Predictor Of Clinical Outcome Research Articles

Arterial Stiffness as a New Predictor of Clinical Outcome in Patients with Polycythemia Vera

Background: Thrombotic adverse events and disease progression are crucial in Polycythemia Vera (PV), as it stands as the leading cause of mortality. The pulse wave velocity (PWV) is a valuable indicator of arterial aging and often plays a significant independent role in contributing to cardiovascular adverse events (CV-AEs). The aim of this study was to examine the relationship between PWV and critical vascular function parameters, with the goal of identifying new predictive factors of vascular damage and exploring a potential connection with disease progression. Methods: Non-invasive aortic stiffness was assessed through carotid–femoral PWV measurement. PWV was measured using the SphygmoCor device. History of arterial or venous thrombosis (TAEs) or other CV-AEs was collected at baseline. PWV measurements were repeated at baseline, at 6 and at 12 months. Results: The study involved 28 PV patients aged 27 to 77 years, with 57.1% being male. Fourteen patients (50%) reported a high-risk thrombotic score at diagnosis, and 60.7% had at least one comorbidity. Multivariable regression models showed that hemoglobin levels were independently associated with PWV (β: 0.68, SE 0.24, p < 0.01). During the follow-up period (median duration 21.3 months, range 6–33), a total of 13 events were documented. Specifically, two patients exhibited a loss of response to treatment, four patients presented an increase in spleen diameters, three patients displayed an escalation of systemic symptoms, and three patients had a clear progression to secondary myelofibrosis. PWV (per 1 m/s: OR 1.70, 95% CI 1.00–2.91, p = 0.047) and leukocyte count (per 1 × 103/μL: OR 1.47, 95% CI: 1.04–2.09, p = 0.043) were significant predictors of events, independently of waist circumference, blood pressure, treatment, and hematocrit. Conclusions: PWV has demonstrated its potential as an effective tool for monitoring PV patients. It stands as a clinical parameter that can predict the risk of progression in PV patients. Further investigation is essential to fully explore this potential. If successful, it could offer clinicians a valuable resource for effectively managing PV patients.

Abstract 4138545: Mitral Valve Replacement is associated with favourable Functional and Clinical Outcome as compared with Restrictive Mitral Annuloplasty in Patients with Severe Ischemic Mitral Regurgitation. A prospective longitudinal analysis

Background: Restrictive mitral annuloplasty (RMA) and chordal-sparing mitral valve replacement (MVR) are common options for treatment of chronic severe ischemic mitral regurgitation. Research question: in patients with severe ischemic mitral regurgitation the most effective surgical approach remains controversial Aim: to test whether MVR provides superior clinical and functional outcomes compared with RMA. Methods: a prospective longitudinal analysis on 187 patients (age: 66 ± 9 year; EF:35 ± 8 %) undergoing MVR or RMA and CABG for severe ischemic mitral regurgitation. Six-minute walking test and echocardiography were performed at preoperative baseline, at 1 year and at a median FU of 5 year (interquartile range: 2.9). Brain natriuretic peptide levels were also obtained. Mitral regurgitation was defined through a comprehensive and integrative approach. Recurrent mitral regurgitation was defined as a vena contracta ≥ 3 mm at follow-up, in patients with no persistent regurgitation at discharge. The primary outcome was a 5-year composite of all-cause mortality and rehospitalization for heart failure. Survival analysis was performed with Kaplan-Meier method. Cox regression analysis was used to verify any independent predictor of composite end-point Results: Baseline preoperative data were similar between the two group. Mitral valve replacement was performed in 49% of patients (n=92) and RMA in 51 % (n=95). At 5 year patients referred to prostheses showed significant improvement in six-minute walking test as compared to RMA (MVR: 290 ± 70 meters vs MRA: 165± 56 meters) (p > 0.01) ( Figure 1 ). The brain natriuretic peptide values did not differ between the two group at 1 year whereas were significantly lower in the MVR group at 5 years (MVR: 135 pg/ml; interquartile range:100 vs RMA: 486 pg/ml; interquartile range: 68 (p<0.01) ( Figure 2 ). At 5 years freedom from all-cause death and rehospitalization for heart failure was higher in the MVR group as compared to RMA (84 ±8.9% vs 61 ±12%, p<0.01) ( Figure 3 ). According to the Cox analysis recurrent mitral regurgitation was found to be a predictor of clinical outcome (HR:5.4, 95% CI:1.3-23.2, p= 0.023). Conclusions: In patients with severe ischemic mitral regurgitation referred for surgery, chordal- sparing MVR and CABG may improve functional capacity, clinical outcome and brain natriuretic peptide levels, compared with RMA and CABG. The impact of these findings remains to be defined by larger studies on longer term

Abstract 4124506: Short Physical Performance Battery as a Marker of Severity and Predictor of Clinical Outcomes in Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Background: ATTR-CM has an age dependent prevalence and is a disorder that almost exclusively affects older adults. Objective evaluations of function are critical to assessing and managing ATTR-CM in older adults. The short physical performance battery (SPPB) is a valid measure of functional capacity that predicts morbidity and mortality in older adults but its utility in ATTR-CM remains unknown. Aims/hypothesis: To establish SPPB as a useful marker of disease severity and predictor of outcomes in ATTR-CM. We hypothesized that SPPB scores would correlate with validated markers of ATTR-CM severity and improve clinical prediction. Methods: This is a retrospective analysis of patients referred to the Columbia University Cardiac Amyloid Program. Patients were stratified into low (SPPB 0-6), moderate (7-9), and high (10-12) cohorts based on initial SPPB score and baseline characteristics were compared between groups. Cox proportional hazard models and Kaplan Meier (KM) curves were generated to assess associations with mortality as well as a composite of death and cardiovascular (CV) hospitalization in follow-up. Results: A total of 263 patients, age 78 years (IQR 73, 84), 86% male, 22% with ATTRv (variant) and 78% with ATTRwt (wild type) were studied. SPPB showed no limitation in 59%, mild limitation in 33%, and severe limitation in 8%. Lower SPPB was associated (p <0.05) with older age, prior stroke/TIA, shorter 6-minute walk test, elevated NT-proBNP and HS-troponin, worse quality of life metrics on Kansas City Cardiomyopathy Questionnaire, more advanced NYHA and Mayo stages, and higher Columbia scores. On multivariate regression (adjusted for age, sex, genotype, NYHA), SPPB was independently associated with the composite of mortality and CV hospitalization, with each point increase corresponding to 13% lower incidence of the outcome (HR 0.87, p=0.01). Chair stands score, one of three SPPB subdomains, was independently associated with the composite and mortality. KM curves showed significant association with SPPB and both the composite and mortality (Fig. 1). Conclusions: SPPB score is a marker of ATTR-CM severity, associated with validated biomarkers and staging systems, and independently predicts clinical outcomes.

Abstract 4116410: A Novel Deep Learning Approach for Prediction of Right Heart Failure After Left Ventricular Assist Device Implantation using Pulmonary Artery Pressure Tracings

Introduction: Left ventricular assist device (LVAD) offers a lifeline for advanced heart failure patients, but ~30% experience post-operative right heart failure (RHF) with significant morbidity and mortality. Current methods for predicting RHF risk have limited accuracy. This study is the first of its kind to explore the feasibility of using a convolutional neural network (CNN) deep learning model with pulmonary artery pressure (PAP) tracings acquired during pre-operative hemodynamic assessment to identify patients at risk for early RHF. Methods: A CNN model was pre-trained on PAP tracings from the MIMIC-III Waveform Database to leverage transferable knowledge and improve model performance. The model learned general features and temporal relationships in hemodynamic tracing morphology for RHF prediction. It was then adapted for classification by modifying the output layers. Post-LVAD RHF was definitively adjudicated for each instance included from our 246 patient single center LVAD database. RHF was adjudicated using the 2020 Academic Research Consortium defintion. The database included 205 non-RHF instances and 41 RHF instances. We developed a novel signal processing method utilizing computer vision to extract PAP waveform data from pre-operative right heart catheterization reports. Data was reviewed to ensure accurate pressure tracing representation. SMOTE-ENN (synthetic oversampling) and class weighting addressed dataset imbalance during training to enhance model generalizability and RHF prediction accuracy. Results: The model achieved strong performance in classifying RHF from non-RHF outcomes, as evidenced by consistent AUC scores of 0.87 and 0.85 on validation and unseen test data, respectively. These findings indicate the potential for hemodynamic tracings to predict RHF after LVAD implantation. Notably, the model maintained its performance on unseen data, highlighting its generalizability. Conclusions: This study explored the feasibility of using a deep learning model for RHF risk stratification in patients with LVADs. The model, pre-trained on PAP tracings, achieved promising classification performance assessed by AUC. Further validation with larger, more diverse datasets will refine model performance and enhance generalizability for clinical application. Leveraging hemodynamic tracings within a deep learning framework holds promise for improved clinical outcome prediction.

BIOM-56. HEAT SHOCK PROTEINS PREDICT CLINICAL RESPONSE AND POTENTIATE LOCAL IMMUNOGENICITY AFTER LITT FOR GLIOBLASTOMA

Abstract Glioblastoma (GBM) remains one of the deadliest cancers despite advances in therapies. Laser interstitial thermal therapy (LITT) is a minimally invasive technique used to ablate intra-axial brain tumors. Non-ablative LITT-induced hyperthermia (33-43˚C) increases intra-tumoral mutational burden and neoantigen production, promoting neoantigen presentation via heat shock proteins (HSPs). HSPs are protein-folding chaperones that present novel intracellular antigens for immune recognition. We investigated HSPs as predictors of local immune response and clinical outcomes of GBM patients undergoing LITT. We conducted immune deconvolution of bulk RNA-sequencing data from The Cancer Genome Atlas to determine the correlation between 97 unique HSPs and tumor infiltration of CD8+, CD4+, B, macrophage, neutrophil, and dendritic cells. We evaluated the association between HSP expression and overall survival (OS). Pre-LITT biopsies from 9 patients (responders and non-responders) were analyzed via immunohistochemistry (IHC) to identify spatial HSP expression. Next-generation sequencing was utilized to validate findings and identify other predictive biomarkers. We identified two HSPs for further investigation: SACS and HSPA5. SACS was associated with improved survival based on TCGA data (14.9 vs. 11 months, HR:1.3, p<0.0001). HSPA5 was associated with worse outcomes (12.1 vs. 15.0 months, HR:0.73, p<0.0001). Immune deconvolution showed HSPA5 positively correlated with dendritic cell infiltration (r=0.50, p=6.1E-27) and SACS with CD8+ infiltration (r=0.31, p=6.8E-11). IHC of 9 patients demonstrated high SACS expression was associated with improved OS (p<0.05) after LITT. Multiplex IHC illustrated that immune cell infiltration was associated with therapeutic response post-LITT. Our ongoing immunohistochemical and genomic analyses aim to clarify the role of HSPs in enhancing immunogenicity in GBM. Further investigation into SACS and immune cell infiltration may reveal how hyperthermia via LITT improves response through neoantigen presentation.

Personal and Clinical Predictors of Voice Therapy Outcomes: A Machine Learning Analysis Using the Voice Handicap Index

In this study, we examine the predictive factors influencing the outcomes of voice treatment in patients with voice-related disorders, using the voice handicap index (VHI) as a key assessment tool. By analyzing various personal habits and clinical variables, we identify the primary factors associated with changes when comparing VHI scores before and after voice treatment. For this research, we employed binomial logistic regression, random forest (RF), and a multilayer perceptron (MLP) model to evaluate the effectiveness of voice treatment. The findings reveal that gender (with female patients showing greater improvements in VHI scores compared to male patients), surgical history, voice use status, and voice training status are significant predictors of therapy outcomes. The MLP model demonstrated high accuracy, sensitivity, and specificity, with an area under the curve (AUC) value of 0.87 indicating its potential as a valuable clinical predictive tool; however, the model’s relatively low specificity suggests the need for further refinement to enhance its predictive accuracy. The results of this study provide valuable insights for clinicians and speech–language pathologists in developing personalized treatment strategies to optimize the effectiveness of voice therapy. Future research should prioritize the validation of these findings in larger and more diverse population samples. Furthermore, it is essential to explore additional predictive variables in order to enhance the model’s accuracy across different types of voice disorders.

EPCO-22. DEEP PHENOTYPING IDENTIFIES TRUNCATING MUTATIONS IN THE NF2 LINKER DOMAIN ASSOCIATED WITH DISEASE SEVERITY IN NEUROFIBROMATOSIS TYPE II

Abstract INTRODUCTION Neurofibromatosis type 2 (NF2) is an autosomal dominant tumor syndrome with protean presentation and variable penetrance. Our objective was to perform deep phenotypic and genetic analysis of a diverse NF2 population to identify predictors of worse clinical outcome. METHODS We evaluated 167 patients with NF2 and followed them for a mean duration of 4.5 years. Detailed clinical and radiographic characteristics were collected on each patient, and Karnofsky performance scale (KPS) scores and within-study mortality were monitored. CLIA certified genotyping was supplemented with a custom sequencing panel targeting NF2 and other schwannomatosis-related genes. Outcome predictors were assessed using multivariable linear or logistic regression. RESULTS Germline mutations (nonsense 36%, splice-site 16%, and large deletions 16%) were grouped by predicted protein effect (truncating 41%, non-truncating 27%, and mosaic 33%) and mapped to the NF2chromosomal locus. Patients with truncating NF2 mutations had lower mean age of diagnosis (19.9 versus 25.7, P = 0.01) and faster tumor growth rates (2.4% versus 1.1% for all tumors, P = 0.01). Patients whose truncating mutations occurred within the NF2 linker domain (exons 8, 11 and 12) had more total tumors (adjusted coefficient 15.0, 95% CI 0.8 – 29.0, P = 0.04), and specifically more schwannomas (adjusted coefficient 7.0, 95% CI 0.2 – 13.9, P = 0.04). Presence of a-helical domain mutations predicted higher within-study mortality (adjusted OR 4.3, 95% CI 1.1 – 16.2, P = 0.03). CONCLUSIONS The NF2 linker domain functions a hinge, facilitating binding between the tail domain and the LATS binding site within the FERM domain. In our study, truncating mutations in the NF2 linker domain were associated with higher tumor burden and over four-fold within-study mortality. The linker domain may constitute a novel therapeutic target in patients with NF2.

Prediction of clinical pregnancy outcome after single fresh blastocyst transfer during in vitro fertilization: an ensemble learning perspective

Prediction of clinical pregnancy outcome after single fresh blastocyst transfer during in vitro fertilization: an ensemble learning perspective

Textual Analysis of CT and MR images in bladder cancer: The promise and pitfalls in systematic review

Introduction: Textual analysis is a new stage in the development and improvement of radiology. Textual analysis (TA) or radiomics is a method of in-depth study of medical images using specialized computer programs. It`s based on the quantification of invisible features and provides tools for researchers to gain deep insights into tumor morphology.A number of mathematically extracted texture features (TF) can be correlate with morphological, molecular and genotypic characteristics of the studied field of interest. Aim: Analysis of the literature and comparative evaluation of publications to perform challenges and possibilities of texture analysis in bladder cancer. Materials and methods: We searched for scientific publications in the PubMed and Google Scholar information and analytical systems for 2016-2024 by keywords: «bladder cancer», «bladder cancer radiomics», «mri bladder cancer»». As a result, 40 articles were selected for analysis. Results: Our review demonstrates the methodology, challenges, opportunities and prospects of TA CT and MP imagesin bladder cancer.Numerous studies have demonstrated high accuracy of radiomics in local staging and estimation of tumor morphology, as well as in prediction of clinical outcomes. Conclusion: TA in controversial clinical cases is a useful way of increasing theinformationobtainable frommedical images. Further validation of these methodis required however.

The Predictive Value of the CatLet Scoring System for Long-Term Prognosis After Percutaneous Coronary Intervention in Patients With Chronic Coronary Syndrome.

Coronary Artery Tree description and Lesion EvaluaTion (CatLet) angiographic scoring system is a newly developed vascular scoring for assessing the degree of coronary artery stenosis and coronary artery variability. Preliminary studies have demonstrated its superiority over the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery (SYNTAX) score in predicting outcome in patients with acute myocardial infarction (AMI). This study aimed to assess the predictive value of the CatLet score in long-term prognosis after PCI for chronic coronary syndrome (CCS). A total of 201 patients, who were diagnosed with chronic coronary syndrome, undergoing coronary DES implantation and calculable Catlet score at the Second Affiliated Hospital of Wannan Medical College in China were consecutively enrolled from January 2020 to June 2021. The primary endpoint was major adverse cardiac events (MACEs), defined as a composite of myocardial infarction, recurrent angina, cardiac death, heart failure and ischemia-driven revascularization, were stratified according to CatLet score tertiles: 0 ≤ CatLet_low ≤ 23(n = 66), CatLet_mid 24-43(n = 68), and CatLet_top ≥ 44(n = 67), respectively. The CatLet score predicted long-term prognosis with a median follow-up of 3.0 years. Of 201 patients analyzed, the rates of MACEs and cardiac death were 25.37% and 3.98%, respectively. The Kaplan-Meier curves for all endpoints showed increasing outcome events with the increasing tertiles of the CatLet score, with p-value < 0.05 on the trend test. For MACE and cardiac death, the area under the curve (AUC) of the CatLet score was 0.744 (95% confidence interval [CI]: 0.668-0.820) and 0.804 (95% CI: 0.672-0.936), respectively; Alone or after adjusting for risk factors, the multivariable-adjusted hazard ratio (95% CI)/unit higher score was 9.41 (3.18-27.85) for MACEs and 1.85 (1.20-2.84) for cardiac death, respectively. The CatLet score is an independent predictor of long-term clinical outcomes in patients with chronic coronary syndrome after percutaneous coronary intervention.

Clinical Efficacy of CBCT and 3D-Printed Replicas in Molar Autotransplantation: A Controlled Clinical Trial.

To evaluate the efficacy of the combined cone-beam (CBCT)/3D-replicas protocol on the clinical and radiographic outcomes of autotransplanted molars. Controlled clinical trial registered ISRCTN13563091 from August 2019 to September 2022. Patients aged 13-22 years requiring permanent premolar extraction and having at least one non-erupted third molar were enrolled at the Institute of Stomatology, Stradins University, Riga, Latvia. Patients in the 3D-replicas (n = 30) underwent maxillary CBCT scans and had 3D-printed replicas of the third molar fabricated, while the control group (n = 28) did not. The clinical outcomes included tooth mobility, bleeding on probing, and periodontal pocket depth assessed at 3, 6, and 12 months. The radiographic outcomes included root development, obliteration, periapical status, and crown changes at 12 months. Of the 55 patients assigned to interventions, 46 completed the study. No significant differences in survival and radiographic outcomes were found between the control (n = 22) and 3D-replica group (n = 24): root development (p = 0.3), root resorption (p = 0.057), periapical status (p = 0.7), and crown/root ratio change (p = 0.4). Logistic regression showed no significant associations between radiologic predictors (root resorption: p = 0.4; periapical status: p > 0.9; root development: p = 0.8). Significant clinical outcome predictors included total operative time (β = 0.0043, p = 0.049), Moorrees' stage (stage 4: β = -0.31, p < 0.001; stage 5: β = -0.39, p < 0.001), and four donor placement times (β = 0.93, p < 0.001), but group assignment was not a significant predictor. The CBCT/3D-replica protocol showed no significant differences in the clinical or radiological outcomes. The high success rates in both groups suggest that the protocol is valuable primarily for optimizing surgical efficiency and as a training tool for clinicians.

Clinical profiles and shortterm outcomes of women with peripartum and dilated cardiomyopathies

Background: We aimed to compare the clinical and sociodemographic characteristics, rate of left ventricular reverse remodeling (LVRR), heart failure hospitalization and allcause mortality of women with peripartum and dilated cardiomyopathies (PPCM and DCM respectively) in Nigeria. Methods: This was a prospective longitudinal study and a total of 130 patients (65 for each group) were recruited consecutively and followed up for 6 months. Results: PPCM patients were younger, but the DCM patients had higher frequency of atrial fibrillation and complete left bundle branch block, higher mean left atrial and LV dimensions, higher LV filling pressures, and worse renal dysfunction, respectively, at baseline. At the end of the 6month followup, 15 female DCM vs 21 PPCM patients (p=0.684) had achieved LVRR, 13 DCM vs 11 PPCM patients (p=0.098) were hospitalized for heart failure, and 10 DCM vs 5 PPCM patients (p=0.098) had died. The odds for achieving LVRR was independently increased by systolic blood pressure (SBP) &gt;100 mmHg and tricuspid annular plane systolic excursion &gt;16 mm at baseline in PPCM patients, and by use of angiotensin converting enzyme inhibitors at baseline in female DCM patients. The odds for mortality were increased by tachycardia and pericardial effusion and reduced by the use of loop diuretics at baseline in DCM patients, and SBP &lt;90 mmHg at baseline increased it by 9fold in PPCM patients. Conclusions: Our results suggest that women with DCM and PPCM differ significantly in their demographic and clinical characteristics, and predictors of clinical outcomes.

Hsa_circ_0109320 Serves as a Novel Circular RNA Biomarker in Non-small Cell Lung Cancer by Promoting Metastasis.

Non-small cell lung cancer (NSCLC), including squamous cell carcinoma and adenocarcinoma, ranks among the top 10 cancers worldwide in terms of prevalence and mortality. NSCLC, a highly malignant tumor, exhibits distant invasion and migration as well as an unfavorable prognosis. As an innovative circular RNA, hsa _circ_0109320 (circ_0109320) has been recognized as a promising cancer modulator. However, our understanding of the influence of circ_0109320 in NSCLC remains insufficient. Our research explored the clinical significance and effects of circ_0109320 on oncogenic non-small cell lung cancer (NSCLC) phenotypes. Microarray analysis and qPCR indicated that circ_0109320 expression in NSCLC specimens increased relative to that in adjacent normal tissues and was further elevated in metastatic lymph nodes. The specimens acquired from 25 patients confirmed these findings. Additionally, circ_0109320 indicated a good score (AUC = 0.688, P = 0.013) on the ROC curves, which suggests its suitability as a promising biomarker for lung cancer. Meanwhile, circ_0109320 was noticeably upregulated in lung cancer (LC) cell lines compared to human bronchial epithelial cells. Next, we performed loss- and gain-of-function experiments to examine the role of circ_0109320 in the tumor phenotypes of the cell lines. We observed that depletion or overexpression of circ_0109320 did not alter cell viability. However, the ectopic removal of circ_0109320 repressed the migration and invasion of A549 and SK-MES-1 cells, whereas circ_0109320 overexpression promoted cell migration and invasion. Furthermore, the examination of epithelial-mesenchymal transition (EMT) markers indicated that circ_0109320 elevates cell EMT activity. In conclusion, circ_0109320 level was highly associated with increased tumor cell proliferation and metastasis. circ_0109320 could be a promising predictor of clinical outcomes and a reliable target to treat NSCLC by inhibiting metastasis.

Which components of the global alignment proportionality score have the greatest impact on outcomes in adult spinal deformity corrective surgery?

To investigate the impact of the Global Alignment and Proportion (GAP) score components on patient outcomes in Adult Spine Deformity (ASD) surgery. Patients included underwent assessment via the GAP score and its individual components: pelvic version (GAP PV), lumbar lordosis (GAP LL), lumbar distribution index (GAP LDI) and spinopelvic component (GAP SP). Multivariable analyses assessed the association between alignment in these components and clinical outcomes in ASD patients. 762 ASD patients met inclusion criteria. Alignment in GAP SP independently predicted meeting MCID for SR-22S and ODI and was associated with a lower likelihood of developing mechanical complications. Patients aligned in GAP SP were less likely to develop proximal junctional kyphosis (OR 0.42, 0.26-0.73, p = 0.01) and PJF (OR 0.3, 0.13-0.74, p = 0.01). Proportioned alignment in GAP SP with disproportioned alignment in GAP LDI contributed to an increased risk of PJK and PJF (OR 2.67, 95% CI 1.95-6.82, p = 0.045). There was no significant association of GAP SP proportionality and GAP RPV (OR 1.1, 0.86-2.15, p = 0.253) or GAP LL (OR 1.34, 0.78-4.23, p = 0.673) disproportionality with outcomes. Disproportioned alignment in GAP SP but proportioned alignment in both GAP LL and GAP LDI was associated with decreased likelihood of PJK (OR 0.53, 95% CI 0.39-0.94, p = 0.02) and PJF (OR 0.31, 95% CI 0.19-0.67, p = 0.001). The spinopelvic component of the GAP score is the most significant independent predictor of clinical outcomes. Its interaction with the other components of the GAP score also aids assessment of the risk for mechanical complications.

Role of tumor-specific and whole-body imaging biomarkers for prediction of recurrence in patients with stage III colorectal cancer.

Imaging biomarkers are emerging as non-invasive predictors of cancer prognosis and clinical outcome. We assessed tumor-specific ("radiomics") and body composition imaging features ("morphomics") extracted from baseline pre-treatment CT for prediction of recurrence in patients with stage III colorectal cancer (CRC). Patients with newly diagnosed stage III CRC were enrolled in this prospective observational study. Patients with available preoperative scans were included (N = 101). The tumor, if visible, was manually segmented and first-order radiomics features were extracted with a commercially available software. The morphomics features (reflecting muscle, fat, and bone characteristics) were extracted in a standardized fashion using a proprietary software and the values were adjusted and normalized based on a reference standard. Time to recurrence was the final outcome. Correlation between demographics, clinical features, radiomics, and morphomics features and outcome were assessed using univariate and multivariate tests as well as Kaplan-Meier and log-rank tests. Morphomic analysis was performed in all 101 patients. 60 patients had discrete tumors suitable for radiomics analysis. These patients had lower ECOG score (p < 0.05), more muscle mass (p > 0.05), and lower fat density (p > 0.05) compared to the patients in whom radiomics analysis could not be performed. Pathological stage (HR: 2.69; p = 0.03), CEA level after surgery (HR: 1.11 for 1ng/mL; p < 0.005), bone mineral density (HR: 1.01 for 1 Hounsfield Unit; p < 0.01), and tumor skewness (HR: 0.33 for 1 unit; p < 0.05) had association with recurrence based on both univariate and multivariate analyses. A model using Cox's regression analyses was able to divide the patients into low-, medium-, and high-risk for recurrence. Both radiomics and morphomics features were independently associated with the risk of CRC recurrence and, when combined, each contributed valuable information to explain risk of recurrence. Clinical trial.gov NCT02842203. Patient recruitment occurred between 22/07/2016 and 18/03/2020.

Prediction of clinical outcomes in ovarian cancer using genomic variation

Prediction of clinical outcomes in ovarian cancer using genomic variation

Lower urinary tract symptoms (LUTS) as a clinical feature of lumbar spinal stenosis (LSS): a prospective study with lumbar spine morphometry analysis

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; To investigate clinical and morphometric characteristics of patients with lower urinary tract symptoms (LUTS) due to lumbar spinal stenosis (LSS).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; This study evaluated LSS patients using clinical assessments of motor, sensory, bladder, and bowel functions, and functional disability scores from the Oswestry Disability Index (ODI) and Swiss Spinal Stenosis Questionnaire (SSSQ). Morphometric analysis included MRI measurements of the anteroposterior diameter of the intervertebral disc and dural sac, and the modified Torg-Pavlov ratio (mTPR), with follow-up re-evaluations at 6 months.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; Of 159 patients, 49 (30.8%) had LUTS and 110 (69.2%) were in the control group. LUTS patients had a significantly higher prevalence of neurogenic claudication (100% vs. 47.3%; p&amp;amp;lt;0.001), lower back pain (93.9% vs. 77.3%; p=0.011), and lower extremity pain (57.1% vs. 34.5%; p=0.008). The LUTS group also had higher ODI (54.0 vs. 50.0; p=0.019) and SSSQ score (44.0 vs. 34.0; p&amp;amp;lt;0.001). Morphometric analysis showed significantly lower mTPR in LUTS patients (median 0.31 vs. 0.45; p&amp;amp;lt;0.001), with an AUC of 0.704 (95%CI 0.627-0.774). mTPR&amp;amp;le;0.31 predicted surgical revision within 6 months (OR:3.4, CI: 1.2-9.8), motor deficiency (OR:2.1, 95%CI: 1.4-5.2), and persistent LUTS post-surgery (OR:4.5, 95%CI: 1.1-18.9). mTPR&amp;amp;le;0.34 was associated with worse follow-up outcome, including increased ODI (&amp;amp;beta;:3.2; 95%CI: 1.1-5.3; p=0.004) and SSSQ score (&amp;amp;beta;:4.8; 95%CI:2.1-7.5).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; LUTS patients with LSS exhibit more severe symptoms and poorer outcome, with mTPR&amp;amp;le;0.34 being a predictor of adverse clinical outcome and the need for surgical revision within 6 months.&amp;lt;/p&amp;gt;

Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia

AbstractVenetoclax, a first-in-class BH3 mimetic drug that targets BCL-2, has improved the outcomes of patients with chronic lymphocytic leukemia (CLL). Early measurements of the depth of the venetoclax treatment response, assessed by minimal residual disease, are strong predictors of long-term clinical outcomes. However, there are limited data on the early changes induced by venetoclax treatment that might inform strategies to improve responses. To address this gap, we conducted longitudinal mass cytometric profiling of blood cells from patients with CLL during the first 5 weeks of venetoclax monotherapy. At baseline, we resolved CLL heterogeneity at the single-cell level to define multiple subpopulations in all patients based on proliferative, metabolic, and cell survival proteins. Venetoclax induced a significant reduction in all CLL subpopulations and caused rapid upregulation of the prosurvival BCL-2, BCL-XL, and mantle cell lymphoma-1 proteins in surviving cells, which had reduced sensitivity to the drug. In mouse models, the venetoclax-induced elevation of survival proteins in B cells and CLL-like cells that persisted was recapitulated, and genetic models demonstrated that extensive apoptosis and access to the B cell cytokine, B cell activating factor (BAFF), were essential. Accordingly, in patients with CLL who were treated with venetoclax or the anti-CD20 antibody obinutuzumab there was marked elevation in BAFF and an increase in prosurvival proteins in leukemic cells that persisted. Overall, these data highlight the rapid adaptation of CLL cells to targeted therapies through homeostatic factors and support cotargeting of cytokine signals to achieve deeper and more durable long-term responses.

AI-based tumor-infiltrating lymphocytes scoring system for assessing HCC prognosis in patients undergoing liver resection

Background & AimsTumor-infiltrating lymphocytes (TILs), particularly CD8+ TILs, are key prognostic markers in many cancers. However, their prognostic value in hepatocellular carcinoma (HCC) remains controversial, with different evidence. Given the heterogeneous outcomes in HCC patients undergoing liver resection, this study aims to develop an AI-based system to quantify CD8+ TILs and assess their prognostic value for HCC patients. MethodsWe conducted a retrospective multicenter study on patients undergoing liver resection across three cohorts (N=514). We trained a deep neural network and a random forest model to segment tumor regions and locate CD8+ TILs in H&E and CD8-stained whole slide images (WSIs). We quantified CD8+ TIL density and established an Automated CD8+ Tumor-infiltrating Lymphocyte Scoring (ATLS-8) system to assess its prognostic value. ResultsIn discovery cohort, the 5-year overall survival (OS) rates were 34.05% for ATLS-8 low-score and 65.03% for ATLS-8 high-score groups (HR 2.40; 95% CI, 1.37–4.19; P = 0.015). These findings were confirmed in validation cohort 1, which had 5-year OS rates of 28.57% and 68.73% (HR 3.38; 95% CI, 1.27–9.02; P = 0.0098), and validation cohort 2, which had 59.26% and 81.48% (HR 2.74; 95% CI, 1.05–7.15; P = 0.031). ATLS-8 improved prognostic model based on clinical variables (C-index 0.770 vs. 0.757; 0.769 vs. 0.727; 0.712 vs. 0.642 in three cohorts). ConclusionWe developed an automated system using CD8-stained WSIs to assess immune infiltration (ATLS-8). In HCC patients undergoing resection, higher CD8+ TIL density correlates with better OS, as per ATLS-8 assessment. This system is a promising tool for advancing clinical immune microenvironment assessment and outcome prediction. Impact and implicationCD8+ TILs have been identified as a prognostic factor associated with many cancers. In this study, CD8+ TILs were identified as an independent prognostic factor for OS in patients with hepatocellular carcinoma who undergoing liver resection. Therefore, ATLS-8, a novel digital biomarker based on WSI-level CD8+ TILs, could play an important role in the prognostic assessment of HCC patients and could be integrated into clinicopathological models to participate in the decision-making and prognostic assessment of patients. The scoring system combined with artificial intelligence is essential for automated, quantitative, WSI- level assessment of TILs, which can be widely applied to quantify the immune profile of multi-cancer disease types with the discussion of subsequent immunotherapy. Clinical trial numberThis is a retrospective study and does not require a clinical trial number.

Surgical Predictors of Clinical Outcome 6 Years After Revision ACL Reconstruction

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have inferior outcomes compared with primary ACL reconstruction. The reasons why remain unknown. Purpose: To determine whether surgical factors performed at the time of revision ACL reconstruction can influence a patient’s outcome at 6-year follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: Patients who underwent revision ACL reconstruction were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline patient characteristics, surgical technique and pathology, and a series of validated patient-reported outcome instruments: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) subjective form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx activity rating score. Patients were followed up for 6 years and asked to complete the identical set of outcome instruments. Regression analysis was used to control for baseline patient characteristics and surgical variables to assess the surgical risk factors for clinical outcomes 6 years after surgery. Results: A total of 1234 patients were enrolled (716 men, 58%; median age, 26 years), and 6-year follow-up was obtained on 79% of patients (980/1234). Using an interference screw for femoral fixation compared with a cross-pin resulted in significantly better outcomes in 6-year IKDC scores (odds ratio [OR], 2.2; 95% CI, 1.2-3.9; P = .008) and KOOS sports/recreation and quality of life subscale scores (OR range, 2.2-2.7; 95% CI, 1.2-4.8; P < .01). Use of an interference screw compared with a cross-pin resulted in a 2.6 times less likely chance of having a subsequent surgery within 6 years. Use of an interference screw for tibial fixation compared with any combination of tibial fixation techniques resulted in significantly improved scores for IKDC (OR, 1.96; 95% CI, 1.3-2.9; P = .001); KOOS pain, activities of daily living, and sports/recreation subscales (OR range, 1.5-1.6; 95% CI, 1.0-2.4; P < .05); and WOMAC pain and activities of daily living subscales (OR range, 1.5-1.8; 95% CI, 1.0-2.7; P < .05). Use of a transtibial surgical approach compared with an anteromedial portal approach resulted in significantly improved KOOS pain and quality of life subscale scores at 6 years (OR, 1.5; 95% CI, 1.02-2.2; P≤ .04). Conclusion: There are surgical variables at the time of ACL revision that can modify clinical outcomes at 6 years. Opting for a transtibial surgical approach and choosing an interference screw for femoral and tibial fixation improved patients’ odds of having a significantly better 6-year clinical outcome in this cohort.