Multivariate Survival Analysis Research Articles

Molecular characteristics and multivariate survival analysis of 43 patients with locally advanced or metastatic esophageal squamous cell carcinoma.

Esophageal cancer (EC) is an aggressive malignant tumor with poor prognosis and high incidence. It is the sixth leading cause of cancer-related death in the world, and the 5-year overall survival (OS) rate is only 12-20%. The rapid development of next-generation sequencing (NGS) has provided powerful help for the treatment and management of EC patients. Tumor tissue and blood samples of 43 Chinese patients with nonsurgical esophageal squamous cell carcinoma (ESCC) were sequenced using a 425 gene-panel. Genomic profiling was explored and and the Cox proportional hazards model was used to analyze the correlations between gene or signaling pathway alterations and prognosis. In this study, the most common mutated genes were TP53 (90.5%), CCND1 (45.2%), FGF19 (38.1%), NOTCH1 (26.2%), PI3KCA (21.4%) and CDKN2A (19%). Among these mutations, PI3KCA and NOTCH1 showed mutual exclusion to some extent. In the univariate model, mutations in NOTCH1, CBLB and TSC2 genes and tumor mutation burden (TMB) ≥7 were independent biomarkers of OS. NOTCH1 (P=0.007, HR =2.87), CBLB (P=0.011, HR =4.68) and TSC2 (P=0.024, HR =3.7) were significantly associated with poorer OS, and patients with TMB ≥7 had longer OS (P=0.151, HR =0.31). In addition, patients who carried alteration in NOTCH signaling pathway had reduced OS (P=0.014, HR =2.54). NOTCH1, CBLB and TSC2 alterations were found to be potential indicators of poor prognosis in patients with ESCC. TMB was also positively correlated with the OS of ESCC patients, providing valuable insights for their treatment strategies.

A nomogram prediction model of pseudomyxoma peritonei established based on new prognostic factors of HE stained pathological images analysis.

Pseudomyxoma peritonei (PMP) is a rare clinical malignant syndrome, and its rarity causes a lack of pathology research. This study aims to quantitatively analyze HE-stained pathological images (PIs), and develop a new predictive model integrating digital pathological parameters with clinical information. Ninety-two PMP patients with complete clinic-pathological information, were included. QuPath was used for PIs quantitative feature analysis at tissue-, cell-, and nucleus-level. The correlations between overall survival (OS) and general clinicopathological characteristics, and PIs features were analyzed. A nomogram was established based on independent prognostic factors and evaluated. Among the 92 PMP patients, there were 34 (37.0%) females and 58 (63.0%) males, with a median age of 57 (range: 31-76). A total of 449 HE stained images were obtained for QuPath analysis, which extracted 40 pathological parameters at three levels. Kaplan-Meier survival analysis revealed eight clinicopathological characteristics and 20 PIs features significantly associated with OS (p < 0.05). Partial least squares regression was used to screen the multicollinearity features and synthesize four new features. Multivariate survival analysis identified the following five independent prognostic factors: preoperative CA199, completeness of cytoreduction, histopathological type, component one at tissue-level, and tumor nuclei circularity variance. A nomogram was established with internal validation C-index 0.795 and calibration plots indicating improved prediction performance. The quantitative analysis of HE-stained PIs could extract the new prognostic information on PMP. A nomogram established by five independent prognosticators is the first model integrating digital pathological information with clinical data for improved clinical outcome prediction.

Relevance of mutations in protein deubiquitinases genes and TP53 in corticotroph pituitary tumors.

Corticotroph pituitary neuroendocrine tumors (PitNETs) develop from ACTH-producing cells. They commonly cause Cushing's disease (CD), however, some remain clinically silent. Recurrent USP8, USP48, BRAF and TP53 mutations occur in corticotroph PitNETs. The aim of our study was to determine frequency and relevance of these mutations in a possibly large series of corticotroph PitNETs. Study included 147 patients (100 CD and 47 silent tumors) that were screened for hot-spot mutations in USP8, USP48 and BRAF with Sanger sequencing, while 128 of these patients were screened for TP53 mutations with next generation sequencing and immunohistochemistry. USP8 mutations were found in 41% CD and 8,5% silent tumors, while USP48 mutations were found in 6% CD patients only. Both were more prevalent in women. They were related to higher rate of biochemical remission, non-invasive tumor growth, its smaller size and densely granulated histology, suggesting that these mutation may be favorable clinical features. Multivariate survival analyses did not confirm possible prognostic value of mutation in protein deubiquitinases. No BRAF mutations were found. Four TP53 mutations were identified (2 in CD, 2 in silent tumors) in tumors with size >10mm including 3 invasive ones. They were found in Crooke's cell and sparsely granulated tumors. Tumors with missense TP53 mutations had higher TP53 immunoreactivity score than wild-type tumors. Tumor with frameshift TP53 variant had low protein expression. TP53 mutation was a poor prognostic factor in CD according to uni- and multivariate survival analyses in spite of low mutations frequency. We confirmed high prevalence of USP8 mutations and low incidence of USP48 and TP53 mutations. Changes in protein deubiquitinases genes appear to be favorable prognostic factors in CD. TP53 mutations are rare, occur in both functioning and silent tumors and are related to poor clinical outcome in CD.

ADHD medications use and risk of mortality and unintentional injuries: a population-based cohort study

We assessed the association between the use of medications for attention-deficit/hyperactivity disorder (ADHD) and the risk of all-cause mortality and unintentional injuries leading to emergency department (ED) or hospital admission in individuals aged ≤24 years with ADHD. We conducted a population-based retrospective cohort study between 2000 and 2021 using Quebec health administrative data. Individuals were followed from the first ADHD diagnosis or ADHD medication claim until turning 25, death, or study end. Exposure was defined as mutually exclusive episodes of ADHD medication use and/or coverage under the public provincial drug plan (PDP): 1) covered and not treated with ADHD medication; 2) covered and treated with ADHD medication; and 3) not covered under the PDP. The risk of all-cause mortality and unintentional injuries associated with exposure episodes was estimated using multivariable survival analyses. The cohort included n = 217 192 individuals aged 1–24 years with a male to female ratio of close to 2:1. Compared to non-medication use, episodes of ADHD medication use, overall, were associated with reduced all-cause mortality (adjusted hazard ratio, aHR 0.61, 95% CI 0.48–0.76) and unintentional injury leading to ED (0.75, 0.74–0.77) or hospitalisation (0.71, 0.68–0.75). Episodes of stimulants were associated with a lower risk of all-cause mortality and reduced risk of unintentional injuries, while episodes with non-stimulants and with both stimulants and non-stimulants concomitantly were associated with reduced risk of unintentional injuries, but not of all-cause mortality. Although residual confounding cannot be excluded, stimulants may have a protective effect in terms of risk of all-cause mortality and both stimulants and non-stimulants for ADHD may reduce the risk of unintentional injuries. The findings of the current study should inform clinical decision making on the choice of starting a pharmacological treatment for ADHD, when a balance needs to be struck between expected benefits and possible risks.

"Expression and prognostic relevance of PD-1, PD-L1 and CTLA-4 immune checkpoints in adrenocortical carcinoma".

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis in advanced stages. While therapies targeting the checkpoint molecules programmed cell death 1 (PD-1), its ligand PD-L1 and the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) have revolutionized treatment in many cancers, the results in ACC were heterogeneous. Their expression in ACC has not been systematically studied and might explain the variable response to checkpoint inhibitors. The expression of PD-1, PD-L1 and CTLA-4 was examined in 162 tumor samples from 122 ACC patients by immunohistochemistry (threshold of >1%) and correlated with tumoral T lymphocyte infiltration and clinical endpoints. Finally, uni- and multivariate analyses of progression-free and overall survival were performed. PD-1 and PD-L1 were expressed in 26.5% and 24.7% of samples, respectively, with low expression in most tumor samples (median positive cells: 2.1% and 21.7%. In contrast, CTLA-4 expression was observed in 52.5% of ACC with a median of 38.4% positive cells. Positive PD-1 expression was associated with longer progression-free survival (HR: 0.50, 95% CI 0.25-0.98, p=0.04) even after considering prognostic factors. In contrast, PD-L1 and CTLA-4 did not correlate with clinical outcome. Additionally, PD-1 and PD-L1 expression correlated significantly with the amount of CD3+, CD4+, FoxP3+ and CD8+ T cells. The heterogeneous expression of PD1, PD-L1, and CTLA-4 in this large series of well-annotated ACC samples might explain the heterogeneous results of the immunotherapies in advanced ACC. In addition, PD-1 expression is a strong prognostic biomarker that can easily be applied in routine clinical care and histopathological assessment.

Extremely Poor Post-discharge Prognosis in Aspiration Pneumonia and Its Prognostic Factors: A Retrospective Cohort Study.

There is little evidence regarding the long-term prognosis of patients with aspiration pneumonia. This study aimed to investigate post-discharge survival time and prognostic factors in older patients hospitalized for aspiration pneumonia. This retrospective cohort study included patients aged ≥ 65years hospitalized for aspiration pneumonia and discharged alive from a tertiary care hospital in Japan between April 2009 and September 2014. Candidate prognostic factors were patient's age, sex, body mass index (BMI), performance status, chronic conditions, CURB-65 score, serum albumin level, hematocrit concentration, nutritional pathway at discharge, and discharge location. Kaplan-Meier curves were determined and multivariable survival analysis using Cox regression model was performed to analyze the effect of each factor on mortality. In total, 209 patients were included in this study. The median age was 85years, 58% of the patients were males, 33% had a performance status of 4 and 34% were discharged home. Among the patients, 65% received oral intake, 23% received tube feeding, and 21% received parenteral nutrition at discharge. During the follow-up period, 77% of the patients died, and the median post-discharge survival time was 369days. Besides male sex and low BMI, tube feeding (adjusted hazard ratio (aHR) = 1.70, 95% confidence interval (CI) 1.11-2.59) and parenteral nutrition (aHR = 4.42, 95% CI 2.57-7.60) were strongly associated with mortality. Long-term prognosis of patients hospitalized for aspiration pneumonia was extremely poor. The nutritional pathway at discharge was a major prognostic factor. These results may be useful for future care and research.

Prognostic value of bioelectrical impedance analysis in head and neck cancer patients undergoing radiotherapy: a VALOR® study.

Bioelectrical impedance analysis (BIA) serves as a method to estimate body composition. Parameters such as phase angle (PA), standardized phase angle (SPA), body mass cell (BCM), BCM index (BCMI), and fat-free mass (FFM) might significantly impact the prognosis of head and neck cancer (HNC) patients. The present study aimed to investigate whether bioelectrical parameters can be used to predict survival in the HNC population and establish the optimal cutoff points for predictive accuracy. A multicenter observational study was performed across 12 tertiary hospitals in Andalusia (a region from the south of Spain). A total of 494 patients diagnosed with HNC between 2020 and 2022 at different stages were included in this study, with a minimum follow-up period of 12 months. The BIA assessment was carried out during the first 2 weeks of radical radiotherapy treatment with chemotherapy or other systemic treatments. A multivariate logistic regression analysis of overall survival, complications, hospital admission, and palliative care and its relationship with BIA nutritional assessment was performed. Significant prognostic factors identified in the multivariable analysis encompassed phase angle (PA), standardized phase angle (SPA), body cell mass (BCM), and BCM index (BCMI). Lower PA and BCM values were significantly associated with adverse clinical outcomes. A BCM threshold above 17 kg/m2 was the most significant predictor for predicting survival within the overall HNC population. The PA values of <5.1° in male and <4.8° in female patients showed the best predictive potential for mortality. Increased PA (as a continuous variable) demonstrated a significantly reduced risk for mortality (OR, 0.64; 95% CI, 0.43-0.94; p < 0.05) and a decreased likelihood of hospital admission (OR, 0.75; 95% CI, 0.52-1.07; p < 0.05). Higher BCM correlated with a lower risk of mortality (OR, 0.88; 95% CI, 0.80-0.96; p < 0.01) and a diminished probability of hospital admission (OR, 0.91; 95% CI, 0.83-0.99; p < 0.05). BIA is a crucial tool in the nutritional assessment of HNC patients. BCM and PA are the main bioelectrical parameters used to predict clinical outcomes in this population. Future studies are needed to validate BIA variables in a large cohort to ensure whether early intensification of nutritional treatment would improve survival.

High-tissue FRMD6 expression predicts better outcomes among colorectal cancer patients

Introduction Colorectal cancer (CRC) is the second most common cause of cancer-related deaths. The hippo pathway works as a regulator of organ growth and is often a target for mutations in cancer. Ferm domain containing protein 6 (FRMD6) is an activator of the hippo pathway. This study aimed to explore the role of FRMD6 in CRC and to determine how well it works as a prognostic factor among CRC patients. Methods The tumor expression of FRMD6 was evaluated using immunohistochemistry in 538 colorectal patients operated on at Helsinki University Hospital. We assessed FRMD6 expression with clinicopathological parameters and the impact of FRMD6 expression on survival. Results Patients with a high FRMD6 expression exhibited a better prognosis (univariable hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.41–0.81), with a 5-year disease-specific survival (DSS) of 66.3%. By contrast, patients with a low FRMD6 expression had a 5-year DSS of 52.8%. A high FRMD6 expression level served as an independent predictor for better survival in the Cox multivariable survival analysis (HR 0.53, 95% CI 0.33–0.86). Discussion To our knowledge, this is the first study to show that a high FRMD6 expression is an independent marker for a better prognosis in CRC and could help determine the prognosis for CRC patients.

Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia

ObjectivesSystemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. MethodsThis multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan–Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. ResultsBased on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389–1.969). ConclusionThis study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

Pre-treatment 68 Ga-PSMA-11 PET/CT Prognostic Value in Predicting Response to 177Lu-PSMA-I&T Therapy and Patient Survival

PurposeTo assess the prognostic value of pre-treatment [68Ga]Ga-PSMA-11 PET/CT and other baseline clinical characteristics in predicting prostate cancer (PCa) patients response to [177Lu]Lu-PSMA (PSMA-I&T), as well as patient survival.ProceduresIn this retrospective study, 81 patients who received [177Lu]Lu-PSMA-I&T between October 2018 and January 2023 were reviewed. Eligible patients had metastatic castration-resistant PCa, underwent pre-treatment [68Ga]Ga-PSMA-11 PET/CT, and had serum prostate-specific antigen (PSA) levels available. On PET/CT images, SUVmax, SULmax, SUVpeak, and SULpeak of the most-avid tumoral lesion, as well as SUVmean of the parotid gland (P-SUVmean) and liver (L-SUVmean), were measured. Also, whole-body PSMA tumour volume (PSMA-TV) and total lesion PSMA (TL-PSMA) were calculated. To interpret treatment response after [177Lu]Lu-PSMA-I&T, a composite of PSA values and [68Ga]Ga-PSMA-11 PET/CT findings were considered. The outcomes were dichotomised into progressive versus controlled (stable disease or partial response) disease. Then, the association of baseline parameters with patient response was evaluated. Also, survival analyses were performed to assess baseline parameters in predicting overall survival.ResultsSixty patients (age:73 ± 8, PSA:185 ± 371) were included. Patients received at least one cycle of [177Lu]Lu-PSMA therapy (median = 4). Overall, half of the patients showed disease progression. In the progressive versus controlled disease evaluation, the highest SULmax, as well as SUVmax and SULmax to both backgrounds (L-SUVmean and P-SUVmean), were significantly correlated with the outcome (p-values < 0.05). In the multivariate analysis, only SULmax to the L-SUVmean remained significant (p-value = 0.038). The best cut-off was 8 (AUC = 0.71). With a median follow-up of 360 days, 11 mortal events were documented. In the multivariate survival analysis, only SULmax to P-SUVmean (cut-off = 2.4; p-value = 0.043) retained significance (hazard ratio = 4.0).ConclusionsA greater level of PSMA uptake, specifically higher tumour-to-background uptake in the hottest lesion, may hold substantial prognostic significance, considering both [177Lu]Lu-PSMA-I&T response and patient survival. These ratios may have the potential to be used for PCa patient selection for radioligand therapy.

Comparison of Clinical Characteristics, Therapy, and Short-Term Prognosis between Blunt and Penetrating Abdominal Trauma: A Multicentric Retrospective Cohort Study.

Large-scale studies on the characteristics and management of abdominal trauma in megacities in China are lacking. The aim of this study was to analyze and present the clinical patterns and treatment status of abdominal trauma in regional medical centers. Cases of abdominal trauma treated at seven medical centers in Beijing from 2010 to 2021 were collected. Clinical information about age, sex, injury cause, geographic distribution, abbreviated injury scale/injury severity score (AIS/ISS) value, injury-hospital time, preoperative time, surgically identified organ injuries, type of surgery, causes of reoperation and 90-day mortality was included in this study. Clinical characteristics, treatment methods, and short-term prognoses (90-days survival) were compared between blunt abdominal trauma (BAT) and penetrating abdominal trauma (PAT) cases. Non-normally distributed data are described as medians (IQR), and the Mann‒Whitney U test was performed; qualitative data were analyzed using the X2 test. Univariate and multivariate survival analyses were performed by the Cox proportional hazards model. A total of 553 patients (86.98% male) with a median age of 36.50 (27.00-48.00) years were included. The BAT group had a significantly higher proportion of serious injury (P=0.001), lower initial hemoglobin level (P=0.001), and a lower laparoscopy surgery rate (P=0.044) compared to the PAT group. Additionally, more BAT cases were from the area around Beijing (P=0.008) and a longer injury-regional hospital time (10.47 (5.18-22.51) hours vs. 7.00 (3.80-15.38) hours, P=0.001). In the hollow viscus injury subgroup, the BAT group had a significantly longer injury-regional hospital time and preoperative time compared to the PAT group (injury-regional hospital time: 10.23 (6.00-21.59) hours vs. 7.07 (3.99-13.85) hours, P=0.002; preoperative time: 3.02 (2.01-5.58) hours vs. 2.81 (1.85-3.63) hours, P=0.047). The overall 90-day mortality was 11.9%, and longer injury-regional hospital time (HR: 1.01, 95% CI: 1.00-1.02, P=0.008), receipt of ICU treatment (HR: 4.69, 95% CI: 2.54-8.65, P=0.001), and severe ISSs (ISS > 25 vs. ISS < 16, HR: 2.78, 95% CI: 1.38-5.601, P=0.004) had a worse impact on survival. More patients with BAT were transferred to higher-level hospital, leading to significantly longer prehospital and preoperation time. In the subgroup of hemodynamically stable individuals, more patients with BAT experienced hollow viscus injuries. For those patients, aggressive diagnostic laparoscopic exploration may be beneficial. Patients with longer injury-regional hospital intervals, the need for ICU care, and higher injury severity scores (ISSs) suffered from worse prognoses.

Risk factors for reoperation for arthrofibrosis following primary anterior cruciate ligament reconstruction.

The purpose of this study is to identify the rate and risk factors for a reoperation for arthrofibrosis following primary anterior cruciate ligament (ACL) reconstruction. Prospective data recorded in the New Zealand ACL Registry were cross-referenced with data from the Accident Compensation Corporation (ACC). Primary ACL reconstructions performed between April 2014 and May 2021 were analysed. The ACC database was used to identify patients who underwent a reoperation for a diagnosis of arthrofibrosis. Multivariable survival analysis was performed to compute adjusted hazard ratios (aHR) and 95% confidence intervals. A total of 12,296 primary ACL reconstructions were analysed, of which 230 underwent a reoperation for arthrofibrosis (1.9%) at a mean follow-up of 3.6 years. A higher risk of arthrofibrosis was observed in females (aHR = 1.76, p = 0.001), patients with a history of previous knee surgery (aHR = 1.82, p = 0.04) and when a transtibial drilling technique was used (aHR = 1.53, p = 0.03). ACL reconstruction >6 months after injury had the lowest rate of arthrofibrosis (1.3%, aHR = 0.45, p = 0.01). There was no difference in risk between early surgery within 6 weeks versus delayed surgery between 6 weeks and 6 months after injury (2.9% versus 2.1%, aHR = 0.78, not significant). Female sex, previous knee surgery and a transtibial drilling technique increased the risk of reoperation for arthrofibrosis. Early surgery within 6 weeks of injury was not associated with an increased risk when compared with surgery between 6 weeks and 6 months after injury. Level III.

Analysis of clinicopathologic and imaging features of dual-phenotype hepatocellular carcinoma

Dual-phenotype hepatocellular carcinoma (DPHCC) is a new subtype of hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the computerized tomography scan (CT) imaging and clinicopathologic features of DPHCC. The CT imaging and clinicopathologic data of 97 HCC cases who underwent radical resection were collected retrospectively. The CT imaging feature was evaluated by the ratio of the average CT value of tumor to liver (TLR) in the plain scan, arterial, portal vein and delayed phases. The association between CT imaging and clinicopathologic features was analyzed using the t-test or chi-square test. Univariate and multivariate recurrence-free survival (RFS) analysis and overall survival (OS) were performed. The positive rates of cytokeratin 7 (CK7) and CK19 were 35.1% and 20.6% respectively. The positive rate of CK19 was significantly higher in cases with age < 47 years (P = 0.005), tumor diameter > 4 cm (P = 0.016) or AFP ≥ 400 ng/ml (P = 0.007). The TLR in the portal vein phase was significantly lower in CK19 positive group (P = 0.024). The recurrence risk was significantly higher in cases with CK19 positive (HR: 2.17, 95% CI 1.16 to 4.04, P = 0.013), tumor diameter > 4 cm (HR: 2.05, 95% CI 1.11 to 3.78, P = 0.019), AFP ≥ 400 ng/ml (HR: 2.50, 95% CI 1.37 to 4.54, P = 0.002) or CA199 ≥ 37 U/ml (HR: 2.23, 95% CI 1.12 to 4.42, P = 0.020). However, imaging features, pathological subtype, CK7 or CK19 expression were not significantly related to HCC OS in the univariate and multivariate analysis (all P > 0.05). The expression of CK19 may be associated with the enhancement feature of the portal vein phase CT image, and CK19 positive may suggest a worse RFS.

Prognostic implications of response to neoadjuvant chemotherapy in breast cancer subtypes

The current study was designed to assess the response to treatment, as well as clinical and survival outcomes, across different breast cancer subtypes in patients who underwent neoadjuvant chemotherapy (NAC). From 2014 to 2019, a total of 139 patients who were histologically confirmed to have breast cancer, underwent NAC, and subsequently received breast and axillary surgery, were retrospectively included in this study. The rates of pathological complete response (pCR) to NAC were significantly higher for HER2-positive and triple-negative subtypes than for luminal A and HER2-negative subtypes (p = 0.013). Multivariate analysis for disease-free survival (DFS) revealed that tumour grade and the presence of pCR were independent prognostic factors. The presence or absence of a pCR with NAC was an independent prognostic indicator in the multivariate analysis for overall survival (OS). Lastly, achieving a pCR was independently predicted by 18F-FDG PET/CT findings, the HER2-positive subtype, and the triple-negative subtype. Despite the inherent methodological limitations, our findings underscore the significance of identifying predictive markers to tailor NAC plans, with the aim of improving survival outcomes.

Abstract TMP80: Hematoma Radiomic Markers of Survival After Supratentorial Intracerebral Hemorrhage on Admission Non-Contrast Head CT

Background: Radiomic features provide quantitative information about lesions morphology and texture on medical images. Recent studies have shown that intracerebral hemorrhage (ICH) radiomics on admission non-contrast head CT are associated with severity of symptoms at baseline and clinical outcomes - providing prognostic information beyond hematoma volume. In this study, we determined hematoma radiomic markers of post-ICH survival on admission head CT. Methods: Using the ATACH-2 trial dataset, we manually segmented ICH on admission head CTs and extracted 1130 radiomic features. Univariate and multivariate survival analyses were performed using the Cox Proportional Hazards model, Kaplan Meier Analysis, and logistic regression. Results: We split our dataset (n=871) to training (n=580) and testing (n=291) cohorts. Increased “original first order Energy” radiomic feature was associated with a higher probability of death (Hazard Ratio=1.64, p &lt;0.0001). LASSO Cox Proportional Hazards modeling also identified “original first order Energy” alongside age, NIHSS, and baseline INR as significant predictors of death. The ROC analysis confirmed the prognostic capability of this feature at 7 days, 30 days, and 90 days post-ICH in training and test cohorts. Kaplan Meier analysis demonstrated that increased “original first order Energy” is associated with a higher probability of death (p &lt; 0.05 at all time points). Logistic regression also showed that this feature is an independent predictor of post-ICH mortality (Odds ratios=2.04, p &lt; 0.001). Conclusions: The “original first order Energy” radiomic feature of hematoma on admission non-contrast head CT scans is a main predictor of survival in supratentorial ICH. This radiomic feature represents the magnitude of voxel values confounded with lesion volume - i.e. brighter larger hematomas on head CT have higher " original first order Energy ", and are associated with higher mortality rates after supratentorial ICH.

To Remplissage or not to Remplissage Part 2: Recurrent Instability After Primary Stabilization Surgery (RIPSS) Risk Tool Assesses Preoperative Failure Rates in On-track Shoulders Undergoing Primary Arthroscopic Anterior Stabilization with or without Remplissage Augmentation

Objectives: Given the high rates of recurrent instability following the initial arthroscopic Bankart repair (ABR), it is crucial to provide recommendations for appropriate surgical interventions for patients at a higher risk of experiencing recurring instability. In Part 1 of the study, it was discovered that on-track Hill-Sachs lesions (HSL) with specific prognostic factors (i.e., younger age, increased shoulder laxity, lower DTD, and 2+ preoperative instability events) were associated with a greater risk of failure. Therefore, the objective of Part 2 was to develop a risk assessment tool that takes into account significant prognostic factors for recurrent shoulder instability following primary ABR and evaluate the role of remplissage augmentation given a patient’s risk profile. Methods: We retrospectively reviewed prospectively collected data of consecutive patients aged 14-40 who underwent either ABR (arthroscopic Bankart repair) or ABR+R (ABR with remplissage) procedures between 2013 and 2021 for anterior glenohumeral instability. Preoperative magnetic resonance imaging was used to determine the values of glenoid bone loss, Hills-Sachs Interval (HSI), glenoid track (GT), and distance-to-dislocation (DTD). On-track lesions have a distance-to-dislocation (DTD) value greater than zero. In addition, within the category of on-track lesions, there is a subset known as “near-track” lesions, with a DTD ranging from 0 to 10 mm. Capsuloligamentous laxity scores were categorized according to hyperlaxity status, defined as external rotation greater than 85 degrees and/or grade 2+ posterior and inferior load-and-shift on examination under anesthesia. Recurrent shoulder instability was defined as recurrent dislocation and/or subjective subluxation postoperatively. Patients were excluded if the indexed surgery was a revision procedure, &lt; 2-year follow-up, or glenoid bone loss (GBL) &gt;20%. A final multivariate survival analysis was constructed using categorical prognostic factors (i.e., patient age, “near-track” status, hyperlaxity, and 2+ preoperative instability episodes) identified in Part 1, while adjusting for GBL. Although contact athlete status was not identified as a significant predictor of recurrent shoulder instability in Part 1, the final model stratified by contact athlete status given its established importance in prior literature. Multivariate hazard ratio estimates were utilized to create a risk assessment tool and correlated with patient-specific risk estimates via post-estimation analysis. Results: One-hundred-and-fifty-five patients were included for analysis (ABR: 116 | ABR+R: 39) with an average age of 21.6 ± 6.2 years and an average follow-up of 5.1 ± 2.0 years (range: 2.0 – 8.7 yrs). Patients with near-track lesions had a three-fold higher risk of recurrent instability (Hazard Ratio [HR]: 2.5, p = 0.03) compared to on-track HSL with DTD &gt; 10mm. Individuals with evidence of hyperlaxity exhibited a five-fold increased risk (HR: 5.4, p=0.03) relative to patients without hyperlaxity. Younger patient groups had twice the risk of recurrent shoulder instability (HR: 2.2, p=0.003) compared to older adjacent groups. Patients with two or more preoperative recurrent instability episodes faced a four-times greater risk (HR: 4.2, p=0.004) for recurrent shoulder instability compared to patients who experienced a single instability event preoperatively. Lastly, patients who underwent primary ABR only had almost 10-times greater risk of recurrent shoulder instability (HR: 9.5, p=0.002) than those who underwent primary ABR+R. The Recurrent Instability after Primary Shoulder Stabilization (RIPSS) risk assessment score considers patient age, near-track status, hyperlaxity, preoperative instability episodes, and surgical technique (ABR vs. ABR+R) as important prognostic indicators, Table 2. The RIPSS score was created with risk stratifying subgroups: Low-risk (0 – 2), Moderate-risk (3 – 6), High-risk (7 – 9), and Extreme-risk (10+). Figure 1 illustrates a strong correlation between patient RIPSS scores with patient-specific hazard ratio estimates derived from the multivariate Cox regression modeling computed in “To Remplissage or not to Remplissage Part 1”. According to RIPSS score subgroups, recurrent shoulder instability rates range from 4.3% among low-risk groups to 54.6% among extreme-risk groups, Figure 1. Conclusions: Patients with a low-risk RIPSS score without ABR+R may not benefit from remplissage augmentation. Their risk for recurrent instability would remain low despite the addition of remplissage. However, patients with a high- or extreme-risk RIPSS score prior to considering ARB+R would likely benefit from remplissage supplementation. The RIPSS score may be an effective risk assessment tool that may help identify patients who may benefit from a primary Bankart repair with remplissage augmentation. The risk assessment tool developed may optimize surgical treatment and allow physicians to determine patient risk scores with and without remplissage augmentation.

Identifying intense inflammatory subtype of esophageal squamous cell carcinoma using clustering approach.

To establish a risk-stratification system for predicting the postoperative recurrence of esophageal squamous cell carcinoma, this study aimed to evaluate the prognostic value of clusters based on blood inflammation and coagulation markers and investigate their correlation with serum cytokines and genetic alteration. This single-center, retrospective cohort study enrolled 491 patients with esophageal cancer who underwent subtotal esophagectomy between 2004 and 2012. For cluster exploration, nonhierarchical cluster analysis and k-means were applied using serum C-reactive protein, albumin, fibrinogen, and platelet-lymphocyte ratio as variables. Then, multivariate survival analysis was conducted to investigate the association of clusters with recurrence-free survival. To characterize the clusters, serum interleukin-6, interleukin-8, and genetic alteration in primary tumors, the PleSSision-Rapid panel, which can evaluate 160 representative driver genes, was used. Patients were classified into clusters 1, 2, and 3, which included 24 (5%), 161 (33%), and 306 (62%) patients, respectively. Compared with cluster 3, cluster 1 or 2 had significantly worse recurrence-free survival. Based on the multivariable analysis using cluster, pStage, and age as covariates, cluster was an independent prognostic factor for recurrence-free survival (hazard ratio, 1.55; 95% confidence interval, 1.08-2.21; P = 0.02). The percentage of serum interleukin-6 and interleukin-8 levels was the highest in cluster 1, followed by clusters 2 and 3. In 23 patients with available genomic profiles, no significant difference in representative genomic alterations was observed. Non-biased clustering using inflammation and coagulation markers identified the intense inflammatory subtype, which had an independent prognostic effect on recurrence-free survival.

The prognostic potential of mammographic growth rate of invasive breast cancer in the Nijmegen breast cancer screening cohort.

Insight into the aggressiveness of potential breast cancers found in screening may optimize recall decisions. Specific growth rate (SGR), measured on mammograms, may provide valuable prognostic information. This study addresses the association of SGR with prognostic factors and overall survival in patients with invasive carcinoma of no special type (NST) from a screened population. In this historic cohort study, 293 women with NST were identified from all participants in the Nijmegen screening program (2003-2007). Information on clinicopathological factors was retrieved from patient files and follow-up on vital status through municipalities. On consecutive mammograms, tumor volumes were estimated. After comparing five growth functions, SGR was calculated using the best-fitting function. Regression and multivariable survival analyses described associations between SGR and prognostic factors as well as overall survival. Each one standard deviation increase in SGR was associated with an increase in the Nottingham prognostic index by 0.34 [95% confidence interval (CI): 0.21-0.46]. Each one standard deviation increase in SGR increased the odds of a tumor with an unfavorable subtype (based on histologic grade and hormone receptors; odds ratio 2.14 [95% CI: 1.45-3.15]) and increased the odds of diagnosis as an interval cancer (versus screen-detected; odds ratio 1.57 [95% CI: 1.20-2.06]). After a median of 12.4 years of follow-up, 78 deaths occurred. SGR was not associated with overall survival (hazard ratio 1.12 [95% CI: 0.87-1.43]). SGR may indicate prognostically relevant differences in tumor aggressiveness if serial mammograms are available. A potential association with cause-specific survival could not be determined and is of interest for future research.

Local Anesthesia for Endovascular Repair of Abdominal Aortic Aneurysm Allows for Accurate Graft Deployment with Durable Results

ObjectiveLocal anesthesia (LA) is sparsely used in endovascular aneurysm repair (EVAR) despite short term benefit, likely secondary to concerns over patient movement preventing accurate endograft deployment. The objective of this study is to examine the association between anesthesia type and endoleak, sac regression, reintervention, and mortality. MethodsThe Vascular Quality Initiative database was queried for all EVAR cases from 2014-2022. Patients were included if they underwent percutaneous elective EVAR with anatomical criteria within instructions for use of commercially approved endografts. Multivariable logistic regression with propensity score weighting lysis was used to determine the association between anesthesia type on the risk of any endoleak noted by intra-operative completion angiogram and sac regression. Multivariable survival analysis with propensity score weighting was used to determine the association between anesthesia type and endoleak at 1 year, long-term reintervention and mortality. Results13932 EVARs met inclusion criteria: 1075 (8%) LA and 12857 (92%) general anesthesia (GA). On completion angiogram, LA was associated with fewer rates of any endoleaks overall (16% vs 24%, p<0.001). On multivariable analysis with propensity score weighting, LA was associated with similar adjusted odds of any endoleak on intra-operative completion angiogram (OR 0.56, 95%CI 0.47-0.68) as well as combined type 1a and type 1b endoleaks (OR 0.72, 05%CI 0.47-1.09). Follow-up computed tomography imaging at 1 year was available for 4892 patients, 377 (8%) LA and 4515 (92%) GA. At 1 year, LA was associated similar rate of freedom from any endoleaks compared to GA (0.66 (95%CI 0.63-0.69) vs 0.71 (95%CI 0.70-0.72), p=0.663) and increased rates of sac regression (50% vs 45% p=0.040). On multivariable analysis with propensity score weighting, LA and GA were associated with similar adjusted odds of sac regression (OR 1.22, 05%CI 0.97-1.55). LA and GA had similar rates endoleak at 1 year (HR 0.14, 95%CI 0.63-1.07), however LA was associated with decreased hazards of combined type 1a and 1b endoleaks at 1 year (HR 0.87, 95%CI 0.80-0.96). LA and GA had similar adjusted long-term reintervention rate (HR 0.77, 95%CI 0.44-1.38) and long-term mortality (HR 1.100, 95%CI 079-1.25). ConclusionLA is not associated with increased adjusted rates of any endoleak on completion angiogram or at 1-year follow-up compared to GA. LA is associated with decreased adjusted rates of yype 1a and type1b endoleak at 1 year, but similar rates of sac regression, long term reintervention and mortality. Concerns for accurate graft deployment should not preclude use of LA and LA should be increasingly considered when deciding on anesthetic type for standard elective EVAR.

Semi-Supervised, Attention-Based Deep Learning for Predicting TMPRSS2:ERG Fusion Status in Prostate Cancer Using Whole Slide Images.

Our study illuminates the potential of deep learning in effectively inferring key prostate cancer genetic alterations from the tissue morphology depicted in routinely available histology slides, offering a cost-effective method that could revolutionize diagnostic strategies in oncology.