Strong Predictor Of Survival Research Articles

Predicting Mortality in Sepsis: The Role of Dynamic Biomarker Changes and Clinical Scores-A Retrospective Cohort Study.

The prognostic value of baseline inflammatory markers in sepsis remains controversial, with conflicting evidence regarding their association with mortality. The dynamic changes in these markers over time might offer additional insights into disease progression and patient outcomes. This retrospective observational study included 138 patients with severe infections. The inflammatory biomarkers procalcitonin (PCT), C-reactive protein (CRP), and lactate (LAC) were measured at three time points: upon hospital admission (baseline), approximately 24-48 h after admission (second measurement; M2), and 48-72 h after admission (third measurement; M3). The primary outcome was 30-day mortality. A Mann-Whitney U test was used to compare the biomarker levels between the survivors and non-survivors. A Spearman's correlation was used to assess the relationships between the baseline parameters. A logistic regression and a receiver operating characteristic (ROC) curve analysis were employed to evaluate the prognostic value of the baseline markers and their dynamic changes. The baseline LAC and SOFA score were significantly associated with 30-day mortality. The percentage decrease in PCT, CRP, and LAC from the baseline to M3 emerged as strong predictors of survival, with the ROC curve analysis demonstrating superior discriminatory ability compared to the baseline values. CRP_Delta exhibited the highest AUC (0.903), followed by PCT_Delta (0.843) and LAC_Delta (0.703). The dynamic changes in these inflammatory biomarkers, particularly PCT, CRP, and LAC, offer valuable prognostic information beyond their baseline levels in predicting 30-day mortality in severe infections. These findings highlight the importance of monitoring biomarker trends for early risk stratification and potential treatment guidance.

Improved outcome of COVID-19 over time in patients treated with CAR T-cell therapy: Update of the European COVID-19 multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party (IDWP) and the European Hematology Association (EHA) Lymphoma Group

COVID-19 has been associated with high mortality in patients treated with Chimeric Antigen Receptor (CAR) T-cell therapy for hematologic malignancies. Here, we investigated whether the outcome has improved over time with the primary objective of assessing COVID-19-attributable mortality in the Omicron period of 2022 compared to previous years. Data for this multicenter study were collected using the MED-A and COVID-19 report forms developed by the EBMT. One-hundred-eighty patients were included in the analysis, 39 diagnosed in 2020, 35 in 2021 and 106 in 2022. The median age was 58.9 years (min-max: 5.2–78.4). There was a successive decrease in COVID-19-related mortality over time (2020: 43.6%, 2021: 22.9%, 2022: 7.5%) and in multivariate analysis year of infection was the strongest predictor of survival (p = 0.0001). Comparing 2022 with 2020–2021, significantly fewer patients had lower respiratory symptoms (21.7% vs 37.8%, p = 0.01), needed oxygen support (25.5% vs 43.2%, p = 0.01), or were admitted to ICU (5.7% vs 33.8%, p = 0.0001). Although COVID-19-related mortality has decreased over time, CAR T-cell recipients remain at higher risk for complications than the general population. Consequently, vigilant monitoring for COVID-19 in patients undergoing B-cell-targeting CAR T-cell treatment is continuously recommended ensuring optimal prevention of infection and advanced state-of-the art treatment when needed.

The impact of tertiary lymphoid structures on tumor prognosis and the immune microenvironment in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a common malignancy whose prognosis and treatment outcome are influenced by many factors. Some studies have found that tertiary lymphoid structures (TLSs) in cancer may contribute to prognosis and the prediction of immunotherapy efficacy However, the combined role of TLSs in NSCLC remains unclear. We accessed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to obtain mRNA sequencing data and clinical information as the TCGA cohort, and used our own sample of 53 advanced NSCLC as a study cohort. The samples were divided into TLS+ and TLS- groups by pathological tissue sections. Patients of the TLS+ group had a better OS (p = 0.022), PFS (p = 0.042), and DSS (p = 0.004) in the TCGA cohort, and the results were confirmed by the study cohort (PFS, p = 0.012). Furthermore, our result showed that the count and size of TLSs are closely associated with the efficacy of immunotherapy. In addition, the TLS+ group was associated with better immune status and lower tumor mutation load. In the tumor microenvironment (TME), the expression levels of CD4+ T cells and CD8+ T cells of different phenotypes were associated with TLSs. Overall, TLSs are a strong predictor of survival and immunotherapeutic efficacy in advanced NSCLC, and T cell-rich TLSs suggest a more ordered and active immune response site, which aids in the decision-making and application of immunotherapy in the clinic.

Stage at diagnosis and survival among adult patients with cancer in Rwanda: A population-based study.

There are marked disparities in cancer survival in low-income countries compared to high-income countries, yet population-based data in the first is largely lacking. In this study, data from the national cancer registry of Rwanda were examined for 542 patients diagnosed with eight of the most common cancers of adults stomach (C16), colorectum (C18-20), liver (C22), breast (female) (C50), cervix (C53), ovary (C56), prostate (C61), and non-Hodgkin lymphomas (C82-85) between 2014 and 2017. Subjects were randomly selected for active followed-up to calculate 1-, 3-, and 5-year observed and relative survival (RS) by cancer type and stage. Overall, 53.7% of cases had died within 5 years of diagnosis. Five-year RS varied by malignancy and ranged from 17.6% (95% confidence interval [CI]: 6.7%-32.6%) for liver cancer to 68% (CI: 51.6%-79.8%) for cancers of the prostate. Stage was assigned for 71.6% of patients (n = 388 of 542), with over half (58%) having advanced stage (III/IV) at diagnosis. For all except liver and ovary, stage was a strong predictor of survival; for example, three-year observed survival was 90.9% and 44.8% (p-value: .002) for early and advanced breast cancer, respectively. This study demonstrates that stage specific survival can be obtained from population based cancer registries in sub Saharan Africa, data that are invaluable for international benchmarking, and for local planning and evaluation of cancer control programs.

Update on the prognostic value of a novel immune-related toxicity grading system (OST score) in patients with advanced solid tumours treated with immune checkpoint inhibitors (ICI).

e14696 Background: Toxicity grading systems have been an asset in managing cancer patients undergoing systemic treatment. In the era of ICI treatment, correlation between toxicity and treatment response is becoming more apparent. A new toxicity score was developed with the aim of better defining the profile of immune-related toxicities (irAEs). Initial analyses also demonstrated its potential in predicting patient outcomes. Here we provide an update on the survival analyses. Methods: Data were collected from the Pathobiology of Adverse Immune Reactions (PAIR) prospective cohort study at Guy’s Hospital from February 2018 until December 2023. Patients with advanced solid tumours naïve to ICI who received at least 1 dose were included. Minimum 6 months of follow-up was required. IrAEs were captured based on the OST score which evaluates the number of affected Organs (O), number of Severe (S) CTCAE (≥G3) toxicities, and Total sum of all grade toxicities (T). OST was calculated as a cumulative score at the end of follow-up or death. Patients were divided in high and low toxicity groups, defined by the median value for each parameter. For the composite OST score analysis, patients were divided in 2 groups based on a point system; 1 point was attributed for each individual OST high parameter; high toxicity OST group included patients with score >1. Descriptive statistics and crude and multivariate survival Cox Proportional Hazards regression analyses were performed accounting for age, tumour type, treatment, and steroid exposure. Results: A total of 148 patients fulfilled the criteria. Median age was 68 years (range 23-87), the majority were white Caucasian (81.8%) and male (56%). Melanoma was the most common tumour type (32.4%) followed by NSCLC (21.6%) and RCC (19.2%). 37.8% of patients received Ipilimumab/Nivolumab, 30.4% Pembrolizumab and 31.8% received other PD(L)-1 monotherapies. Twenty-eight patients (18.9%) had an autoimmune disorder at baseline; hypothyroidism was most common (5.4%). At end of follow-up, 82 deaths (55.4%) had occurred. Across the three OST parameters, Organ (O) was the strongest predictor of survival [HR (95%CI) 0.480 (0.265-0.869)]. After adjustment, multivariate analysis showed that risk of death was significantly lower in the high vs low Organ and Total toxicity groups [HR (95%CI) 0.379 (0.216-0.663) and 0.544 (0.302-0.982) respectively], but not for Severity [0.664 (0.338-1.306)]. In the OST combined score, the high toxicity group had favourable prognosis compared to low groups (mOS 56.6 vs 13 months) [HR (95%CI) 0.439 (0.275-0.702)]. Conclusions: Our new score manages to efficiently capture immune-mediated toxicity profile of patients treated with ICI as well as predict their outcomes. Further prospective evaluation, integration of laboratory markers and external validation is currently ongoing.

Prognostic factors for survival in NSCLC treated with immunotherapy: An institutional analysis.

e20591 Background: Immune check point inhibitors (ICIs) are the cornerstone of treatment for patients with advanced NSCLC. However, not all patients benefit from ICIs and some develop significant immune-mediated toxicities. There is limited data regarding prognostic factors in NSCLC patients treated with ICIs. Imaging features can complement clinical variables in predicting response to ICIs. This study aims to evaluate CEA, blood leukocyte markers, and novel CT-derived radiomic features as factors predictive of survival in this patient population. Methods: In this retrospective study, clinical data from patients with advanced stage NSCLC treated with ICIs at Stony Brook University Hospital from 2016 to 2021 were collected. Baseline and subsequent CEA (carcinoembryonic antigen), ANC (absolute neutrophil count), ALC (absolute lymphocyte count), NLR (neutrophil to lymphocyte ratio), AEC (absolute eosinophil count), and AMC (absolute monocyte count) were evaluated as independent prognostic factors. 3-D segmentation of ipsilateral lung lobe was obtained using U-Net and radiologist report of tumor location. 600 stable IBSI-standardized features were extracted from the region using PyRadiomics. The discriminative ability of clinical and image-derived variables was assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. Results: This study included 80 patients. Objective response rate (ORR) was 25.0% with 1-year OS of 58.0%. PD-L1 expression ≥ 50% was significantly associated with survival (p < 0.02). Decrease in CEA (p < 0.01) and 5% increase in AEC (p = 0.027) significantly correlated with survival. Age, sex, clinical stage, ANC, ALC, NLR, AMC did not significantly predict survival. Three image biomarkers that correlated with median enhancement of tissue on chest CT, and degree of tissue heterogeneity were significant predictors of mortality (p < 0.02). A multivariable model with clinical inputs outperformed one with radiomic features only (C-index 0.70 vs. 0.64). Clinical and radiomic inputs together performed well in predicting survival (C-index 0.76). Conclusions: Changes in CEA and AEC were the strongest predictors of survival in advanced NSCLC patients treated with ICIs. This study suggests that combined clinical and radiomic biomarkers (quantifying local lobar heterogeneity) can identify patients most likely to benefit from immunotherapy. [Table: see text]

Incomplete reverse remodeling in aged mice exposed to pulmonary hypertension-induced right ventricular failure

Right ventricle (RV) function is the strongest predictor of survival in pulmonary hypertension (PH) and age-related HF; however no therapies exist to improve RV function. Understanding mechanisms by which the RV undoes pathological remodeling (reverse remodeling) might aid in identifying therapies for this unmet need. Our objective was to determine whether the aged RV can undergo reverse remodeling following pathological afterload (PH). We hypothesized that return to normoxia after hypoxia-induced PH would result in attenuation of RV mass and improved RV function. We exposed male and female aged (~18 months) C57Bl6 mice to hypobaric hypoxia (HH) for 4 weeks before returning them to normoxia for 3 (WK3RR) or 6 (WK6RR) weeks. HH induced RV hypertrophy by RV myocyte area which was attenuated at Wk3RR and WK6RR in both male (Con: 425 μm2 ± 104, HH: 740 μm2 ± 125, WK3RR: 447 μm2 ± 129, WK6RR: 530 μm2 ± 187) and female mice (Con: 340 μm2 ± 116, HH: 770 μm2 ± 35, WK3RR: 516 μm2 ± 186, WK6RR: 655 μm2 ± 224). HH stimulated fibrosis by collagen deposition that was also reversed during normoxia re-exposure in male mice only (Con: 4.1% ± 1.0, HH: 10.8% ± 0.8, WK3RR: 4.2% ± 0.8, WK6RR: 2.5% ± 0.7). However, HH decreased RV systolic function by fractional area change (FAC) that was also not rescued by normoxia re-exposure. The aged RV can undergo morphological reverse remodeling in response to HH; however RV function does not improve with resolution of afterload. Further investigation into the mechanisms of reverse remodeling may identify potential drug therapies for maladaptive RV remodeling. AHA-Predoctoral Fellowship 897622 (BDM). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Stage at diagnosis and survival by stage for the leading childhood cancers in Rwanda.

The lack of accurate population-based information on childhood cancer stage and survival in low-income countries is a barrier to improving childhood cancer outcomes. In this study, data from the Rwanda National Cancer Registry (RNCR) were examined for children aged 0-14 diagnosed in 2013-2017 for the eight most commonly occurring childhood cancers: acute lymphoblastic leukaemia, Hodgkin lymphoma (HL), Burkitt lymphoma (BL), non-Hodgkin lymphoma excluding BL, retinoblastoma, Wilms tumour, osteosarcoma and rhabdomyosarcoma. Utilising the Toronto Childhood Cancer Stage Guidelines Tier 1, the study assigned stage at diagnosis to all, except HL, and conducted active follow-ups to calculate 1-, 3- and 5-year observed and relative survival by cancer type and stage at diagnosis. The cohort comprised 412 children, of whom 49% (n=202) died within 5years of diagnosis. Five-year survival ranged from 28% (95% confidence interval [CI]: 12.5%-45.6%) for BL to 68% (CI: 55%-78%) for retinoblastoma. For the cancers for which staging was carried out, it was assigned for 83% patients (n=301 of 362), with over half (58%) having limited or localised stage at diagnosis. Stage was a strong predictor of survival; for example, 3-year survival was 70% (95% CI: 45.1%-85.3%) and 11.8% (2.0%-31.2%) for limited and advanced non-HL, respectively (p<.001). This study is only the second to report on stage distribution and stage-specific survival for childhood cancers in sub-Saharan Africa. It demonstrates the feasibility of the Toronto Stage Guidelines in a low-resource setting, and highlights the value of population-based cancer registries in aiding our understanding of the poor outcomes experienced by this population.

Effects of transitional care interventions on quality of life in people with lung cancer: A systematic review and meta-analysis.

To identify and appraise the quality of evidence of transitional care interventions on quality of life in lung cancer patients. Quality of life is a strong predictor of survival. The transition from hospital to home is a high-risk period for patients' readmission and death, which seriously affect their quality of life. Systematic review and meta-analysis. The PubMed, Embase, Cochrane Library, Web of Science and CINAHL databases were searched from inception to 22 October 2022. The primary outcome was quality of life. Statistical analysis was conducted using Review Manager 5.4, results were expressed as standard mean difference (SMD) with a 95% confidence interval (CI). The risk of bias of the included studies was assessed using the Cochrane risk of bias assessment tool. This study was complied with PRISMA guidelines and previously registered in PROSPERO (CRD42023429464). Fourteen randomized controlled trials were included consisting of a total of 1700 participants, and 12 studies were included in the meta-analysis. It was found that transitional care interventions significantly improved quality of life (SMD = 0.21, 95% CI: 0.02 to 0.40, p = .03) and helped reduce symptoms (SMD = -0.65, 95% CI: -1.13 to -0.18, p = .007) in lung cancer patients, but did not significantly reduce anxiety and depression, and the effect on self-efficacy was unclear. This study shows that transitional care interventions can improve quality of life and reduce symptoms in patients, and that primarily educational interventions based on symptom management theory appeared to be more effective. But, there was no statistically significant effect on anxiety and depression. This study provides references for the application of transitional care interventions in the field of lung cancer care, and encourages nurses and physicians to apply transitional care plans to facilitate patients' safe transition from hospital to home. No Patient or Public Contribution.

Survival of Professional Counter-Strike: Global Offensive Teams: What Matters? A Research Note

The role of national diversity in sports and esports teams is a well-established field of research. Nevertheless, earlier studies primarily concentrated on assessing performance, based on criteria like prize money or the frequency of podium finishes. In this paper, we analyze the esports data of professional Counter-Strike: Global Offensive teams to shed light on the question of whether diverse teams survive longer. As a measure of diversity, we focus on the nationality of the players. The period investigated spans from 2012 to the middle of 2021. More than 200 teams are considered in the empirical analysis; 65% of these teams fail and do not survive. We also control for prize money as a time-dependent covariate. In addition, we account for the degree of competition over time. Our main findings are that prize money is a strong predictor of survival. There is a tendency for a higher degree of internationalization to increase the failure rate.

Survival of a polymorphic species in seasonally snow‐covered forests

Color polymorphism is an adaptive strategy in which a species exhibits multiple color phenotypes in a population. Often, phenotypes are variably suited to different environmental conditions which may buffer the population against variable conditions. Modern climate change is creating novel selective pressures for many species, especially in winter habitats. Few studies have quantified the benefits of polymorphism for allowing species to cope with climate‐induced environmental change, particularly for species with more cryptic differences between morphs. We investigated how color polymorphism mediates selective pressures in ruffed grouse Bonasa umbellus, a winter‐adapted bird species of North American forests. Ruffed grouse display phenotypic variation in plumage color, ranging from red to gray. Over five winters (2015–2022), we monitored weather conditions, habitat use, and weekly survival for 94 grouse to test whether individuals had lower survival when phenotypically mismatched with snow cover (e.g. a gray bird on a snowless landscape or a red bird in snow). Grouse phenotypically mismatched with snow cover had lower survival, but only when winter survival rates were lowest. During winters of lower overall survival, red grouse exhibited higher survival during snow‐free periods, whereas gray grouse had higher survival when snow was present. We also found that open habitat negatively impacted survival, regardless of color. While the effect of phenotypic mismatch was variable among years, it was a stronger predictor of survival than land cover, suggesting that snow is an important habitat feature mediating overwinter survival. Our work offers an advancement in understanding how environmental variability affects geographic variation in and maintenance of multiple color phenotypes in seasonally‐snow covered environments. Our finding that interactions between color morph and snow cover are important for conferring winter survival provides further evidence that color polymorphism may serve as a buffer against rapidly changing conditions and a pathway for persistence of polymorphic species.Keywords: Bonasa umbellus, color polymorphism, phenotypic mismatch, ruffed grouse, winter ecology, Wisconsin

Structural and Functional Cardiac Parameters in Patients with AL Amyloidosis Correlate with Uptake of the Amyloidophilic Radiotracer Iodine ( 124I) Evuzamitide

Background: The deposition of fibrillar aggregates of monoclonal free light chains in the heart is a characteristic feature of light chain associated (AL) amyloidosis. Cardiac amyloid is the major cause of morbidity and mortality in these patients. Structural and functional sequelae of cardiac amyloidosis can be appreciated clinically using echocardiography, cardiac magnetic resonance imaging, and measurement of serum NT-proBNP and troponins. These measures are not particularly amyloid-specific, and the correlation between parameters derived from these evaluations and amyloid burden remain enigmatic. The iodine-124 labeled peptide (p5+14), iodine ( 124I) evuzamitide, is a novel radiotracer that is being evaluated for the detection of systemic amyloidosis, of any type, by PET/CT imaging. As an amyloid binding peptide, this radiotracer has the potential to serve as a first line diagnostic agent capable of providing whole body semi-quantitative estimation of organ-specific amyloid load. Nascent studies of the relationship between 124I-evuzamitide uptake and established clinical parameters in patients with amyloidosis are underway. Here we report a single site, open label pilot study of 18 ( n=18) patients with AL ( n=8) and ATTR amyloidosis ( n=10) that evaluates the cardiac uptake of 124I-evuzamitide with contemporaneous echocardiographic and serum biomarkers (NCT05968846). Methods: The data described herein was collected as part of an open label single site repeat imaging study that plans to enroll up to 20 ( n=20) patients with AL ( n=10) and ATTR ( n=10) amyloidosis. To date, eight ( n=8) patients with AL and ten ( n=10) with ATTR amyloidosis have undergone 124I-evuzamitide PET/CT imaging with contemporaneous transthoracic echocardiography and assessment of serum NTproBNP within ~30 h of imaging. Patients received 37 or 74 MBq 124I-evuzamitide, and PET/CT imaging was performed at ~5 h post injection. Images were interpreted by a single reviewer, experienced in evaluating this tracer, for positive cardiac uptake. A fully manual 2D region of interest (ROI) analysis was performed encompassing the free left ventricular (LV) wall, LV lumen and interventricular septum (IVS). Blood pool was used as a reference tissue to determine standard uptake value ratios (SUVR mean) and to control for the rate of tracer clearance from the central compartment. Cardiac uptake of radiotracer was compared with free LV wall thickness (cm), IVS thickness (cm), global longitudinal strain (GLS, %), and serum NT-proBNP (pg/mL) measurements. Pearson and Spearman correlations were used to test for associations between variables. Results: Patients with AL amyloidosis were 2012 Mayo Stage I ( n=2/8) or Stage II ( n=6/8). The mean serum NTproBNP was 672.9±762.4 pg/mL (min=98, max=2327). With singular exception, all patients with AL amyloidosis had visually evident cardiac uptake of 124I-evuzamitide in the PET/CT images. In patients with AL amyloidosis ( n=8), the SUVR mean (encompassing the LV, lumen and IVS) correlated strongly with LV thickness (cm) (Pearson r=0.83, p=0.011) and GLS (%) (Pearson r=0.74, p=0.037), but not the IVS thickness (cm) (Pearson r=0.57, p=0.142). In contrast, in patients with ATTR ( n=10), there was no significant correlation of SUVR mean with GLS ( p=0.395), but a moderate significant correlation of SUVR mean with the LV ( p=0.037) and IVS ( p=0.017) thickness was observed. Similarly, in this pilot cohort, we observed a strong positive correlation between serum NTproBNP and cardiac SUVR mean (Pearson r=0.81, p=0.015), but not for patients with ATTR amyloidosis (Pearson r=0.58, p=0.079). Conclusion: Serum NTproBNP is a validated and qualified measure of overall survival for patients with AL amyloidosis (PMID: 27416985). Global longitudinal strain, with or without inclusion of other structural parameters such as left atrial volume, is a strong predictor of survival in patients with AL amyloidosis (PMID: 29111123, PMID: 37143609). PET/CT imaging using 124I-evuzamitide is a promising technique for diagnosing and monitoring AL and other types of amyloidosis. In light of these early results that demonstrate a strong relationship between validated metrics of all cause mortality in patients with AL, larger studies should seek to evaluate similar relationships with some metric of 124I-evuzamitide uptake in the heart, and indeed other organs.

Treosulfan-Based Conditioning Prior to Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) for Patients with Myelodysplastic Syndrome (MDS): Comparative Analysis of a Randomized Controlled Trial and Real-World Data

Introduction MDS is a clonal myeloid disorder manifested by diverse genotypes and phenotypes, characterized by ineffective hematopoiesis. AlloHSCT is the only potential curative therapy for MDS. Myeloablative conditioning regimens are integral part of alloHSCT that allow engraftment and provide a therapeutic effect. Treosulfan has myeloablative and immunosuppressive properties and provides less transplantation related mortality than some of the traditionally used myeloablative conditioning regimens like busulfan-based treatments. In our analysis, we compared the results from the MDS subgroup of the randomized controlled trial (RCT) MC-FludT.14/L (NCT00822393) with real-world data (RWD) of patients treated at the University Hospital Münster and the University Hospital Dresden. Methods MDS patients conditioned with treosulfan (30 g/m²) and fludarabine in the RCT (June 2013 to January 2018) and the data obtained from 2 hospitals (RWD) (August 2017 to February 2023) were compared. Baseline characteristics, overall survival, relapse-free survival, relapse (or progression), non-relapse mortality, time to engraftment, and safety profiles between the RCT and RWD were compared. A sensitivity analysis was conducted using propensity score matching (PSM). Additionally, subgroup analyses evaluated the clinical effectiveness of treosulfan by baseline morphologic blast count and the revised International Prognostic Scoring System (IPSS-R). Results Overall, 195 MDS patients (RCT 84, RWD 111) with at least 12 months follow-up were analyzed. Median age was 62 years (range 39-76 years). Baseline characteristics only differed between the RCT and RWD with respect to age, IPSS-R categories, Hematopoietic Cell Transplantation Co-Morbidity Index total score (HCT-CI), and neutrophil count, indicating some heterogeneity between the RCT and RWD patients. In the PSM analysis, 106 (RCT 53, RWD 53) patients were matched to address the heterogeneity. The Kaplan-Meier estimates for overall survival (OS) at 2 years were 73% (95% CI 62-81%) and 72% (95% CI 62-81%) for the RCT and RWD (Figure 1), and for relapse-free survival (RFS) at 2 years were 68% (95% CI 57-77%) and 67% (95% CI 56-76%), respectively. Cumulative incidence of relapse at 2 years was 11% (95% CI 4-18%) and 15% (95% CI 7-23%), and for non-relapse mortality (NRM) was 21% (95% CI 12-30%) and 18% (95% CI 10-26%) for the RCT and RWD, respectively. In addition, cumulative incidence of neutrophil engraftment at 28 days was 93% (95% CI 87-98%) and 94% (95% CI 89-98%) for the RCT and RWD, while the median engraftment time was later in the RCT (19 days vs 15 days). Cumulative incidence of platelet engraftment at 28 days was 89% (95% CI 83-96%) and 93% (95% CI 88-98%) for the RCT and RWD, with the same median time 14 days. Further, the PSM sensitivity analysis showed comparable efficacy between the RCT and RWD. Interestingly, bone marrow blast count prior to conditioning and IPSS-R subgroups only had minor, statistically not significant impact on survival endpoints (Table 1). The number of deaths were 27 (32%) and 28 (25%) in the RCT and RWD, respectively. The most frequent cause of death was transplantation related (20% vs 14%). One patient experienced primary graft failure in the RCT and none in the RWD. More patients had acute GVHD with at least grade 2 in the RCT (27%) than in RWD (18%). Conclusions The efficacy and safety of treosulfan-based conditioning therapy prior to alloHSCT in post-authorization real world setting was comparable with the results obtained from the RCT. Our data suggest that bone marrow blast count is no strong predictor for survival after alloHSCT. Therefore, we conclude that the approved treosulfan-based conditioning therapy for patients with MDS, including those with increased blasts, has promising outcomes after alloHSCT.

Impact of antibiotic allergy labels on timely and appropriate antibiotics for sepsis in the emergency department

Abstract Objectives Time to initiation of effective antibiotic therapy is a strong predictor of survival for patients with sepsis presenting to the Emergency Department (ED). Antibiotic allergy labels (AALs) are a known barrier to timely sepsis management. The aim was to evaluate the influence of AALs on timely sepsis management for ED sepsis presentations in an Australian hospital. Methods A retrospective cohort study was conducted for ED presentations requiring direct ICU admission for suspected sepsis, comparing patients with and without an AAL using propensity scores. Results Between November 2018 and June 2021, 377 patients were included. The prevalence of an AAL was 29.6% (86/377). The median time to antibiotic administration was similar in the AAL versus non-AAL groups (51 versus 60 min, P = 0.11); there was no difference in mortality (14.1% versus 14.0%, P = 0.98) and length of stay (9.21 versus 10.10 days). The median time to antibiotic administration was shorter in those with Emergency Medicine (EM) pharmacist attendance versus those without (50 versus 92 min, P = 0.0001). Appropriateness of antibiotic prescription was 91.0% (343/377) for the overall cohort and was not associated with AALs, possibly due to our clear antimicrobial sepsis guidelines; however, EM pharmacist involvement was associated with increased antibiotic appropriateness (97.3% versus 88.4%, P = 0.00048). Conclusions In our Australian ED, AALs were not found to impact timeliness of antibiotic administration in patients with sepsis. EM pharmacist involvement was associated with improved timeliness and appropriateness of antibiotic selection in patients presenting with sepsis.

Outcome prediction by myocardial external efficiency from 11 C-acetate positron emission tomography in cardiac amyloidosis.

This study aimed to study the prognostic value of myocardial oxygen consumption (MVO2 ) and myocardial external efficiency (MEE) from 11 C-acetate positron emission tomography (PET) in cardiac amyloidosis (CA) patients. Forty-eight CA patients, both transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis, and 20 controls were included. All subjects were examined with 11 C-acetate PET and echocardiography. MVO2 , forward stroke volume (FSV), and left ventricular mass (LVM) were derived from 11 C-acetate PET and used to calculate MEE. CA patients were followed for survival and the prognostic impact of clinical, echocardiographic, and 11 C-acetate PET parameters was analysed. MVO2 and MEE were reduced in CA compared with controls, but without significant difference between deceased and surviving CA patients. The ratio of 11 C-acetate PET-derived FSV and LVM was also reduced in CA and significantly lowered in deceased patients compared with survivors. In univariate analysis, New York Heart Association class, N-terminal pro-brain natriuretic peptide, and the 11 C-acetate PET parameters FSV/LVM and MEE were the strongest prognostic factors. Of the 11 C-acetate PET parameters, FSV/LVM was the strongest survival predictor with hazard ratio of 0.56 per 0.1mL/g (95% confidence interval 0.39-0.81, P=0.002) and independently prognostic in a multivariate model. MEE significantly separated deceased from surviving CA patients with the cut-off of 15.7% (P=0.032). Survival was significantly shorter with FSV/LVM below 0.27mL/g (P<0.001), also when separating AL- and ATTR-CA. Reduced MEE was associated with shorter survival in CA patients, but FSV/LVM was the strongest survival predictor and the only independently prognostic 11 C-acetate PET parameter in multivariate analysis.

Effect of perioperative anticoagulant prophylaxis in patients with traumatic subdural hematoma and a history of anticoagulant use: a propensity-matched National Trauma Data Bank analysis.

The use of anticoagulation to prevent venous thromboembolism (VTE) is controversial in the setting of neurosurgical decompression for traumatic subdural hematoma (SDH). In these patients, there is concern that anticoagulation may cause secondary hemorrhage, increasing the risk of death and other complications. Patients with a history of anticoagulant use are at further risk of VTE, but the effect of VTE prophylaxis (VTEP) following neurosurgery for SDH has not been thoroughly investigated in this population. This study aims to investigate the differences in in-hospital outcomes in patients with SDH and preexisting anticoagulant use who received VTEP following neurosurgical intervention compared with those who did not. The National Trauma Data Bank was queried from 2017 to 2019 for all patients with preexisting anticoagulant use presenting with an SDH who subsequently underwent neurosurgical intervention. Patients who received VTEP were propensity score matched with patients who did not based on demographics, insurance type, injury severity, and comorbidities. Paired Student t-tests, Pearson's chi-square tests, and Benjamini-Hochberg multiple comparisons correction were used to compare differences in in-hospital complications, length of stay (LOS), and mortality rate between the two groups. A logistic regression model was developed to identify risk factors for in-hospital mortality. Two thousand seven hundred ninety-four patients matching the inclusion criteria were identified, of whom 950 received VTEP. Following one-to-one matching and multiple comparisons correction, the VTEP group had a lower mortality rate (18.53% vs 34.53%, p < 0.001) but longer LOS (14.09 vs 8.57 days, p < 0.001) and higher rates of pressure ulcers (2.11% vs 0.53%, p = 0.01), unplanned intensive care unit admission (9.05% vs 3.47%, p < 0.001), and unplanned intubation (9.47% vs 6.11%, p = 0.021). The multivariable logistic regression showed that use of unfractionated heparin (UH; OR 0.36, p < 0.001) and low-molecular-weight heparin (LMWH; OR 0.3, p < 0.001) were associated with lower odds of in-hospital mortality. In patients with traumatic SDH and a history of anticoagulant use, perioperative VTEP was associated with increased LOS but provided a mortality benefit. LMWH and UH use were the strongest predictors of survival.

381. PROGRESSIVE LOSS OF BONE DENSITY IN PATIENTS WITH ESOPHAGEAL CANCER

Abstract Background Changes in body composition are common in esophageal cancer (EC). A majority of patients, regardless of stage, display signs of cachexia, including weight loss, skeletal and cardiac muscle atrophy and fat wasting. Bone loss is also common in cancer, secondary to shared signaling pathways that contribute to lean body loss. In this study, we hypothesized that bone density decreases progressively in patients with EC and that the continued loss of bone associated with oncologic outcomes. Methods We performed a retrospective review of all patients that received esophagectomy between 2012 and 2020 at our facility. Body composition was measured using PET/CT scans, and patients were classified by muscle mass according to sex- and BMI-dependent cutoffs. Bone density was measured by determining the radiation attenuation of the lumbar (L1-L5) vertebral bodies. The change in bone density was normalized by time and compared to tumor pathologic variables. A p-value less than 0.05 was considered statistically significant. Results Bone density was significantly reduced in patients with cachexia relative to those with appropriate muscle mass (108 ± 37.2 HU v. 146 ± 55.0 HU, p = 0.003). Furthermore, bone density correlated with muscle mass (p &amp;lt; 0.00001, R = 0.5055) and muscle quality/radiodensity (p = 0.0002, R = 0.4736). Mean rate of bone loss was −12.0 ± 27.9 HU/100d. Patients with regional lymph node metastases at surgery had more bone loss than those with N0 disease (−26.6 ± 30.8 HU/100d v. -2.71 ± 22.1 HU/100d, p = 0.03). Similarly, patients with positive lymphovascular invasion (−41.8 ± 32.6 HU/100d v. -3.53 ± 20.1 HU/100d, p = 0.005) and positive perineural invasion (−29.8 ± 32.4 HU/100d v. -3.12 ± 21.1 HU/100d, p = 0.01) progressively lost more bone. Conclusion Reduced bone mineral density is a key component of cachexia in patients with EC. We demonstrate herein that osteopenia in EC patients associates with several cachexia measures and that progressive loss of bone may predict early metastasis. Bone density may serve as a strong predictor of survival and stratification tool for clinical trials. These findings further highlight the need to study mechanisms that lead to bone wasting in tumor bearing hosts.

What predicts survival in glioblastoma? A population-based study of changes in clinical management and outcome.

Glioblastoma is the most common and most aggressive primary brain tumor in adults. Despite multimodal treatment, the median survival time is 15-16 months and 5-year survival rate 5%-10%. The primary goal of this study was to identify prognostic factors for survival in an unselected population of patients operated for glioblastoma. The secondary goal was to explore changes in outcome and the clinical management of this patient group over time. We identified 222 consecutive adults operated for glioblastoma between November 2012 and June 2016 at the Department of Neurosurgery, Sahlgrenska University Hospital in Gothenburg, serving a health care region in the western part of Sweden with 1.900.000 inhabitants. Clinical variables were identified and tested as predictors for prognosis in extended Poisson regression models. The results were compared with a previously published cohort from 2004 to 2008, before current standard of care based on molecular tumor diagnosis was fully implemented. Median overall survival was 1.07 years, which was significantly longer than in the 2004-2008 cohort (1.07 vs. 0.73 y, age- and sex adjusted HR = 1.89, p < 0.0001). Variables associated with longer survival in the multivariable model were MGMT promoter hypermethylation, non-central tumor location, complete resection of enhancing tumor, WHO performance status 0-1, unilateral tumor location, fewer lobes involved, younger age and no comorbidities. The median survival for patients with glioblastoma treated according to current standard treatment has moderately but significantly increased, with MGMT promoter hypermethylation as the strongest predictor for survival.

Metformin protects against pulmonary hypertension-induced right ventricular dysfunction in an age- and sex-specific manner independent of cardiac AMPK.

Right ventricular (RV) function is the strongest predictor of survival in age-related heart failure as well as other clinical contexts in which aging populations suffer significant morbidity and mortality. However, despite the significance of maintaining RV function with age and disease, mechanisms of RV failure remain poorly understood and no RV-directed therapies exist. The antidiabetic drug and AMP-activated protein kinase (AMPK) activator metformin protects against left ventricular dysfunction, suggesting cardioprotective properties may translate to the RV. Here, we aimed to understand the impact of advanced age on pulmonary hypertension (PH)-induced right ventricular dysfunction. We further aimed to test whether metformin is cardioprotective in the RV and whether the protection afforded by metformin requires cardiac AMPK. We used a murine model of PH by exposing adult (4-6 mo) and aged (18 mo) male and female mice to hypobaric hypoxia (HH) for 4 wk. Cardiopulmonary remodeling was exacerbated in aged mice compared with adult mice as evidenced by elevated RV weight and impaired RV systolic function. Metformin attenuated HH-induced RV dysfunction but only in adult male mice. Metformin still protected the adult male RV even in the absence of cardiac AMPK. Together, we suggest that aging exacerbates PH-induced RV remodeling and that metformin may represent a therapeutic option for this disease in a sex- and age-dependent manner, but in an AMPK-independent manner. Ongoing efforts are aimed at elucidating the molecular basis for RV remodeling as well as delineating the mechanisms of cardioprotection provided by metformin in the absence of cardiac AMPK.NEW & NOTEWORTHY Right ventricular (RV) function predicts survival in age-related disease, yet mechanisms of RV failure are unclear. We show that aged mice undergo exacerbated RV remodeling compared with young. We tested the AMPK activator metformin to improve RV function and show that metformin attenuates RV remodeling only in adult male mice via a mechanism that does not require cardiac AMPK. Metformin is therapeutic for RV dysfunction in an age- and sex-specific manner independent of cardiac AMPK.

Regulation of the Innate Immune System as a Therapeutic Approach to Supporting Respiratory Function in ALS

Amyotrophic lateral sclerosis (ALS) is a clinical diagnosis used to define a neurodegenerative process that involves progressive loss of voluntary muscle function and leads to death within 2-5 years after diagnosis, in most cases because of respiratory function failure. Respiratory vital capacity (VC) measurements are reproducible and strong predictors of survival. To understand the role of the innate immune response in progressive VC loss we evaluated ALS clinical trial and biomarker results from a 6-month phase 2 study of NP001, a regulator of innate immune function. All ALS baseline values were similar between treated and controls except for those > 65 years old who were excluded from analysis. Treated patients with plasma CRP ≥ 1.13 mg/L (high CRP) showed a 64% slower rate of VC decline compared with placebo and those with plasma CRP < 1.13 mg/L (low CRP) who showed no response. High CRP patients showed no age associated loss of VC whereas low CRP patients showed an age dependent loss of VC function. Plasma levels of serum amyloid A (SAA) were similarly elevated in high CRP patients consistent with ongoing innate immune activation. Plasma TGFB1 in high CRP treated patients was 95% higher than placebo at 6-months, confirming the activation and release of this anti-inflammatory factor by the innate immune alpha 2 macroglobulin (A2M) system. This report is the first to link a biomarker confirmed regulation of the innate immune system with a therapeutic approach for controlling VC loss in ALS patients.