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Abstract Background Conflicting evidence exists regarding the functional and prognostic significance of hypertensive response to exercise (HRE), commonly defined as peak systolic blood pressure (SBP) >210 mmHg in males and >190 mmHg in females. No study yet has explored the impact of sex-specific, workload-indexed HRE in patients at different stages of the heart failure (HF) spectrum, as defined by the American College of Cardiology/American Heart Association HF staging system. Purpose We evaluated the SBP/Workload slope during exercise across the HF spectrum and investigated the hemodynamic, functional and prognostic correlates of HRE. Methods Fifty-eight healthy controls, 201 subjects at risk of developing HF (HF Stages A-B), and 369 patients with a definite diagnosis of HF (Stage C) were enrolled; among the latter, 143 had preserved (HFpEF) and 226 reduced (HFrEF) left ventricular ejection fraction. All patients underwent a combined cardiopulmonary-exercise stress echocardiography test. For each patient, we recorded at least two BP measurements during exercise: the first within the first minute of exercise and the last at peak effort. The SBP/Workload slope was calculated as the difference in SBP over the corresponding increment in watts (W): (SBPpeak – SBPfirst)/(Wpeak – Wfirst). In each ACC/AHA HF Stage, we divided patients according to SBP/Workload slope tertiles; HRE was defined as the highest sex-specific SBP/Workload slope tertile. A composite of all-cause mortality and hospitalization for cardiovascular reasons was chosen as the primary outcome. Results The median SBP/Workload slope was 0.53 (interquartile range 0.36-0.72) mmHg/W and was steeper in women than in men in all subgroups (p<0.0001). After adjusting for age and sex, SBP/Workload slope was significantly higher in Stages A-B (0.61, 0.47-0.75 mmHg/W) and HFpEF (0.63, 0.42-0.86 mmHg/W) compared to controls (0.43, 0.35-0.57 mmHg/W) and HFrEF (0.47, 0.30-0.63 mmHg/W, Figure 1). In all subgroups, patients with HRE showed significantly lower peak oxygen consumption and peripheral oxygen extraction (Table). After a median follow-up of 16 months, HRE was an independent predictor of adverse outcomes (Hazard Ratio 2.05, 95% confidence interval 1.81-5.18), while rest and peak absolute SBP values did not. Kaplan-Meier analysis confirmed a worse survival probability for patients with HRE in Stages A-B and HFpEF but not in HFrEF. After adjusting for confounding factors, the patients with the highest SBP/Workload slope had a 47% higher risk of the primary outcome than subjects in the lowest tertile (Figure 2). Conclusions Across the HF spectrum, patients with HRE, as evaluated by the SBP/Workload slope, present with peculiar pathophysiological features and impaired functional capacity. This is especially true for those in Stages A-B and patients with HFpEF. In these subgroups, HRE may portend an increased risk of adverse cardiovascular outcomes.SBP/workload slopesKaplan-Meier curves and Hazard Ratios

Introduction: Medical trainees experience a high degree of stress that predisposes them to burnout. This pilot study tested a scalable approach to deliver a validated resilience program (Stress Management and Resiliency Training (SMART)) among Hematology/Oncology fellows at an academic medical center. Methods: This was a mixed-methods, prospective, single-arm clinical trial involving Hematology/Oncology fellows at Mayo Clinic in Rochester, MN, USA. Four one-hour training sessions were conducted virtually with 26 fellows. Stress, burnout, and emotional resilience were measured at baseline, three months, and six months post-intervention using the Perceived Stress Scale (PSS-10), Maslach Burnout Inventory (MBI-HSS), and Connor-Davidson Resilience Scale (CD-RISC2). Changes in mean scores were assessed using paired t-tests. Feasibility and acceptability data were obtained during a virtual focus group. Results: Statistically significant improvements in mean stress (p = 0.004) and professional achievement (p < 0.001) were seen at three months post-intervention. At six months post-intervention, mean stress (p < 0.001) and professional achievement (p = 0.032) continued to improve, while improvements in emotional exhaustion (p = 0.001) and depersonalization (p < 0.001) also became significant. Focus group participants found the program beneficial and reported improved stress and work performance as a result of participation. Conclusion: Virtual implementation of the SMART program is feasible and resulted in improvements in stress and burnout. Focus group participants found the training beneficial, reporting lower stress and improved work performance.

Background: Secondary Furlow (Furlow) and buccal myomucosal flaps (BMMF) treat velopharyngeal insufficiency by lengthening the palate and retropositioning the levator veli palatini muscles. The criteria for choosing one operation over the other remain unclear. Methods: A single-center retrospective cohort study was conducted. Thirty-two patients with nonsyndromic, repaired cleft palate were included. All patients underwent a Furlow or BMMF. Outcome measures included (1) resolution of hypernasality 12 months postoperatively, (2) degree of improvement of hypernasality severity; and (3) change in velar length, as measured on magnetic resonance imaging scans obtained preoperatively and 12 months postoperatively. All measures were performed by raters blinded to participants’ medical and surgical history. Results: Hypernasality was corrected to normal in 80% of the Furlow group and in 56% of the BMMF group. Patients receiving BMMF had more severe hypernasality during preoperative speech evaluation. Both groups had a median decrease of two scalar rating points for severity of hypernasality (P = 0.58). On postoperative magnetic resonance imaging, patients who underwent Furlow had a median increased velar length of 6.9 mm. Patients who received BMMF had a median increased velar length of 7.5 mm. There was no statistically significant difference between groups regarding increase in velar length (P = 0.95). Conclusions: Furlow and BMMF procedures increase velar length with favorable speech outcomes. The same degree of improvement for hypernasality was observed across groups, likely explained by the similar increase in velar length achieved. Anatomic changes in palate length and levator veli palatini retropositioning persist 1 year after surgery.

AbstractIntroductionStudies have reported a higher risk of suboptimal neurodevelopment among children who are HIV‐exposed uninfected (HEU) compared to children HIV‐unexposed uninfected (HUU). Actual academic performance among school‐aged children by HIV exposure status has not been studied.MethodsAcademic performance in Mathematics, Science, English, Setswana and overall among children enrolled in the Botswana‐based FLOURISH study who were attending public primary school and ranging in age from 7.1 to 14.6 years were compared by HIV exposure status using a Cochran‐Mantel‐Haenszel test. Lower academic performance was defined as a grade of “C” or lower (≤60%). Unadjusted and adjusted logistic regression models were fit to assess for an association between HIV exposure and lower academic performance.ResultsBetween April 2021 and December 2022, 398 children attending public primary school enrolled in the FLOURSH study, 307 (77%) were HEU. Median age was 9.4 years (IQR 8.9–10.2). Only 17.9% of children HEU were breastfeed versus 100% of children HUU. Among children HEU, 80.3% had foetal exposure to three‐drug antiretroviral treatment, 18.7% to zidovudine only and 1.0% had no antiretroviral exposure. Caregivers of children HEU were older compared to caregivers of children HUU (median 42 vs. 36 years) and more likely to have no or primary education only (15.0% vs. 1.1%). In unadjusted analyses, children HEU were more likely to have lower overall academic performance compared to their children HUU (odds ratio [OR]: 1.96 [95% confidence interval (CI): 1.16, 3.30]), and lower performance in Mathematics, Science and English. The association was attenuated after adjustment for maternal education, caregiver income, breastfeeding, low birth weight and child sex (aOR: 1.86 [95% CI: 0.78, 4.43]).ConclusionsIn this Botswana‐based cohort, primary school academic performance was lower among children HEU compared to children HUU. Biological and socio‐demographic factors, including child sex, appear to contribute to this difference. Further research is needed to identify modifiable contributors, develop screening tools to identify the risk of poor academic performance and design interventions to mitigate risk.

Abstract The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

Abstract Disclosure: A. Blinder: None. K. Nanba: None. D. Sapiro: None. J. Baker: None. C. Liu: None. I. Bancos: None. M. Lyden: None. W. Young: None. H. Wachtel: None. D. Cohen: None. J. Luther: None. T.A. Williams: None. M. Reincke: None. T. Else: None. T.J. Giordano: None. A. Udager: None. W.E. Rainey: None. Background: There is accumulating evidence that changes in adrenal histology and regulation of renin-angiotensin-aldosterone system occur with age. Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Recent clinical studies suggest unique characteristics of PA in elderly patients, including high prevalence of comorbidities and low clinical cure rate after adrenalectomy. However, histologic and genetic features of PA in late adulthood have not been well elucidated. Objective: To determine histologic and genetic characteristics of PA in late adulthood. Methods: Seventy-six patients who underwent unilateral adrenalectomy at the age of 60 or older were included in this study. Formalin-fixed, paraffin-embedded (FFPE) sections of resected adrenal tissue were used for the analysis. Aldosterone synthase (CYP11B2) immunohistochemistry (IHC) was performed to identify the source of inappropriate aldosterone production. Histologic classification was made according to the HISTALDO (histopathology of primary aldosteronism) consensus. CYP11B2 IHC-guided DNA capture followed by sequencing analysis using direct Sanger sequencing or ion torrent based next-generation sequencing (NGS) was performed. Results: Median age of the studied patients was 70 (interquartile range: 64-73). Based on the CYP11B2 IHC, histologic diagnosis was made as follows; aldosterone-producing adenoma (APA, n=23), aldosterone-producing nodule (APN, n=41), and non-functioning adrenocortical adenoma (NFA, n=6). The remaining six cases had multiple CYP11B2-expressing neoplastic lesions, including APA with APN (n=2) and multiple APNs (n=4). Co-existence of NFA with APA or APN(s) was also observed in 13. Sequencing analysis revealed that somatic KCNJ5 mutation was the most frequent genetic alteration in APA (7/23, 30%), whereas somatic CACNA1D mutation was the most common genetic cause of APN (20/39 with successful sequencing, 51%). Of the 18 sequenced NFA DNA samples, two had somatic mutations in CTNNB1 (n=1) and GNAS (n=1). Conclusion: APN is the major histologic feature of PA in late adulthood. Co-existence of NFA also appears to be a frequent observation in this age population. Somatic CACNA1D and KCNJ5 mutations are common in APN and APA, respectively. Presentation: Friday, June 16, 2023

Background: There are different types of grafts for rhinoplasty, each with certain advantages and disadvantages. Fresh frozen cadaveric costal allograft (CCA) provides an alternative to rhinoplasties. The aim of this study was to compare the outcomes of fresh frozen CCA and traditional autologous costal cartilage in cosmetic and reconstructive rhinoplasty procedures. Methods: This is a prospective, single-center, nonrandomized, open-label clinical trial. Objective assessment to evaluate warping, resorption, and displacement of the cartilage was achieved by measuring the differences of standardized values (deviation angle, nasofrontal angle, total facial convexity, nasofacial angle, and nasolabial angle) obtained at 6-months and 12-months postoperative follow-up on standard two-dimensional photographs (Δ = ∣measurement6 − measurement12∣). Subjective assessment was measured by the FACE-Q assessment. Results: Fifty eligible patients between March 2017 and October 2020 were included. The average age was 43.9 ± 16.6 years and the mean follow-up period was 14.8 months. In the control group, the changes (Δ) in the deviation angle and nasolabial angle were greater than in the CCA group (P < 0.05). In the CCA group, the mean score of satisfaction with nose improved at 6 months and 1 year postoperatively (P < 0.05). The mean score of satisfaction with nostrils and overall facial appearance also increased in the CCA group at 6 months postoperatively (P < 0.05). Six patients from the CCA group and 10 patients from the control group experienced postoperative complications. Conclusions: Fresh frozen CCA is a safe and reliable source of rhinoplasty grafts. It is aseptic, readily available, and free of donor site complications.

INTRODUCTION: The coronavirus disease 19 (COVID-19) pandemic disrupted endoscopy practices, creating unprecedented decreases in cancer screening and surveillance services. We aimed to assess the impact of the pandemic on the proportion of patients diagnosed with Barrett's esophagus (BE) and BE-related dysplasia and adherence to established quality indicators. METHODS: Data from all esophagogastroduodenoscopies in the GI Quality Improvement Consortium, a national repository of matched endoscopy and pathology data, were analyzed from January 2018 to December 2022. Four cohorts were created based on procedure date and COVID-19 data: pre-pandemic (January 2018 to February 2020), pandemic-phase I (March 2020 to July 2020), pandemic-phase II (August 2020 to May 2021), and pandemic-phase III (June 2021 to December 2022). Observed and expected number of BE and BE-related dysplasia cases per month and adherence to the Seattle biopsy protocol and recommended surveillance intervals for nondysplastic BE (NDBE) were evaluated. RESULTS: Among 2,446,857 esophagogastroduodenoscopies performed during the study period, 104,124 (4.3%) had pathology-confirmed BE. The histologic distribution was 87.4% NDBE, 1.8% low-grade dysplasia, 2.4% indefinite for dysplasia, and 1.4% high-grade dysplasia. The number of monthly BE (−47.9% pandemic-phase I, −21.5% pandemic-phase II, and −19.0% pandemic-phase III) and BE-related dysplasia (high-grade dysplasia: 41.2%, −27.7%, and −19.0%; low-grade dysplasia: 49.1%, −35.3%, and −26.5%; any dysplasia: 46.7%, −32.3%, and −27.9%) diagnoses were significantly reduced during the pandemic phases compared with pre-pandemic data. Adherence rates to the Seattle protocol and recommended surveillance intervals for NDBE did not decline during the pandemic. DISCUSSION: There was a significant decline in the number of BE and BE-related dysplasia diagnoses during the COVID-19 pandemic, with an approximately 50% reduction in the number of cases of dysplasia diagnosed in the early pandemic. The absence of a compensatory increase in diagnoses in the pandemic-phase II and III periods may result in deleterious downstream effects on esophageal adenocarcinoma morbidity and mortality.

Abstract Across scar studies, there is a lack of dark‐skinned individuals, who have a predisposition for keloid formation, altered pigmentation and poorer quality of life (QOL). There is a need for patients of colour to be included in scar scale development and validation. In this study, we evaluate the racial diversity of patients included in the validation of scar assessment scales. A systematic review was conducted for articles reporting on the validation of a scar assessment tool. Racial, ethnic and Fitzpatrick skin type (FST) data were extracted. Fifteen scar scale validation studies were included. Nine of the studies did not mention FST, race or ethnicity of the patients. Two of the studies that reported FST or race information only included White patients or included no FST V/VI patients: mapping assessment of scars (MAPS) and University of North Carolina ‘4P’. Only four studies included non‐White patients or dark‐skinned patients in the validation of their scar scale: the modified Vancouver Scar Scale (VSS), modified Patient and Observer Scar Assessment Scale (POSAS), acne QOL and SCAR‐Q scales. The patients included in the modified VSS validation were 7% and 13% FST V/VI, 14% African in the modified POSAS and 4.5% FST V/VI in the SCAR‐Q. We highlight the severe lack of diversity in scar scale validation, with only 4 out of 15 studies including dark‐skinned patients. Given the susceptibility of darker‐skinned individuals to have poorer scarring outcomes, it is critical to include patients of colour in the very assessment tools that determine their scar prognosis. Inclusion of patients of colour in scar scale development will improve scar assessment and clinical decision‐making.