine. Results: A total of 579 (52.6%) patients received RNB, and 521 (47.4%) received LIA. Mean oral morphine equivalents (OMEs) during the first four hours postoperatively were significantly lower for LIA group (p < 0.001). However, the numeric pain rating scale in the post-anesthesia care unit (PACU) was similar between groups. Patients with LIA had significantly greater first ambulation distance in the PACU (p < 0.001), higher successful same-day discharge rate (p = 0.029), fewer falls (p = 0.041), and less refill OMEs post-discharge (p < 0.001) than RNB. Conclusions: In the setting of similar pain management between groups and better functional outcomes for LIA, the use of minimally invasive procedures like LIA for pain control following THA is favorable.

Development of Novel Bacterial Topoisomerase Inhibitors Assisted by Computational Screening.

Multidrug-resistant bacterial infections pose an ever-evolving threat to public health. Since the outset of the antibacterial age, bacteria have developed a multitude of diverse resistance mechanisms that suppress the effectiveness of current therapies. New drug entities, such as Novel Bacterial Topoisomerase Inhibitors (NBTIs), can circumvent this major issue. A computational docking model was employed to predict the binding to DNA gyrase of atypical NBTIs with novel pharmacophores. Synthesis of NBTIs based on computational docking and subsequent antibacterial evaluation against both Gram-positive and Gram-negative bacteria yielded congeners with outstanding anti-staphylococcal activity and varying activity against select Gram-negative pathogens.

Replacing non-biomedical concepts improves embedding of biomedical concepts.

Objectives: Concept embeddings are low-dimensional vector representations of concepts such as MeSH:D009203 (Myocardial Infarction), whose similarity in the embedded vector space reflects their semantic similarity. Here, we test the hypothesis that non-biomedical concept synonym replacement can improve the quality of biomedical concepts embeddings. Materials and methods: We developed an approach that leverages WordNet to replace sets of synonyms with the most common representative of the synonym set. Results: We tested our approach on 1055 concept sets and found that, on average, the mean intra-cluster distance was reduced by 8% in the vector-space. Assuming that homophily of related concepts in the vector space is desirable, our approach tends to improve the quality of embeddings. Discussion and Conclusion: This pilot study shows that non-biomedical synonym replacement tends to improve the quality of embeddings of biomedical concepts using the Word2Vec algorithm. We have implemented our approach in a freely available Python package available at https://github.com/TheJacksonLaboratory/wn2vec.

The Influence of Disparities on Prostate Cancer at Diagnosis in the Charlotte Metropolitan Area.

INTRODUCTION: Prostate cancer (PCa) is the most diagnosed noncutaneous malignancy and second leading-cause of cancer death in men, yet screening is decreasing. As PCa screening has become controversial, socioeconomic disparities in PCa diagnosis and outcomes widen. This study was designed to determine the current disparities influencing PCa diagnosis in Charlotte, NC. METHODS: The Levine Cancer Institute database was queried for patients with PCa, living in metropolitan Charlotte. Socioeconomic status (SES) was determined by the Area Deprivation Index (ADI); higher ADI indicated lower SES. Patients were compared by their National Comprehensive Cancer Network risk stratification. Artificial intelligence predictive models were trained and heatmaps were created, demonstrating the geographic and socioeconomic disparities in late-stage PCa. RESULTS: Of the 802 patients assessed, 202 (25.2%) with high-risk PCa at diagnosis were compared with 198 (24.7%) with low-risk PCa. High-risk PCa patients were older (69.8 ± 9.0 vs. 64.0 ± 7.9 years; p < 0.001) with lower SES (ADI block: 98.4 ± 20.9 vs. 92.1 ± 19.8; p = 0.004) and more commonly African-American (White: 66.2% vs. 78.3%, African-American: 31.3% vs. 20.7%; p = 0.009). On regression, ADI block was an independent predictor (odds ratio [OR] = 1.013, 95% confidence interval [CI] 1.002-1.024; p = 0.024) of high-risk PCa at diagnosis, whereas race was not (OR = 1.312, 95% CI 0.782-2.201; p = 0.848). A separate regression demonstrated higher ADI (OR = 1.016, 95% CI 1.004-1.027; p = 0.006) and older age (OR = 1.083, 95% CI 1.054-1.114; p < 0.001) were independent predictors for high-risk PCa. Findings, depicted in heatmaps, demonstrated the geographic locations where men with PCa were predicted to have high-risk disease based on their age and SES. CONCLUSIONS: Socioeconomic status was more closely associated with high-risk PCa at diagnosis than race. Although, of any variable, age was most predictive. The heatmaps identified areas that would benefit from increased awareness, education, and screening to facilitate an earlier PCa diagnosis.

The Practice Experience of an Adult Reconstruction Surgeon: A Cross-Sectional Analysis and Survey of the American Association of Hip and Knee Surgeons Membership.

Background: As demand for total hip arthroplasty and total knee arthroplasty increases, more surgeons have pursued subspecialty training in adult reconstruction. However, little information is available regarding the practice environment in which these fellowship-trained surgeons practice. The purpose of this study was to describe the practice environments of contemporary adult reconstruction surgeons. Methods: A survey was developed and distributed to members of the American Association of Hip and Knee Surgeons from December 2022 to January 2023. Information was collected on surgeon demographics, practice setting, call requirements, and educational debt. Responses were recorded using frequencies and proportions. Results: A total of 886 of 2471 (36%) surgeons completed the survey, with 93% identifying as male and 81% as white. The primary surgical practice locations were: community hospital 53%, academic/tertiary hospital 24%, specialty orthopedic hospital 17%, and ambulatory surgery center 7%. Nearly half (49%) of the respondents practiced in orthopedic specialty groups, and 60% spent 50%-66% of their clinical time in the office. The majority of surgeons performed between 101-250 (20%) and 251-400 (31%) arthroplasty cases per year, though this varied considerably. Call was taken by 77% of surgeons, yet only 54% received compensation. Conclusions: The most common practice setting for adult reconstruction surgeons was in a community-based hospital as part of a large orthopedic specialty group. Despite the considerable variability in annual procedure volume, the majority of surgeons spent over half their clinical time in office and had call obligations with variable compensation models.

Lymphovascular Invasion is an Independent Negative Prognostic Factor in Esophageal Adenocarcinoma.

BACKGROUND: The significance of lymphovascular invasion (LVI) in esophageal adenocarcinoma (EAC) has not yet been described. Potential utility as an adjunct to current staging guidelines remains unknown. METHODS: The National Cancer Database was queried from 2006 to 2020. Univariate and multivariable models, Kaplan Meier method, and log-rank test were used. Subgroup analyses by pN stage were conducted. RESULTS: Of 9,689 patients, 23.2% had LVI. LVI was an independent prognostic factor (hazard ratio [HR] 1.401, 95% confidence interval [CI] 1.307-1.502, p < 0.0001) with reduction in median survival to 20.0 months (95% CI 18.9-21.4) from 39.7 months (95% CI 37.8-42.3, p < 0.0001). Multivariable survival analysis adjusted on pN and pT stage found that patients with LVI had decreased survival in a given pN stage (p < 0.001). pN0/LVI+ patients had a similar prognosis to the higher staged pN1/LVI- (28.6 months), although pN1/LVI- patients did slightly worse (p = 0.0135). Additionally, patients with pN1/LVI+ had equivalent survival compared with pN2/LVI- (p = 0.178) as did pN2/LVI+ patients compared with pN3/LVI- (p = 0.995). CONCLUSIONS: In these data, LVI is an independent negative prognostic factor in EAC. LVI was associated with a survival reduction similar to an upstaged nodal status irrespective of T stage. Patients with LVI may be better classified at a higher pN stage.