Predictor Of Poor Clinical Outcome Research Articles

Defining the correlates of lymphopenia and independent predictors of poor clinical outcome in adults hospitalized with COVID-19 in Australia

Lymphopenia is a common feature of acute COVID-19 and is associated with increased disease severity and 30-day mortality. Here we aim to define the demographic and clinical characteristics that correlate with lymphopenia in COVID-19 and determine if lymphopenia is an independent predictor of poor clinical outcome. We analysed the ENTER-COVID (Epidemiology of hospitalized in-patient admissions following planned introduction of Epidemic SARS-CoV-2 to highly vaccinated COVID-19 naïve population) dataset of adults (N = 811) admitted for COVID-19 treatment in South Australia in a retrospective registry study, categorizing them as (a) lymphopenic (lymphocyte count < 1 × 109/L) or (b) non-lymphopenic at hospital admission. Comorbidities and laboratory parameters were compared between groups. Multiple regression analysis was performed using a linear or logistic model. Intensive care unit (ICU) patients and non-survivors exhibited lower median lymphocyte counts than non-ICU patients and survivors respectively. Univariate analysis revealed that low lymphocyte counts associated with hypertension and correlated with haemoglobin, platelet count and negatively correlated with urea, creatinine, bilirubin, and aspartate aminotransferase (AST). Multivariate analysis identified age, male, haemoglobin, platelet count, diabetes, creatinine, bilirubin, alanine transaminase, c-reactive protein (CRP) and lactate dehydrogenase (LDH) as independent predictors of poor clinical outcome in COVID-19, while lymphopenia did not emerge as a significant predictor.

Coma in adult cerebral venous thrombosis: The BEAST study.

Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.

Progressive sarcopenia and myosteatosis predict prognosis of advanced HCC patients treated with immune checkpoint inhibitors.

Immunotherapy stands as a pivotal modality in the therapeutic landscape for the treatment of advanced hepatocellular carcinoma, yet responses vary among patients. This study delves into the potential impact of sarcopenia, myosteatosis and adiposity indicators, as well as their changes during immunotherapy, on treatment response and prognosis in patients with advanced hepatocellular carcinoma treated with immune checkpoint inhibitors. In this retrospective analysis, 116 patients with advanced hepatocellular carcinoma receiving immune checkpoint inhibitors were recruited. Skeletal muscle, intramuscular, subcutaneous, and visceral adipose tissue were assessed by computed tomography at the level of the third lumbar vertebrae before and after 3 months of treatment. Sarcopenia and myosteatosis were evaluated by skeletal muscle index and mean muscle density using predefined threshold values. Patients were stratified based on specific baseline values or median values, along with alterations observed during the treatment course. Overall survival (OS) and progression-free survival (PFS) were compared using the log-rank test and a multifactorial Cox proportional risk model. A total of 116 patients were recruited and divided into two cohorts, 81 patients for the training set and 35 patients for the validating set. In the overall cohort, progressive sarcopenia (P=0.021) and progressive myosteatosis (P=0.001) were associated with objective response rates, whereas progressive myosteatosis (P<0.001) was associated with disease control rates. In the training set, baseline sarcopenia, myosteatosis, and subcutaneous and visceral adipose tissue were not significantly associated with PFS and OS. In multivariate analysis adjusting for sex, age, and other factors, progressive sarcopenia(P=0.002) and myosteatosis (P=0.018) remained independent predictors of PFS. Progressive sarcopenia (P=0.005), performance status (P=0.006) and visceral adipose tissue index (P=0.001) were all independent predictors of OS. The predictive models developed in the training set also had good feasibility in the validating set. Progressive sarcopenia and myosteatosis are predictors of poor clinical outcomes in patients with advanced hepatocellular carcinoma receiving immune checkpoint inhibitors, and high baseline visceral adiposity is associated with a poorer survival.

Optimal intraventricular hemorrhage volume cutoff for predicting poor outcome in patients with intracerebral hemorrhage

Background and objectivesThe prognosis of patients with spontaneous intracerebral hemorrhage (ICH) is often influenced by hematoma volume, a well-established predictor of poor outcome. However, the optimal intraventricular hemorrhage (IVH) volume cutoff for predicting poor outcome remains unknown. MethodsWe analyzed 313 patients with spontaneous ICH not undergoing evacuation, including 7 cases with external ventricular drainage (EVD). These patients underwent a baseline CT scan, followed by a 24-hour CT scan for measurement of both hematoma and IVH volume. We defined hematoma growth as hematoma growth > 33 % or 6 mL at follow-up CT, and poor outcome as modified Rankin Scale score≥3 at three months. Cutoffs with optimal sensitivity and specificity for predicting poor outcome were identified using receiver operating curves. ResultsThe receiver operating characteristic analysis identified 6 mL as the optimal cutoff for predicting poor outcome. IVH volume> 6 mL was observed in 53 (16.9 %) of 313 patients. Patients with IVH volume>6 mL were more likely to be older and had higher NIHSS score and lower GCS score than those without. IVH volume>6 mL (adjusted OR 2.43, 95 % CI 1.13-5.30; P = 0.026) was found to be an independent predictor of poor clinical outcome at three months in multivariable regression analysis. ConclusionsOptimal IVH volume cutoff represents a powerful tool for improving the prediction of poor outcome in patients with ICH, particularly in the absence of clot evacuation or common use of EVD. Small amounts of intraventricular blood are not independently associated with poor outcome in patients with intracerebral hemorrhage. The utilization of optimal IVH volume cutoffs may improve the clinical trial design by targeting ICH patients that will obtain maximal benefit from therapies.

Where you live matters: Area deprivation predicts poor survival and liver transplant waitlisting

Social determinants of health (SDOH) are important predictors of poor clinical outcomes in chronic diseases, but their associations among the general cirrhosis population and liver transplantation (LT) are limited. We conducted a retrospective, multiinstitutional analysis of adult (≥18-years-old) patients with cirrhosis in metropolitan Chicago to determine the associations of poor neighborhood-level SDOH on decompensation complications, mortality, and LT waitlisting. Area deprivation index and covariates extracted from the American Census Survey were aspects of SDOH that were investigated. Among 15 101 patients with cirrhosis, the mean age was 57.2 years; 6414 (42.5%) were women, 6589 (43.6%) were non-Hispanic White, 3652 (24.2%) were non-Hispanic Black, and 2662 (17.6%) were Hispanic. Each quintile increase in area deprivation was associated with poor outcomes in decompensation (sHR [subdistribution hazard ratio] 1.07; 95% CI 1.05-1.10; P < .001), waitlisting (sHR 0.72; 95% CI 0.67-0.76; P < .001), and all-cause mortality (sHR 1.09; 95% CI 1.06-1.12; P < .001). Domains of SDOH associated with a lower likelihood of waitlisting and survival included low income, low education, poor household conditions, and social support (P < .001). Overall, patients with cirrhosis residing in poor neighborhood-level SDOH had higher decompensation, and mortality, and were less likely to be waitlisted for LT. Further exploration of structural barriers toward LT or optimizing health outcomes is warranted.

Minor head injury in anticoagulated patients: Outcomes and analysis of clinical predictors. A prospective study

BackgroundThe optimal management of patients taking oral anticoagulants who experience minor head injury (MHI) is unclear. The availability of validated protocols and reliable predictors of prognosis would be of great benefit. We investigated clinical factors as predictors of clinical outcomes and intracranial injury (ICI). MethodsWe conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The primary outcome was the occurrence of MHI-related death or re-admission to ED at day +30. The secondary outcome was the rate of delayed ICI (dICI), defined as second positive CT scan after a first negative CT scan. We assessed some clinical predictors derived from guidelines and clinical prediction rules as potential risk factors for the outcomes. Results450 patients with a negative first CT scan who underwent a second CT scan composed our ‘study population’. The rate of the primary outcome was 4%. The rate of the secondary outcome was 4.7%. Upon univariate and multivariate analysis no statistically significant predictors for the outcomes were found. ConclusionsPrevious retrospective studies showed a lot of negative predictive factors for anticoagulated patients suffering a minor head injury. In our prospective study no clinical factors emerged as predictors of poor clinical outcomes and dICI. So, even if we confirmed a low rate of adverse outcomes, the best management of these patients in ED remains not so clear and future trials are needed.

Pulmonary hypertension is an adverse risk factor for peri-procedural complications in patients undergoing pulmonary vein isolation and ablation for atrial fibrillation

Abstract Background Recent studies have identified Pulmonary hypertension (PHT) as a predictor for poor clinical outcomes in Atrial fibrillation (AF) with increased fold in mortality. PHT is associated with right ventricular pressure and volume overload eventually leading to right heart failure. These structural changes can lead to electrophysiological abnormalities, with AF being one of the most common. Percutaneous catheter ablation and pulmonary vein isolation is becoming more common ground for management of paroxysmal atrial fibrillation (AF). We sought to investigate the impact of PHT as an adverse risk factor for patients undergoing pulmonary vein isolation and ablation for AF. Methods We utilized the National Inpatient Sample from 2016-2019 to identify roughly 49,425 hospitalized adults who underwent AF Ablation. These hospitalizations were further stratified based on the presence of PHT. A multivariate regression model was used to adjust for confounders and analyze the variables. Results Of those who underwent AF Ablation, 5,329 (10.7%) had PHT. In-hospital mortality was higher in those with PHT (2.5% vs 0.9%; p&amp;lt;0.001). Figure 1 shows the Forrest plot for multivariate analysis of in-hospital outcomes when adjusted for patient demographics, comorbidities, and hospital characteristics. When adjusted similarly, patients with AF and PHT had longer length of stay (LOS) by 2.9 days (p&amp;lt;0.001) and had additional hospital costs (HC) of $25,122 (p&amp;lt;0.001). Conclusion In this study, patients undergoing AF ablation with co-existing PHT had significantly worse outcomes in terms of in-hospital mortality, LOS, HC, atrial flutter, ventricular tachycardia, AKI, sepsis, pneumonia, and endotracheal intubation. One major limitation of our study is the lack of outpatient follow up. Given that overall outcomes are worse in the setting of PHT, potential strategies for aggressive rate and volume control prior to the ablation for AF should be pursued to avoid negative outcomes. AF patients with co-existing PHT should be aggressively monitored during hospitalizations for AF ablation as they have the potential to have worse periprocedural outcomes.

Frailty measured using an electronic frailty index and outcomes in older patients with myocardial infarction

Abstract Background Frailty is common amongst older patients with myocardial infarction and is an independent predictor of poor clinical outcomes. Despite this, frailty is not systematically or objectively measured nor routinely used in risk stratification. The electronic Frailty Index (eFI) is a frailty assessment tool which uses electronic health records to identify and classify frailty and has been shown to correlate well with in-person frailty assessment. However, the performance of the eFI in disease specific populations and its ability to predict individual patient outcomes is unclear. Purpose To assess the relationship between frailty, measured using the eFI, and the management and outcomes of older patients with myocardial infarction. Methods Consecutive patients admitted to hospital in the South East of Scotland between 01/10/2014 and the 01/03/2021 with a primary diagnosis of myocardial infarction were identified using International Classification of Disease (ICD-10) code I21 or I22. Patients under the age of 65 (n= 3,601) and those with no biomarker evidence of myocardial injury were excluded (n=1,301). The provision of guideline recommended therapy, recurrent hospital admission due to myocardial infarction, heart failure or stroke and 12-month all-cause mortality were compared between groups based on eFI classification (fit, mild, moderate or severely frail). Results Of the 3,930 patients (mean age 78 [SD 8] years, 43% female, 83% Caucasian), 2,324 (59%) were classified as frail with 1,421 (36%), 664 (17%), and 239 (6%) classified as mild, moderate and severely frail, respectively. The eFI was measurable in all patients. Patients with any degree of frailty were less likely to receive anti-platelet therapy, ACE inhibitor or angiotensin receptor blocker or beta-blocker therapy or undergo revascularisation with fewer than 1 in 10 patients with severe frailty undergoing inpatient coronary catheterisation (7.5% vs 57% non-frail, P &amp;lt;0.001 for all). Frailty was independently associated with an increased incidence of recurrent myocardial infarction, heart failure or stroke within 12 months with the odds greatest in those with severe frailty (OR 1.93 (95% CI 1.42-2.61%)). The primary outcome of all-cause death at 12-months occurred in 355 (25%), 226 (34%) and 109 (46%) patients with mild, moderate and severe frailty compared with 176 (11%) in non-frail patients (Figure 1). Frailty status was an independent risk factor for all-cause mortality with the risk of death greatest in those with severe frailty (HR 2.64 (95% CI 1.63 – 3.67, p&amp;lt;0.001)). Conclusion The eFI identified patients at increased risk of in-patient death, major adverse cardiovascular events, and all-cause mortality within 12 months following myocardial infarction. Measurement of the eFI from linked healthcare data is feasible and could be used to aide personalised risk stratification and service utilisation in older patients admitted with myocardial infarction.Cumulative incidence plotForest plot with adjusted hazard ratio

Endovascular treatment as first-line therapy in Spetzler-Martin grade III brain arteriovenous malformations: a multicenter retrospective study.

The management of Spetzler-Martin grade (SMG) III brain arteriovenous malformations (bAVMs) may be challenging, whatever the exclusion treatment modality chosen. The purpose of this study was to evaluate the safety and effectiveness of endovascular treatment (EVT) as a first-line treatment of SMG III bAVMs. The authors performed a retrospective, two-center, observational cohort study. Cases recorded in institutional databases between January 1998 and June 2021 were reviewed. Patients who were ≥ 18 years of age, had ruptured or unruptured SMG III bAVMs, and received EVT as first-line therapy were included. Baseline characteristics of patients and bAVMs, procedure-related complications, clinical outcome according to the modified Rankin Scale, and angiographic follow-up were assessed. The independent risk factors of procedure-related complications and poor clinical outcome were assessed using binary logistic regression. One hundred sixteen patients with 116 SMG III bAVMs were included. The mean age of the patients was 41.9 ± 14.0 years. The most common presentation was hemorrhage (66.4%). Forty-nine (42.2%) bAVMs were found to be completely obliterated by EVT alone at follow-up. Complications occurred in 39 patients (33.6%), including 5 (4.3%) major procedure-related complications. There was no independent predictor of procedure-related complication. Age > 40 years and poor preoperative modified Rankin Scale score were the independent predictors of poor clinical outcome. EVT of SMG III bAVMs provides encouraging results but needs further improvement. When the embolization procedure performed with intent to cure appears difficult and/or risky, a combined technique (with microsurgery or radiosurgery) may be a safer and more effective strategy. In terms of safety and effectiveness, the benefit of EVT (alone or included in a multimodal management strategy) for SMG III bAVMs needs to be confirmed by randomized controlled trials.

Anemia as a risk factor for disease progression in patients admitted for COVID-19: data from a large, multicenter cohort study

In respiratory infections, anemia is both a consequence of acute inflammation and a predictor of poor clinical outcomes. There are few studies investigating the role of anemia in COVID-19, suggesting a potential role in predicting disease severity. In this study, we aimed to assess the association between the presence of anemia at admission and incidence of severe disease and death in patients hospitalized for COVID-19. Data from all adult patients admitted for COVID-19 in University Hospital “P. Giaccone” Palermo, and University Hospital of Bari, Italy, were retrospectively collected from 1st of September 2020 to 31 August 2022. The association between anemia (defined as Hb < 13 g/dl and < 12 g/dl in males and females, respectively), in-hospital mortality and severe COVID-19 was tested using a Cox’s regression analysis. Severe COVID-19 forms were defined as admission to intensive or sub-intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. p values were calculated using the Student’s t test for continuous variables and the Mantel–Haenszel Chi-square test for categorical ones. The association between anemia and the mortality was made using a Cox’s regression analysis, adjusted, in two models, for the potential confounders and using a propensity score. Among the 1562 patients included in the analysis, prevalence of anemia was 45.1% (95% CI 43–48%). Patients with anemia were significantly older (p < 0.0001), reported more co-morbidities, and presented higher baseline levels of procalcitonin, CRP, ferritin and IL-6. Overall, the crude incidence of mortality was about four times higher in patients with anemia compared to those without. After adjusting for 17 potential confounders, the presence of anemia significantly increased the risk of death (HR = 2.68; 95% CI: 1.59–4.52) and of risk of severe COVID-19 (OR = 2.31; 95% CI: 1.65–3.24). The propensity score analysis substantially confirmed these analyses. Our study provides evidence that, in patients hospitalized for COVID-19, anemia is both associated with a more pronounced baseline pro-inflammatory profile and higher incidence of in-hospital mortality and severe disease.

Abstract 3588: Multiplex proteomics profiling with the imaging mass cytometry (IMC) identifies immune cell phenotypes associated with high NOS2/COX2 expression in ER- negative and TNBC patients

Abstract Elevated expression of Inducible Nitric oxide Synthase-2 (NOS2) occurs during acute and chronic inflammation and wound healing processes however, it is also a predictor of bad prognosis in aggressive ER-negative tumors. Overexpression of NOS2 correlates with other prognostic biomarkers making it a unique multifunctional oncoprotein. Cyclooxygenase-2 (COX2) is another enzyme associated with cancer inflammation and is overexpressed in &amp;gt;50% of breast cancers. In our previous studies, we have shown that NOS2/COX2 co-expression is a strong predictor of poor clinical outcome and promotes CD8+ T cell exclusion from tumor epithelia in Triple-negative breast cancers (TNBC). This observation was further explored using multiplexing proteomics technologies. Imaging Mass Cytometry (IMC) has revolutionized tumor microenvironment research by allowing the interrogation of over 35 protein markers simultaneously for the elucidation of the spatial distribution of immune and tumor cells at sub-cellular resolution. Herein, we used multiplex capability IMC to explore the interactions of immune and tumor cell counterparts in ER-negative and TNBC tumors. We employed Formalin-fixed paraffin-embedded (FFPE) tissue from 26 ER-negative and TNBC samples from a clinical cohort of African American breast cancer patients in the Baltimore MD area. We developed a panel of 15 protein metal-labeled antibody markers including antibodies targeting NOS2, COX2, T cells (CD45, CD3, CD4, CD8,) endothelium (CD31), monocytes (CD14), macrophages (CD68), basal markers (α-SMA), cancer stem cells (CD44v6), cancer cells (Pan-CK, B7H4, Cadherin), and serine proteases (granzyme B) secreted by T cells or Natural Killer (NK) cells. Single section slides of 4 µm size were stained with the cocktail of metal-labeled antibodies. Multiple regions of interest (ROIs) representing the tumor and immune cells compartments and tumor-facing stromal cell areas were ablated with the Hyperion Imaging system. The data analysis was performed by the Bodenmiller lab pipeline and VisioPharm software packages. Our preliminary data suggest that patient tumors with high or low NOS2/COX2 expression showed variable levels of CD68 positive macrophage population and T cells. We are currently analyzing the remaining data to understand the cell phenotypes associated with the immunosuppressive and immune-rich clinical samples and performing neighborhood analysis of tumor cells to immune cells and vessels. Citation Format: Milind Pore, Lisa Ridnour, Paul Mallory, Ashley Cardamone, Stephen Lockett, William Bocik, David Wink. Multiplex proteomics profiling with the imaging mass cytometry (IMC) identifies immune cell phenotypes associated with high NOS2/COX2 expression in ER- negative and TNBC patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3588.

Prognostic value of sarcopenia in patients with lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors or immune checkpoint inhibitors.

It remains controversial whether sarcopenia has any significant impact on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Therefore, in this study, we aimed to assess the association between sarcopenia and clinical outcomes in patients with advanced NSCLC receiving EGFR-TKIs or ICIs as a first-line therapy. We retrospectively enrolled 131 patients with advanced NSCLC treated with first-line EGFR-TKIs or ICIs between 1 March 2019 and 31 March 2021. To estimate sarcopenia, we calculated skeletal muscle index (SMI) as the ratio of skeletal muscle area (cm2) to height squared (m2). Associations between sarcopenia and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and log-rank tests, respectively. A Cox proportional hazards regression model was used to assess the factors associated with OS and PFS. The Student's t-test or Mann-Whitney U test was used to compare the SMI between patients with or without objective response and disease control. The chi-squared test was used to compare adverse events (AEs) between patients with and without sarcopenia. Among the 131 patients, 35 (26.7%) were diagnosed with sarcopenia. Sarcopenia was an independent predictor of poor OS and PFS (p < 0.05) overall and in the EGFR-TKI- and ICI-treated cohorts. Among all patients, those with sarcopenia showed significantly shorter OS and PFS than those without sarcopenia (median OS and PFS: 13.0 vs. 26.0 months and 6.4 vs. 15.1 months; both p < 0.001). These associations were consistent across the subtypes of most clinical characteristics. Statistically significant differences between the objective response (OR) and non-OR groups were also observed in the mean SMI (OR group, 43.89 ± 7.55 vs. non-OR group, 38.84 ± 7.11 cm2/m2; p < 0.001). In addition, we observed similar results with disease control (DC) and non-DC groups (DC group, 42.46 ± 7.64 vs. non-DCR group, 33.74 ± 4.31 cm2/m2; p < 0.001). The AEs did not differ significantly between the sarcopenia and non-sarcopenia groups. Sarcopenia before treatment might be a significant predictor of poor clinical outcomes (shorter OS and PFS, fewer ORs, less DC) in patients with advanced NSCLC treated with EGFR-TKIs or ICIs as the first-line therapy.

Abstract P2-11-13: High PD-L2 Protein Expression in Cancer Cells is an Independent Marker of Unfavorable Prognosis in Luminal Breast Tumors

Abstract Background PD-1 inhibitors have shown significant efficacy in triple negative breast cancer (BC), however, durable responses are less common in estrogen receptor-positive (ER+) BC. Better markers are therefore needed that will identify likely responders to PD-1 inhibitors among patients with luminal BC. While most efforts have focused on the immune checkpoint protein PD-L1, the alternative PD-1 ligand, PD-L2, has been largely overlooked. We aimed to determine if PD-L2 is associated with unfavorable prognosis in ER+ BC. Methods PD-L2 protein levels in cancer cells and stromal cells were measured retrospectively by quantitative immunofluorescence histocytometry in tissue microarrays of therapy-naïve, localized or locoregional ER+ BC and correlated with progression-free survival (PFS). Evaluable tumor PD-L2 data were derived from a main study cohort A diagnosed between 1988-2005 (n=684) with extensive clinical and outcome data and from an independent validation cohort B diagnosed between 1992-2012 (n=273). Patients received standard-of-care adjuvant therapy without immune checkpoint inhibitors after tumor resection. Results Univariate analysis of the main cohort A revealed that high PD-L2 expression in cancer cells was associated with shorter PFS (HR=1.8; 95%CI:1.3-2.6; p=0.001), an observation that was validated in an independent cohort B (HR=2.3, 95%CI:1.1-4.8; p=0.026). Approximately one third of ER+ BC cases were classified as high PD-L2. After multivariable adjustment for common clinicopathological variables, high cancer cell levels of PD-L2 remained independently predictive of early recurrence (HR=2.0; 95%CI:1.4-2.9; p&amp;lt; 0.001). Sub-analysis of ER+ BC cases treated with adjuvant chemotherapy (n=197) suggested that high PD-L2 levels in cancer cells was associated with particularly increased risk of progression (multivariable HR=3.4; 95%CI:1.9-6.2; p&amp;lt; 0.001). The observed frequent expression of PD-L2 protein in BC provided scientific rationale for the design of our ongoing phase II clinical trial (NCT04243616) of neoadjuvant combined PD-1 inhibitor (cemiplimab; Regeneron Pharmaceuticals Inc) and chemotherapy in patients diagnosed with PD-L1+ and/or PD-L2+ BC. The primary objective of this trial is to assess pathologic responses to neoadjuvant treatment with secondary objective of assessing the correlation between PD-L1/PD-L2 status and tumor responses. Pathologist review of PD-L1 and PD-L2 expression in an initial set of ER+ tumors (n=15) screened for trial eligibility revealed frequent discordance between cancer cell positivity for PD-L1 and PD-L2 protein (PD-L1: median=0%; range 0-2% vs. PD-L2: median=18%; range &amp;lt; 1-60%) as well as immune cell positivity (PD-L1: median=5%; range 0-50% vs. PD-L2: median=0; range 0-50%). Conclusions In treatment-naïve ER+ breast tumors, high cancer cell expression of PD-L2 protein was an independent predictor of poor clinical outcome, with evidence of further elevated risk of progression in patients who received adjuvant chemotherapy. Preliminary analyses of ER+ tumors from our ongoing clinical trial showed frequent discordance between baseline PD-L1 and PD-L2 protein expression in both cancer cells and immune cells. Collectively, our analyses indicate that PD-L2 has prognostic value for ER+ BC, and our progress justify further studies to determine whether PD-L2, alone or in combination with PD-L1, may serve as a predictive marker of response to PD-1 inhibitors. Citation Format: Lubna N. Chaudhary, Inna Chervoneva, Amy R. Peck, Yunguang Sun, Misung Yi, John F. Langenheim, Julie M. Jorns, Sailaja Kamaraju, Yee Chung Cheng, John Burfeind, Christopher R. Chitambar, Jeffrey A. Hooke, Albert J. Kovatich, Craig Shriver, Hai Hu, Juan P. Palazzo, Marluce Bibbo, Terry Hyslop, Richard Pestell, Edith P. Mitchell, Hallgeir Rui. High PD-L2 Protein Expression in Cancer Cells is an Independent Marker of Unfavorable Prognosis in Luminal Breast Tumors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-13.

Abstract Number ‐ 20: Predictors of Outcomes for Patients with Malignancy and Acute Ischemic Stroke Undergoing Endovascular Therapy

Introduction Patients with active cancer face an increased risk for stroke. Randomized trials studying the efficacy of endovascular therapy for patients with large vessel occlusions generally excluded patients with cancer. Herein, we sought to better understand predictors of outcome for active cancer patients undergoing mechanical thrombectomy for acute ischemic stroke. Methods We conducted a retrospective cohort study of stroke thrombectomy cases performed at our institution from January 2010 to November 2021. Baseline clinical characteristics (age, gender, cancer type, use of anticoagulation, NIHSS, use of tPA, time to reperfusion) were recorded. Study outcomes were successful endovascular reperfusion (≥ TICI 2b) and poor clinical outcome, defined as inpatient death or disposition to hospice. Pearson Chi‐square test and Fisher’s exact test were used to analyze categorical variables, and Mann‐Whitney U tests were used for continuous variables. Multivariable logistic regression analyses were performed to evaluate for independent associations between baseline characteristics and study outcomes. Results Between 2010–2021, we identified 49 patients with active cancer who underwent mechanical thrombectomy for stroke. Their mean age was 63 years (SD, 12), and 43% were men. The leading cancer types were lung (33%) and colorectal (14%). Successful reperfusion was achieved in 78% (95% CI, 66–90%) of patients, and 49% (95% CI, 34–63%) ultimately had a poor clinical outcome. Multivariable analyses yielded no significant predictors for successful reperfusion, while higher NIHSS (1.03, 95% CI, 1.01‐1.06, p = 0.011) and higher cancer stage (1.19, 95% CI, 1.04‐1.34, p = 0.014) were found to be predictors for poor clinical outcome. Conclusions The link between cancer and stroke has become increasingly appreciated. As tPA is often contraindicated in cancer patients with stroke because of recent bleeding or anticoagulant use, thrombectomy may be the only intervention to preserve one’s quality of life. However, we found that despite a high successful reperfusion rate, nearly half of these patients died or were made hospice during the index hospitalization. Future studies should investigate the reasons for poor clinical outcomes in these patients and whether different antithrombotic, blood pressure, or anti‐neoplastic strategies after thrombectomy could improve outcomes.

Stigma and self-stigma in patients with delusional disorder: a systematic review.

IntroductionThe association between insight, stigma and self-concept has been considered as a potential predictor of poor clinical outcomes and global functioning in psychosis. In patients with delusional disorder (DD), the effects of stigma and self-stigma have been poorly explored.ObjectivesOur main goal was to systematically review studies addressing stigma and self-stigma in DD to assess whether these phenomena have an impact on clinical symptoms.MethodsA systematic review was conducted through PubMed and Google Scholar databases from inception to 2022 (PRISMA guidelines). Search terms: (Stigma OR self-stigma) AND (“delusional disorder” OR psychosis OR paranoia). Studies were considered eligible if they included patients with DD.ResultsA total of 875 records were retrieved, from which 18 were included.Stigma: (1) Stigma is associated with poor quality of life, poor adherence to medications and acceptation of diagnosis. (2) Support at workplaces would improve stigma and discrimination in DD. (3) Poor interpersonal competence may increase stigma experience in DD.Self-stigma: (1) Women show higher level of self-stigma than men. (2) Higher rates of psychiatric hospitalizations and higher severity of symptoms associated with greater degree of self-stigma. (3) Suicidal ideation was associated with negative self-schema but not self-stigma, particularly in patients with persecutory delusions. (4) Self-stigmatization negatively associated with quality of life. (5) Depressive symptoms associated with higher levels of self-stigma. (6) Promotion interventions should address self-stigma content.ConclusionsFurther longitudinal studies are needed to test the influence of stigma and self-stigma on adherence to follow-up and specific interventions to improve them.Disclosure of InterestNone Declared

Acute kidney injury in neurocritical patients: a retrospective cohort study.

Acute kidney injury (AKI) is a significant complication in critical care units (CCU). Non-neurological complications such as AKI are an independent predictor of poor clinical outcomes, with an increase in morbidity and mortality, financial costs, and worse functional recovery. This work aims to estimate the incidence of AKI and evaluate the risk factors and complications of AKI in neurocritical patients hospitalized in the CCU. A retrospective cohort study was conducted. Patients admitted to the neurocritical care unit between 2016 and 2018 with a stay longer than 48h were retrospectively analyzed in regard to the incidence, risk factors, and outcomes of AKI. The study population comprised 213 neurocritical patients. The incidence of AKI was 23.5%, with 58% KDIGO 1 and 2% requiring renal replacement therapy. AKI was an independent predictor of prolonged use of mechanical ventilation, cerebral edema, and mortality. Cerebral edema [OR 4.40 (95% CI 1.98-9.75) p < 0.001] and a change in chloride levels greater than 4mmol/L at 48h (OR 2.44 (95% CI 1.10-5.37) p = 0.027) were risk factors for developing AKI in the first 14days of hospitalization. There is a high incidence of AKI in neurocritical patients; it is associated with worse clinical outcomes regardless of the CCU admission etiology or AKI severity.

Predictors of poor clinical outcomes including in-hospital death and low ability to perform activities of daily living at discharge in hospitalized patients with chronic obstructive pulmonary disease exacerbation.

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. Many patients with COPD experience exacerbations that require hospitalization, which is associated with an increased risk of in-hospital death and impaired ability to perform activities of daily living (ADL). Declining ability to perform ADL is a critical issue for these patients. To identify predictors of poor clinical outcomes, including in-hospital death and low ability to perform ADL at discharge, in patients who are hospitalized with exacerbation of COPD. This retrospective study involved a cohort of patients with exacerbation of COPD who were admitted to Iwata City Hospital in Japan between July 2015 and October 2019. We collected clinical data, measured the cross-sectional area of the erector spinae muscles (ESMCSA) on computed tomography (CT) scans at admission, and investigated the associations of poor clinical outcomes (in-hospital death and severe dependence when performing ADL, defined as a Barthel Index (BI) of ⩽40 at discharge) with clinical parameters. Overall, 207 patients were hospitalized for exacerbation of COPD during the study period. The incidence of poor clinical outcomes was 21.3%, and the in-hospital mortality rate was 6.3%. Multivariate logistic regression analyses showed that older age, long-term oxygen therapy, an elevated D-dimer concentration, and a reduced ESMCSA on chest CT at admission were significantly associated with poor clinical outcomes (in-hospital death and a BI of ⩽40). Hospitalization for exacerbation of COPD was associated with high rates of in-hospital mortality and a BI of ⩽40 at discharge, which may be predicted by assessment of ESMCSA.

PS-BPC05-2: ADMISSION AND DISCHARGE BLOOD PRESSURE INFLUENCE MEDICAL PRESCRIPTION AND CLINICAL OUTCOMES OF PATIENTS WITH DECOMPENSATED HEART FAILURE

Background: There has been no study evaluating whether admission blood pressure (BP) influences medical treatment and clinical outcomes in acute decompensated heart failure patients. Methods: We analyzed the data form Korean Acute Heart Failure (KorHF) Registry. A total of 3,200 acute decompensated heart failure patients were included in the registry. We investigated the association of initial blood pressure at admission and clinical outcomes and prescription of ACEI, ARB and beta-bolcker(BB). The primary outcome was composite of mortality and readmission during 1-year after hospital discharge. Results: Admission systolic (SBP) and diastolic BP (DBP) increase was associated with decrease in primary outcomes (by 1mmHg increase of SBP, crude hazard ratio [HR] 0.9963, 95% CI: 0.9943–0.9982, p &lt; 0.0001 and by 1mmHg increase of DBP, crude HR 0.99, 95% CI: 0.9867–0.9932, p &lt; 0.0001). By multiple regression analysis DBP was an independent risk factors of mortality and re-hospitalization (HR 0.9927, 95% CI 0.9867–0.9988, p &lt; 0.0196), but SBP was not. Age, history of heart failure, hypertension, cholesterol level and ACE/ARB use were also associated with primary outcomes. The cut-off value of SBP and DBP for increasing clinical outcomes were 118.5 mmHg (sensitivity 0.3965, specificity 0.6727) and 78.5mmHg (sensitivity 0.5682, specificity 0.5228), respectively by ROC curve. The SBP &lt; 118.5 mmHg and DBP &lt; 78.5mmHg were independent predictor for primary outcomes (adjusted HR 1.33, 95% CI 1.15–1.54, p &lt; 0.0001 and adjusted HR 1.23, 95% CI 1.12–1.48, p = 0.0004, respectively). The cut off SBP/ DBP value of not using in-hospital ACE/ARB/BB were 129.5/80.5mmHg. DBP of 80.5mmHg was an independent determinants of not prescribing the drugs (adjusted OR 0.755, 95% CI: 0.582–0.977, p = 0.0329). Both lower SBP (&lt; 129.5) and DBP (&lt; 80.5mmHg) combined with no use of the drugs were independent predictor of poor clinical outcomes at 1-year. (adjusted HR 1.677, 95% CI: 1.380–2.037, p &lt; 0.0001 and adjusted HR 1.653, 95% CI: 1.355–2.017, P &lt; 0.0001, respectively) Conclusions: Lower blood pressure at admission increase mortality, re-hospitalization at 1-year and decrease in-hospital prescription of ACE/ARB and BB in patients with acute decompensated heart failure. The cut-off value of SBP/DBP for primary outcome was 118.5/78.5 mmHg and that for use of ACE/ARB/BB was 129.5/80.5mmHg.

Human Immunodeficiency Virus Is Associated With Poor Overall Survival Among Patients With Head and Neck Cancer.

Head and neck squamous cell cancer (HNSCC) occurs at higher rates among persons with HIV (PWH). This study compares the impact of sociodemographic and clinicopathologic characteristics on outcomes among PWH-HNSCC compared with HNSCC patients without HIV. Patient data from HNSCC individuals were collected at a single academic hospital center between 2002 and 2018. Forty-eight patients with HIV (HIV-HNSCC) and 2894 HNSCC patients without HIV were included. Multivariate analysis determined predictors of survival using Cox proportional hazards regression model. HIV-positive and -negative tumors were analyzed by quantitative immunofluorescence for expression of CD4, CD8, CD20 and PD-L1. HIV-HNSCC patients had a lower median overall survival than HNSCC patients without HIV (34 [18-84] vs 94 [86-103] months; P < .001). In multivariate analysis that included age, sex, race/ethnicity, stage, site, tobacco use, time to treatment initiation, and insurance status, HIV was an independent predictor of poorer survival, with a hazard ratio of 1.98 (95% CI: 1.32-2.97; P < .001). PWH with human papillomavirus (HPV)-positive oropharyngeal tumors also had worse prognosis than HPV-positive oropharyngeal tumors in the population without HIV (P < .001). The tumor microenvironment among HIV-HNSCC patients revealed lower intratumoral CD8 infiltration among HIV+ HPV+ tumors compared with HIV- HPV+ tumors (P = .04). HIV-HNSCC patients had worse prognosis than the non-HIV population, with HIV being an independent predictor of poor clinical outcomes when accounting for important sociodemographic and clinicopathologic factors. Our findings highlight differences in tumor biology that require further detailed characterization in large cohorts and increased inclusion of PWH in immunotherapy trials.

The comprehensive comparison of imaging sign from CT angiography and noncontrast CT for predicting intracranial hemorrhage expansion: A comparative study.

Expansion of intracranial hemorrhage (ICH) is an important predictor of poor clinical outcomes. Various imaging markers on non-contrast computed tomography (NCCT) or computed tomographic angiography (CTA) have been reported as predictors of ICH expansion. We aimed to compare the associations between various CT imaging markers and ICH expansion. Patients with spontaneous ICH who underwent initial NCCT, CTA, and subsequent NCCT between January 2016 and December 2019 were retrospectively identified. ICH expansion was defined as a volume increase of > 33% or > 6 mL. We analyzed the presence of imaging markers such as the black hole sign, blend sign, island sign, or swirl sign on initial NCCT or spot sign on CTA. An alternative free-response receiver operating characteristic curve analysis was performed using a 4-point scoring system based on the consensus of the reviewers. The predictive value of each marker was assessed using univariate and multivariate logistic regression analyses. A total of 250 patients, including 60 (24.0%) with ICH expansion, qualified for the analysis. Among the patients with spontaneous ICH, 118 (47.2%) presented with a black hole sign, 52 (20.8%) with a blend sign, 93 (37.2%) with an island sign, 79 (31.6%) with a swirl sign, and 56 (22.4%) with a spot sign. In univariate logistic regression, the initial ICH volume (P = .038), initial intraventricular hemorrhage (IVH) presence (P < .001), swirl sign (P < .001), and spot sign (P < .001) were associated with ICH expansion. Multivariate analysis confirmed that the presence of initial IVH (odds ratio, 4.111; P = .002) and spot sign (odds ratio, 109.5; P < .001) were independent predictors of ICH expansion. Initial ICH volume, IVH, swirl sign, and spot sign are associated with ICH expansion. The presence of spot signs and IVH were independent predictors of ICH expansion.