Types of Septic Cardiomyopathy: Prognosis and Influencing Factors - A Clinical Study.

Objective: To explore the prognostic outcomes associated with different types of septic cardiomyopathy and analyze the factors that exert an influence on these outcomes. Methods: The data collected within 24 hours of ICU admission included cardiac troponin I (cTnI), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP); SOFA (sequential organ failure assessment) scores, and the proportion of vasopressor use. Based on echocardiographic outcomes, septic cardiomyopathy was categorized into left ventricular (LV) systolic dysfunction, LV diastolic dysfunction, and right ventricular (RV) systolic dysfunction. Differences between the mortality and survival groups, as well as between each cardiomyopathy subgroup and the non-cardiomyopathy group were compared, to explore the influencing factors of cardiomyopathy. Results: A cohort of 184 patients were included in this study, with LV diastolic dysfunction having the highest incidence rate (43.5%). The mortality group had significantly higher SOFA scores, vasopressor use, and cTnI levels compared to the survival group; the survival group had better LV diastolic function than the mortality group (p < 0.05 for all). In contrast to the non-cardiomyopathy group, each subgroup within the cardiomyopathy category exhibited elevated levels of cTnI. The subgroup with left ventricular diastolic dysfunction demonstrated a higher prevalence of advanced age, hypertension, diabetes mellitus, coronary artery disease, and an increased mortality rate; the RV systolic dysfunction subgroup had higher SOFA scores and NT-proBNP levels, and a higher mortality rate (P < 0.05 for all); the LV systolic dysfunction subgroup had a similar mortality rate (P > 0.05). Conclusion: Patients with advanced age, hypertension, diabetes mellitus, or coronary artery disease are more prone to develop LV diastolic dysfunction type of cardiomyopathy; cardiomyopathy subgroups had higher levels of cTnI. The RV systolic dysfunction cardiomyopathy subgroup had higher SOFA scores and NT-proBNP levels. The occurrence of RV systolic dysfunction in patients with sepsis significantly increased the mortality rate.

Patterns of B-cell lymphocyte expression changes in pre- and post-malignant prostate tissue are associated with prostate cancer progression.

BACKROUND: Inflammation characterized by the presence of T and B cells is often observed in prostate cancer, but it is unclear how T- and B-cell levels change during carcinogenesis and whether such changes influence disease progression. METHODS: The study used a retrospective sample of 73 prostate cancer cases (45 whites and 28 African Americans) that underwent surgery as their primary treatment and had a benign prostate biopsy at least 1 year before diagnosis. CD3+, CD4+, and CD20+ lymphocytes were quantified by immunohistochemistry in paired pre- and post-diagnostic benign prostate biopsy and tumor surgical specimens, respectively. Clusters of similar trends of expression across two different timepoints and three distinct prostate regions-benign biopsy glands (BBG), tumor-adjacent benign glands (TAG), and malignant tumor glandular (MTG) regions-were identified using Time-series Anytime Density Peaks Clustering (TADPole). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of time to biochemical recurrence associated with region-specific lymphocyte counts and regional trends. RESULTS: The risk of biochemical recurrence was significantly reduced in men with an elevated CD20+ count in TAG (HR = 0.81, p = 0.01) after adjusting for covariates. Four distinct patterns of expression change across the BBG-TAG-MTG regions were identified for each marker. For CD20+, men with low expression in BBG and higher expression in TAG compared to MTG had an adjusted HR of 3.06 (p = 0.03) compared to the reference group that had nominal differences in CD20+ expression across all three regions. The two CD3+ expression patterns that featured lower CD3+ expression in the BBG compared to the TAG and MTG regions had elevated HRs ranging from 3.03 to 4.82 but did not reach statistical significance. CONCLUSIONS: Longitudinal and spatial expression patterns of both CD3+ and CD20+ suggest that increased expression in benign glands during prostate carcinogenesis is associated with an aggressive disease course.

The Impact of Environmental Benzene, Toluene, Ethylbenzene, and Xylene Exposure on Blood-Based DNA Methylation Profiles in Pregnant African American Women from Detroit.

African American women in the United States have a high risk of adverse pregnancy outcomes. DNA methylation is a potential mechanism by which exposure to BTEX (benzene, toluene, ethylbenzene, and xylenes) may cause adverse pregnancy outcomes. Data are from the Maternal Stress Study, which recruited African American women in the second trimester of pregnancy from February 2009 to June 2010. DNA methylation was measured in archived DNA from venous blood collected in the second trimester. Trimester-specific exposure to airshed BTEX was estimated using maternal self-reported addresses and geospatial models of ambient air pollution developed as part of the Geospatial Determinants of Health Outcomes Consortium. Among the 64 women with exposure and outcome data available, 46 differentially methylated regions (DMRs) were associated with BTEX exposure (FDR adjusted p-value < 0.05) using a DMR-based epigenome-wide association study approach. Overall, 89% of DMRs consistently exhibited hypomethylation with increasing BTEX exposure. Biological pathway analysis identified 11 enriched pathways, with the top 3 involving gamma-aminobutyric acid receptor signaling, oxytocin in brain signaling, and the gustation pathway. These findings highlight the potential impact of BTEX on DNA methylation in pregnant women.

Tumor-Associated Lymphocytes and Breast Cancer Survival in Black and White Women.

This case series evaluates whether differences in immune filtration are associated with breast cancer risk in Black vs White women.

Identification and validation of the diagnostic signature associated with immune microenvironment of acute kidney injury based on ferroptosis-related genes through integrated bioinformatics analysis and machine learning.

Background: Acute kidney injury (AKI) is a common and severe disease, which poses a global health burden with high morbidity and mortality. In recent years, ferroptosis has been recognized as being deeply related to Acute kidney injury. Our aim is to develop a diagnostic signature for Acute kidney injury based on ferroptosis-related genes (FRGs) through integrated bioinformatics analysis and machine learning. Methods: Our previously uploaded mouse Acute kidney injury dataset GSE192883 and another dataset, GSE153625, were downloaded to identify commonly expressed differentially expressed genes (coDEGs) through bioinformatic analysis. The FRGs were then overlapped with the coDEGs to identify differentially expressed FRGs (deFRGs). Immune cell infiltration was used to investigate immune cell dysregulation in Acute kidney injury. Functional enrichment analysis and protein-protein interaction network analysis were applied to identify candidate hub genes for Acute kidney injury. Then, receiver operator characteristic curve analysis and machine learning analysis (Lasso) were used to screen for diagnostic markers in two human datasets. Finally, these potential biomarkers were validated by quantitative real-time PCR in an Acute kidney injury model and across multiple datasets. Results: A total of 885 coDEGs and 33 deFRGs were commonly identified as differentially expressed in both GSE192883 and GSE153625 datasets. In cluster 1 of the coDEGs PPI network, we found a group of 20 genes clustered together with deFRGs, resulting in a total of 48 upregulated hub genes being identified. After ROC analysis, we discovered that 25 hub genes had an area under the curve (AUC) greater than 0.7; Lcn2, Plin2, and Atf3 all had AUCs over than this threshold in both human datasets GSE217427 and GSE139061. Through Lasso analysis, four hub genes (Lcn2, Atf3, Pir, and Mcm3) were screened for building a nomogram and evaluating diagnostic value. Finally, the expression of these four genes was validated in Acute kidney injury datasets and laboratory investigations, revealing that they may serve as ideal ferroptosis markers for Acute kidney injury. Conclusion: Four hub genes (Lcn2, Atf3, Pir, and Mcm3) were identified. After verification, the signature's versatility was confirmed and a nomogram model based on these four genes effectively distinguished Acute kidney injury samples. Our findings provide critical insight into the progression of Acute kidney injury and can guide individualized diagnosis and treatment.

Corrigendum: No safe renal warm ischemia time-The molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury.

[This corrects the article DOI: 10.3389/fmolb.2022.1006917.].

Early Diastolic Peak Velocity of Mitral Valve Annulus and Right Ventricular Systolic Tricuspid Annular Velocity as Predictors in Assessing Prognosis of Patients with Sepsis.

Objective: To analyze the epidemiological data of patients with septic cardiomyopathy and investigate the relationship between ultrasonic parameters and prognosis of patients with sepsis. Methods: In this study, we enrolled patients with sepsis who were treated at the Department of Critical Care Medicine in the Beijing Electric Power Hospital (No.1 Taipingqiao Xili, Fengtai District, Beijing) from January 2020 to June 2022. All patients received standardized treatment. Their general medical status and 28-day prognosis were recorded. Transthoracic echocardiography was performed within 24 hours after admission. We compared the ultrasound indexes between the mortality group and the survival group at the end of 28 days. We included parameters with significant difference in the logistic regression model to identify the independent risk factors for prognosis and evaluated their predictive value using receiver operating characteristic (ROC) curve. Results: We included 100 patients with sepsis in this study; the mortality rate was 33% and the prevalence rate of septic cardiomyopathy was 49%. The peak e' velocity and right ventricular systolic tricuspid annulus velocity (RV-Sm) of the survival group were significantly higher than those of the mortality group (P < 0.05). Results of logistic regression analysis showed that the peak e' velocity and RV-Sm were independent risk factors for prognosis. The area under curve of the peak e' velocity and the RV-Sm was 0.657 and 0.668, respectively (P < 0.05). Conclusion: The prevalence rate of septic cardiomyopathy in septic patients is high. In this study, we found that the peak e' velocity and right ventricular systolic tricuspid annulus velocity were important predictors of short-term prognosis.

Identification of Environmental Exposures Associated with Risk of Sarcoidosis in African Americans.

Rationale: Sarcoidosis is a racially disparate granulomatous disease likely caused by environmental exposures, genes, and their interactions. Despite increased risk in African Americans, few environmental risk factor studies in this susceptible population exist. Objectives: To identify environmental exposures associated with the risk of sarcoidosis in African Americans and those that differ in effect by self-identified race and genetic ancestry. Methods: The study sample comprised 2,096 African Americans (1,205 with and 891 without sarcoidosis) compiled from three component studies. Unsupervised clustering and multiple correspondence analyses were used to identify underlying clusters of environmental exposures. Mixed-effects logistic regression was used to evaluate the association of these exposure clusters and the 51 single-component exposures with risk of sarcoidosis. A comparison case-control sample of 762 European Americans (388 with and 374 without sarcoidosis) was used to assess heterogeneity in exposure risk by race. Results: Seven exposure clusters were identified, five of which were associated with risk. The exposure cluster with the strongest risk association was composed of metals (P < 0.001), and within this cluster, exposure to aluminum had the highest risk (odds ratio, 3.30; 95% confidence interval [95% CI], 2.23-4.09; P < 0.001). This effect also differed by race (P < 0.001), with European Americans having no significant association with exposure (odds ratio, 0.86; 95% CI, 0.56-1.33). Within African Americans, the increased risk was dependent on genetic African ancestry (P = 0.047). Conclusions: Our findings support African Americans having sarcoidosis environmental exposure risk profiles that differ from those of European Americans. These differences may underlie racially disparate incidence rates that are partially explained by genetic variation differing by African ancestry.

Convolutional Neural Network Quantification of Gleason Pattern 4 and Association With Biochemical Recurrence in Intermediate-Grade Prostate Tumors.

Differential classification of prostate cancer grade group (GG) 2 and 3 tumors remains challenging, likely because of the subjective quantification of the percentage of Gleason pattern 4 (%GP4). Artificial intelligence assessment of %GP4 may improve its accuracy and reproducibility and provide information for prognosis prediction. To investigate this potential, a convolutional neural network (CNN) model was trained to objectively identify and quantify Gleason pattern (GP) 3 and 4 areas, estimate %GP4, and assess whether CNN-predicted %GP4 is associated with biochemical recurrence (BCR) risk in intermediate-risk GG 2 and 3 tumors. The study was conducted in a radical prostatectomy cohort (1999-2012) of African American men from the Henry Ford Health System (Detroit, Michigan). A CNN model that could discriminate 4 tissue types (stroma, benign glands, GP3 glands, and GP4 glands) was developed using histopathologic images containing GG 1 (n = 45) and 4 (n = 20) tumor foci. The CNN model was applied to GG 2 (n = 153) and 3 (n = 62) tumors for %GP4 estimation, and Cox proportional hazard modeling was used to assess the association of %GP4 and BCR, accounting for other clinicopathologic features including GG. The CNN model achieved an overall accuracy of 86% in distinguishing the 4 tissue types. Furthermore, CNN-predicted %GP4 was significantly higher in GG 3 than in GG 2 tumors (P = 7.2 × 10-11). %GP4 was associated with an increased risk of BCR (adjusted hazard ratio, 1.09 per 10% increase in %GP4; P = .010) in GG 2 and 3 tumors. Within GG 2 tumors specifically, %GP4 was more strongly associated with BCR (adjusted hazard ratio, 1.12; P = .006). Our findings demonstrate the feasibility of CNN-predicted %GP4 estimation, which is associated with BCR risk. This objective approach could be added to the standard pathologic assessment for patients with GG 2 and 3 tumors and act as a surrogate for specialist genitourinary pathologist evaluation when such consultation is not available.

Survival Outcomes in Women with Unilateral, Triple-Negative, Breast Cancer Correlated with Contralateral Prophylactic Mastectomy.

BACKGROUND: Despite increased utilization of contralateral prophylactic mastectomy (CPM), there is insufficient evidence that it improves survival in average-risk women with unilateral breast cancer. CPM may be of heightened interest to patients with triple negative breast cancer (TNBC) because these patients are more likely to have BRCA1 mutation-associated disease and are not candidates for the chemoprevention benefits of adjuvant endocrine therapy. METHODS: Survival and recurrence outcomes were evaluated for all TNBC patients from a multi-institutional database (1999-2018) at two academic cancer programs in two metropolitan cities of the Northeast and Midwest. Median follow-up time was 3.7 years. RESULTS: Seven hundred and nighty six TNBC patients were evaluated and 15.45% underwent CPM. Women undergoing CPM were more likely to be white (p < 0.001), younger (p < 0.001), and underwent genetic testing (p < 0.001). A borderline survival benefit was observed for TNBC patients undergoing CPM (5-year overall survival 95.1% vs. 85.0%; p = 0.05). There was no difference in survival when BRCA mutation carriers were excluded (5-year overall survival 94.1% vs. 85.2%; p = 0.12). For BRCA mutation carriers, a numeric trend was observed for improved survival for patients undergoing CPM (5-year overall survival 97.2% vs. 84.1%; p = 0.35). Among patients not undergoing CPM, the rate of developing a new primary breast cancer was 2.2% (15/673). Among these 15 patients, 20% (3/15) were known BRCA mutation carriers. CONCLUSIONS: Our data demonstrate no survival benefit for TNBC patients without BRCA1/2 mutations undergoing CPM.

No safe renal warm ischemia time-The molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury.

Ischemic acute kidney injury (AKI) has always been a hot and difficult research topic in the field of renal diseases. This study aims to illustrate the safe warm ischemia time of kidney and the molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury. We established varying degrees of renal injury due to different ischemia time (0 min, 16 min, 18 min, 20 min, 22 min, 24 min, 26 min, 28 min, and 30 min) on unilateral (left kidney) ischemia-reperfusion injury and contralateral (right kidney) resection (uIRIx) mouse model. Mice were sacrificed 24 h after uIRIx, blood samples were harvested to detect serum creatinine (Scr), and kidney tissue samples were harvested to perform Periodic Acid-Schiff (PAS) staining and RNA-Seq. Differentially expressed genes (DEGs) were identificated, time-dependent gene expression patterns and functional enrichment analysis were further performed. Finally, qPCR was performed to validated RNA-Seq results. Our results indicated that there was no absolute safe renal warm ischemia time, and every minute of ischemia increases kidney damage. Warm ischemia 26min or above in mice makes severe kidney injury, renal pathology and SCr were both significantly changed. Warm ischemia between 18 and 26 min makes mild kidney injury, with changes in pathology and renal molecular expression, while SCr did not change. No obvious pathological changes but significant differences in molecular expression were found less than 16min warm ischemia. There are two key time intervals in the process of renal ischemia injury, 0 min-16 min (short-term) and 26 min-28 min (long-term). Gene expression of immune-related pathways were most significantly down-regulated in short-term ischemia, while metabolism-related pathways were the mainly enriched pathway in long-term ischemia. Taken together, this study provides novel insights into safe renal artery occlusion time in partial nephrectomy, and is of great value for elucidating molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury, and key genes related to metabolism and immune found in this study also provide potential diagnostic and therapeutic biomarkers for AKI.

Amelioration of Maternal Immune Activation-Induced Autism Relevant Behaviors by Gut Commensal Parabacteroides goldsteinii.

Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. Probiotics have been demonstrated to play a promising role in managing the severity of ASD. However, there are no effective probiotics for clinical use. Identifying new probiotic strains for ameliorating ASD is therefore essential. Using the maternal immune activation (MIA)-based offspring ASD-like mouse model, a probiotic-based intervention strategy was examined in female mice. The gut commensal microbe Parabacteroides goldsteinii MTS01, which was previously demonstrated to exert multiple beneficial effects on chronic inflammation-related-diseases, was evaluated. Prenatal lipopolysaccharide (LPS) exposure induced leaky gut-related inflammatory phenotypes in the colon, increased LPS activity in sera, and induced autistic-like behaviors in offspring mice. By contrast, P. goldsteinii MTS01 treatment significantly reduced intestinal and systemic inflammation and ameliorated disease development. Transcriptomic analyses of MIA offspring indicated that in the intestine, P. goldsteinii MTS01 enhanced neuropeptide-related signaling and suppressed aberrant cell proliferation and inflammatory responses. In the hippocampus, P. goldsteinii MTS01 increased ribosomal/mitochondrial and antioxidant activities and decreased glutamate receptor signaling. Together, significant ameliorative effects of P. goldsteinii MTS01 on ASD relevant behaviors in MIA offspring were identified. Therefore, P. goldsteinii MTS01 could be developed as a next-generation probiotic for ameliorating ASD.

African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.

Retrospective motion correction for preclinical/clinical magnetic resonance imaging based on a conditional generative adversarial network with entropy loss.

Multishot scan magnetic resonance imaging (MRI) acquisition is inherently sensitive to motion, and motion artifact reduction is essential for improving the image quality in MRI. This work proposes and validates a new end-to-end motion-correction method for the multishot sequence that incorporates a conditional generative adversarial network with minimum entropy (cGANME) of MR images. The cGANME contains an encoder-decoder generator to obtain motion-corrected images and a PatchGAN discriminator to classify the image as either real (motion-free) or fake (motion-corrected). The entropy of the images is set as one loss item in the cGAN's loss as the entropy increases monotonically with the motion artifacts. An ablation experiment of the different weights of entropy loss was performed to evaluate the function of entropy loss. The preclinical dataset was acquired with a fast spin echo pulse sequence on a 7.0-T scanner. After the simulation, we had 10,080/2880/1440 slices for training, testing, and validating, respectively. The clinical dataset was downloaded from the Human Connection Project website, and 11,300/3500/2000 slices were used for training, testing, and validating after simulation, respectively. Extensive experiments for different motion patterns, motion levels, and protocol parameters demonstrate that cGANME outperforms traditional and some state-of-the-art, deep learning-based methods. In addition, we tested cGANME on in vivo awake rats and mitigated the motion artifacts, indicating that the model has some generalizability.

Impact of the COVID-19 breast cancer screening hiatus on clinical stage and racial disparities in New York City.

BACKGROUND: The impact of the COVID-19 mammography screening hiatus as well as of post-hiatus efforts promoting restoration of elective healthcare on breast cancer detection patterns and stage distribution is unknown. METHODS: Newly diagnosed breast cancer patients (2019-2021) at the New York Presbyterian (NYP) Hospital Network were analyzed. Chi-square and student's t-test compared characteristics of patients presenting before and after the screening hiatus. RESULTS: A total of 2137 patients were analyzed. Frequency of screen-detected and early-stage breast cancer declined post-hiatus (59.7%), but returned to baseline (69.3%). Frequency of screen-detected breast cancer was lowest for African American (AA) (57.5%) and Medicaid patients pre-hiatus (57.2%), and this disparity was reduced post-hiatus (65.3% for AA and 63.2% for Medicaid). CONCLUSIONS: The return to baseline levels of screen-detected cancer, particularly among AA and Medicaid patients suggest that large-scale breast health education campaigns may be effective in resuming screening practices and in mitigating disparities.

Feline herpesvirus infection and pathology in captive snow leopard.

Feline herpesvirus type 1 (FHV-1) is a common causative agent of domestic cats' rhinotracheitis in domestic cats, and it increasingly threatens wild felids worldwide. The endangered snow leopard (Panthera uncia) belongs to the family Felidae, and it is the top predator on the Tibetan Plateau. Here we report the identification and isolation of FHV-1 from three dead captive snow leopards that presented with sneezing and rhinorrhea. To explore the relationship between FHV-1 and their deaths, organs and nasal swabs were collected for histopathology, viral isolation and sequence analysis. The results revealed that all three snow leopards were infected with FHV-1. The first animal died primarily of cerebral infarction and secondary non-suppurative meningoencephalitis that was probably caused by FHV-1. The second animal died mainly of renal failure accompanied by interstitial pneumonia caused by FHV-1. The cause of death for the third animal was likely related to the concurrent reactivation of a latent FHV-1 infection. The gD and gE gene sequence alignment of the isolated FHV-1 isolate strain revealed that the virus likely originated from a domestic cat. It was found that FHV-1 infection can cause different lesions in snow leopards than in domestic cats and is associated with high risk of disease in wild felids. This suggests that there should be increased focus on protecting wild felids against FHV-1 infections originating from domestic cats.

Measuring case severity: a novel tool for benchmarking and clinical documentation improvement.

BACKGROUND: Severity of illness (SOI) is an All Patients Refined Diagnosis Related Groups (APR DRG) modifier based on comorbidity capture. Tracking SOI helps hospitals improve performance and resource distribution. Furthermore, benchmarking SOI plays a key role in Quality Improvement (QI) efforts such as Clinical Documentation Improvement (CDI) programs. The current SOI system highly relies on the 3 M APR DRG grouper that is updated annually, making it difficult to track severity longitudinally and benchmark against hospitals with different patient populations. Here, we describe an alternative SOI scoring system that is grouper-independent and that can be tracked longitudinally. METHODS: Admission data for 2019-2020 U.S. News and World Report Honor Roll facilities were downloaded from the Vizient Clinical Database and split into training and testing datasets. Elixhauser comorbidities, body systems developed from the Healthcare Cost and Utilization Project (HCUP), and ICD-10-CM complication and comorbidity (CC/MCC) indicators were selected as the predictors for orthogonal polynomial regression models to predict patients' admission and discharge SOI. Receiver operating characteristic (ROC) and Precision-Recall (PR) analysis, and prediction accuracy were used to evaluate model performance. RESULTS: In the training dataset, the full model including both Elixhauser comorbidities and body system CC/MCC indicators had the highest ROC AUC, PR AUC and predication accuracy for both admission (ROC AUC: 92.9%; PR AUC: 91.0%; prediction accuracy: 85.4%) and discharge SOI (ROC AUC: 93.6%; PR AUC: 92.8%; prediction accuracy: 86.2%). The model including only body system CC/MCC indicators had similar performance for admission (ROC AUC: 92.4%; PR AUC: 90.4%; prediction accuracy: 84.8%) and discharge SOI (ROC AUC: 93.1%; PR AUC: 92.2%; prediction accuracy: 85.6%) as the full model. The model including only Elixhauser comorbidities exhibited the lowest performance. Similarly, in the validation dataset, the prediction accuracy was 86.2% for the full model, 85.6% for the body system model, and 79.3% for the comorbidity model. With fewer variables and less model complexity, the body system model was more efficient and was determined to be the optimal model. The probabilities generated from this model, named J_Score and J_Score_POA, successfully measured SOI and had practical applications in assessment of CDI performance. CONCLUSIONS: The J_Scores generated from the body system model have significant value in evaluating admission and discharge severity of illness. We believe that this new scoring system will provide a useful tool for healthcare institutions to benchmark patients' illness severity and augment Quality Improvement (QI) efforts.

Race Differences in Telomere Length in Benign Prostate Biopsies and Subsequent Risk of Prostate Cancer.

BACKGROUND: Telomere shortening is linked to aging and may be associated with increased risk for cancer. Most cancer studies have used telomere length in leukocytes rather than in the target tissue of cancer origin. METHODS: A case-control study of 524 case-control pairs with a benign prostate biopsy nested within a historical cohort of 10,478 men was conducted to determine whether premalignant prostate telomere length (assessed using a modified qRT-PCR) is associated with prostate cancer risk. RESULTS: Telomere lengths in benign prostate biopsies of cases versus controls were similar (1.46 ± 0.38 vs. 1.45 ± 0.42; P = 0.49). African American (AA) men had significantly shorter telomeres compared with White men (1.51 ± 0.38 vs. 1.63 ± 0.39; P < 0.0001). In race-stratified analyses, increasing telomere length was more strongly associated with prostate cancer risk in White men, wherein those with telomere length in the highest quartile had 1.9-fold greater adjusted risk of prostate cancer compared with men with prostate telomere lengths in the lowest quartile [OR = 1.90; 95% confidence interval (CI) = 1.08-3.36]. Men in the highest telomere length quartile also had a greater risk of aggressive prostate cancer compared with men with telomere lengths in the lowest quartile (OR = 2.78; 95% CI = 1.25-6.19). CONCLUSIONS: White men have longer telomeres in benign prostate tissue compared with AA men, and those with the longest telomeres may be at increased risk for prostate cancer, particularly the more aggressive form of the disease. IMPACT: Race-specific telomere length measures may be an early biomarker of aggressive prostate cancer.

Benefit of adjuvant chemotherapy in node-negative T1a versus T1b and T1c triple-negative breast cancer.

PURPOSE: National comprehensive cancer network guidelines recommend delivery of adjuvant chemotherapy in node-negative triple-negative breast cancer (TNBC) if the tumor is > 1 cm and consideration of adjuvant chemotherapy for T1b but not T1a disease. These recommendations are based upon sparse data on the role of adjuvant chemotherapy in T1a and T1b node-negative TNBC. Our objective was to clarify the benefits of chemotherapy for patients with T1N0 TNBC, stratified by tumor size. METHODS: We performed a retrospective analysis of survival outcomes of TNBC patients at two academic institutions in the United States from 1999 to 2018. Primary tumor size, histology, and nodal status were based upon surgical pathology. The Kaplan-Meier plot and 5-year unadjusted survival probability were evaluated. RESULTS: Among 282 T1N0 TNBC cases, the status of adjuvant chemotherapy was known for 258. Mean follow-up was 5.3 years. Adjuvant chemotherapy was delivered to 30.5% of T1a, 64.7% T1b, and 83.9% T1c (p < 0.0001). On multivariable analysis, factors associated with delivery of adjuvant chemotherapy were tumor size and grade 3 disease. Improved overall survival was associated with use of chemotherapy in patients with T1c disease (93.2% vs. 75.2% p = 0.008) but not T1a (100% vs. 100% p = 0.3778) or T1b (100% vs. 95.8% p = 0.2362) disease. CONCLUSION: Our data support current guidelines indicating benefit from adjuvant chemotherapy in node-negative TNBC associated with T1c tumors but excellent outcomes were observed in the cases of T1a and T1b disease, regardless of whether adjuvant chemotherapy was delivered.