Clinical Management Research Articles

Esophageal adenocarcinoma models: a closer look

Esophageal adenocarcinoma (EAC) is a subtype of esophageal cancer with significant morbidity and mortality rates worldwide. Despite advancements in tumor models, the underlying cellular and molecular mechanisms driving EAC pathogenesis are still poorly understood. Therefore, gaining insights into these mechanisms is crucial for improving patient outcomes. Researchers have developed various models to better understand EAC and evaluate clinical management strategies. However, no single model fully recapitulates the complexity of EAC. Emerging technologies, such as patient-derived organoids and immune-competent mouse models, hold promise for personalized EAC research and drug development. In this review, we shed light on the various models for studying EAC and discuss their advantages and limitations.

Abstract 4119869: Automatic assignment of CAD-RADS categories in coronary CTA reports using large language model

Background: The effectiveness of different large language models (LLM) in extracting important information from CT angiography (CTA) radiology reports is unknown. Purpose: The Coronary Artery Disease-Reporting and Data System (CAD-RADS) is a standardized reporting system for CTA that categorizes the severity of coronary artery disease to aid in clinical decision-making. To evaluate the agreement between human readers and LLMs in assigning CAD-RADS categories based on CTA reports. Materials and Methods: This retrospective study analyzed reports from patients who underwent coronary CTA for screening or diagnosis at Johns Hopkins Hospital. Reports with CAD-RADS 0–5 findings were collected from Jan. 2020 to Oct. 2023. Initially, 6,212 CTA reports were retrieved. After excluding non-organized reports and retaining only those with CAD-RADS scores, 590 reports remained. Board-certified radiologists and three large language models (GPT-3.5, GPT-4, and Llama3) assigned CAD-RADS categories based on the original radiologists' findings. Two radiologists reviewed the CAD scores, with only one discrepancy in the 590 reports, indicating high inter-agreement. Agreement between human readers and LLMs for CAD-RADS categories was assessed using the Gwet agreement coefficient (AC1 value). Frequencies of changes in CAD-RADS category assignments that could potentially affect clinical management (CAD-RADS 0-2 vs. 3-5) were calculated and compared. Typically, CAD-RADS 0-2 indicates mild disease leading to conservative management, while CAD-RADS 3-5 denotes further testing or disease requiring aggressive intervention to prevent adverse cardiovascular events. Results: Among 590 reports, agreement between original and reviewing radiologists was almost perfect (AC1 = 0.985). Good agreement was also found between original radiologists and Llama3, GPT-3.5, and GPT-4 (AC1 = 0.861, 0.907, 0.941, respectively). Differences in CAD-RADS category upgrades/downgrades potentially affecting clinical management were observed: 0 of 590 (0%) for human readers, 56 of 590 (9.4%) for Llama3, 33 of 590 (5.5%) for GPT-3.5, and 23 of 590 (3.9%) for GPT-4 upgrading CAD-RADs; 8 of 590 (1.4%) for human readers, 19 of 590 (3.2%) for Llama3, 22 of 590 (3.7%) for GPT-3.5, and 12 of 590 (2.0%) for GPT-4 downgrading RAD-CADs. Conclusion: LLMs showed good agreement with human readers in assigning CAD-RADS categories on CTA reports. However, they were more likely to upgrade CAD-RADS category when compared to radiologists.

Abstract 4120821: Electrochemical Impedance Spectroscopy Unmasks High-Risk Atherosclerotic Features in Human Coronary Artery Disease

Background: Coronary plaque rupture remains the prominent mechanism of myocardial infarction. Accurate identification of rupture-prone plaque may improve clinical management. This study assessed the discriminatory performance of electrochemical impedance spectroscopy (EIS) in human cardiac explants to detect high-risk atherosclerotic features that portend rupture risk. Methods: In this single-center, prospective study, n=26 cardiac explants were collected for EIS interrogation of the three major coronary arteries. Vessels in which advancement of the EIS catheter without iatrogenic plaque disruption was rendered impossible were not assessed. N=61 vessels underwent EIS measurement and histological analyses. Plaques were dichotomized according to previously established high rupture-risk parameter thresholds. Diagnostic performance was determined via receiver operating characteristic areas-under-the-curve (AUC). Results: Necrotic cores were identified in n=19 vessels (median area 1.53 mm 2 ) with median fibrous cap thickness of 62 μm. Impedance was significantly greater in plaques with necrotic core area ≥1.75 mm 2 vs <1.75 mm 2 (19.8±4.4 kΩ vs 7.2±1.0 kΩ, P =0.019), fibrous cap thickness ≤65 μm vs >65 μm (19.1±3.5 kΩ vs 6.5±0.9 kΩ, P =0.004), and ≥20 macrophages per 0.3 mm-diameter high-power field (HPF) vs <20 macrophages per HPF (19.8±4.1 kΩ vs 10.2±0.9 kΩ, P=0.002). Impedance identified necrotic core area ≥1.75 mm 2 , fibrous cap thickness ≤65 μm, and ≥20 macrophages per HPF with AUCs of 0.889 (95% CI: 0.716–1.000) ( P =0.013), 0.852 (0.646—1.000) ( P =0.025), and 0.835 (0.577—1.000) ( P =0.028), respectively. Further, phase delay discriminated severe stenosis (≥70%) with an AUC of 0.767 (0.573—0.962) ( P =0.035). Conclusions: EIS discriminates high-risk atherosclerotic features that portend plaque rupture in human coronary artery disease and may serve as a complementary modality for angiography-guided atherosclerosis evaluation.

Abstract 4136136: Left Ventricular Global Longitudinal Strain: An Imaging Marker Associated with Improved Survival in Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis

Background: The optimal clinical management and timing of intervention are less well defined in paradoxical low-flow, low-gradient severe aortic stenosis (PLFLG AS). Left ventricular global longitudinal strain (LV-GLS) has been shown to predict outcomes in high flow severe AS, but there is lack of data in patients with PLFLG AS. Given the exaggerated LV hypertrophy and remodeling pattern in PLFLG AS, LV-GLS may be a mechanistic imaging marker for worse outcomes. Hypothesis: In patients with PLFLG AS, LV-GLS is associated with adverse clinical outcomes by detecting subclinical myocardial fibrosis resulting from myocardial remodeling due to LV pressure overload. Methods: We examined patients with PLFLG AS defined as AVA <1cm 2 , mean gradient <40mmHg and preserved left ventricular ejection fraction (LVEF) ≥50%, with low-flow state defined as transvalvular flow rate (Q) ≤210 ml/sec. Exclusion criteria included moderate or greater mitral or aortic regurgitation and presence of atrial fibrillation at the time of echocardiogram. LV strain analysis was performed using 2D-strain imaging software (TomTec, Chicago, IL). Clinical outcome data were obtained via the electronic health record. The primary outcome was defined as all-cause mortality. Patients were stratified by LV-GLS above and below the median value. Results: A total of 198 patients were included in the analysis, with a median LV-GLS of -12.3% [IQR: (-9.8,-16.3)]. Over a median follow-up time of 1.2 years, 130 deaths (65.6%) were identified. Patients with less negative LV-GLS (n=101) had worse survival than those with more negative LV-GLS (n=97; 22 vs 38%; p=0.02) (Fig 1). After multivariable adjustment for potential confounders (stroke volume index, aortic valve mean gradient, relative wall thickness, age, sex, heart failure, hypertension, coronary artery disease, and diabetes), less negative LV-GLS was independently associated with adverse outcomes (HR 1.56; 95% CI (1.03-2.38); p=0.04). Conclusions: In patients with PLFLG AS as defined by a transvalvular flow rate (Q) ≤210 ml/sec, reduced LV-GLS is associated with increased all-cause mortality. LV-GLS may serve as an imaging marker to help guide clinical decision making in PLFLG AS.

An adaptive decision support system for outpatient appointment scheduling with heterogeneous service times.

Appointment scheduling (AS) plays a crucial role in outpatient clinic management. Traditional methods involve patient grouping using pre-defined rules and scheduling based on these groups. However, pre-defined rules may not adequately capture the heterogeneity in patients' service times (i.e., consultation duration). Advanced machine learning (ML) methods can address individual-level heterogeneity but pose challenges for practical scheduling. To strike a balance, we propose a data-driven AS decision support system, Cluster-Predict-Schedule (CPS), integrating both supervised and unsupervised ML for efficient patient grouping and scheduling. The novelty of CPS lies in its adaptability to service time heterogeneity through a data-driven approach, determining patient groups based on data rather than pre-defined rules. Additionally, CPS includes a generic and efficient algorithm for generating appointment templates adaptable to any number of patient groups. Our system's efficacy is demonstrated using a real-world dataset. Evaluated by the weighted sum of patient wait times, physician idle time, and overtime, CPS achieves up to 15.0% cost reduction compared to the FCFA (first-call, first-appointment) scheme and over 4.7% savings against the common New/Return classification with traditional sequencing candidate (TSC) rules. In addition, CPS enhances outpatient operational efficiency without compromising fairness.

Clinical Management of Uterine Prolapse in a Multiparous Persian Cat: A Case Report

This case report deals with the clinical management of uterine prolapse in a 3.5 years old Persian cat with the history of prior parturition. The prolapsed mass was displaying congestion, enlargement, edema and mild straining with no lacerations or injuries. After thorough cleaning, reduction of edema and antiseptic dressing, the prolapsed uterus was repositioned properly. Purse string suture was applied to prevent reoccurrence. The queen showed good response to the manual correction, with no complications. This report demonstrates effective clinical management of postpartum uterine prolapse by manual repositioning in a queen cat avoiding surgical intervention.

Clinical Management of Ovarian Function Suppression in Premenopausal Women With Breast Cancer: A Survey of Members of ASCO.

Ovarian function suppression (OFS) with gonadotropin-releasing hormone agonists (GnRHas) is a standard of care for premenopausal patients with high-risk stage II/III hormone receptor-positive breast cancer (BC). Practical guidance on the optimal choice of GnRHa, timing, schedule, and monitoring is limited. Our aim was to determine how oncologists use OFS in routine care. We designed a questionnaire to determine the choice of GnRHa, schedule, duration, initiation, use of bone modifiers, and monitoring of estradiol (E2). The questionnaire was sent to oncologists treating BC, in practice for >1 year and participating in the ASCO Research Survey Pool (RSP). It was also forwarded by investigators to oncologists meeting these criteria. The survey was open between November 14, 2023, and January 5, 2024. Of 996 oncologists participating in the ASCO RSP, 178 (18%) completed the survey. An additional 56 oncologists contacted by investigators responded. Respondents were from the United States (57%), Asia (15%), and Europe (14%). Goserelin (54%) and leuprolide (39%) were the most frequently used GnRHas and were administered once every month by 46%. Approaches to starting GnRHas were varied. Most continued them for the duration of aromatase inhibitor therapy (57%). Estradiol monitoring was performed regularly, sometimes, or never by 43%, 27%, and 27%, respectively. The E2 assays used were standard (65%), ultrasensitive (16%), and unknown (14%). Interpreting E2 assay results were considered difficult by 55%; however, 62% of oncologists changed treatment on the basis of them. A total of 92% of respondents would like ASCO guidance on the practical use of OFS. Considerable practice variation exists for similar clinical scenarios in OFS administration. Respondents would welcome ASCO guidance on all aspects of OFS.

A rare primary cutaneous myoepithelial carcinoma in the axilla accompanied by lymph node metastasis: A case report.

Primary cutaneous myoepithelial carcinoma is an extremely rare tumor, and to the best of our knowledge, it has never been reported to occur in the axilla. Furthermore, the pathological and clinical factors of cutaneous myoepithelial carcinoma are poorly understood and may considerably affect prognosis and treatment. Here, we report a case of a 44-year-old male patient who was diagnosed with primary cutaneous myoepithelial carcinoma in the axilla accompanied by extensive lymph node metastasis. After an enlarged resection of the left axillary mass, axillary lymph node dissection, and the administration of postoperative chemotherapy and local radiotherapy, there were no signs of tumor recurrence or metastasis. At the time of manuscript preparation, the patient was recurrence-free. This case may contribute to the clinical management, diagnosis, and treatment of primary cutaneous myoepithelial carcinoma.

Integrated multi-omics identifies pathways governing interspecies interaction between A. fumigatus and K. pneumoniae.

Polymicrobial co- and superinfections involving bacterial and fungal pathogens pose serious challenges for diagnosis and therapy, and are associated with elevated morbidity and mortality. However, the metabolic dynamics of bacterial-fungal interactions (BFI) and the resulting impact on disease outcome remain largely unknown. The fungus Aspergillus fumigatus and the bacterium Klebsiella pneumoniae are clinically important pathogens sharing common niches in the human body, especially in the lower respiratory tract. We have exploited an integrated multi-omics approach to unravel the complex and multifaceted processes implicated in the interspecies communication involving these pathogens in mixed biofilms. In this setting, A. fumigatus responds to the bacterial challenge by rewiring its metabolism, attenuating the translational machineries, and by connecting secondary with primary metabolism, while K. pneumoniae maintains its central metabolism and translation activity. The flexibility in the metabolism of A. fumigatus and the ability to quickly adapt to the changing microenvironment mediated by the bacteria highlight new possibilities for studying the impact of cross-communication between competing interaction partners. The data underscore the complexity governing the dynamics underlying BFI, such as pronounced metabolic changes mounted in A. fumigatus interacting with K. pneumoniae. Our findings identify candidate biomarkers potentially exploitable for improved clinical management of BFI.

Progress and challenges in clinical diagnosis and treatment of co-existent lung cancer and pulmonary tuberculosis

Lung cancer is the leading cause of malignancy-related morbidity and mortality in China and worldwide, posing a significant threat to human well-being. Tuberculosis (TB) is the second leading cause of death from a single infectious source, after COVID-19 infection, and represents a public health crisis. Recent research has shown that TB is an independent risk factor for lung cancer, while patients with lung cancer may also be at increased risk of TB. The occurrence of TB poses to a challenge to the implementation of the anti-cancer therapy in lung cancer. Early identification and appropriate treatment are essential for the prognosis improvement. Therefore, in this review, we aimed to highlight the research advances and challenges in the diagnosis and treatment of lung cancer and TB co-existence, with the further aim of providing new insights into the clinical management of patients and future research.

Abstract 4138306: Impact of Early Menopause and Hormonal Replacement Therapy on Aortic Stenosis Progressio

Background: Early menopause is associated with an increased risk of cardiovascular disease and mortality in women. The present study aimed to examine the impact of early menopause and hormonal replacement therapy (HRT) on the progression of aortic stenosis (AS). Methods: Thirty-three postmenopausal women (mean age 65 ± 10 years) with mild or moderate AS prospectively recruited in the PROGRESSA study (NCT01679431) were included in this sub-analysis. All patients underwent multidetector computed tomography and Doppler-echocardiography at least twice during follow-up to assess both anatomic and hemodynamic AS severity, based on aortic valve calcification (AVC), mean pressure gradient (MG), and aortic valve area indexed to body surface area (AVA). Annualized changes in AVC, MG and AVAi were calculated between baseline and the last follow-up. Results: Over a median follow-up of 2 [1-4] years, early menopausal women had a faster progression rate of AVC, MG, and AVAi compared to other women: (100[58-130] vs. 23[2-71] AU/year, p=0.03); (2.37[0.82-3.61] vs. 0.31[0.01-1.78] mmHg/year, p=0.04); and (-0.12[-0.23-0.002] vs. -0.004[-0.07-0.08] cm 2 /m 2 /year, p=0.08) respectively. In multivariate analysis adjusted for age, AS severity at baseline, and comorbidities, early menopause remained significantly associated with faster AVC progression (p=0.003). Moreover, after comprehensive adjustment, women who received HRT (45%) had a slower progression rate of AVC (20[10-42] AU/year vs. 62[2-100], adjusted p=0.04). Conclusion: Early menopause is associated with faster progression of AS, both anatomically and hemodynamically. However, the use of HRT is associated with slower progression of AS. Integrating female-specific risk factors, particularly menopausal history and hormonal therapy status, into the clinical management of AS could enhance patient care.

NIMG-14. HEAD-TO-HEAD COMPARISON OF18F-FET PET AND68GA-PSMA-11 PET IN DISTINGUISHING SMALL VOLUME TUMOR PROGRESSION VS TREATMENT-RELATED CHANGE IN POST-STANDARD OF CARE TREATMENT OF HIGH-GRADE GLIOMA USING DYNAMIC ACQUISITION AND KINETIC MODELING

Abstract BACKGROUND The inability to accurately distinguish between tumor progression and treatment-related changes in patients with high-grade glioma on routine imaging can negatively impact patient management and in some cases, outcome. Various imaging methods have been used to address this issue, including 18F-fluoro-ethyl-tyrosine (FET) PET and MR perfusion. However, these methods may not provide reliable results in cases of small lesion size or hemorrhage within the treatment site. The prostate-specific membrane antigen (PSMA) has been observed to be expressed by neovasculature in brain tumors. Since PSMA cannot cross the blood brain barrier, uptake of PSMA in the brain carries high-level of suspicion for residual tumor. Still, further work is needed to better understand PSMA uptake in the tumor bed following standard of care (SOC) treatment and to compare to currently available neuro-oncologic radiotracers, such as FET. We hypothesize that PSMA imaging of glioma neovasculature will provide unique diagnostic information that will aid in the differentiation of small volume tumor progression from treatment-related changes in the post-SOC treatment setting. METHODS Patients who underwent clinical Expanded Access PET/MR imaging with 18F-FET were re-imaged in a research protocol that collected a brain 68Ga-PSMA-11 PET/CT scan, as well as a repeat 18F-FET PET/CT. Kinetic modeling of dynamic radiotracer uptake was performed. Scans were assessed for correlation with subsequent imaging and changes in clinical management. RESULTS All PSMA scans that were performed were concordant with the initial clinical FET scan, subsequent imaging follow up and appropriate changes in clinical management. The PSMA-detected site was confirmed to be tumor in a single case with subsequent tissue sampling. One patient who was started on bevacizumab after their clinical FET demonstrated a significant decrease in uptake on the research FET scan, but persistent uptake on PSMA. CONCLUSION PSMA may effectively show tumor recurrence in post-SOC treatment high-grade glioma patients.

Active tuberculosis disease among people living with HIV on ART who completed tuberculosis preventive therapy at three public hospitals in Uganda.

Tuberculosis (TB) preventive therapy (TPT) reduces the incidence of TB among people living with the human immunodeficiency virus (PLHIV). However, despite an increase in TPT uptake, TB/HIV coinfection remains stagnant in Uganda especially in areas of increasing HIV incidence such as the Bunyoro sub-region. This study was a retrospective review records (antiretroviral therapy [ART] files) of PLHIV who were active on ART and completed TPT in 2019/2020 at three major hospitals in the Bunyoro sub-region, Uganda: Masindi General Hospital, Hoima Regional Referral Hospital, and Kiryandongo General Hospital. The sample size (987) for each facility was determined using a proportionate sampling method to ensure the study's power and precision. Factors independently associated with acquiring TB disease post TPT were determined using modified Poisson regression analysis. An adjusted prevalence risk ratio (aPRR) with corresponding 95% confidence intervals were reported. The participants' mean age was 38.23 (±11.70) and the majority were female (64.94%). Overall, 9.63% developed active TB disease post TPT completion. In the adjusted analysis, factors associated with active TB disease were a history of an unsuppressed viral load after TPT (aPRR 4.64 (2.85-7.56), p<0.001), opportunistic infections after TPT completion (aPRR 4.31 (aPRR 2.58-7.2), p<0.001), a history of TB active TB disease (aPRR 1.60 (1.06-2.41), p = 0.026), and chronic illness during or after TPT (aPRR 1.68 (1.03-2.73), p = 0.038). To reduce the development of TB disease post TPT thereby improving the effectiveness of TPT, ART adherence should be emphasized to resolve viral suppression and active management of chronic and opportunistic infections. Further clinical management consideration and research is needed for PLHIV who receive TPT but have a previous history of TB disease.

NIMG-63. LEVERAGING LLMS FOR ACCURATE DIFFERENTIATION OF RADIATION NECROSIS AND TUMOR PROGRESSION IN BRAIN MRI REPORTS: A STUDY ON AUTOMATED SCORING AND CLINICAL IMPLICATIONS

Abstract BACKGROUND Accurate differentiation between radiation necrosis and tumor progression or recurrence in patients treated with stereotactic radiosurgery for brain metastases is critical for guiding clinical management. This study leverages the advanced natural language processing capabilities of Meta Llama3, an artificial intelligence (AI) large language model (LLM), combined with prompt engineering, to rapidly categorize brain magnetic resonance imaging (MRI) radiology reports. Our objective was to develop an automated scoring system to classify concern for radiation necrosis, tumor progression, equivocal findings, or stable exams. METHODS Using a comprehensive dataset of reports annotated by expert radiologists, we ran inference on a 70-billion parameter Llama3 model (temperature 0.2, top_p 0.9) with specific prompts designed to capture the nuanced language and diagnostic criteria related to radiation necrosis or tumor progression. RESULTS The first pass was performed on a training dataset of 107 reports and did not predefine the clinical conditions. This demonstrated 43.4% accuracy in scoring when compared to a human user’s classification of each report. Agreement between the human reader and Llama3 was assessed using the Gwet agreement coefficient, AC1=0.411 (99%CI 0.396-0.426). Multiple iterations of targeted prompt engineering were then employed to narrow the definition of radiation necrosis and tumor progression, with specific examples and nuanced language used to achieve a higher degree of accuracy at 72.0%, AC1=0.719 (99%CI 0.717-0.722). DISCUSSION/FUTURE DIRECTIONS This surpasses recent demonstration of lower human-LLM agreement in radiographic score assignment, with further room for calibration on a dataset of several thousand reports. Next, we will correlate automated interpretations with actual clinical management decisions for radiation necrosis (e.g., initiation of steroids, bevacizumab, Laser Interstitial Thermal Therapy, and/or repeat imaging). This automated scoring system holds significant potential for LLMs in clinical applications. Future work will focus on integrating this model into clinical workflows and expanding its capabilities to include longitudinal monitoring of patient outcomes.

Management of opioid use disorder: 2024 update to the national clinical practice guideline.

In an evolving landscape of practices and policies, reviewing and incorporating the latest scientific evidence is necessary to ensure optimal clinical management for people with opioid use disorder. We provide a synopsis of the 2024 update of the 2018 National Guideline for the Clinical Management of Opioid Use Disorder, from the Canadian Research Initiative in Substance Matters. For this update, we followed the United States Institute of Medicine's Standards for Developing Trustworthy Clinical Practice Guidelines and used the Appraisal of Guidelines Research and Evaluation-Recommendation Excellence tool to ensure guideline quality. We carried out a comprehensive systematic literature review, capturing the relevant literature from Jan. 1, 2017, to Sept. 14, 2023. We drafted and graded recommendations according to the Grading of Recommendations, Assessments, Development and Evaluation approach. A multidisciplinary external national committee, which included people with living or lived experience of opioid use disorder, provided input that was incorporated into the guideline. From the initial 11 recommendations in the 2018 guideline, 3 remained unchanged, and 8 were updated. Specifically, 4 recommendations were consolidated into a single revised recommendation; 1 recommendation was split into 2; another recommendation was moved to become a special consideration; and 2 recommendations were revised. Key changes have arisen from substantial evidence supporting that methadone and buprenorphine are similarly effective, particularly in reducing opioid use and adverse events, and both are now considered preferred first-line treatment options. Slow-release oral morphine is recommended as a second-line option. Psychosocial interventions can be offered as adjunctive treatment but should not be mandatory. The guideline reaffirms the importance of avoiding withdrawal management as a standalone intervention and of incorporating evidence-based harm reduction services along the continuum of care. This guideline update presents new recommendations based on the latest literature for standardized management of opioid use disorder. The aim is to establish a robust foundation upon which provincial and territorial bodies can develop guidance for optimal care.

The Lachnospiraceae-butyric acid axis and its role in glucocorticoid-associated osteonecrosis.

Glucocorticoids (GCs) are key inducers of osteonecrosis, yet not all patients treated with GCs develop glucocorticoid-associated osteonecrosis (GAON). The factors mediating this relationship are unclear. Studies have shown that gut microbiota and their metabolites influence bone metabolism, but their role in GAON is unclear. This study aimed to explore the connection between GAON and gut microbiota. Through bidirectional Mendelian randomization analysis, we identified 14 gut microbial taxa, including Lachnospiraceae (IVW, P = 0.011), associated with GAON. RNA-seq analysis revealed that GAON differentially expressed genes (DEGs) were enriched for intestinal inflammatory response mechanisms. We then compared patients who developed GAON (17 cases), those who did not (GAnON, 15 cases), and those untreated with GCs (Blank, 15 cases) for gut microbiota composition, short-chain fatty acids (SCFAs), and serum inflammatory factors. Our findings indicated a decrease in Lachnospiraceae abundance (GAON 17.13%, GAnON 12.51%, Blank 24.52%) in GC-treated patients. Serum inflammatory factors (IL-17A, IL-33, and TNF-α) associated with GAON (59.603 ± 12.147, 89.337 ± 20.714, 42.584 ± 9.185) showed significant differences between Blank (1.446 ± 0.683, 11.534 ± 4.705, 4.682 ± 1.48) and GAnON (25.353 ± 8.181, 32.527 ± 7.352, 12.49 ± 3.217) groups, with a negative correlation between these factors and Lachnospiraceae levels. Butyric acid levels in SCFAs varied among groups (P<0.01) and correlated with Lachnospiraceae and inflammatory factors. Controlled experiments in GAON rats demonstrated butyric acid's osteoprotective role in GAON development (P<0.01). In conclusion, our study suggests that reduced Lachnospiraceae and butyric acid levels, along with increased inflammation due to GCs use, contribute to GAON. Butyric acid may mediate the effects of Lachnospiraceae and inflammation. Butyrate supplementation could potentially reduce GAON incidence, offering a novel approach for its clinical management.

Study protocol for a consortium linking health medical records, biospecimens, and biosignals in Korean patients with acute kidney injury (LINKA cohort).

Acute kidney injury (AKI) may transition into acute kidney disease (AKD) or chronic kidney disease (CKD), leading to subacute and chronic deterioration, respectively. Despite extensive research on AKI, a significant gap exists in understanding the specific biomarkers and development of individualized treatments prior to progression to AKD and CKD. As a consortium linking health medical records, biospecimens, and biosignals, eight Korean tertiary hospitals participated in the establishment of a retrospective and prospective cohort, each comprising approximately 1,500 patients with AKI receiving continuous kidney replacement therapy (CKRT). Other information included AKI-related information, CKRT prescriptions, and patient outcomes. Follow-up timeframes were set at baseline, 1 week, 3 months, and 1 year after the initiation of CKRT. Human biospecimens will be collected from the prospective cohort. An artificial intelligence model was developed using the retrospective cohort to predict the prognosis of AKD and its subsequent sequelae and to formulate patient-individualized treatments, with validation planned in a prospective cohort. Follow-up studies are scheduled to identify biomarkers related to outcomes using biospecimens. Finally, based on the results and literature review, decision-making on the prevention and management of diseases, as well as the development of treatment guidelines, are being planned. This study will provide scientific evidence on clinical insights and appropriate management targets for AKI and AKD, which will form the basis for relevant treatment guidelines. Additionally, these findings may facilitate a more personalized approach to patient care, enabling clinicians to tailor treatments based on individual biomarker profiles and predictive models.

Long-term results of intensive care patients with post-intubation tracheal stenosis: 7 years follow-up.

Benign tracheal stenosis (TS) is a potentially life-threatening condition caused by iatrogenic events resulting from endotracheal intubation and tracheostomy. The study aimed to determine the clinical characteristics, management, and long-term outcomes of patients with simple or complex post-intubation tracheal stenosis (PITS) who were admitted to the intensive care unit (ICU). Retrospective analysis of patients admitted to the ICU between June 2016 and June 2022 and diagnosed with PITS were performed until June 2023. 76 patients (mean age 54.9 ± 17.3%, 63.2% male, 61.8% complex stenosis) admitted to the ICU were analysed. The diagnosis of PITS was made by fiberoptic bronchoscopy (FOB) in 53.9% and computed tomography (CT) in 46.1%. The most common location of stenosis was the upper trachea area (57.9%, n = 44). The median stenosis length of the TS was 1.9cm (median 2cm for complex stenosis, 1cm for simple stenosis, p < 0.001). Complex stenosis was associated with longer intubation time and multiple intubation history (p = 0.011, p = 0.028). At the same; complex stenosis was associated with prolonged and high stenosis percentage (p < 0.001). While dilatation and cryotherapy were sufficient for treatment in all patients with simple stenosis, the stent was applied to 34% patients with complex stenosis. Recurrence was higher in complex stenosis after bronchoscopic procedure (complex stenosis 95.7%, simple stenosis 17.2%). 19 (25%) patients required surgical operation, and all of these patients had complex stenosis (p < 0.001). Median follow-up was 33 months for simple stenosis and 34 months for complex stenosis. ICU length of stay (LOS) was longer in patients with complex stenosis. There was no statistically significant difference between TS classes in terms of ICU mortality (p = 0.466), 1-year mortality (p = 0.951), and mortality during follow-up (p = 0.608). PITS is a challenging situation in ICU patients. In patients with a preliminary diagnosis of PITS, bronchoscopy should be performed without delay, and it should be known that interventional bronchoscopy is not only a diagnostic tool but an effective strategy in treatment management after the diagnosis is finalised. The advantage of interventional bronchoscopy is that it alleviates symptoms that necessitate hospitalisation in the ICU and eliminates the need for ICU of patients.

Contemporary Clinical Characteristics, Imaging, Management, and Surgical and Nonsurgical Outcomes of Adult Patients With Subaortic Stenosis.

Subaortic stenosis (SAS) is characterized by a fibromuscular membrane located just below the aortic valve, causing fixed outflow tract obstruction. There is a paucity of studies evaluating this condition. This cohort study reviewed the contemporary characteristics and outcomes of SAS in adult patients in a single large referral center. We retrospectively studied adult patients with SAS evaluated at our center during 2011 to 2022. The primary outcome was all-cause mortality and heart failure hospitalizations during follow-up, with secondary end points including recurrence of SAS and repeat surgery after initial SAS surgery. Among 484 patients with SAS, key characteristics included mean age 55±18 years, 67.5% female, left ventricular outflow tract peak velocity 352±140 cm/s and gradient 57±40 mm Hg, left ventricular ejection fraction 60%±14%, 54.8% had prior SAS surgery, and 45.1% had surgery during follow-up. Over a median follow-up of 5.5 (1.5-12.3) years, 11.5% (n=56) died, 6.8% (n=33) had heart failure hospitalizations, 8.0% (n=39) experienced SAS recurrence, and 14 (5.9%) underwent repeat SAS surgery. Multivariable analyses identified older age per 10-years (hazard ratio [HR], 1.37 [95% CI, 1.12-1.68]) and baseline New York Heart Association class (HR, 2.48 [95% CI, 1.54-3.99]) to be statistically significantly associated with the primary end point; higher body mass index, New York Heart Association class, and peak left ventricular outflow tract gradient were also statistically significantly associated with SAS recurrence and redo surgery. Almost half of patients with SAS had surgery in the past or during follow-up, and a significant minority had mortality or morbidity events during follow-up. Identified prognosticators warrant further research to guide management.

PATH-37. A NEW SUBTYPE OF DIFFUSE MIDLINE GLIOMA, H3 K27 AND BRAF/FGFR1 CO-ALTERED, EXHIBITS SPECIFIC BIOLOGICAL CHARACTERISTICS AND NEW THERAPEUTIC VULNERABILITIES

Abstract Diffuse midline gliomas (DMG) H3 K27-altered are incurable grade 4 gliomas and represent a major challenge in neuro-oncology. This tumor type is classified in four subtypes by the 2021 edition of the WHO Classification of the Central Nervous System tumors. However, we recently identified a new subtype of DMG by assembling a retrospective cohort of 60 adult and pediatric DMG cases harboring BRAF or FGFR1 mutations in addition to the H3K27M mutation or EZHIP overexpression. Comprehensive clinical, histological, radiological, and genomic, analyses allowed to identify distinct genotype-phenotype characteristics. Contrary to other DMG, these tumors occur more frequently in the thalamus (27% vs. 70% for BRAFV600E or 58% for FGFR1MUT), and in adults in the case of FGFRMUT tumors. Importantly, these patients display a longer overall survival with a median above three years. Unsupervised analysis of DNA methylation profiles regrouped these MAPK-altered DMG in a methylation cluster distinct from other DMG H3K27, but also lower-grade midline tumors driven by FGFR1 or BRAF mutations Additionally, this new DMG subtype harbors atypical radiological and histopathological profiles with calcification and/or a solid tumor component both for BRAFV600E and FGFR1MUT cases that can suggest this differential diagnosis. Further analyses of the transcriptome of these tumors compared to canonical DMG H3K27-altered showed an expression signature of senescence with activation of a TP53/CDKN1A axis, together with a strong upregulation of the PI3K/AKT/MTOR pathway. Our current modelling of the drug response using patient-derived models of these specific DMG will permit to rapidly prioritize treatment strategies. Additionally, our clinical experience in treating these patients suggests a higher response to everolimus and imipridone ONC201 in this specific subtype. In conclusion, DMG H3 K27 and BRAF/FGFR1 co-altered, represent a new subtype of DMG with distinct specific characteristics compared to canonical DMG H3K27 and data accumulated strongly support their separate stratification in clinical trials and specific therapeutic managements.