Seonam University

Introduction & Objective: Previous work showed that genetic polymorphisms of the nuclear gene Klotho (KL), were associated with longevity and altered risk of various aging-related diseases. However, genetic variations of KL specifically associated with diabetes have not been published. In this study, we assessed the association of KL SNPs with diabetes, and performed a demonstration of identifying mitochondrial genetic variants that interact with KL SNPs to modulate diabetes risk. Methods: We used the data from 10,121 participants of the Health and Retirement Study (70.3% non-Hispanic White, 60% women), a prospective observational study including adults aged 50 year and older from the United States. First, we performed single gene-wide association scan to identify KL SNPs associated with diabetes. Next, we performed a nuclear mitochondrial interaction test (NuMIT) in which we use an identified KL SNP from the gene-wide scan to evaluate potential interactions with 85 mitochondrial SNPs in relation to diabetes. All analyses were run separately within ethnic group and by sex. Results: The prevalence of diabetes in non-Hispanic Whites was 23.8%. A KL SNP rs9563121 was associated with lower prevalence of diabetes in non-Hispanic white women (OR 0.86; P = 0.020), but this association was not significant in men or in other ethnic groups. A NuMIT analysis identified eight mitochondrial SNPs which showed significant interactions with rs9563121 in relation to diabetes. Most strikingly, MitoG15929A diminished the potential beneficial effect of KL rs9563121 on diabetes in women. In addition, in men with the MitoG15929A variant, KL rs9563121 was associated with higher prevalence of diabetes. Conclusion: The NuMIT approach revealed significant interactions between mitochondrial and nuclear DNA variants of KL. Furthermore, MitoG15929A may be a critical risk modifier for diabetes in a sex-dependent manner. Disclosure T. Oh: None. T.E. Arpawong: None. H. Kumagai: None. K. Yen: None. E. Crimmins: None. P. Cohen: None.

To investigate the outcomes of children, adolescents, and young adults (AYAs) with malignant ovarian germ cell tumors (MOGCTs), we analyzed the data of 61 patients aged ≤39 years diagnosed with MOGCT between 2006 and 2022. Among 59 patients who received chemotherapy after initial diagnosis, 57 received BEP (standard dose of bleomycin with 30 units per week, n = 13) or bEP (reduced dose of bleomycin with 15 units/m2 on day 1, n = 44). The 5-year overall survival (OS) and event-free survival (EFS) rates were 98.3% and 84.9%, respectively. Reduced bleomycin dose did not adversely affect survival. Normalization of tumor markers within 3 months after surgery was significantly associated with better EFS (p < 0.01). Of the 59 surviving patients, 8 experienced surgery-related menopause, while 49 demonstrated menstrual recovery. After completion of chemotherapy, there was no significant difference in pulmonary function regarding bleomycin dose, and no overt nephrotoxicity. Approximately 60% and 25% of survivors experienced peripheral neuropathy at the end of chemotherapy and after 1 year, respectively (p < 0.01). Children and AYAs with MOGCT have favorable survival rates with minimal long-term toxicity, which are not influenced by a reduced bleomycin dose. Rapid normalization of tumor markers is associated with improved outcomes.

Aims This study aimed to describe global, regional, and national trends in the incidence and prevalence of EoE from 1976 to 2021, and analyze their associations with geographic, demographic, and social factors through a systematic review.

AimsWe compared diagnostic performance, costs, and association with major adverse cardiovascular events (MACE) of clinical coronary computed tomography angiography (CCTA) interpretation versus semiautomated approach that use artificial intelligence and machine learning for atherosclerosis imaging‐quantitative computed tomography (AI‐QCT) for patients being referred for nonemergent invasive coronary angiography (ICA).MethodsCCTA data from individuals enrolled into the randomized controlled Computed Tomographic Angiography for Selective Cardiac Catheterization trial for an American College of Cardiology (ACC)/American Heart Association (AHA) guideline indication for ICA were analyzed. Site interpretation of CCTAs were compared to those analyzed by a cloud‐based software (Cleerly, Inc.) that performs AI‐QCT for stenosis determination, coronary vascular measurements and quantification and characterization of atherosclerotic plaque. CCTA interpretation and AI‐QCT guided findings were related to MACE at 1‐year follow‐up.ResultsSeven hundred forty‐seven stable patients (60 ± 12.2 years, 49% women) were included. Using AI‐QCT, 9% of patients had no CAD compared with 34% for clinical CCTA interpretation. Application of AI‐QCT to identify obstructive coronary stenosis at the ≥50% and ≥70% threshold would have reduced ICA by 87% and 95%, respectively. Clinical outcomes for patients without AI‐QCT‐identified obstructive stenosis was excellent; for 78% of patients with maximum stenosis < 50%, no cardiovascular death or acute myocardial infarction occurred. When applying an AI‐QCT referral management approach to avoid ICA in patients with <50% or <70% stenosis, overall costs were reduced by 26% and 34%, respectively.ConclusionsIn stable patients referred for ACC/AHA guideline‐indicated nonemergent ICA, application of artificial intelligence and machine learning for AI‐QCT can significantly reduce ICA rates and costs with no change in 1‐year MACE.

Excellent long-term results have been reported with conventional length cementless femoral stems in total hip arthroplasty; however, proximal stress shielding and thigh pain are still a concern. Metaphyseal engaging bone conserving short stems provide theoretical benefits compared with conventional length cementless stems, including avoiding proximal-distal mismatch, decreasing proximal stress shielding, and limiting perioperative fractures. The purpose of the ultra-short bone conserving cementless stem was to reproduce natural load transfer with an ultra-short stem obtaining optimal stability using the morphology of the proximal femur. Loss of stability of the stem and failure of osseous ingrowth is a potential concern with the use of ultra-short proximal loading cementless femoral stems. Ultra-short, metaphyseal-fitting anatomic or non-anatomic cementless femoral stems provided stable fixation without relying on diaphyseal fixation in young and elderly patients, suggesting that metaphyseal-fitting alone is sufficient in young and elderly patients who have good bone quality.

There are inconsistencies between some of the data in the Methods and Results sections of the Abstract and the Methods and Results sections in the main text. Additionally, there are some sentences in the Discussion section that are unclear. We will clarify those inconsistencies and provide more precise sentences below. The data in the last sentence of the Methods section in the Abstract is incorrect and does not match the data in the Methods section of the main text. The sentence should read: “To minimize the chance of type-2 error and increase the power of our study, we assumed the difference in the Knee Society score to be 25 points to match the MCID of the Knee Society score with a SD of 5; to be able to detect a difference of this size, we calculated that a total of 628 patients would be needed in each group in order to achieve 80% power at the α = 0.05 level.” Next, there are multiple errors in the Results section of the Abstract. The third-to-last sentence in the Results section of the Abstract is incorrect and does not match the data in the Results section of the main text. The sentence should read: “In all, 0.6% of knees (four) in each group had a superficial infection, and they were treated with intravenous antibiotics for 2 weeks.” Similarly, the data in the last sentence in the Results section of the Abstract is incorrect and does not match the data in the Results section of the main text. The sentence should read: “In the conventional TKA group, 0.6% of knees (four) had motion limitation (< 60°).” Moving to the main text, in the Patients and Methods section, Fig. 1 has an error. The total number of knees in the CONSORT flow diagram should be: “1965 knees”. The third sentence under Statistical Analysis in the Patients and Methods section is incorrect. The sentence should read: “We performed an a priori sample size calculation using what we believed to be a clinically relevant difference in the Knee Society score of 25 points (which was the MCID of that score as reported by Lee et al. [21]), with an SD of 5 points. For this calculation, we set the power to 80% (β = 0.20) and α to 0.05. This calculation showed that a total of 628 patients would be needed in each group.” In the Discussion section, the last sentence of the first paragraph is unclear. The sentence should read: “Although we found a small reduction in the proportion of knees aligned 0° to 3° away from neutral when robotic assistance was used, we found no between-group difference in outliers more severe than 3°, and no reduction in aseptic loosening in the robotic-assisted group.” Finally, the second sentence of the last paragraph in the Discussion section is not as precise as it should be. The sentence should read: “Although we observed a small improvement in the proportion of knees with a 0° to 3° deviation from a neutral mechanical axis in the robotic TKA group, there was no such difference if the definition of an outlier was taken to be > 3° as is commonly done.” The authors of the study apologize for these errors.