Blood pressure response index trajectories identify distinct hemodynamic phenotypes and predict mortality in septic shock: a two-database retrospective cohort study

Introduction: Myelodysplastic syndromes (MDS) refer to disorders originating from clonal stem cells, marked by ineffective hemopoiesis and cytopenias. Patients with MDS have a higher incidence of cardiovascular mortality, with heart failure playing a significant role. This has been linked to persistent anemia, excess iron accumulation and a systemic inflammatory state. Patients with MDS have significantly higher rates of infectious events, with pneumonia (PNA) and sepsis being the most common infections. The influence of systolic heart failure (SHF) or diastolic heart failure (DHF) on the risk of infections in patients with MDS is unclear. We evaluated whether chronic SHF or DHF, as well as acute SHF or DHF in concomitance with MDS, affected the rates of PNA, septic shock and overall mortality. Method: A retrospective study identified patients with MDS using specific ICD 10 codes (D46.9, D46A-C and D46.22) from the National Inpatient Sample 2019-2021. Patients with acute and chronic SHF or DHF were obtained using particular ICD 10 codes (I50.2 - I50.4). The incidence rates of PNA, septic shock and overall mortality were compared between MDS patients with each of these types of HFs versus those without any HF using multivariate logistic regression adjusting for demographic characteristics, hospital-related factors, and common comorbidities. Results: A total of 223,975 patients were identified with MDS. Patients with MDS who had chronic SHF (n=11,505) showed increased rates of PNA (OR:1.4, p<0.001) and septic shock (OR: 1.4, p <0.001) but no significant difference in overall mortality (p=0.603) compared to those without any HF. Patients with MDS and acute SHF (n=12,560) had enhanced rates of PNA (OR: 1.4, p<0.001), septic shock (OR: 1.9, p<0.001), and overall mortality (OR:1.6, p<0.001) versus those without any HF. Patients with MDS and chronic DHF (n=18,990) had no difference in rates of PNA (p=0.2), septic shock (p=0.16), or overall mortality (p=0.1). Acute DHF (n=16,700) led to a greater incidence of PNA (OR: 1.5, p<0.001) and overall mortality (OR: 1.2, p<0.001), but no significant difference in the incidence of septic shock (p=0.07) in patients with MDS. Conclusion: Acute SHF was associated with significantly elevated rates of PNA and septic shock in patients with MDS, whereas acute DHF was linked to an increased incidence of PNA. Chronic SHF demonstrated higher occurrences of both PNA and septic shock. Furthermore, acute SHF and DHF correlated with increased mortality rates. Consequently, fostering early collaboration between hematology specialists and those in cardio-oncology is essential for effectively managing patients who have both MDS and HF. This would enable the implementation of timely preventive measures and therapeutic interventions, leading to more comprehensive care strategies that may improve clinical outcomes for these patients. Citation Format: Karnav Modi, Himil Mahadevia, Simran Chandra, Ibrahim Khamees, Parth Sharma, Deepthi Vodnala, Taiyeb Khumri. Effect of heart failure on incidence rates of pneumonia, septic shock and overall mortality in patients with myelodysplastic syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 790.

Cancer Biology and Survival Analysis in Cancer Trials: Restricted Mean Survival Time Analysis versus Hazard Ratios

Fundamental researches have shown that soluble CD73 (sCD73) can inhibit inflammatory response and limit excessive tissue damage caused by continuous immune cell activation. A Finnish prospective, observational study of acute kidney injury (FINNAKI) showed no association between sCD73 and 90-day mortality in sepsis patients. Clinical data of this study was used for secondary analysis to explore whether the relationship between sCD73 and 90-day mortality was consistent in septic shock and non-septic shock patients. The FINNAKI study was a prospective, observational cohort study conducted in 17 intensive care units (ICUs) in Finland from September 1st, 2011 to February 1st, 2012. Sepsis/septic shock was defined according to Sepsis-1 definition. Demographic characteristics, treatment, comorbidities and 90-day mortality of the patients were analyzed. To evaluate the difference (interaction test) between the relationship of sCD73 and 90-day mortality in septic shock and non-septic shock patients, likelihood ratio test was used to integrate the product term (sCD73×septic shock or non-septic shock) into multivariable Logistic regression. Sensitivity analysis was performed with the definition of Sepsis-3. The interaction between sCD73 and 90-day mortality in patients with septic shock and non-septic shock were verified by generalized additive model (GAM). A total of 588 patients with severe sepsis/septic shock were enrolled. 164 patients died in 90 days, and the 90-day mortality was 27.89%. Based on the Sepsis-1 definition, there were 159 non-septic shock patients and 429 septic shock patients. Compared with the non-septic shock patients, lactate (Lac) level, sequential organ failure assessment (SOFA) score, fluid balance on the first day, and ratio of mechanical ventilation, 12-hour acute kidney injury (AKI), renal replacement therapy (RRT), and postoperative ICU transition in the septic shock patients were significantly increased and the proportion of emergency admission to ICU was significantly decreased. Based on the Sepsis-3 definition, there were 383 non-septic shock patients and 205 septic shock patients; the results of clinical data analysis between the two groups were similar to those based on Sepsis-1. Based on Sepsis-1, there was no significant difference in 90-day mortality between non-septic shock and septic shock patients [23.90% (38/159) vs. 29.37% (126/429), P > 0.05]. However, based on Sepsis-3, the 90-day mortality of patients with septic shock was significantly higher than that of patients with non-septic shock [37.56% (77/205) vs. 22.72% (87/383), P < 0.01]. Multivariate Logistic regression analysis and interaction test showed that after adjusting all confounding factors (except the number of complications) in non-sepsis shock and sepsis shock patients, sCD73 and 90-day mortality were significantly different in both Sepsis-1 and Sepsis-3. The P values for interaction tests were 0.046 and 0.027, respectively. In patients with non-septic shock, sCD73 tended to be positively associated with 90-day mortality [Sepsis-1: odds ratio (OR) = 1.46, 95% confidence interval (95%CI) was 0.99-2.13, P = 0.053; Sepsis-3: OR = 1.34, 95%CI was 1.02-1.74, P = 0.034]. In septic shock patients, sCD73 tended to be negatively associated with 90-day mortality (Sepsis-1: OR = 0.91, 95%CI was 0.69-1.20, P = 0.494; Sepsis-3: OR = 0.80, 95%CI was 0.55-1.17, P = 0.249). The results of GAM model validation were consistent with the results of Logistic regression equation cross validation. The relationship between sCD73 and 90-day mortality is significantly different from patients with non-sepsis shock and sepsis shock. In patients with non-sepsis shock, sCD73 is trend to positively associated with 90-day mortality, and there is a negative trend between sCD73 and 90-day mortality in patients with septic shock.

Purpose: 65.7% of US adults age 20 years and older are overweight (BMI 25-30) and 30.6% are obese (BMI >30). These statistics are reflected in the ICU patient population. We studied the effect of BMI on survival and LOS in patient with septic shock. Methods: Subjects were patients from the ICU Project Impact Database admitted to Cooper University Hospital ICU in septic shock over a three year period from 2008-2011. A total number of 293 patients were evaluated and separated based on whether they survived or not. Variables analyzed “BMI, length of stay, and others thought to play a role in mortality septic shock lactate, chronic kidney disease (CKD), cirrhosis”. BMI was classified into four groups: underweight (<18); normal (18-24.9); overweight (25-29.9) and obese (>30). Univariate analysis was used to compare the two groups (alive or deceased) for any significant differences. Subsequently, each of the variables found to be significantly different [p<0.05] were then analyzed using multivariate analysis to evaluate whether any were independent predictors of mortality in patients with septic shock. Results: When comparing mortality in septic shock patients with normal BMI (40%) using univariate analysis there was a trend for a decreased mortality in underweight (30.8%; p=0.526) and obese patients (35.6%; p=0.561) although not statistically significant. When evaluating median LOS in patients among all BMI classifications there was no significant difference in median ICU LOS or hospital LOS. Variables found to be statistically significant in relation to mortality were patients with CKD (Deceased 25% vs. Alive 15%) [p= 0.05], Multiple Organ Dysfunction (MOD) >2 (Deceased 87% vs. Alive 76.2%) [p=0.03] and elevated lactate on admission (Deceased 3.5 vs. Alive 2.7) [p=0.05]. Age, APACHE II, and cirrhosis were also found to be significant. When looking at differences in percent mortality using multivariate analysis, only age (Deceased 66.03 vs. Alive 58.49) [p=0.00], APACHE II (Deceased 23.95 vs. Alive 17.49) [p=0.00] and presence of cirrhosis (Deceased 9.4% vs. Alive 0.7%) [p=0.03] were found to be independent predictors of mortality in Septic shock patients. Conclusion: There was a trend for a protective effect on mortality in septic shock patients who were underweight BMI although this trend was not statistically significant. There was no significant difference among the BMI groups in relation to ICU or hospital LOS. The study was sufficiently powered to detect a difference between BMI groups suggested by the finding of significant independent predictors for mortality in septic shock with age, APACHE score, and presence of cirrhosis all of which had previously been reported.Table: No Caption available.Table 2: . No Caption available.

Rationale: Previous studies have demonstrated that prompt antibiotic treatment is associated with improved outcomes in septic shock. However, the precise impact of the timeliness of appropriate of initial antimicrobials in the subset of septic shock patients with neutropenia is not well defined. This study aims to evaluate the relationship between antibiotic timing and patient mortality in neutropenic septic shock. Methods: A retrospective cohort study was conducted for periods between July 1989 toJune 2018 in 29 academic and community hospitals in Canada, the United States, and Saudi Arabia. The primary outcome of this study was in-hospital mortality. Logistic regression was used to evaluate the association between antimicrobial timing in relation to the onset of persistent/recurrent hypotension with mortality, while multivariable regression analyses were performed to adjust for confounding factors, including clinical and treatment variables. Results: Among the 508 adult septic shock patients with neutropenia assessed, the overall mortality rate was 27.0%. The median time to effective antimicrobial administration from the onset of hypotension was 6.33 hours (IQR: 2.7-15.75 hours). Mortality risk was lowest, at 32.3%, for patients who received antibiotics within the first 2 hours. Delays in antibiotic administration were significantly associated with increased mortality, with an adjusted ratio of 1.045 per hour of delay (95% CI: 1.035-1.056; p &amp;lt; 0.0001). Compared to the 1st hrs, delays of &amp;gt;4-6 hrs were associated with increased mortality (p&amp;lt;0.001)(Fig 1).Delays extending beyond 24 hours were associated with a substantial increase in mortality risk, reaching 98.4% (p &amp;lt; 0.001). Conclusions: Delays in appropriate antibiotic treatment are strongly associated with increased mortality in septic shock patients with neutropenia. Figure 1: The association between delayed antimicrobial initiation and risk of mortality, demonstrates a significantly higher mortality rate for patients treated after delays of 4-6 hours compared to those treated within the first hour of hypotension.

Sepsis and Myocardial Depression in a Young Woman

Background Septic shock remains a leading cause of morbidity and mortality in children, particularly in resource-limited settings. Early recognition of high-risk patients is essential to improve outcomes. The Inotropic Score (IS) and Vasoactive-Inotropic Score (VIS) quantify cardiovascular support and reflect illness severity. This study aimed to evaluate the usefulness of the Wernovsky Inotropic Score (WIS) and VIS in predicting mortality among children with septic shock admitted to a tertiary care PICU. Objectives: To assess the predictive accuracy of the Wernovsky Inotropic Score (WIS) and Vasoactive-Inotropic Score (VIS) for in-hospital mortality in pediatric septic shock. Methodology This prospective, longitudinal study was conducted over 18 months (September 2022–March 2024) in the PICU of a tertiary care teaching hospital. Children aged 1 month to 18 years admitted with septic shock requiring vasoactive therapy were included. Patients who had received inotropes for more than 6 hours before admission or had ≥2 organ dysfunctions were excluded. The Inotropic Score (IS) was calculated as [IS = Dobutamine + Dopamine + 100 × Epinephrine (μg/kg/min)] at 24 and 48 hours. Data were analysed using appropriate statistical tests, and ROC curves were plotted to determine predictive accuracy. Results Among 21 patients, 13 (61.9%) died. Mean VIS and WIS were significantly higher in nonsurvivors (VIS: 53.55 ± 16.71 vs 29.04 ± 13.11, p = 0.002; WIS: 39.80 ± 14.78 vs 20.72 ± 12.57, p = 0.006). ROC analysis showed strong predictive performance (VIS AUC = 0.837; WIS AUC = 0.865). Conclusion Both WIS and VIS are reliable predictors of mortality in pediatric septic shock. VIS demonstrated higher sensitivity, while WIS showed better specificity, aiding early prognostication and management of critically ill children. Recommendations WIS and VIS can be used to help predict mortality among children with septic shock.

Enfortumab vedotin (EV) exhibited superior efficacy in the EV-301 trial; however, real-world outcomes stratified by trial eligibility criteria remain unclear. We evaluated the real-world efficacy of EV in Japanese patients with metastatic urothelial carcinoma (mUC) via EV-301 eligibility stratification and restricted mean survival time (RMST) analysis. This multicenter retrospective study analyzed 115 Japanese mUC patients treated with EV following platinum-based chemotherapy and immune checkpoint inhibitors. Patients were categorized as eligible (n=81, 70.4%) or ineligible (n=34, 29.6%) based on EV-301 criteria. The primary endpoint was overall survival (OS) evaluated via RMST at multiple time points. Reconstructed individual patient data from EV-301 enabled comparative analysis, with Bayesian power prior methodology integrating evidence sources. Eligible patients exhibited significantly higher OS than ineligible ones (HR 2.19, 95% CI 1.24-3.89, P=.009). RMST analysis at 12months revealed OS of 9.65months (95% CI 8.67-10.63) and 7.11months (4.79-9.44) in eligible and ineligible patients, respectively. Significant RMST differences were observed between the eligible and ineligible groups at 6months (1.18months, P=.017) and 12months (2.54months, P=.049). Bayesian analysis with moderate borrowing (α=0.5) revealed posterior RMST of 9.40months (95% credible intervals 8.80-9.98) at 12months. Eligible patients showed comparable RMST outcomes to EV-301 trial participants, with no significant differences. EV exhibited real-world efficacy in Japanese mUC patients comparable to the eligible patients' outcomes in the EV-301 trial. Ineligible patients showed statistically inferior outcomes.

This study aims to conduct a comprehensive meta-analysis of the effects of postoperative complications (PCs) on survival following esophagectomy using the restricted mean survival time (RMST) analysis. A systematic literature search was performed in PubMed, Embase, Web of Science, Cochrane, and Medline, including articles published up to July 2024. Data were reconstructed from Kaplan-Meier curves, and the difference in RMST (RMSTD) and the RMST/restricted mean time loss (RMTL) ratios were calculated to examine the effects of PCs on overall survival. A total of 12 articles, including 7925 patients, met the inclusion criteria. RMSTD estimates indicate that patients with overall PCs survived an average of 0.04 years shorter (RMSTD = -0.04, 95% CI: -0.06, -0.03) than those without PCs at the 1-year follow-up and 0.39 years shorter (RMSTD = -0.39, 95% CI: -0.55, -0.22) at the 5-year follow-up. Patients with anastomotic leaks survived an average of 0.34 years shorter (RMSTD = -0.34, 95% CI: -0.49, -0.19), and patients with pulmonary complications survived an average of 0.63 years shorter (RMSTD = -0.63, 95% CI: -0.81, -0.45) at the 5-year follow-up. Additionally, RMTL ratios were estimated to be 1.21 (95% CI: 1.12, 1.31) for overall PCs, 1.19 (95% CI: 1.11, 1.28) for anastomotic leaks, and 1.53 (95% CI: 1.36, 1.73) for pulmonary complications at the 5-year follow-up, respectively. Our findings quantified the annual negative impact of PCs of esophageal cancer on overall patient survival following esophagectomy. Increased efforts are needed to enhance prevention, early screening, and timely treatment for complications, particularly for patients with pulmonary complications.

Long-term adult congenital heart disease survival after heart transplantation: A restricted mean survival time analysis

The restricted mean survival time (RMST) analysis has been used extensively in clinical research involving time-to-event endpoints. The threshold time up to which the restricted mean survival is calculated has a critical impact on the analysis results. However, identifying an optimal threshold time for treatment comparison, which corresponds to the greatest restricted mean lifetime difference between groups, remains unclear in practice, and no analytical method has been developed on this topic. We present a novel method for determining the threshold time in the RMST analysis to compare two groups. Simulation studies indicate that this method leads to high statistical power and controlled type I error rate compared with existing methods. The proposed method is illustrated in two applications: (1) a clinical oncology study for non-small-cell lung cancer treatments comparison given a programmed death-ligand 1 biomarker measurement, and (2) a gerontology study of instrumental activities for care recipients with dementia.

To demonstrate whether fluconazole reduces multiple organ failure and mortality in early septic shock (<24 hrs). A prospective randomized double-blind study. A medical and surgical adult intensive care unit in a tertiary referral center. Values were obtained from 71 general adult intensive care unit patients. During a 2.5-yr period, December 1998-June 2001, 71 patients with septic shock attributed to either nosocomial pneumonia (n = 37) or intra-abdominal sepsis (n = 34) were admitted to our intensive care unit and met the criteria of early septic shock and were entered into this study. All patients were randomized by our clinical pharmacist to receive daily either 200 mg of fluconazole in isotonic saline (fluconazole group = 32) or isotonic saline alone (placebo group = 39) intravenously during the course of their septic shock. All patients were closely monitored with pulmonary artery catheters and parameters to calculate daily organ dysfunction and Acute Physiology and Chronic Health Evaluation II scores. There was a highly significant increase in 30-day survival in the fluconazole-treated patients compared with the placebo patients (78% vs. 46%). However, fluconazole was found to be more effective in patients with septic shock attributed to intra-abdominal sepsis than to nosocomial pneumonia. Increased survival in the intra-abdominal sepsis clinical category was mirrored by a significantly lower number of organ failures in the treated group compared with the placebo group whereas the number of organ failures in the fluconazole group attributed to nosocomial pneumonia were not significantly increased compared with the control group. The septic shock state was considered in all cases to be attributed to bacterial and not to disseminated yeast infection with the exception of one patient in the control group who was admitted with candidemia. The mechanisms by which fluconazole exerts its protective effect against septic shock in patients is far from clear. However, fluconazole has been shown to enhance bactericidal activity of neutrophils and also to inhibit transmigration and adhesion of neutrophils in capillaries of distant organs. The development of organ failure and mortality in septic shock was significantly reduced by fluconazole given intravenously. The mechanism of action of fluconazole in reducing multiple organ dysfunction in this group of patients may be attributed to the ability of fluconazole to increase recruitment, improve bactericidal activity of neutrophils, and to contain microorganisms locally.

Disclosure: J.H. Lee: None. Z. Sumer-Bayraktar: None. R. Rushworth: None. M. Nenke: None. M. Thaysen-Andersen: None. E.J. Meyer: None. D.J. Torpy: None. Low serum corticosteroid binding globulin (CBG) concentration (&amp;lt;200 nmol/L) is independently associated with 3-fold greater intensive care unit (ICU) mortality in septic shock patients. CBG deficient mice have greater mortality on sepsis simulation via lipopolysaccharide (LPS) administration; restoration of CBG reduced mortality to that of controls. CBG is variably glycosylated at six sites, and Asn347 site glycosylation affects susceptibility to neutrophil elastase (NE) cleavage. NE cleavage of CBG results in irreversible reduction in cortisol binding affinity by 90%. We hypothesized that CBG Asn347 glycosylation is associated with septic shock clinical outcome, possibly by affecting tissue cortisol delivery. Asn347 site glycosylation profiling of CBG was performed by mass spectrometry following CBG immunoprecipitation from serum of 135 septic shock patients taken on day 1 and last day (up to day 7) of ICU admission. This was correlated with clinical outcome data including ICU mortality, requirement for mechanical ventilation, inotropes and renal replacement therapy, and Sequential Organ Failure Assessment (SOFA) score, a measure of sepsis severity. Mean serum triantennary trisialylated (TS3) Asn347 CBG glycoform concentrations were lower in septic shock non-survivors compared to survivors (29.74 vs 45.16 nmol/L, P=0.007). Lower triantennary trisialylated core-fucosylated (TS3F) glycoform concentrations were associated with mechanical ventilation requirement (37.9 vs 52.6 nmol/L, P=0.002), and higher total SOFA score (r= -0.335, P &amp;lt;0.001), indicative of greater illness severity. No clinical associations were seen with other CBG Asn347 glycoforms. Throughout ICU admission, concentrations of TS3 and TS3F CBG Asn347 glycoforms showed the most pronounced reduction of 38.8% (42.3 vs 25.9 nmol/L, P&amp;lt;0.001) and 22.9% (44.2 vs 34.1 nmol/L, P=0.002), respectively, compared to 13.2% reduction in BS2 (101.8 vs 88.4 nmol/L, P=0.03), and no change in BS2F (22.4 vs 22.4 nmol/L, P=0.99). Low concentrations of CBG Asn347 TS3 and TS3F glycoforms are associated with mortality and morbidity in septic shock, respectively. Hence, the association between low total CBG and septic shock mortality reported previously seem to be attributable to the depletion of the TS3/TS3F Asn347 CBG glycoforms, specifically. This has significant therapeutic implications in considering CBG administration as treatment for septic shock. Presentation: Saturday, July 12, 2025

Purpose: Fatty Liver is increasingly common among healthy patients than previously thought. Its effect on sepsis is unknown. It is known that Cirrhosis and low albumin have increased mortality in sepsis. We wanted to study the effect of fatty liver on survival in patients with septic shock. Methods: Patients were selected based on those who were admitted to Cooper University Hospital ICU in septic shock over a three year period from 1/2008-1/2011. A total number of 293 patients were evaluated and separated based on mortality. Variables were collected and analyzed thought to play a role in mortality in septic shock such as lactate, CKD, cirrhosis, Albumin and Fatty Liver. Univariate analysis was used to compare the two groups (alive or deceased) for any significant differences (Table 1). Subsequently, each of the variables found to be significantly different [p<0.05] were then analyzed using multivariate analysis, to evaluate whether any were independent predictors of mortality in patients with septic shock (Table 2).Table 1: . No Caption available.Table 2: . No Caption available.Results: Using univariate analysis, those alive or deceased were compared looking at the number and percent of people with Fatty liver. 11.8% had fatty liver out of the alive group vs 8.4% in the deceased group, but the difference was not significant [p=0.39]. Variables found to be statistically significant were in patients with chronic kidney disease (CKD) [p= 0.05], having Multiple Organ Dysfunction (MOD) >2 [p=0.03] and patients with median Lactate within 24 hours [p=0.05]. Age, APACHE II, and cirrhosis were also found to be significant. These significant variables were then evaluated using multivariate analysis. When looking at differences in mortality, only Age [p=0.00], APACHE II [p=0.00] and presence of cirrhosis [p=0.03] were found to be independent predictors of mortality in Septic shock patients. Conclusion: Based on the collected data, it appears that presence of fatty liver does not have any significant effect on mortality in septic shock. Variables that were found to be significant independent predictors in relation to mortality in septic shock were mean age, mean APACHE II score, and presence of Cirrhosis all of which had previously been illustrated in prior studies.

Prognostic factors associated with mortality in septic shock: a systematic review and meta-analysis.