Specific Patient Characteristics Research Articles

Gastric Organoid, a Promising Modeling for Gastric Stem Cell Homeostasis and Therapeutic Application.

The elucidation of the pathophysiology underlying various diseases necessitates the development of research platforms that faithfully mimic in vivo conditions. Traditional model systems such as two-dimensional cell cultures and animal models have proven inadequate in capturing the complexities of human disease modeling. However, recent strides in organoid culture systems have opened up new avenues for comprehending gastric stem cell homeostasis and associated diseases, notably gastric cancer. Given the significance of gastric cancer, a thorough understanding of its pathophysiology and molecular underpinnings is imperative. To this end, the utilization of patient-derived organoid libraries emerges as a remarkable platform, as it faithfully mirrors patient-specific characteristics, including mutation profiles and drug sensitivities. Furthermore, genetic manipulation of gastric organoids facilitates the exploration of molecular mechanisms underlying gastric cancer development. This review provides a comprehensive overview of recent advancements in various adult stem cell-derived gastric organoid models and their diverse applications.

Patient experiences and needs in cancer care– results from a nationwide cross-sectional study in Germany

BackgroundPatient-centredness has become a central quality indicator for oncology care. Elements include shared decision-making, patient navigation and integration of psychosocial care, which impact patient-reported and clinical outcomes. Despite efforts to promote patient-centred care in Germany in recent decades, implementation remains fragmented. Further, research on patient experiences with cancer care and its determinants is limited. Therefore, this study examines which patient- and facility-specific factors are associated with patient-centred quality care delivery.MethodsA cross-sectional study was conducted among 1,121 cancer patients in acute treatment, rehabilitation, and aftercare for different cancer entities across Germany. A participatory developed questionnaire was used. Outcome measures were the quality of physician-patient interaction and provision of psychosocial care during acute care. Predictors comprised patient-specific characteristics and treatment facility-specific factors. Multiple linear regression and multivariate binary logistic regression analyses were performed. In addition, a content analysis of open-ended comments on the patients’ overall cancer care needs was applied.ResultsMultiple linear regression analysis showed recent diagnosis (β=−0.12, p = < 0.001), being male (β=−0.11, p = 0.003), and having a preference for passive decision-making (β=−0.10, p = 0.001) to be significantly associated with higher interaction quality, but not age, education and health insurance type. An overall low impact of patient characteristics on interaction quality was revealed (adj. R2 = 0.03). Binary logistic regression analysis demonstrated the availability of central contact persons (OR = 3.10, p < 0.001) followed by recent diagnosis (p < 0.001), having breast cancer (p < 0.001) and being female (OR = 1.68, p < 0.05) to significantly predict offering psycho-oncological counselling to patients in acute care facilities. The availability of peer support visiting services (OR = 7.17, p < 0.001) and central contact persons (OR = 1.87, p < 0.001) in the care facility, breast cancer diagnosis (p < 0.001) and a higher level of education (p < 0.05) significantly increased the odds of patients receiving information about peer support in the treatment facility. Despite relatively satisfactory quality of physician-patient interactions in cancer care (M = 3.5 (± 1.1)), many patients expressed that better patient-centred communication and coordinated, comprehensive cancer care are needed.ConclusionThe findings reflect effective developments and improvements in cancer care and suggest that patients’ social characteristics are less decisive for delivering patient-centred quality care than systemic factors surrounding the care facilities. They can serve to inform oncology care in Germany.

Trends, safety, and efficacy of wearable male sexual devices.

The prevalence of male sexual dysfunction (MSD) increases with age, with >50% of men aged >40years reporting erectile dysfunction (ED). In recent years, wearable male sex devices (WMSDs) have been increasingly utilized by patients and recommended by sexual medicine clinicians. This study seeks to investigate the safety and efficacy of products currently marketed for the treatment of MSD. Available products for WMSDs were reviewed by analyzing product websites, forums, advertisements, and clinical recommendations. Qualitative comparisons were based on patient reviews, cost, and specific features. Investigatory evidence and Food and Drug Administration status were also reviewed. Additionally, Google Trends was used to determine the popularity of devices over time. Eight WMSDs for the treatment of MSD and enhancement of sexual pleasure were reviewed. Constriction bands, such as the Maintain Ring Loop, Eddie by Giddy, and Xialla, have shown significant benefits in clinical trials and were the most popular devices among patients. Smart devices can provide real-time feedback on erectile quality and/or sexual performance. Similar to the RigiScan, the Adam sensor provides feedback on erectile quality while monitoring changes in penile tumescence during sleep with additional analysis available through a mobile application. Neuromodulation devices such as the Morari Patch and vPatch/in2 Patch use electrical stimulation to delay ejaculation and improve sexual function. The FirmTech Performance Ring uses sensors to track the vital signs of erectile fitness with clinical trials ongoing. Overall, this review describes the available investigatory evidence for a range of WMSDs and highlights the potential benefits and limitations of these devices in treating MSD and enhancing sexual pleasure. Further research is needed to evaluate the effectiveness of these devices and to determine which ones may be the most suitable for individual patients.

Tackling carbapenem resistance: ceftazidime - avibactam in contemporary clinical scenarios

Antimicrobial resistance poses a formidable challenge in treating severe infections, with the prevalence of extended-spectrum beta-lactamase (ESBL) - producing, Klebsiella pneumoniae carbapenemase (KPC) - producing, and multidrug-resistant (MDR) organisms on the rise. This necessitates careful consideration of various factors, including local resistance patterns, patient-specific characteristics, and drug properties, in treatment decisions for critically ill patients. Ceftazidime-Avibactam demonstrates efficacy against aerobic Gram-negative bacteria and offers a crucial advancement against carbapenem-resistant organisms (CRO) with its effectiveness against key pathogens, including ESBL, AmpC, KPC, and OXA-48-producing Enterobacteriaceae and drug-resistant P. aeruginosa. Ceftazidime-Avibactam emerges as a valuable option for critically ill patients with limited treatment choices. The drug's excellent safety profile demonstrated in clinical trials, further positions it as a crucial addition to antimicrobial treatment options. As the global threat of drug-resistant bacteria grows, Ceftazidime-Avibactam plays a pivotal role in addressing this challenge and offers a promising solution for critically ill patients facing infections caused by antimicrobial-resistant pathogens. The article delves into therapeutic efficacy and the prospective role of Ceftazidime-Avibactam in managing MDR Gram-negative organisms, underscoring the critical role of appropriate antibiotic administration in reducing mortality associated with Gram-negative infections.

The Effect of Osteoporosis on Complications and Reoperation Rates After Surgical Management of Adult Thoracolumbar Spinal Deformity: A Systematic Review and Meta Analysis.

Systematic Review. While substantial research has explored the impact of osteoporosis on patients undergoing adult spinal deformity (ASD) correction, the literature remains inconclusive. As such, the purpose of this study is to synthesize and analyze existing studies pertaining to osteoporosis as a predictor of postoperative outcomes in ASD surgery. We performed a systematic review and meta-analysis to determine the effect that a diagnosis of osteoporosis, based on ICD-10 coding, dual-energy X-ray absorptiometry (DEXA) or computed tomography, has on the incidence of adverse outcomes following surgical correction of ASD. Statistical analysis was performed using Comprehensive Meta-Analysis (Version 2) using a random effects model to account for heterogeneity between studies. After application of inclusion and exclusion criteria, 36 and 28 articles were included in the systematic review and meta-analysis, respectively. The meta-analysis identified greater rates of screw loosening amongst osteoporotic patients (70.5% vs 31.9%, P = .009), and decreased bone mineral density in patients who developed proximal junctional kyphosis (PJK) (.69 vs .79g/cm2, P = .001). The systematic review demonstrated significantly increased risk of any complication, reoperation, and proximal junctional failure (PJF) associated with reduced bone density. No statistical difference was observed between groups regarding fusion rates, readmission rates, and patient-reported and/or functional outcome scores. This study demonstrates a higher incidence of screw loosening, PJK, and revision surgery amongst osteoporotic ASD patients. Future investigations should explore outcomes at various follow-up intervals in order to better characterize how risk changes with time and to tailor preoperative planning based on patient-specific characteristics.

Clinical Prediction Models for Prognosis of Colorectal Liver Metastases: A Comprehensive Review of Regression-Based and Machine Learning Models

Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of “high-risk” patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to derive prediction models for these patients, and lately, focus has shifted to artificial intelligence-based models, with employment of variable supervised and unsupervised techniques. Multiple endpoints, like overall survival (OS), disease-free survival (DFS) and development or recurrence of postoperative complications have all been used as outcomes in these studies. This review provides an extensive overview of available clinical prediction models focusing on the prognosis of CRLM and highlights the different predictor types incorporated in each model. An overview of the modelling strategies and the outcomes chosen is provided. Specific patient and treatment characteristics included in the models are discussed in detail. Model development and validation methods are presented and critically appraised, and model performance is assessed within a proposed framework.

Knee Cartilage Injuries in Football Players: Clinical Outcomes and Return to Sport After Surgical Treatment: A Systematic Review of the Literature.

To systematically review the literature and analyze clinical outcomes and return-to-sport after surgical management of cartilage injuries in football players. A systematic literature review was performed in August 2023 on PubMed, WebOfScience, and Cochrane Library to collect studies on surgical strategies for cartilage lesions in football players. Methodological quality and risk of bias were assessed with the modified Coleman Methodology score and RoB2 and RoBANS2 tools. Fifteen studies on 409 football players (86% men, 14% women) were included: nine prospective and two retrospective case series, one randomized controlled trial, one prospective comparative study, one case report, and one survey. Bone marrow stimulation (BMS) techniques were the most documented. The lesion size influenced the treatment choice: debridement was used for small lesions (1.1 cm2), BMS, osteochondral autograft transplantation (OAT), matrix-assisted autologous chondrocytes transplantation (MACT), and scaffold-augmented BMS for small/mid-size lesions (2.2-3.0 cm2), and autologous chondrocytes implantation (ACI) for larger lesions (5.8 cm2). The surgical options yielded different results in terms of clinical outcome and return-to-sport, with fastest recovery for debridement and scaffold-augmented BMS. The current evidence is limited with large methodological quality variation (modified Coleman Methodology score 43.5/100) and a high risk of bias. Decision-making in cartilage injuries seems to privilege early return-to-sport, making debridement and microfractures the most used techniques. The lesion size influences the treatment choice. However, the current evidence is limited. Further studies are needed to confirm these findings and establish a case-based approach to treat cartilage injuries in football players based on the specific patient and lesion characteristics and the treatments' potential in terms of both return-to-sport and long-term results. Systematic review, level IV.

Approach to the patient: Concept and application of targeted radiotherapy in the paraganglioma patient.

Paragangliomas can metastasize, posing potential challenges in both symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and 177Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians' knowledge of the stepwise approach to treat these patients with paraganglioma targeted radiotherapies. It comprehensively discusses current approaches to selecting paraganglioma patients for targeted radiotherapies and how to choose between the two radiotherapies based on specific patient and tumor characteristics, when either therapy is feasible, or one is superior to another one. The safety, efficacy, toxicity profiles, and optimization of these radiotherapies are also discussed, along with other therapeutic options including radiotherapies, available for patients besides these two therapies. As conclusion, perspectives in radiotherapies of paraganglioma patients are outlined since they hold near future promising approaches that can improve patient outcomes.

Individualized center-based analysis of urinary and sexual functional outcome after radical prostatectomy based on the prostate cancer outcome study: a post hoc pathway to patient outcome measurement analysis for quality improvement.

We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center. All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution. Logistic regression analyses were performed to examine the correlation between individual surgeons, patient characteristics, patient clinical data, and their urinary continence and sexual function. In total, data of 429 men were analyzed: unstratified mean (SD) EPIC-26 domain score for urinary function decreased from 93.3 (0.7) to 60.4 (1.5) one year after RPE, respectively for sexual function from 64.95 (1.6) to 23.24 (1.1). Patients with preoperative adequate urinary function (EPIC-26 score > 80) reported significantly different mean urinary function scores between 53.35 (28.88) and 66.25 (25.15), p= 0.001, stratified by surgeons experience. On binary logistic regression analyses, only nerve sparing techniques (OR: 1,83, 95% CI: 1.01;3.21; p = 0.045) and low body mass index (OR: 0.91, CI: 0.85;0.99, p= 0.032) predicted adequate postoperative urinary function. The results show how using provider-specific data from a larger cohort study enables to develop institution-specific analysis for functional outcomes after RPE. These models can be used for internal quality improvement as well as enhanced and provider-specific patient communication and shared decision making.

An overview of current assessment techniques for evaluating cutaneous perfusion in reconstructive surgery.

This article provides a comprehensive analysis of modern techniques used in the assessment of cutaneous flaps in reconstructive surgery. It emphasizes the importance of preoperative planning and intra- and perioperative assessment of flap perfusion to ensure successful outcomes. Despite technological advancements, direct clinical assessment remains the gold standard. We categorized assessment techniques into non-invasive and invasive modalities, discussing their strengths and weaknesses. Non-invasive methods, such as acoustic Doppler sonography, near-infrared spectroscopy, hyperspectral imaging thermal imaging, and remote-photoplethysmography, offer accessibility and safety but may sacrifice specificity. Invasive techniques, including contrast-enhanced ultrasound, computed tomography angiography, near-infrared fluorescence angiography with indocyanine green, and implantable Doppler probe, provide high accuracy but introduce additional risks. We emphasize the need for a tailored decision-making process based on specific clinical scenarios, patient characteristics, procedural requirements, and surgeon expertise. It also discusses potential future advancements in flap assessment, including the integration of artificial intelligence and emerging technologies.

Advances in neuropathic pain management: A review of real-world studies

Abstract Neuropathic pain (NP) is defined as a process occurring after a primary lesion or disease of the somatosensory nervous system. The diagnosis of NP is a comprehensive process. The assessment begins with the medical history of the patient, conducting neurological assessments, and using pain scales to quantify pain intensity and measure sensory thresholds. NP treatment involves a diversity of pharmacological and nonpharmacological interventions, based on patient-specific characteristics, causal factors, medical history, and intensity of pain. Sociodemographic characteristics, psychological factors, and medical conditions are the potential predictors of the treatment response for an outcome. NP severely affects the quality of life of the patient. This review has reviewed the diagnostic approaches and management of NP through real-world evidence on the effectiveness of different lines of treatment.

Screening for Relative Energy Deficiency in Sport and Female Athlete Triad: A Survey of Pediatric Sports Medicine Professionals

BACKGROUND: Relative Energy Deficiency in Sport, or RED-S, is a multi-scale physiological response to a mismatch between energy intake and exercise energy expenditure that affects up to 50% of adolescent athletes. RED-S symptomology was first described as the Female Athlete Triad (the Triad) and includes specifically low energy availability with or without disordered eating, menstrual dysfunction, and low bone mineral density. Despite the wide impact of RED-S/the Triad, there is a lack of standardization of screening in adolescent athletes. Therefore, the purpose of this study was to assess if there are differences in practitioner demographics when screening for RED-S/the Triad in adolescent athletes. In addition, we sought to assess if providers’ screening habits differ based on specific patient characteristics.  METHODS: We conducted a cross-sectional online questionnaire of members of the Pediatric Research in Sports Medicine (PRiSM) Society. PRiSM is an interdisciplinary group of professionals who are dedicated to advancing the research and medical care of young athletes. The questionnaire assessed screening tools that members used to assess for RED-S/the Triad, practices implemented when providers were concerned for RED-S/the Triad, demographic data, and type of training. RESULTS: Of 389 PRiSM members, 60 completed the survey and were included in subsequent analyses (15% response rate). Most participants were primary care sports medicine physicians (37%), orthopaedic surgeons (27%), or physical therapists (23%), and about half of respondents identified as a cis gender woman (55%). There was a trend toward more women screening for RED-S routinely than men (55% vs. 33%: p=0.10), and orthopaedic surgeons were less likely to screen than other specialties (25% vs. 52%, p = 0.06). Eating disorders (88%), menstrual dysfunction (76%), and bone stress injury (74%) were reported as specific red flags that make providers screen for RED-S/the Triad. Participants reported that lack of time (57%) and lack of resources (37%) were barriers to screen for RED-S/the Triad. The most commonly utilized tools to screen for RED-S/the Triad were the Female Athlete Screening Tool (FAST), Female Athlete Triad Risk Scale, Female Athlete Triad Consensus Panel Screening questions, and RED-S Specific Screening Tool (RST). CONCLUSION: Orthopaedic surgeons were less likely than other health care professionals to screen for RED-S/the Triad. Barriers that prevent healthcare providers from screening for RED-S/the Triad included limited time and resources. By describing current practices, we have identified gaps and areas of need to enhance screening for RED-S/the Triad across multiple sports medicine disciplines.

Safety of Clopidogrel vs. Ticagrelor in Dual Antiplatelet Therapy Regimens for High-Bleeding Risk Acute Coronary Syndrome Patients: A Comprehensive Meta-analysis of Adverse Outcomes.

Patients of acute coronary syndrome (ACS) at a high-bleeding risk (HBR) often require dual antiplatelet therapy (DAPT) to reduce the risk of recurrent cardiovascular events. Clopidogrel and ticagrelor are the most commonly used antiplatelet agents in DAPT regimens. However, the safety profiles of these drugs in ACS patients at HBR remain a subject of ongoing debate. To investigateany difference between the safety of clopidogrel and ticagrelor used as a part of DAPT regimen in ACS patients at HBR. A systematic search on PubMed, Cochrane Library, and Google Scholar was conducted to identify experimental and observational studies published up to the knowledge cutoff date in September 2023. Studies comparing the safety of clopidogrel and ticagrelor in ACS patients at HBR were included for analysis. The primary outcomes assessed were major bleeding events, stroke, and myocardial infarction (MI), while secondary outcomes included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical and cerebral events (NACCE). We included a total of 8 observational studies in our meta-analysis. The pooled analysis revealed a statistically significant increase in the risk of MI (pooled RR = 1.43; 95% CI 1.12-1.83; P = 0.005) in the patients using clopidogrel. There were no statistically significant differences in major bleeding events (pooled RR = 0.94; 95% CI 0.82-1.09; P = 0.44), stroke (pooled RR = 1.36; 95% CI 0.86-2.14; P = 0.18), all-cause mortality (pooled RR = 1.17; 95% CI 0.97-1.41; P = 0.10), MACCE (pooled RR = 1.07; 95% CI 0.76-1.50; P = 0.69) and NACCE (pooled RR = 0.95; 95% CI 0.66-1.37; P = 0.78) between the two groups. Subgroup analyses based on region were performed. Both drugs are generally safe for treating ACS patients with HBR at baseline, although a higher risk of MI was observed with the use of clopidogrel. Nevertheless, drug choice should factor in regional variations, patient-specific characteristics, cost, accessibility, and potential drug interactions.

84 Using Opportunistic Sampling and Remnant Blood Samples to Develop Pediatric Pharmacokinetic Models to Inform Antidepressant Dosing

OBJECTIVES/GOALS: Developing pharmacokinetic (PK) models to guide selective serotonin reuptake inhibitor (SSRI) dosing in youth is costly, time-intensive, and requires large numbers of participants. We evaluated the use of remnant blood samples from SSRI-treated youth and developed precision PK dosing strategies. METHODS/STUDY POPULATION: Following IRB approval, we used a clinical surveillance platform to identify patients with routine phlebotomy within 24 hours of escitalopram or sertraline dosing. Remnant blood samples were obtained from youth aged 5–18 years, escitalopram and sertraline concentrations were determined, and clinical characteristics (e.g., age, sex, weight, concomitant medications that inhibit sertraline or escitalopram metabolism) and phenotypes for CYP2C19, the predominant enzyme that metabolizes these SSRIs, were extracted from the electronic medical record (EMR). A population PK analysis of escitalopram and sertraline was performed using NONMEM. The influence of clinical variables, CYP2C19, and dosing was evaluated from simulated concentration-time curves. RESULTS/ANTICIPATED RESULTS: Over 21 months, we collected315 samples from escitalopram-treated patients (N=288) and 265 samples from sertraline-treated patients (N=255). In youth, escitalopram and sertraline exposure (concentrations over time) and specific pharmacokinetic parameters (e.g., clearance) were influenced by CYP2C19 phenotype, concomitant CYP2C19 inhibitors, and patient-specific characteristics. Escitalopram and sertraline concentrations from remnant blood samples were 3.98-fold higher and 3.23-fold higher, respectively, in poor metabolizers compared to normal metabolizers (escitalopram, p&lt;0.001) and compared to normal, rapid, and ultrarapid metabolizers combined (sertraline, p&lt;0.001). DISCUSSION/SIGNIFICANCE: Combining remnant blood sampling with pharmacogenetic-integrated EMR data can facilitate large-scale population PK analyses of escitalopram and sertraline in youth. This real-world approach can be used to rapidly develop precision SSRI dosing strategies, including slower titration and reduced target doses in CYP2C19 poor metabolizers.

Period of hospitalization and mortality in transferred versus non-transferred COVID-19 patients: results from Germany

COVID-19 was a challenge for health-care systems worldwide, causing large numbers of hospitalizations and inter-hospital transfers. We studied whether transfer, as well as its reason, was associated with the duration of hospitalization in non-ICU and ICU patients. For this purpose, all patients hospitalized due to COVID-19 between August 1st and December 31st, 2021, in a network of hospitals in Southern Germany were comprehensively characterized regarding their clinical course, therapy, complications, transfers, reasons for transfer, involved levels of care, total period of hospitalization and in-hospital mortality, using univariate and multiple regression analyses. While mortality was not significantly associated with transfer, the period of hospitalization was. In non-ICU patients (n = 545), median (quartiles) time was 7.0 (4.0–11.0) in non-transferred (n = 458) and 18.0 (11.0–29.0) days in transferred (n = 87) patients (p < 0.001). In ICU patients (n = 100 transferred, n = 115 non-transferred) it was 12.0 (8.3–18.0) and 22.0 (15.0–34.0) days (p < 0.001). Beyond ECMO therapy (4.5%), reasons for transfer were medical (33.2%) or capacity (61.9%) reasons, with medical/capacity reasons in 32/49 of non-ICU and 21/74 of ICU patients. Thus, the transfer of COVID-19 patients between hospitals was associated with longer periods of hospitalization, corresponding to greater health care utilization, for which specific patient characteristics and clinical decisions played a role.

ASSESSMENT OF THE THERAPEUTIC EFFICACY OF PROPRANOLOL FOR THE TREATMENT OF INFANTILE HEMANGIOMAS

Infantile hemangiomas (IHs) are common vascular tumors affecting pediatric populations, often necessitating medical intervention due to their potential for complications. Propranolol has emerged as a promising therapeutic option for IHs, although optimal dosing regimens and treatment outcomes remain areas of ongoing research. This prospective observational study aimed to evaluate the therapeutic efficacy, safety profile, and clinical characteristics associated with propranolol treatment in pediatric patients with IHs. Eighty infants aged one month to 1 year were included in the study, with IH occurrence and treatment initiation predominantly observed within the first 12 months of life. Propranolol was administered orally at a starting dose of 2 mg/kg/day, titrated up to 3-4 mg/kg/day as tolerated. Assessment of therapeutic response revealed significant reductions in IH size and vascularity, with 31.3% of patients demonstrating an excellent response and 37.5% showing a good response. Adverse effects were minimal, with diarrhea (22.5%) and decreased heart rate (7.5%) being the most commonly reported side effects. Anatomical distribution analysis identified the parotid region as the most common site of lesion occurrence, highlighting the heterogeneous nature of IHs. Overall, our findings support the favorable outcomes of propranolol therapy in pediatric patients with IHs, emphasizing the need for individualized treatment approaches tailored to patient-specific characteristics.

Patient-specific factors for deformity after upper blepharoplasty in an Asian population.

The success of upper blepharoplasty depends on both surgeon experience and skill as well as patient factors. Therefore, we aimed to identify patient-specific characteristics that may contribute to poor prognoses by analyzing data derived from patients with various deformities after undergoing upper blepharoplasty. This study included 202 patients who underwent revision surgery for upper blepharoplasty. We explored relationships between types of deformities before revisions and relevant patient factors before initial surgery using statistical analyses. Age > 30 years, thick upper lid skin, medial epicanthus, and other patient factors were significantly associated with the deformities. Asymmetrical, disappeared, shallow, and low creases were the most prevalent deformities. For these four most prevalent deformities, the concordance indices and 95% confidence limits of the risk prediction models were 0.654 (0.575-0.734), 0.724 (0.637-0.810), 0.783 (0.702-0.863), and 0.750 (0.655-0.844), respectively. Among the four most prevalent prognostic deformities, significant patient factors included medial epicanthus, thick upper eyelid skin, weak levator palpebrae superioris, age > 30 y, and a short gap between eyes and brows. We also attempted to clarify the clinical importance of these patient factors. Our findings provide a guide and reference for future investigations into upper blepharoplasty.

Abstract 3564: Survival-based grouping of genetic variants: A novel statistical framework with an application to TP53 mutations

Abstract Advancements in genotyping and sequencing techniques, coupled with the growing magnitude of genome databases, have led to comprehensive investigations into the impact of genetic variants on human diseases, including cancers. It is commonly acknowledged that genetic variants have homogeneous effects on clinical outcomes, i.e., variants exhibit similar effects within a certain group but are distinct from those in other groups. However, such grouping information is typically unknown, and identification of the underlying genetic variation groups is crucial for understanding their functional consequences, facilitating patient management, and improving risk prediction. To resolve this challenge, we introduce a novel statistical framework called Survival-based Clustering of Predictors (SCP) in Cox regression to group genetic variants based on patient survival outcomes. Built upon a penalized Cox regression model, SCP considers different genetic variants, as well as additional patient-specific features if needed, as survival predictors and then searches for homogeneity among the coefficients for individual variants to recover the underlying grouping structure. Focusing on TP53, the most frequently mutated gene in cancer that has resulted in a wide range of functions and clinical outcomes, we apply SCP to group TP53 germline mutations with the age of cancer diagnosis as the time-to-event. Using datasets from four Li-Fraumeni syndrome (LFS) cohorts at MD Anderson, NCI, and DFCI, we obtained 75 recurring TP53 germline mutations from 513 patients and clustered these mutations into high-, medium-, and low-risk groups. Hotspot mutations such as R175H, R248Q, G245S, and R273C are in the high-risk group as supported in many TP53 studies, while several non-hotspot mutations such as R290H, V218G, and G244D also exhibit strong positive effects and are grouped together with hotspot mutations. Overall, mutations in all three risk groups, obtained through applying SCP, are highly consistent with a yeast functional assay-based approach for grouping TP53 mutations, supporting the utility of SCP for survival-based grouping of genetic variants. The contribution of our study is three-fold. Statistically, our method fills a critical gap in the survival analysis literature, offering a novel statistical framework for clustering predictors in Cox regression based on survival outcomes. Clinically, we provide a timely solution to the patient outcome-based grouping of TP53 mutations, facilitating clinical management of TP53 mutation carriers. Biologically, we bring fresh insights into knowledge for the most frequently observed genetic variants in cancer, providing new hypotheses to TP53-related biological research. Citation Format: Xiaoqian Liu, Haoming Shi, Emilie Montellier, Pierre Hainaut, Wenyi Wang. Survival-based grouping of genetic variants: A novel statistical framework with an application to TP53 mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3564.

Abstract 3906: Ex vivo breast tumors for understanding the patient specific tumor microenvironment remodeling and drug responses

Abstract Breast cancer is a heterogeneous disease driven by cell-intrinsic and cell-extrinsic signaling cues. Many of these cues derive from the tumor microenvironment (TME), which is composed of adipocytes, vasculature, stem cells, immune cells, and the extracellular matrix (ECM). Through these diverse components, the TME modulates cellular proliferation, survival, and ultimately response to therapy. Despite this high-level understanding of tumor-TME crosstalk, no existing pre-clinical models accurately capture the TME in vitro. We overcame that hurdle by developing a method to maintain healthy human breast tissue (HBT) alive ex vivo for at least 8 weeks. By culturing breast cancer cells in that HBT, we created ex vivo breast tumors (EVBTs) that retained patient-specific features relevant to breast cancer including menopause status, obesity status, and response to therapy. Using these EVBTs, we demonstrate breast cancer subtype-specific alterations in lipid accumulation, ECM remodeling, and cytokine profiles. RNA sequencing showed that breast cancer cell line signatures were retained in the EVBTs system at 1 week and 2 weeks in vitro. We demonstrated donor-specific transcriptional changes to the core matrisome gene set. Finally, we demonstrate that our EVBTs retained patient-specific heterogeneity in response to standard of care endocrine therapy and neoadjuvant chemotherapies. Our novel tumor model allows for 1) real-time examination of breast cancer interactions with HBT and the TME and 2) the isolation of breast cancer-specific factors vs. patient-specific factors in the development and progression of breast cancer. Citation Format: Elizabeth Martin, Megan Benz, Katie Hebert, Ethan Byrne, Frank Lau. Ex vivo breast tumors for understanding the patient specific tumor microenvironment remodeling and drug responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3906.

Impact of Pressure Guidewire on Model-Based FFR Prediction.

Fractional Flow Reserve (FFR) is used to characterize the functional significance of coronary artery stenoses. FFR is assessed under hyperemic conditions by invasive measurements of trans-stenotic pressure thanks to the insertion of a pressure guidewire across the coronary stenosis during catheterization. In order to overcome the potential risk related to the invasive procedure and to reduce the associated high costs, three-dimensional blood flow simulations that incorporate clinical imaging and patient-specific characteristics have been proposed. Most CCTA-derived FFR models neglect the potential influence of the guidewire on computed flow and pressure. Here we aim to quantify the impact of taking into account the presence of the guidewire in model-based FFR prediction. We adopt a CCTA-derived FFR model and perform simulations with and without the guidewire for 18 patients with suspected stable CAD. Presented results show that the presence of the guidewire leads to a tendency to predict a lower FFR value. The FFR reduction is prominent in cases of severe stenoses, while the influence of the guidewire is less pronounced in cases of moderate stenoses. From a clinical decision-making point of view, including of the pressure guidewire is potentially relevant only for intermediate stenosis cases.