Patient Information Research Articles

Risk Factors for Adverse Events of Nanoliposomal Irinotecan Plus 5-Fluorouracil and L-leucovorin.

The regimen with nanoliposomal irinotecan plus 5-fluorouracil and L-leucovorin (nal-IRI/FL) is used for metastatic pancreatic cancer. A clinical study has indicated that the uridine diphosphate-glucuronosyltransferase (UGT) 1A1 polymorphism is associated with neutropenia during nal-IRI/FL treatment; however, no studies have reported risk factors for the occurrence of adverse events in the clinical setting. This study aimed to explore the risk factors for adverse events of nal-IRI/FL. This study included patients with metastatic pancreatic cancer who started nal-IRI/FL treatment. Patient information, including laboratory data before nal-IRI/FL initiation and adverse events during nal-IRI/FL treatment, was retrospectively obtained from medical records. This study consisted of 36 patients, including 16, 16, and 4 with UGT1A1*6 or *28 wild-type (-/-), heterozygous (+/-), and homozygous (+/+), respectively. Patients with UGT1A1*6 or *28 (+/+) exhibited significantly lower nadir counts of white blood cells (p=0.033) and neutrophils (p=0.043). Multiple regression analyses revealed that the decreased white blood cell count was significantly associated with the genotype of UGT1A1*6 or *28 (+/+) (p=0.009), high aspartate aminotransferase (AST) value before the therapy (p=0.019), and pancreatic head cancer (p=0.030). Also, the decreased neutrophil count was significantly related to the genotype of UGT1A1*6 or *28 (+/+) (p=0.017). Patients with UGT1A1*6 or *28 (+/+) should be especially concerned about neutropenia and leukopenia during nal-IRI/FL treatment. Additionally, high AST value and pancreatic head cancer may be risk factors for leukopenia during nal-IRI/FL treatment.

Tele-dentistry in COVID-19 era: A conduit for dental care in uncertain times.

Tele-dentistry encompasses all sorts of digital technologies that involve the exchange of patient's clinical data from a distant site for the provision of dental health care. Tele-dentistry has emerged from the concept of telemedicine, which has been in practice since the 19th century. In recent times, an upsurge in the digital technologies was noted, which has made the possibility of remote access to dental care. The outbreak of COVID- 19 pandemic has restricted the normal routine ways of clinical practice. In these challenging times, tele-dentistry serves as effective platform for providing dental health care. Tele-dentistry has vast applications across various disciplines of dentistry, including preventive dentistry, paediatric dentistry, oral medicine, and oral pathology etc. In these pandemic times, tele-dentistry can be efficiently used for identification of dental emergencies, allowing effective triage and subsequent management. There are different communication platforms available for tele-dentistry. The most common technologies used are web-based video conferencing and smart phone-based applications. As the clinicians are not aware of these digital technologies utilised in tele-dentistry, there are certain challenges associated with its use. In conclusion, tele-dentistry serves as an effective tool in providing health care in challenging times, but it has been underutilised by the dental fraternity. The legislative authorities should establish proper standard protocols to ensure the safety and confidentiality of patient information while using these digital platforms.

Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) – A cluster- randomised controlled trial and mixed methods process evaluation

ObjectiveTo evaluate a nurse-led decision coaching programme aiming to redistribute health professionals’ tasks to support immunotherapy decision-making in people with multiple sclerosis (MS). MethodsCluster-randomised controlled trial with an accompanying mixed methods process evaluation (2014 - 2018). We planned to recruit 300 people with clinically isolated syndrome or relapsing-remitting MS facing immunotherapy decisions in 15 clusters across Germany. Participants in the intervention clusters received up to three decision coaching sessions by a trained nurse and access to an evidence-based online information platform. In the control clusters, participants also had access to the information platform. The primary outcome was informed choice after six months, defined as good risk knowledge and congruent attitude and uptake. ResultsTwelve nurses from eight clusters participated in the decision coaching training. Due to insufficient recruitment, the randomised controlled trial was terminated prematurely with 125 participants (n = 42 intervention clusters, n = 83 control clusters). We found a non-significant difference between groups for informed choice favouring decision coaching: odds ratio 1.64 (95% CI 0.49–5.53). ConclusionsResults indicate that decision coaching might facilitate informed decision-making in MS compared to providing patient information alone. Practice implicationsBarriers have to be overcome to achieve structural change and successful implementation.

Abstract PO3-13-02: Genomic and intrinsic subtype correlates of serum thymidine kinase activity in patients with metastatic breast cancer treated with palbociclib and fulvestrant in the PYTHIA trial

Abstract Background: Serum thymidine kinase activity (sTKa) is a novel non-invasive proliferation biomarker providing prognostic, predictive and monitoring information in patients (pts) with metastatic breast cancer (MBC). We have shown in PYTHIA that high baseline sTKa and lack of sTKa clearance at day 15 of the first cycle of treatment with palbociclib (P)+ fulvestrant (F) are poor prognostic factors in terms of PFS. Here we characterized the molecular features of tumor samples from PYTHIA, and their relation with sTKa. Methods: PYTHIA (IBCSG 53- 14/BIG 14-04; NCT02536742) is a phase II biomarker discovery trial downstream of the AURORA molecular program (BIG 14-01; NCT02102165) which enrolled 122 pts with endocrine-resistant, ER+ and HER2 - MBC receiving P+F. Intrinsic subtypes of metastatic samples from 24 pts were estimated using RNA-Seq. Somatic mutations (mut) from 66 pts were identified using an NGSpanel of 411 cancer-related genes (36 primary and 48 metastatic samples). sTKa was measured using DiviTumÒ TKa (Biovica International) before treatment (D0) and at day 15 (D15) of cycle 1 of P+F. sTKa clearance at D15 was defined as sTKa below the limit of detection (LOD). Intrinsic subtypes and ESR1 mut were assessed in metastatic samples, PIK3CA and TP53 mut were derived from a combined cohort, wheremetastatic samples were used when available and primary samples otherwise. Association of mut and continuous sTKa with PFS was assessed using Cox regression. Results: In metastatic samples, sTKa levels at D0 tended to be higher in luminal B and HER2-enriched subtypes. Lack of sTKa clearance at D15 was observed in 14% of the cases, all classified as luminal B. PIK3CA and TP53 were the most frequently altered genes (38% and 27%, respectively). ESR1 mut were found in 8% of primary and 25% of metastatic samples. Only TP53 was associated with worse PFS. sTKa levels at D0 tended to be higher in pts with TP53 mut vs wild-type (wt) and lower in PIK3CA mut vs wt. Interestingly, lack of sTKa clearance at D15 was more frequent in TP53 mut vs wt and less frequent in PIK3CA mut vs wt. Levels of sTKa were similar in pts with ESR1 mut vs wt both at D0 and at D15 (Table 1). The inclusion of TP53 as a predictor of PFS in bivariate Cox models with sTKa at either D0 (likelihood ratio test p=0.44) or D15 (p=0.21) did not add to the prognostic value provided by sTKa alone. Conclusions: Tumors with high proliferation and poor prognostic features (luminal B, HER2-enriched and TP53 mut) tend to have higher baseline sTKa and less sTKa response on-treatment, in line with sTKa being a circulating dynamic biomarker of tumor cell proliferation. After accounting for sTKa values, TP53mutational status did not contribute to prognosis. This suggests that high sTKa at D0 and lack of sTKa clearance at D15 might be associated with a worse prognosis independently of TP53 status. Further validation in larger datasets is warranted. Table 1: Results summary Citation Format: Svitlana Tyekucheva, Thayane Crestani, Michail Ignatiadis, Patrick Neven, Marco Colleoni, Stéphanie Henry, Konstantinos Papadimitriou, Antonio Bernardo, Elena Seles, Francois Duhoux, Iain Macpherson, Alastair Thomson, David Mark Davies, Mattias Bergqvist, Ilenia Migliaccio, Gabriele Zoppoli, Roswitha Kammler, Heidi De Swert, Barbara Ruepp, Angel Guerrero, Arnau Llinas, Danai Fimereli, Amal Arahmani, David Cameron, Sherene Loi, Martine Piccart, Meredith Regan, Matteo Benelli, Luca Malorni. Genomic and intrinsic subtype correlates of serum thymidine kinase activity in patients with metastatic breast cancer treated with palbociclib and fulvestrant in the PYTHIA trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-13-02.

Abstract PO1-28-10: Tumor Infiltrating Lymphocytes identify patients with stage I TNBC with excellent outcome without chemotherapy

Abstract Introduction International guidelines recommend chemotherapy for most patients with stage I triple negative breast cancer (TNBC), except for special histological subtypes. However, the absolute benefit of systemic treatment for all stage I TNBC patients is not well known and no tools are yet available to select patients with an excellent prognosis for whom the chemotherapy can be safely omitted. High levels of stromal tumor infiltrating lymphocytes (sTILs) are strongly associated with favorable prognosis in TNBC, however, data solely focusing on patients with stage I TNBC who did not receive chemotherapy are lacking. Methods Patients with pT1N0M0 TNBC diagnosed between 2005 and 2015 not treated with (neo)adjuvant chemotherapy were identified from the nationwide Netherlands Cancer Registry (NCR) and linked to the national pathology database (PALGA). Newly sectioned hematoxylin & eosin (H&E) slides were used for central review of the histology and sTILs scoring following the International TIL working group guidelines (www.tilsinbreastcancer.org). Cause of death was provided by Statistics Netherlands (CBS). Primary endpoint was breast-cancer specific survival (BCSS) at 5-, 10- and 15-years for prespecified sTILs cut-offs of 30%, 50% and 75% sTILs. Results sTILs were evaluated for 1,041 patients with stage I TNBC who did not receive (neo)adjuvant chemotherapy. Mean age at diagnosis was 64.4 years [range 26 – 96] and median sTILs value was 5%. Most tumors (91.5%) were invasive ductal adenocarcinomas of no special type (NST) and 6.6% were of histological special types. In 52% of the patients the tumor was >1cm (pT1cN0). Median follow-up was 9.4 years in which 335 patients had died, of whom 107 due to breast cancer. Patients with pT1abN0 tumors had a favorable prognosis compared with patients with a pT1cN0 tumor (HR 0.47, CI 0.32- 0.72). 10-year BCSS in patients with pT1ab was 91.8% and 85.8% in patients with pT1c tumors. In the overall cohort, sTILs-levels of at least 30% were associated with better BCSS compared to sTILs < 30% (HR 0.45, CI 0.26 – 0.77), with 10year-BCSS of 96% and 87%, respectively (table 1). Patients with TNBC of special histological subtype had low sTILs (median 1%). A univariate cox model showed no association between sTILs (continuous) and BCSS in TNBC of special histological subtype (p = 0.56). Next, the prognostic value of sTILs was evaluated separately for pT1ab and pT1c. High sTILs ≥50% were not associated with improved BCSS compared to low sTILs < 50% in patients with pT1ab (HR 1.35, CI 0.65 – 2.82, p = 0.42). In contrast, high sTILs ≥50% showed a strong prognostic importance over low sTILs < 50% (HR 0.27, CI 0.10 – 0.74) in patients with pT1C tumors. We found excellent 10year-BCSS of 95% for patients if sTILs ≥50%, which further increases to 98% with sTILs ≥75% contrasting 10year-BCSS of 83% for patients with sTILs < 30%. Conclusions sTILs-levels provide important prognostic information in patients with stage I TNBC who did not receive (neo)adjuvant chemotherapy. The outcome of patients with pT1c TNBC and sTILs ≥50% was excellent, with 10year-BCSS of 95%, and 98% if sTILs >75%. This large registry study provides a foundation for clinical trials in patients with stage I TNBC with high TILs to prospectively confirm their excellent survival without chemotherapy. Citation Format: Veerle Geurts, Sara Balduzzi, Hugo Horlings, Tessa G Steenbruggen, Sabine Siesling, Sylvia Adams, Gabe Sonke, Roberto Salgado, Marleen Kok. Tumor Infiltrating Lymphocytes identify patients with stage I TNBC with excellent outcome without chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-28-10.

CLINICAL CASE REPORT OF ACUTE HEART INJURY AND ACUTE RHABDOMYOLYSIS DUE TO CYANUA POISONING

Cyanide poisoning is one of the most dangerous poisonings, it can be absorbed into the body through the mouth, inhalation and through the skin. A 32-year-old female patient was admitted to our poison control center because of high fever, severe vomiting, and seizures. Physical examination found that the patient was drowsy, had a high fever of 40 degrees Celsius, pulse of 140 beats/minute, and increased tendon and bone reflexes. Exploiting the patient's information, it was discovered that the patient bought Cyanide to drink with the intention of committing suicide. The patient was quickly treated with gastric lavage and activated charcoal. Echocardiography recorded EF: 35%, reduced movement of the entire myocardium. CK blood test: 4562 U/L. The patient's condition rapidly deteriorated and the patient was made ECMO, IHD and CVVHDF. After 3 days of treatment, the patient's condition did not improve, so the family asked for the patient to go home. This article aims to describe the rapidly progressing and severe damage to the heart and muscles of patients with cyanide poisoning.

Abstract PO2-20-06: Using the Australian Cardio-Oncology Registry to study long-term cancer therapy related cardiac dysfunction in adult oncology patients – The Chris O’Brien Lifehouse experience

Abstract Background Cancer therapy related cardiac dysfunction (CTRCD) is a significant side effect of several chemotherapies, targeted agents, and immunotherapies integral to treatment. Anthracyclines are an example of a commonly used chemotherapy drug class that can cause irreversible early and late onset heart failure. CTRCD often leads to dose reductions and treatment delays or cessation, limiting treatment success and contributing to increased mortality and life-long morbidity in oncology survivors. In Australia, there are currently no multi-centre, longitudinal studies examining CTRCD in adult oncology patients. Trial design The Australian Cardiology-Oncology Registry (ACOR) is a prospective observational non-interventional study involving 14 sites across Australia. Patient information is obtained from hospital medical records and de-identified upon entry into the registry. Patient demographics, medical history, cancer diagnosis, treatment, cardiac evaluations, and the management of demonstrated CTRCD are recorded. Data is collected at baseline (prior to treatment), and then at six-monthly intervals thereafter. Additionally, patients who develop anthracycline-induced cardiotoxicity (ACT) will be asked to participate in the biobanking study, which will involve a one-off 12mL peripheral blood draw that will be processed at an external site for whole genome exome sequencing and the development of pluripotent derived stem cell cardiomyocytes. Eligibility criteria Inclusion Criteria • Adult oncology patients (>18+ years of age) treated with cardiotoxic therapies within the last 5-years Exclusion Criteria • Diagnosis of Trisomy 21 • Patients being treated with palliative intent Specific aims Chris O’Brien Lifehouse aims to use the ACOR to explore the epidemiology, clinical presentation, and management of CTRCD amongst adult oncology patients receiving cardiotoxic therapies. In addition, a biobanking sub-study will attempt to identify gene polymorphisms predisposing individuals to developing ACT. It is hoped that such longitudinal data collection can lead to the introduction of an ACT susceptibility genetic screening test allowing for the inclusion of patient risk stratification prior to anthracycline exposure in routine cancer treatment. Statistical methods Descriptive statistics will be used for variables for quantitative analysis. Kaplan Meier analyses will be used for survival curves, freedom from cardiac failure since enrolment and freedom from arrhythmia since enrolment. An annual report will be produced. Present accrual and target accrual At the time of submission, 224 adult oncology patients have been recruited to the ACOR via Chris O’Brien Lifehouse with the opening of the biobanking sub-study currently in progress. The ACOR anticipates with full registered site capacity to capture 600 patients annually. Citation Format: Jocelyn Finney, Ben Felmingham, Sanjeev Kumar, Alina Mahmood, Lisa Horvath, David Celermajer, Rachel Conyers. Using the Australian Cardio-Oncology Registry to study long-term cancer therapy related cardiac dysfunction in adult oncology patients – The Chris O’Brien Lifehouse experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-06.

Abstract PO5-15-06: NVIGEN X® Comprehensive Liquid Biopsy for Sensitive ctDNA, Circulating Tumor Cells (CTC), and Protein Detection in Breast Cancer: Next-Generation Sequencing, Patient Case Studies, and Clinical Implications

Abstract Background Breast cancer (BC) represents the most prevalent cancer and is a leading cause of cancer related mortality among women worldwide. Despite notable therapeutic advancements, concern for metastatic recurrence remains a significant challenge. Liquid biopsy has emerged as a promising method for monitoring cancer treatment efficacy and disease progression. However, existing technologies predominantly focus on ctDNA, and their clinical utility is hindered by limited detection sensitivity and accuracy. To address these challenges, NVIGEN has developed NVIGEN X® comprehensive liquid biopsy, a novel minimally invasive approach that integrates ctDNA, CTC, and protein biomarkers. This comprehensive method could enable longitudinal monitoring of tumor dynamics, offering valuable insights into cancer biology, treatment responses, and emerging therapeutic targets. Here, we showcase compelling patient case studies, and the potential clinical implications of our technology for an exciting and evolving field in cancer diagnostics. Method Patients with advanced breast cancer were prospectively identified and consented. 10mL blood per timepoint was collected in Streck tubes. ctDNA, CTC and proteins were captured from a single tube of blood using NVIGEN magnetic nanoparticles according to established protocols. Following DNA extraction, ctDNA and CTC samples underwent NVIGEN’s highly sensitive sample workflow, optimized for NGS data accuracy and efficiency, employing hybridization capture with a 180 gene customizable cancer panel. Sequenced data were processed with NVIGEN’s proprietary high-sensitivity data analysis pipeline. Gene alterations identified from both ctDNA and CTC samples were analyzed and integrated to provide a comprehensive view of the tumor profile. Protein biomarkers of interest were detected using NVIGEN’s on-beads ELISA assay. Correlation analysis was performed to examine the relationship between the detected gene alterations, protein biomarkers, ctDNA/CTC data, and clinicopathologic features. Treatment response and identification of potential new treatment targets were evaluated based on the integrated analysis of ctDNA, CTC, protein biomarkers, and patient information. Result We collected 94 blood samples from 85 patients. Here we will present data from initial 36 patient samples. Of these 36 patients, 18 were tested with ctDNA/protein biomarkers (duo assays), and 18 were tested with ctDNA/CTC/protein biomarkers (trio assays). Comparison between duo and trio samples revealed that trio samples provided 2.5 times the number of detected variants compared to duo samples, with the median of variant numbers in duo assays being 52 (range 22-442), and in trio assays being 130 (range 73-703). Over 50% of the detected variants fell within the 0.1-0.5% variant allele frequency (VAF) range (number 2599) with total variant number being 5123. Several patient case studies were conducted using serial blood samples. These case studies revealed notable patterns of important gene alterations, such as ESR1, ERBB2 and PIK3CA, and demonstrated trends in the presence of these genes in ctDNA, CTC, or their coexistence. Protein biomarker information was correlated with ctDNA, CTC NGS data, and patient clinical status. Conclusions The analysis of the presented data from 36 patient samples with advanced breast cancer highlight the clinical relevance and potential significance of utilizing ctDNA, CTC and protein biomarkers in monitoring disease dynamics, treatment response, and guiding personalized treatment approaches. Our results suggest that individual protein biomarker analysis may be crucial in supporting personalized diagnostics and enabling more effective personalized medicine strategies. Citation Format: Aihua Fu, Minh Ton, Kevan Wang, Weiwei Gu, Henry Jin, Nuzhat Shaikh, Sasha Madan, Shreya Perepa, Tianhong Li, Minetta Liu, Heather Parsons, George Sledge, Fauzia Riaz. NVIGEN X® Comprehensive Liquid Biopsy for Sensitive ctDNA, Circulating Tumor Cells (CTC), and Protein Detection in Breast Cancer: Next-Generation Sequencing, Patient Case Studies, and Clinical Implications [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-15-06.

Abstract PO4-02-11: Optimizing Taxane-based Chemotherapy in Breast Cancer: Retrospective study comparing 4 cycles of TC to 6 cycles of TC

Abstract Breast cancer remains one of the most prevalent cancers among women worldwide. First-line chemotherapy options include anthracycline (AC-T) and Taxane (TC) based regimens. While anthracycline-based chemotherapy is most commonly used, the use of anthracycline-sparing regimens is also approved. The US Oncology 9735 trial conducted in the mid 2000s showed that four cycles of docetaxel and cyclophosphamide (TC4) were superior to four cycles of Doxorubicin and cyclophosphamide (AC). The follow-up ABC trials compared six cycles of TC(TC6) to AC-T. This trial showed that while AC-T was superior to TC, the difference was modest. AC-T has remained the standard of care, but TC is an acceptable option. One retrospective analysis involving 143 patients showed TC4 was non-inferior to TC6, and suggested that TC4 had fewer adverse events; however, statistical significance was not reached. The question remains whether six cycles of TC is required, or if four cycles is adequate. Methods: Patient information was retrieved from the EMR of a large private oncology group. The EMR was screened for all breast cancer patients who began treatment with TC between 1/1/2011 and 12/31/2021. Patients were required to have continuous follow-up, documented up to at least 6/30/2022. Only patients receiving TC as the first-line setting were included, while patients with metastatic disease were excluded. Adjusted Kaplan Meier curves for overall survival (OS) and disease-free survival (DFS) were generated. A log-rank test was used to determine the statistical difference between the two curves. OS was defined from the date of the last chemotherapy given to death. DFS is defined from the date of the last chemotherapy given to disease recurrence. The Chi-square analysis test of homogeneity was conducted to evaluate the differences in reported symptoms. Statistical analysis was completed with IBM SPSS version 29. Ethical approval was obtained from The Brooklyn Hospital Center Institutional Review Board. Results: A total of 376 charts were reviewed, out of which 224 met the criteria for inclusion. Of these 191 patients received TC4 and 33 received TC6. TC4 patients were noted to be older than TC6 patients. There were a higher percentage of hormone-positive cancers in the TC4 group while the TC6 group had a larger proportion of triple-negative breast cancers. There was a larger proportion of stage III patients that received TC6 than in TC4. TC6 patients were also noted to receive neo-adjuvant chemotherapy at a substantially higher rate. A greater proportion of patients in the TC4 group received breast-conserving surgery, with radiation than the TC6 group. TC6 had a completion rate of 76 % (Table 1). There was a significant difference in DFS noted between TC4 and TC6 (p = 0.016) with TC6 patients having a higher rate of relapse. No difference was noted in the overall survival. No differences were seen in side effects between TC4 and TC6, however, there was a trend toward high rates of neutropenia, anemia, and neuropathy seen in the TC6 group (Table 2). Conclusions: This real-world retrospective study reviewed patients who received TC in a large community oncology practice. The study reaffirms conclusions seen in previous retrospective studies conducted in the academic setting that there is no difference in overall survival when using six cycles of TC compared to four cycles of TC. Slight detriment was seen in the DFS setting when using TC6 however the small sample size along with the larger proportion of patients with stage III disease make it challenging to interpret this finding. There was a trend towards higher toxicities with TC6 that did not reach significance. Until a prospective randomized study comparing four vs six cycles of TC is conducted no definitive conclusions can be drawn, however, this study contributes to the current body of evidence that four cycles of TC is adequate and could potentially improve the quality of life of patients with early breast cancer. Table. Patient characteristics Patient characteristics including age, hormone status, stage, type of surgery, radiation, and treatment setting. Table. Adverse effects Adverse effect information obtained from physician documentation, and CBC reports documented at time of treatment with TC. Citation Format: Amith Ahluwalia, Michelle Koifman, Jaspreet Nannar, Bhavya Vachhani, Kanwal Ashraf, Maxim Shulimovich. Optimizing Taxane-based Chemotherapy in Breast Cancer: Retrospective study comparing 4 cycles of TC to 6 cycles of TC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-11.

Expression and Prognosis of Differential Gene Troponin T1 Between Right and Left Colon Cancers.

Colorectal cancer (CRC) is one of the most common digestive tract tumors in humans. At present, many scholars believe that the primary site of the tumor has a direct and profound impact on its curative effect. There are significant differences in the expression of many genes, tumor microenvironment, and prognosis between the left and right colon. However, there is a lack of detailed studies on whether the differentially expressed genes in the left and right colon significantly impact the prognosis of patients with CRC. Troponin T1 (TNNT1) is an important gene that affects the prognosis difference between left and right colon cancer screening from "The Cancer Genome Atlas" database. By analyzing the differential gene expression data and clinical data of the left and right hemicolons in the database, the online prognostic database was used to screen the key molecules that significantly affect the tumor immune microenvironment and patient prognosis and to predict their functions and pathways. Quantitative reverse transcription-polymerase chain reaction was used to verify the expression difference of TNNT1 in CRC cell lines SW480 and HCT116, and normal human colorectal epithelial cell line FHC. The relationship between TNNT1 expression in 88 pairs of CRC samples and clinical information and pathologic parameters of patients with CRC was analyzed to judge the impact of TNNT1 expression on patient survival. Database analysis showed that TNNT1 was significantly overexpressed in CRC, and TNNT1 was one of the main differential genes between left colon cancer (LCC) and right colon cancer (RCC). The expression of TNNT1 was significantly increased in RCC, which could lead to poor prognosis of patients. Quantitative reverse transcription-polymerase chain reaction indicated that the expression of TNNT1 was significantly up-regulated in CRC cell lines SW480 and HCT116. Eighty-eight immunohistochemistry (IHC) of CRC tissues and adjacent tissues suggested that the expression of TNNT1 in CRC was significantly higher than that in normal adjacent tissues. By analyzing the clinical information and pathologic indicators matched with these clinical samples, we found that high TNNT1 expression in the primary tumor location (right colon) and high N stage (N2, N3) were unfavorable factors affecting the prognosis of patients with CRC. Multivariate Cox regression analysis suggested that high expression of TNNT1 may be an independent risk factor for the prognosis of patients with CRC. As one of the main differential genes between LCC and RCC, TNNT1 is representative to some extent. Its high expression may be one of the reasons why the prognosis of patients with RCC is worse than that of patients with LCC.

Abstract PO3-15-06: Identification of a Novel Five Ferroptosis-Related Gene Signature as a Promising Prognostic Model for Breast Cancer

Abstract Background: Breast cancer (BCa) is a major challenge for women's health worldwide. Ferroptosis is closely related to tumorigenesis and cancer progression. However, the prognostic value of ferroptosis-related genes in BCa remains unclear, and more accurate prognostic models are urgently needed. Methods: Gene expression profiles and clinical information of BCa patients were collected from public databases. LASSO and multivariate Cox regression analysis were utilized to construct the prognostic gene signature. Kaplan-Meier plotter, Receiver Operating Characteristic (ROC) curves, and nomogram were used to validate the prognostic value of the gene signature. Gene set enrichment analysis was performed to explore the molecular functions and signaling pathways. Results: Differentially expressed ferroptosis-related genes between BCa samples and normal tissues were obtained. A novel five-gene signature including BCL2, SLC40A1, TFF1, APOOL, and PRAME was established for prognosis prediction. Patients stratified into high-risk or low-risk group displayed significantly different survival. Kaplan-Meier and ROC curves showed a good performance for survival prediction in different cohorts. Biological function analysis revealed that the five-gene signature was associated with cancer progression, immune infiltration, immune response, and drug resistance. Nomogram including the five-gene signature was established. Conclusions: A novel five ferroptosis-related gene signature and nomogram could be used for prognostic prediction in BCa. Key words: breast cancer, ferroptosis, gene signature, overall survival, prognosis Citation Format: Tian-cheng Cheng, Jia-hao Wu, Bei Zhu, Lin Zheng, Wei-xian Chen. Identification of a Novel Five Ferroptosis-Related Gene Signature as a Promising Prognostic Model for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-15-06.

Current utility of first-line FT4 and TSH in screening for central hypothyroidism.

Thyroid testing strategies vary across laboratories. First-line combined thyroid stimulating hormone (TSH) and freeT4 (FT4) have historically been preferred by many laboratories as this detects individuals with undiagnosed central hypothyroidism who can be missed with a first-line TSH-only strategy. However, an up-to-date evaluation of the utility of this approach is lacking. We investigated the clinical utility of first-line TSH and FT4 in the detection of central hypothyroidism in current day practice. The All-Wales laboratory information system was queried to identify thyroid function tests in patients aged ≥16 years with decreased FT4 and inappropriate TSH (low-FT4). The 1-year incidence of low-FT4 was determined using mid-year population data. Clinical information of patients with low-FT4 was reviewed to determine causes of low-FT4 and the incidence of central hypothyroidism. The incidence of low-FT4 varied according to FT4 assay method (range: 98-301 cases/100,000 population/year). Fifteen new cases of central hypothyroidism were detected in two health boards, equivalent to 2 cases/100,000 population/year. Positive predictive value of low-FT4 for central hypothyroidism was 2%-4%. In a cross-section of primary care patients, low-FT4 was detected in 0.5% of all thyroid tests with assay-related differences in detection rates. Although low-FT4 is a common laboratory finding, the incidence of central hypothyroidism remains rare. With the currently increased rates of thyroid testing and increased use of medications that decrease FT4, low-FT4 has a much lower predictive value for central hypothyroidism than previously reported. Thyroid screening strategies will need to balance the yield from first line TSH and FT4 testing with the cost of investigating individuals with non-pathological laboratory abnormalities.

Abstract PO5-06-11: RPL27A promotes the growth and metastasis of triple negative breast cancer by regulating Ribosome biogenesis

Abstract Background: Ribosome is a complex structure in cells for protein synthesis. It has been considered always have a constant composition. Recent studies have revealed that the Ribosome composition of tumor cells is heterogeneous. The Ribosome protein composition, post-translational modification, rRNA modification, and rRNA variants can lead to the existence of specialized "onco-ribosomes" in tumor cells, which regulates the rate of translation and protein synthesis, and can affect the occurrence and development of tumors significantly. The abnormal expression of multiple Ribosome proteins in triple-negative breast cancer may be the target of its diagnosis and treatment, also, an independent factor in prognosis evaluation. Methods: To learn the expression levels of Ribosome biogenesis related genes in normal breast cells and abnormal breast cells with different pathological subtypes of breast cancer, the following studies have been done: 1. Bioinformatics analysis on TCGA database and single-cell sequencing data; 2. IHC detection on TNBC tissue and adjacent tissues; 3. Determine the expression level of RPL27A in TNBC cells, and analyze the correlation between the expression of RPL27A and clinical information of patients. To explore the effect of RPL27A on Ribosome biogenesis, protein synthesis and other signaling pathways through Proteomics and molecular biology experiments have been designed and tested. The effects of RPL27A on malignant biological behaviors such as proliferation, migration, infiltration, and clonal formation of TNBC cells were studied through cell biology experiments and mouse experiments. Results: The analysis of TCGA database and single-cell sequencing data showed that the RPL27A was significantly increased in TNBC group. Immunohistochemical experiments showed that RPL27A was highly expressed in TNBC tissue and was impressively positively correlated with tumor size, lymph node metastasis, and bone metastasis. There was significantly negatively correlated with overall survival (OS) and disease free survival (DFS). It can be an independent factor for evaluating the prognosis of TNBC. By knocking out RPL27A in TNBC cell line, label free proteomics analysis showed that Ribosome biogenesis, protein synthesis, cell cycle regulation and other signaling pathways were obviously down regulated. Cell biology experiments have implied that the high expression of RPL27A in TNBC promotes cell proliferation, enhances cell migration, infiltration, and cloning ability, leads to more malignant biological behavior of tumor cells. Further research demonstrates that the high expression of RPL27A in TNBC significantly activated the EIF3C signal, cause changes in the composition of Ribosome in TNBC cells, promoted the formation of "onco-ribosomes", and distinctly increased the rate of protein synthesis. The study of PDX mice and Organoid showed that the knock out of RPL27A significantly reduced the growth rate and transfer ability of TNBC. Conclusion: The obvious over expressing of RPL27A in TNBC, which can significantly promote the growth and metastasis of tumor cells by influencing the Ribosome biogenesis process. Citation Format: Weipeng Zhao, Jingyi Zhang, Ye Zhu, Xin Yang, Xichuan Li. RPL27A promotes the growth and metastasis of triple negative breast cancer by regulating Ribosome biogenesis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-11.

Abstract PO5-11-05: Fertility, sexuality and other unmet needs of young breast cancer survivor during and at the end of treatment in France: a national qualitative study by the French Network of Cancer Registries (FRANCIM)

Abstract Introduction In recent decades, the living conditions of breast cancer (BC) survivors have received particular attention, especially among the youngest who face problems related to fertility and sexuality. Integrating women's needs into medical decisions is becoming increasingly essential for high-quality care. This study aimed to describe and understand the experiences of young women after BC, examined the scope and content of information transmitted on fertility and sexuality during routine appointments during the management of BC, and identify unmet support needs. Methods This study follows on from a quantitative study using self-questionnaires, in which patients met the following inclusion criteria (Non-metastatic invasive BC women diagnosed from 2009 to 2016, aged ≤ 40 years at diagnosis were identified through the FRANCIM Network). Interviews were conducted with a sample of 29 women drawn at random from among eligible women who completed the self-questionnaires in the quantitative study. The sample were stratified by age, department, socio-professional category and socio-economic level. Individual face-to-face semi-structured interviews were conducted either by videoconference or face-to-face, in patient's homes or in any other location of their choice during October to December 2022. The interviews were audio-recorded, transcribed verbatim, and analyzed thematically. Results Findings revealed that during treatments, women would like physicians (oncologists, surgeons, radiologists, gynecologist, etc.) to be more empathetic, more humane, and show tact and attentiveness when announcing the disease and treatments during the course of care. They would like to be better informed about the post-treatment side effects and better prepared by the physicians, for the feeling of abandonment felt in the aftermath of cancer due to the absence of medical appointments. The mains unmet needs of BC survivors were more numerous at the end of the treatments. In fact they more deplore the lack of coverage and reimbursement of aesthetic care and paramedical care essential to women to compensate for the persistent side effects and the repercussions of the disease and post-cancer treatments (eg: a more aesthetic and better reimbursed breast reconstruction at the end of the treatments, support by psychologists, etc.). With regard to sexuality, in the absence of systematic information for patients on the side effects of treatments on sexuality at diagnosis, it would be desirable to ask the woman if she would like to be informed. In addition, psychological support for the couple during and after treatment in terms of sexuality is necessary to avoid divorce and separation. In terms of fertility, there is a lack of systematic information for young women on the side effects of treatment on fertility, as well as questioning by physicians about any pregnancy plans women may have at the time of diagnosis. The introduction of fertility preservation with the possibility of it being systematically offered to all young women at diagnosis is important (or, failing that, the subject should be discussed more with the women), as it represents a gap in support). For women who had a pregnancy plan at diagnosis, the majority felt a lack of listening by doctors and adaptation of care to their pregnancy plan at diagnosis. Conclusions This study showed that, despite the high quality of care provided to young women diagnosed with BC in France, they felt they had unmet needs in terms of sexuality, fertility and access to paramedical care at the end of treatment. Indeed, these women face psychological suffering that they would like physicians to see beyond their physical suffering based on their experience. The results of this study could help public authorities and physicians improve care and life after cancer for young women diagnosed with BC. Citation Format: Emerline Assogba, Agnès Dumas, Cynthia Morgny, Myriam Borel, Véronique Brun, Nicolas Nicolas Meunier-Beillard, Ariane Mamguem, Charles Coutant, Isabelle Desmoulins, Sandrine Dabakuyo. Fertility, sexuality and other unmet needs of young breast cancer survivor during and at the end of treatment in France: a national qualitative study by the French Network of Cancer Registries (FRANCIM) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-11-05.

Analysis of the Use of Hospital Management Information Systems with Jobs to be Done to Increase Innovation Simplifying Administrative Processes at CHP Hospitals

The Hospital Management Information System (HMIS) must be developed and implemented in every hospital, in accordance with Minister of Health Regulation Number 82 of 2013, to provide the best service to the Indonesian public, the quality of hospital services must be continuously improved. The management of patient information, data, data processing, and all activities related to a good hospital depend heavily on this. It is important to understand how the implementation of the Hospital Management Information System can improve healthcare service standards in Indonesia after its implementation. Thirty-two samples were used in this study, and SEM-PLS data were analyzed using the Jobs To Be Done approach. The findings indicate that human, organizational structure, and system usage within the Hospital Management Information System (HMIS) can enhance healthcare technology innovation by simplifying administration in hospital services.

Abstract PO4-16-12: Patient initiated centricity towards improved communication, side effect management and follow-up care by Real World Evidence Survey from patients for patients – Preview of the Breast BRIDGister Platform

Abstract Background Treatment adherence is crucial for outcome improvement. Still up to 50% of patients interrupt e.g. endocrine treatment or other effective treatment choices due to side effects or miscommunication. Reasons may include limited time spent for patient information in daily routine and the intrinsic barriers to frankly tell the truth to the attending physicians. Therefore, a patient initiated survey has been compiled to comprehensively address all clinical, diagnostic and critical aspects of importance for patients by decentral data capture from patients at home via smart devices in a pseudonymized & interactive fashion to refocus on challenges regarding patients needs, fears and wishes to support evidence based statistical analysis of Real World Data. Materials and Methods Establishing a cloud-based IT Platform enabling nationwide, decentral data entry using Climedo clinical trial software tools without the need of any commercial app utilities and therefore obeying GDPR conform standards to create an interconnected online platform integrating 36 interconnected surveys comprising >1.200 singular questions has been set up between 2020 and 2022 based on patients content elaboration & wishes. The questionnaires address all Real World experiences e.g. at initial diagnosis, during primary treatment and all subsequent lines as well as side effect management with complementary medicine and follow up care realities. After 100 patients a preplanned statistical analysis has been performed to evaluate the feasibility of the patient oriented ePRO approach and demonstrate relevance of proof-of-concept results before entering international trial expansion. Descriptive analysis by Excel as well as Correlation analysis; Chi square and Partitioning tests using the SAS JMP® 9.0.0 software were performed. Results Despite in depth complexity > 85% of patients completed the whole survey. Age distribution of the pilot cohort revealed comparably younger patient age (28% between 30-39 years, 40% between 40-49 years, 24% between 50-59 and 10% being above 60 years) and dominance of Triple Negative Patients (~39%) participating the online survey in the pilot cohort. 97% of patients were treated in certified breast centers (50% in larger centers of bigger towns,15% in central clinics, 23% in university sites, 5% in local hospitals and 7% at office based doctors). Interestingly, 25% of patients did not or only partially understand their diagnosis and upcoming treatment. Time spent for communicating initial breast cancer diagnosis was less than 10 minutes for 25% of patients, while 13% did not remember. Exclusively one treatment option was discussed with 86% of patients. 78% have been informed about their initial breast cancer diagnosis in personal meetings, while 21% were informed by phone calls. 37% of patients had been informed about their patient rights. At preplanned interim analysis 38% of patients were lymphnode positive and 6% metastasized at initial diagnosis. 56% of patients were satisfied with their guideline conform follow-up-care, while 42% did pay for additional follow up care on their own. 85% of patients wished to have a risk-adopted, more individualized follow-up care. Conclusion Despite complexity and lengthiness > 85% of patients did complete the survey. There is an apparent need to have more time for initial confrontation with diagnosis and treatment options. Patients are frequently not informed about alternative treatment options as well as patient rights. Patients frequently feel under pressure in their life threatening situation and suffer substantial lack of information as well as appropriate personal communication. Patient centricity should focus on elaborated communication and information systems that support treatment decision acceptance and adherence. Further details analysis will become available in upcoming subanalysis of the Breast BRIDGister platform survey. Citation Format: Cornelia Stuewe, Ralph Wirtz, Christa Gress, Lena Schmidt, Veronika Schweighart, Sebastian Eidt, Claudia Schumacher, Julia Habraschka, Heidi Lehmann, Katrin Schuere. Patient initiated centricity towards improved communication, side effect management and follow-up care by Real World Evidence Survey from patients for patients – Preview of the Breast BRIDGister Platform [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-12.

Abstract PO3-20-10: Case Series: Invasive Secretory Carcinoma

Abstract Secretory variant invasive ductal carcinoma is not well described in the literature but is defined by its unique histopathology. These tumors stain positive for S100 and are typically triple negative hormonal cancers with an overall good prognosis. There is speculation that secretory carcinoma in adults is more aggressive with a greater likelihood for tumor recurrence. We present two case studies of this rare histopathologic diagnosis. First, a 76-year-old female with a recurrent secretory variant, invasive ductal carcinoma of the left breast. Second, a 68-year-old male who presented with invasive and in situ secretory carcinoma. A thorough chart review of all available institutional and outside institution records was performed from initial diagnosis to current treatment. Background information and de-identified patient information was summarized for this case series. This is a 76-year-old female who presented to her physician in 2011 with a palpable left breast and axillary mass. Her workup demonstrated ER+/PR+/HER2- invasive ductal carcinoma with lobular features of the left breast measuring 2.3 cm, along with a 1.5 cm malignant axillary lymph node. She underwent a left breast lumpectomy with axillary dissection. She underwent adjuvant whole breast radiation, axillary nodal radiation, and was placed on anastrozole therapy for 5 years. Seven years later a recurrence was noted in the superior aspect of the left breast. MRI guided biopsy revealed recurrent left breast cancer with pathology of invasive ductal carcinoma, secretory variant. She elected to undergo lumpectomy alone. Final pathology demonstrated invasive ductal carcinoma, secretory variant, ER negative (0%), PR negative (0%), HER2 negative (0%), pT1bNx. She underwent accelerated adjuvant partial breast radiation. Follow up and surveillance with bilateral breast MRI two years later demonstrated a new left breast mass, found to be triple negative, recurrent secretory variant invasive ductal carcinoma. She underwent definitive treatment with a left skin sparing mastectomy, right sentinel lymph node biopsy, and a latissimus dorsi flap with implant placement. Final pathology demonstrated multifocal recurrent secretory carcinoma, two foci measuring 6 and 11 mm. Our second patient was a 68-year-old male who initially presented to the clinic for evaluation of a ventral incisional hernia. During his initial assessment, a palpable retro-areolar nodule was noted on physical exam. Subsequent mammography demonstrated a hypoechoic mass with irregular margins measuring 2.8 x 2.3 x 1.7 cm along with increased vascularity and calcifications. An ultrasound guided biopsy demonstrated invasive secretory carcinoma. Initial pathologic testing of the tumor demonstrated ER positive (5%), PR positive (1%), and HER2 negative. The patient was taken to the operating room for a total mastectomy with sentinel lymph node biopsy. His postoperative pathology demonstrated negative margins, and invasive secretory carcinoma with lymph nodes negative for metastatic disease. Secretory variant of invasive ductal carcinoma is rare and is determined by its unique immunohistochemical features. We present two cases of secretory carcinoma at our institution. Data suggests that local recurrence is common in patients with secretory breast cancer, occurring in 33-44% of cases. Ki-67 index has been used as a prognostic indicator for metastases and recurrence of disease. Current treatment regimens are diverse; however, surgery is favored as the primary method. This report shows that although indolent, multifocality and recurrence is plausible. Given the limited data on this subset of carcinoma, more investigation is warranted to describe the effectiveness of adjuvant treatment options. Case 1 –insert figure image– Histopathologic examination at 200x shows invasive carcinoma with dense eosinophilic secretory material. By immunohistochemistry, the cells are negative for ER (0%) and PR (0%) with a HER2Neu score of 0, supporting the diagnosis of invasive secretory carcinoma. Case 2 –insert figure image– Histopathologic examination at 200x shows invasive carcinoma with dense eosinophilic secretory material. The tumor cells are positive for CK5/6 (patchy), CD117, ER (focal and weakly), and S100; negative for p63 and calponin, supporting the diagnosis of invasive secretory carcinoma. NTRK3 gene rearrangement was detected on fluorescence in situ hybridization (FISH). Citation Format: Lauren Geisel, Hemanth Venkatesh, Alyssa Obermiller, Quyen Chu, Jessica Gielow, Danielle Henry. Case Series: Invasive Secretory Carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-10.

Causes de plaintes après arthroplastie totale primaire de hanche en France : données assurantielles de 240 expertises de 2014 à 2017

Introduction: Total hip arthroplasty (THA) is one of the most frequent orthopedic surgery procedures, and orthopedic surgeons are among the most frequently accused of malpractice by their patients. Identifying the main reasons for malpractice claims after THA is a prior condition to reducing their frequency. The quality of the preoperative risk information given to the patient by the surgeon is crucial for these purposes. Data specific to THA are sparse in France, and we therefore conducted a retrospective study 1) to determine whether the outcome of medico-legal expert appraisal correlated with the quality and traceability of preoperative information, and 2) to identify the most frequent grounds for complaint after primary THA.Hypothesis: The quality of patient information partly determines expert appraisal.Material and Method: A retrospective study was conducted based on data from the Branchet medical professional insurance agency for malpractice claims following THA over the period 2014-2017, with 240 complete files, for 125 women and 115 men. Data comprised: type of procedure, main grounds of complaint (complications), positive or negative expert appraisal, quality of preoperative patient information, amounts of compensation accorded and fees paid, and the practitioner’s liability. We assessed correlations between information quality and liability.Results: Surgical site infection and neurologic deficit were the two main grounds for malpractice claims. In the 240 files, cases for 106 operations (44.2%) were submitted to arbitration, 95 (39.6%) were brought to court, and 39 (16.2%) were settled out of court. The practitioner was held at least partly liable in 40 files (16.7%). Information to the patient was deemed imperfect or poor for 119 files (49.6%) and good in 121 (50.4%). Mean compensation was euro 30,940 (range, euro 0 to euro 198,100).In 27 of the 40 cases of liability (67.5%), the information to the patient was deemed imperfect or poor. Twenty-six of the 40 cases (65%) were settled out of court.In case of poor information, there was a significant risk for the practitioner to be held liable: 7.5% vs 25% (p=0.003).Discussion: The present study listed the main complications underlying malpractice claims after THA: infection, neurologic complications, and limb-length discrepancy. This should enable practitioners to improve patient information so as to reduce the rate of malpractice claims or at least decrease the practitioner’s liability, as the study found a correlation between information quality and expert appraisal.Level of evidence: IV; retrospective study.

Aortic Valve Calcification Density Measured by MDCT in the Assessment of Aortic Stenosis Severity.

Aortic valve calcification (AVC) indexation to the aortic annulus (AA) area measured by Doppler echocardiography (AVCdEcho) provides powerful prognostic information in patients with aortic stenosis (AS). However, the indexation by AA measured by multidetector computed tomography (AVCdCT) has never been evaluated. The aim of this study was to compare AVC, AVCdCT, and AVCdEcho with regard to hemodynamic correlations and clinical outcomes in patients with AS. Data from 889 patients, mainly White, with calcific AS who underwent Doppler echocardiography and multidetector computed tomography within the same episode of care were retrospectively analyzed. AA was measured both by Doppler echocardiography and multidetector computed tomography. AVCdCT severity thresholds were established using receiver operating characteristic curve analyses in men and women separately. The primary end point was the occurrence of all-cause mortality. Correlations between gradient/velocity and AVCd were stronger (both P≤0.005) using AVCdCT (r=0.68, P<0.001 and r=0.66, P<0.001) than AVC (r=0.61, P<0.001 and r=0.60, P<0.001) or AVCdEcho (r=0.61, P<0.001 and r=0.59, P<0.001). AVCdCT thresholds for the identification of severe AS were 334 Agatston units (AU)/cm2 for women and 467 AU/cm2 for men. On a median follow-up of 6.62 (6.19-9.69) years, AVCdCT ratio was superior to AVC ratio and AVCdEcho ratio to predict all-cause mortality in multivariate analyses (hazard ratio [HR], 1.59 [95% CI, 1.26-2.00]; P<0.001 versus HR, 1.53 [95% CI, 1.11-1.65]; P=0.003 versus HR, 1.27 [95% CI, 1.11-1.46]; P<0.001; all likelihood test P≤0.004). AVCdCT ratio was superior to AVC ratio and AVCdEcho ratio to predict survival under medical treatment in multivariate analyses (HR, 1.80 [95% CI, 1.27-1.58]; P<0.001 compared with HR, 1.55 [95% CI, 1.13-2.10]; P=0.007; HR, 1.28 [95% CI, 1.03-1.57]; P=0.01; all likelihood test P<0.03). AVCdCT ratio predicts mortality in all subgroups of patients with AS. AVCdCT appears to be equivalent or superior to AVC and AVCdEcho to assess AS severity and predict all-cause mortality. Thus, it should be used to evaluate AS severity in patients with nonconclusive echocardiographic evaluations with or without low-flow status. AVCdCT thresholds of 300 AU/cm2 for women and 500 AU/cm2 for men seem to be appropriate to identify severe AS. Further studies are needed to validate these thresholds, especially in diverse populations.

Trends in Elbow Ulnar Collateral Ligament Repairs and Reconstructions and an Analysis Between Low- and High-Volume Surgical Centers: A 10-Year Study in New York State.

Elbow ulnar collateral ligament (UCL) reconstruction (UCLR) is the gold standard for operative treatment of UCL tears, with renewed interest in UCL repairs. To (1) assess trends in rates of UCLR and UCL repair and (2) identify predictors of complications by demographic, socioeconomic, or surgical center volume factors. Descriptive epidemiology study. Patients who underwent UCLR or UCL repair at New York State health care facilities between 2010 and 2019 were retrospectively identified; concomitant ulnar nerve procedures among the cohort were also identified. Surgical center volumes were classified as low (<99th percentile) or high (≥99th percentile). Patient information, neighborhood socioeconomic status quantified using the Area Deprivation Index, and complications within 90 days were recorded. Poisson regression analysis was used to compare trends in UCLR versus UCL repair. Multivariable regression was used to determine whether center volume, demographic, or socioeconomic variables were independent predictors of complications. A total of 1448 UCL surgeries were performed, with 388 (26.8%) concomitant ulnar nerve procedures. UCLR (1084 procedures; 74.9%) was performed more commonly than UCL repair (364 procedures; 25.1%), with patients undergoing UCL repair more likely to be older, female, and not privately ensured and having undergone a concomitant ulnar nerve procedure (all P < .001). With each year, there was an increased incidence rate ratio for UCL repair versus UCLR (β = 1.12 [95% CI, 1.02-1.23]; P = .022). The authors identified 2 high-volume centers (720 UCL procedures; 49.7%) and 131 low-volume centers (728 UCL procedures; 50.3%). Patients undergoing UCL procedures at high-volume centers were more likely to be younger and male and receive workers' compensation (all P < .001). UCL repair and ulnar nerve-related procedures were both more commonly performed at low-volume centers (P < .001). There were no significant differences in 3-month infection, ulnar neuritis, instability, arthrofibrosis, heterotopic ossification, or all-cause complication rates between low- and high-volume centers. The only significant predictor for all-cause complication was Medicaid insurance (OR, 2.91 [95% CI, 1.20-6.33]; P = .011). A rising incidence of UCL repair compared with UCLR was found in New York State, especially among female patients, older patients, and nonprivate payers. There were no differences in 3-month complication rates between high- and low-volume centers, and Medicaid insurance status was a predictor for overall complications within 90 days of operation.