Citations

Abstract Aims Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although lipoprotein(a) [Lp(a)] is known to be a well-established risk factor for atherosclerotic cardiovascular disease, its role in the development of AF, independent of this association, remains unclear. Methods and results Adult patients from the three Mayo Clinic sites with a baseline Lp(a) and without AF history were included. Patients were categorized into two groups based on their Lp(a) levels: high Lp(a) (≥50 mg/dL) and low Lp(a) (<50 mg/dL). Survival probabilities free from incident AF were compared between Lp(a) groups, during a follow-up period up to 15 years, using the Kaplan–Meier curve and the log-rank test. Multivariable Cox regression analysis was also conducted. A total of 75 376 patients were included (median age: 55 years, 59% males), with a median follow-up duration of 8.8 (inter-quartile range: 3.4, 14.8) years. Incident AF was detected in 5738 (7.6%) patients. Survival probability free from incident AF was significantly lower in patients with elevated Lp(a) (86%) compared with those with low Lp(a) (88%, log-rank P < 0.001). Multivariable analysis adjusted for potential risk factors of AF showed a statistically significant association of elevated Lp(a) with an 11% increase in AF risk (adjusted hazard ratio: 1.11, 95% confidence interval: 1.05–1.18). Conclusion Our study suggests that elevated Lp(a) (≥50 mg/dL) is an independent risk factor for incident AF. Future prospective studies are warranted to validate our results and to test if reducing Lp(a) could mitigate the burden of AF.

BACKGROUND: Increased specialty competitiveness, alongside the inception of virtual interviews, has increased the number of applications submitted to the Electronic Residency Application Service (ERAS) in anesthesiology. ERAS introduced signals to provide applicants with a means to demonstrate interest in a select group of residency programs. In the 2023 to 2024 application cycle, anesthesiology applicants had the opportunity to send 5 gold and 10 silver signals in a tiered system. METHODS: This multicenter, cross-sectional (exempt) research survey was created by members of the executive council of the Association of Anesthesiology Core Program Directors (AACPD) and housed and distributed through REDCap and the University of Nebraska Medical Center. Publicly available contact information of anesthesiology core program directors was obtained from the Accreditation Council for Graduate Medical Education (ACGME) website and membership roster of the AACPD. In total, 174 anesthesiology programs were identified. A survey invitation was distributed on March 12, 2024, to all programs via e-mail with reminders. The survey closed on April 30, 2024. Survey responses were collected anonymously, with instructions to provide 1 response per program. All statistical summaries and analyses were performed using SAS 9.3 (SAS Institute). RESULTS: The survey was sent to all 174 identified programs, with a response rate of 48.9%. Small programs were defined as having <44 residents, medium 44 to 62 residents, and large >62 residents. Small programs received significantly fewer applications (median 1255) than medium (1420) and large (1558) programs ( P = .0005). There was a statistically significant difference in the number of gold signals received based on program size, with large programs receiving significantly more than medium (169 vs 116, P = .0238) or small programs (168 vs 71, P < .0001). Applicants sending gold signals were more likely to receive an interview compared to those who sent silver signals (56.7% vs 31%, P ≤ .0001). Of the those interviewed, applicants who sent gold signals comprised 42% (28.7%–52.6%), whereas applicants who sent silver signals comprised 45.5% (33%–54.7%). Applicants who did not send a program signal but signaled geographically made up a smaller portion of the interview group at 3% (0%–15.4%). The percentage of matched residents sending gold signals made up 66.7% (47.1%–82.4%) of a program’s match list, whereas those sending silver signals were 25% (11.1%–33.3%) of the matched cohort. CONCLUSIONS: Anesthesiology applicants who sent program signals were selected for a large majority of available interview positions, and interviewed applicants who submitted gold and silver signals comprised the vast majority of matched resident cohorts.

Importance Obesity is a risk factor associated with multiple myeloma (MM) and its precursor, monoclonal gammopathy of unknown significance (MGUS). However, it is unclear how cumulative exposure to obesity affects the risk of MGUS progression to MM. Objective To determine the association of cumulative exposure to excess body mass index (EBMI), defined as BMI (calculated as weight in kilograms divided by height in meters squared) greater than 25, with risk of MGUS progression to MM. Design, Setting, and Participants This cohort study included patients with MGUS, including immunoglobin G, immunoglobin A, or light chain MGUS, from the nationwide US Veterans Health Administration database from October 1, 1999, to December 31, 2021. A published natural language processing–assisted model was used to confirm diagnoses of MGUS and progression to MM. Data were analyzed from February 12 to November 4, 2024. Exposures Cumulative EBMI was calculated by area under the curve of measured BMI subtracting the reference BMI at 25 during the first 3 years after MGUS diagnosis. Main Outcomes and Measures The main outcome was progression from MGUS to MM. Multivariable Fine-Gray time-to-competing-event analyses, with death as the competing event, were used to determine associations. Results The cohort included 22 429 patients with MGUS (median [IQR] age, 70.5 [63.5-77.9] years; 21 613 [96.4%] male), with 8329 Black patients (37.1%) and 14 100 White patients (62.9%). There were 4862 patients (21.7%) with reference range BMI (18.5 to &amp;lt;25), 7619 patients (34.0%) with BMI 25 to less than 30, and 8513 patients (38.0%) with BMI 30 or greater at the time of MGUS diagnosis. Compared with reference range BMI at MGUS diagnosis, patients with BMI 25 to less than 30 (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.03-1.34) or 30 or greater (aHR, 1.27; 95% CI, 1.09-1.47) at MGUS diagnosis had higher risk of progression to MM. In patients with reference range BMI at MGUS diagnosis, each 1-unit increase of EBMI per year was associated with a 21% increase in progression risk (aHR, 1.21; 95% CI, 1.04-1.40). However, for patients with BMI 25 or greater at MGUS diagnosis, the incremental risk associated with cumulative EBMI exposure was not statistically significant. Conclusions and Relevance This cohort study found that, for patients with BMI 18.5 to less than 25 at the time of MGUS diagnosis, cumulative exposure to BMI 25 or greater was associated with an increased risk of progression. These findings suggest that for these patients, maintaining a healthy and stable weight following MGUS diagnosis may prevent progression to MM.

BACKGROUND: The activation and polarization of T cells play a crucial role in atherosclerosis and dictate athero-inflammation. The epigenetic enzyme EZH2 (enhancer of zeste homolog 2) mediates the H3K27me3 (trimethylation of histone H3 lysine 27) and is pivotal in controlling T cell responses. METHODS: To detail the role of T cell EZH2 in atherosclerosis, we used human carotid endarterectomy specimens to reveal plaque expression and geography of EZH2. Atherosclerosis-prone Apoe (apolipoprotein E)–deficient mice with CD (cluster of differentiation) 4 + or CD8 + T cell–specific Ezh2 deletion (Ezh2 cd4 -knockout [KO], Ezh2 cd8 -KO) were analyzed to unravel the role of T cell Ezh2 in atherosclerosis and T cell–associated immune status. RESULTS: EZH2 expression is elevated in advanced human atherosclerotic plaques and primarily expressed in the T cell nucleus, suggesting the importance of canonical EZH2 function in atherosclerosis. Ezh2 cd4 -KO, but not Ezh2 cd8 -KO, mice showed reduced atherosclerosis with fewer advanced plaques, which contained less collagen and macrophages, indicating that Ezh2 in CD4 + T cells drives atherosclerosis. In-depth analysis of CD4 + T cells of Ezh2 cd4 -KO mice revealed that absence of Ezh2 results in a type 2 immune response with increased Il-4 (interleukin 4) gene and protein expression in the aorta and lymphoid organs. In vitro, Ezh2 -deficient T cells polarized macrophages toward an anti-inflammatory phenotype. Single-cell RNA-sequencing of splenic T cells revealed that Ezh2 deficiency reduced naive, Ccl5 + (C-C motif chemokine ligand 5) and regulatory T cell populations and increased the frequencies of memory T cells and invariant natural killer T (iNKT) cells. Flow cytometric analysis identified a shift toward Th2 (type 2 T helper) effector CD4 + T cells in Ezh2 cd4 -KO mice and confirmed a profound increase in splenic iNKT cells with increased expression of Plzf (promyelocytic leukemia zinc finger), which is the characteristic marker of the iNKT2 subset. Likewise, Zbtb16 ([zinc finger and BTB domain containing 16], the Plzf-encoding gene) transcripts were elevated in the aorta of Ezh2 cd4 -KO mice, suggesting an accumulation of iNKT2 cells in the plaque. H3K27me3–chromatin immunoprecipitation followed by quantitative polymerase chain reaction showed that T cell–Ezh2 regulates the transcription of the Il-4 and Zbtb16 genes. CONCLUSIONS: Our study uncovers the importance of T cell EZH2 in human and mouse atherosclerosis. Inhibition of Ezh2 in CD4 + T cells drives type 2 immune responses, resulting in an accumulation of iNKT2 and Th2 cells, memory T cells and anti-inflammatory macrophages that limit the progression of atherosclerosis.

BACKGROUND: The creation of operative reports is a tedious documentation task that increases administrative burden, which is a potential driver of burnout. Additionally, operative reports are inherently subjective and may contain inaccuracies and incomplete information. Recent advances in artificial intelligence (AI) technology have enabled computer vision systems to accurately detect operative steps on surgical video. We aim to develop a platform for the automated creation of video-based AI surgical operative reports in robotic-assisted radical prostatectomy. STUDY DESIGN: An AI computer vision algorithm was used to automatically detect surgical steps. Each step detected on video was mapped to prespecified text, which was then compiled into a narrative AI operative report. The accuracy of the AI operative reports was compared with operative reports written by surgeons, using expert review of raw surgical video footage as the ground truth. RESULTS: A total of 158 cases from a tertiary referral center were included. In surgeon operative reports, 84 cases (53.2%) had at least 1 discrepancy between the operative report and surgical video. Of these, 43 cases (27.2%) had a clinically significant discrepancy based on expert video review. In AI operative reports, 46 cases (29.1%) had at least 1 discrepancy between the operative report and surgical video. Of these, 20 cases (12.7%) had a clinically significant discrepancy. Overall accuracy was higher for AI operative reports compared with surgeon operative reports (87.3% vs 72.8%, p = 0.001). CONCLUSIONS: Operative reports created by AI achieved higher accuracy than those written by surgeons. To our knowledge, this is the first report of automated video-based AI surgical documentation. Future studies are warranted to explore the potential for this novel tool to reduce documentation burden, improve operative report accuracy, promote surgical transparency, and decrease subjectivity in surgical documentation.

ABSTRACT Rituximab, gemcitabine, and oxaliplatin (R‐GemOx) is a commonly used chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL), but there are limited real‐world data. In a multicenter retrospective study from a cohort of eight US academic centers (LEO CReWE), we evaluated 183 patients with R/R DLBCL and high‐grade B cell lymphoma treated with R‐GemOx, including subgroups treated without intent for consolidation with autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T cell therapy ( n = 100), those utilizing R‐GemOx as a bridge to ASCT or CAR T ( n = 83), and those aged 70 and older ( n = 71). Overall response rates (ORRs) for all patients treated with R‐GemOx were 45% with a complete response (CR) rate of 29%. The median event‐free survival (EFS) was 2.3 months, and the median overall survival (OS) was 13.5 months. Patients receiving R‐GemOx without intent for ASCT or CAR T had ORR and CR rates of 33% and 18%, respectively, with median EFS and OS of 2.0 and 9.5 months, respectively. Patients receiving R‐GemOx as a bridge to ASCT or CAR T had ORR and CR rates of 57% and 36%, respectively, with median EFS and OS of 3.5 and 17.4 months, respectively. Patients receiving R‐GemOx aged 70 and older had ORR and CR rates of 53% and 33%, respectively, with median EFS and OS of 2.2 and 13.9 months, respectively. These data provide a benchmark for R‐GemOx in the rapidly evolving landscape of R/R DLBCL therapies.

AbstractObjectiveThe primary goal of this study was to measure health‐state utility values (HUVs) in patients with facial paralysis before and after treatment. A secondary objective was to compare these values with those of other chronic diseases and currently available treatments.Study DesignA retrospective chart review.SettingA tertiary medical center.MethodsAdults with flaccid and non‐flaccid facial paralysis were included. Baseline demographics, medical comorbidities, facial paralysis history, treatment details, and disease‐specific quality‐of‐life scores were collected. Utility values were derived using the Short‐Form 6D health index at baseline and after treatment.ResultsThe mean baseline Short‐Form 6D utility value for patients with facial paralysis (n = 134) was 0.73 (± 0.14) (95% confidence interval [CI]: 0.71‐0.75). Baseline utility values significantly correlated with disease‐specific quality of life as measured by the Facial Clinimetric Evaluation Scale (r = 0.400; P < .001), but not with Sunnybrook Facial Grading Scale or Synkinesis Assessment Questionnaire scores. Post‐treatment utility values showed a mean improvement of 0.03 (95% CI: −0.01 to 0.08; P = .14) in the overall cohort. The flaccid group showed a greater average improvement compared to the non‐flaccid group (0.05 [± 0.17] vs 0.02 [± 0.17]; P = .62).ConclusionPatients with flaccid and non‐flaccid facial paralysis reported HUVs that were significantly lower than the US population norm. Treatment improved utility values in both groups. These findings provide initial data for future cost‐effectiveness analyses of surgical and non‐surgical treatment options for facial paralysis.

AbstractThis study compares delays in otolaryngologic care between patients in Mekelle, Ethiopia and Harare, Zimbabwe using the Three Delays model. Patient surveys conducted among 46 patients in Zimbabwe during October 2022 and 105 patients in Ethiopia during June 2023 revealed a significantly higher prevalence of delays in seeking and reaching care in Ethiopia. This was in the aftermath of the Tigray War, which damaged the region's health care infrastructure and diminished the trust of patients. In Zimbabwe, there was poor awareness among patients and nonotolaryngologist providers of otolaryngology disease and care capacity leading to delays in seeking and reaching care. Patients in both countries faced delays in receiving appropriate care due to resource limitations, with Ethiopia's constraints worsened by the recent war and Zimbabwe's by consistent health care underfunding. The longest delays were observed in head and neck oncology care. These findings provide a foundation for understanding otolaryngologic care delays in these low‐ and middle‐income countries.