Higher Risk Of Death Research Articles

Expression of Trop2, Nectin-4, and FOLR1 cell surface markers in biliary tract cancers: Is it time to repurpose drugs?

637 Background: Biliary tract cancers (BTC), including gall bladder cancer, intrahepatic and extrahepatic cholangiocarcinoma are aggressive malignancies, with poor prognosis. Despite advances in frontline setting, and in biomarker selected population (IDH1, FGFR2, Her2, BRAF, HRD), there is a dire need to advance therapy in subsequent lines. Methods: We identified BTC patients (pts) at Roswell Park Cancer Center who underwent curative intent surgery between 01/2006-01/2020. After excluding duplicate samples and those with insufficient tissue, we found 78 pts with adequate follow up for analysis. Expression of trophoblast cell surface antigen 2 (Trop2), nectin4, folate receptor alpha (FOLR1) was assessed by immunohistochemistry and correlated with clinical outcomes. H score, a weighted index score that factor in, the % of cells across different intensity was calculated. H scores were classified as negative (0) and positive (>1). Positive H scores were grouped as weak (1-100), intermediate (101-200) and strong (201-300). Descriptive statistics were conducted, and multivariate analyses performed (R studio) to study any correlation between expression of markers and survival outcomes. Results: The median age of our cohort was 67.5 years (range 40-87) with 58% male; 24.4%, 30.8%, 20.5%, 7.7% had stages I, II, III, IV disease. Staging information was missing in 16.7% of pts. Of 73 analyzable samples for Trop2, all were positive for Trop2, with a mean H score of 86, SD of 68.9. 56.4% of patients had a weak H score, 30.8% had an intermediate H score and 6.4% had a strong H score for Trop2. Median overall survival (mOS) among low, intermediate and high expressing group of pts with Trop2 was 48.9 months (m), 23.9 m, and 41.9 m with median Progression Free Survival (mPFS) of 37.8m, 15.3 m, and 37.4 m, respectively. Of 75 analyzable samples for FOLR1 and Nectin4, FOLR1 was expressed in 51.3% with a mean H score of 6.97 (SD 21.9). Nectin4 was expressed in 78.2%, with a mean H score of 13.7 (SD 26.3). Pts with Trop2 expression had a mOS of 39.5 m and a mPFS of 28.7 m. There were no significant differences in mOS (48.9 m vs 33.3 m, p =0.14) and mPFS (37.8 m vs 26.2 m, p =0.35) among patients with positive vs negative FOLR1 respectively. There was no difference in mOS (41.6 m vs 38.3 m, p=0.92) and mPFS (32.8 vs 26.4 m, p-value=0.5) in patients with positive vs negative Nectin4. Multivariate analyses showed that pts with intermediate Trop2 (H score=101-200) had a high risk of death (HR 21.44, CI 2.81-163.4, p= 0.003). Conclusions: Though no difference was seen in clinical outcomes in pts with strong Trop2 expression, FOLR1, and Nectin4 expression, this could be explained by the small sample size. Trop2 is frequently expressed in BTCs and patients with Intermediate Trop2 H score had lower mOS and mPFS, with a higher risk of mortality. This warrants further investigation into potential use of Antibody Drug conjugates against Trop2 in BTC.

Abstract TP158: Collaboration Between Neurology and Endocrine Improves Uncontrolled Diabetes for Patients with Acute Ischemic Stroke

Background: Research suggests that the absolute number of strokes among people with diabetes is increasing as the population with diabetes grows. Stroke patients with poorly controlled diabetes are more likely to experience poor functional recovery, longer recovery times, recurrent stroke, and higher risk of death. In response to a finding from the 2021 Joint Commission survey for not addressing an HbA1c=9.3, we launched a quality improvement project to enhance diabetic management among patients admitted for ischemic stroke. Methods: This interdisciplinary collaboration involved endocrinology, hospital medicine, and neurology. For patients admitted to our Thrombectomy-Capable Stroke Center for ischemic stroke with an HbA1c ≥ 9.0% or blood glucose glucoses≥250mg/dl, a mandatory inpatient endocrine consult would be provided, in addition to diabetic educator consult. The patient’s HbA1c levels were followed every 3 months for a year. Results: A total of 66 patients were admitted in 2022 (n=32) and 2023 (n= 34) for ischemic stroke with HbA1c ≥ 9.0%. The median HbA1C for 2022 cohort dropped from 11.2% (range 9.0% – 16.6%) to 8.5% (range 5.0% - 14.1%) in a year (p<0.05); and 10.3% (range 9.0% - 14.6%) to 7.75% (range 6.0% - 11.7%) in a year (p<0.05). 2024 data showed similar improvement with drop of HbA1c from 10.55% to 9.75% at 3 months and 9.45% at 6 months. Conclusion: Inpatient endocrinology involvement for high-risk stroke patients with previously uncontrolled diabetes improves diabetic control over time. Endocrinologists can offer personalized treatment plans considering various factors such as comorbid conditions, patient lifestyle, and specific diabetes complications. This single center intervention is congruent with published data showing that patients under specialist care often experience HbA1c reductions of 0.5% to 1.0% or more compared to those managed by general practitioners. In high risk and high complexity cases, this improvement may potentially lead to reduced risk of stroke recurrence and complications. We postulate that this improvement is attributed to the endocrinologist’s expertise in complex diabetes management, advanced treatment options, personalized care approaches, and resources in post-discharge management. If confirmed in a multicenter clinical study, it can become a generalizable approach to improve the quality of care and outcomes of high-risk stroke patients.

Persistent Mortality Risk From Device-related Healthcare-associated Infection in Kidney Transplant Recipients Despite Multifaceted Interventions Action Calls for a Zero-tolerance Policy.

Although multifaceted control intervention actions (bundles) are highly effective in reducing the risk of device-related healthcare-associated infections (d-HAIs), no studies have explored their impact on the outcomes of kidney transplant recipients (KTRs) or the extent of risk reduction achievable through the bundle implementation. Seven hundred ninety-eight prevalent KTRs admitted to the intensive care unit (ICU) requiring invasive devices were included: 449 patients from the bundle preimplementation period and 349 from the postimplementation period. The primary outcome was mortality within 90 d of ICU admission. Using Poisson regression models, the magnitude of risk reduction for d-HAIs after the bundle implementation and the impact of d-HAIs on the risk of death was estimated. The 90-d survival rate was significantly lower in patients with d-HAIs (37.7% versus 71.7%; P < 0.001). The bundle implementation reduced the risk of d-HAIs by 58% (relative risk, 0.42; P = 0.005). Despite the significant reduction in d-HAIs after the bundle implementation, d-HAIs were associated with a 2.6-fold higher risk of death (hazard ratio [HR], 2.63; P < 0.001) regardless of the study period. Additional variables associated with increased risk of death included age (HR, 1.03; P < 0.001), baseline immunosuppression (HR based on mycophenolate versus others 0.74; P = 0.02), time since transplantation (HR, 1.003; P < 0.001), platelet count at ICU admission (HR, 0.998; P < 0.001), and sepsis as the reason for ICU admission (HR, 1.67; P < 0.001). The persistent risk associated with d-HAIs, despite the implementation of multifaceted control intervention actions in an ICU specialized in KTR care, underscores the need for a zero-tolerance policy toward d-HAIs.

3D is superior to 2D echocardiography in identifying high risk patients with heart failure with reduced ejection fraction and indication for device therapy

Abstract Background In patients with heart failure with reduced ejection fraction (HFrEF), a left ventricular ejection fraction (LVEF) less than 35% has been identified as a significant risk factor for increased mortality. As a result, all studies assessing the indications and outcomes of implantable cardioverter-defibrillators and cardiac resynchronization therapy in HFrEF used this cut-off, measured by 2-dimensional echocardiography (2DE). However, many patients with HFrEF and a LVEF &amp;gt;35% by 2DE, who do not qualify for device therapy, still experience significant mortality. Purpose To investigate whether, in patients hospitalized with both ischemic and non-ischemic HFrEF, the LVEF measured by 3-dimensional echocardiography (3DE) could identify better patients at high risk of death, thereby indicating the need for device therapy. Methods 322 consecutive patients (60±11 years, 72% men), hospitalized for HFrEF or HFmrEF, were assessed using both 2DE and 3DE, including full-volume acquisitions of the LV. From 2D datasets, LV end-systolic (LVESV) and LV end-diastolic (LVEDV) volumes, and LVEF were estimated. From the 3D volumes, the same parameters were measured. Patients were discharged on optimal HF treatment, according to current ESC guidelines, and were followed for 24±8 months after the initial event. The primary outcome was cardiovascular death (CD). Results At admission, 43% patients were in NYHA class II, 25% in NYHA class III, and 33% in NYHA class IV. There was a similar burden of ischemic and non-ischemic etiology (52% vs 48%). Mean 2D LVEF was 31±11%, while mean 3D LVEF was 30±10% (p=NS). There were 62 CD (19%) during follow-up. Binary logistic regression for the 2D and 3DE parameters showed that only 3D LVEF was a significant predictor of death (β=-0.04, OR 0.96, 95%CI 0.93-0.98, p=0.003). By 2DE, 206 patients (64%) had LVEF &amp;lt;35%, of whom 47 patients died (23%) and 159 patients survived (77%), whereas by 3DE, 215 patients (67%) had LVEF &amp;lt;35%, of whom 60 patients died (28%) and 155 patients survived (72%). Consequently, 2D LVEF &amp;lt;35% identified 47 out of 62 deaths (76%), whereas 3D LVEF &amp;lt;35% identified 60 out of 62 deaths (97%). By ROC Analysis, 3DE was superior to 2DE for prediction of survival: AUC 0.62, p=0.03 for 3D LVEF vs. AUC 0.56, p=0.09 for 2D LVEF. Kaplan-Meier analysis (Figure) showed that 2D LVEF &amp;lt;35% discriminated between survivors and non-survivors with a Chi-square of 6.8, p=0.01, whereas 3D LVEF &amp;lt;35% discriminated between survivors and non-survivors with a Chi-square of 30.3, p&amp;lt;0.001. Conclusion 3DE assessment of LVEF and its cut-off of 35% enhances the identification of patients with HFrEF at high risk of death. This suggests that 3DE should be utilized for risk stratification in HFrEF, potentially leading to more accurate indications for device therapy. Survival according to 2D vs 3D LVEF

Prognostic role of right atrial strain in patients with secondary tricuspid regurgitation: insights from the CARE-TR registry

Abstract Background Recently, right atrial (RA) deformation evaluated with speckle tracking echocardiography has emerged as prognostic parameter in patients with pulmonary hypertension and tricuspid regurgitation (TR). Purpose To explore the prognostic role of right atrial reservoir strain (RASr) in patients atrial and ventricular secondary TR (ASTR; VSTR). Methods The Consecutive pAtients with seveRE Tricuspid Regurgitation evaluated in heart failure (HF) and Valve Clinics (CARE-TR) registry collected data from patients with at least severe TR enrolled at 3 Italian Centres between January 2020 and December 2022. The present analysis includes 402 patients with STR and complete data on right atrial function. Patients were classified as ASTR in presence of all the following echocardiographic parameters: left ventricular ejection fraction ≥ 50%, pulmonary artery systolic pressure ≤ 50 mmHg, right ventricular (RV) mid end-diastolic diameter (RVEDD) ≤ 38 mm and/or RV end-diastolic area ≤ 13 cm2/m2, RV fractional area change ≥ 35% and/or RV free wall longitudinal strain (RVFWLS) ≥ 17%. Right atrial indexed volume (RAVI) and RASr were collected. The lack of at least one of these parameters identified the VSTR aetiology. The study endpoint was a composite of all-cause mortality and heart failure hospitalization at 18-months follow-up. Results Patients’ median age was 79 years (IQR 72-83) and 45% were male. At 18-months follow-up, 139 patients (46%) reached the primary endpoint. After adjustment for age, male sex, glomerular filtration rate (GFR), New York Heart Association (NYHA) class, RAVi and loop diuretic dose, RASr was the only independent predictor of events in patients with ASTR (HR 0.91, 95% CI 0.86-0.96, p = 0.001); in patients with V-FTR after adjustment for age, male sex, coronary artery disease, GFR, NYHA class, loop diuretic dose and RAVi, RVEDD (HR 1.04, 95% CI 1.01-1.07, p = 0.029) and RVFWLS (HR 1.07, 95% CI 1.01-1.12, p = 0.049) were the only echocardiographic parameters associated with poor prognosis, while RASr was not. At receiver operating characteristic analysis, the best cut-off of RASr to predict the composite outcome in the whole population was 12% (sensitivity 74%, specificity 70%, area under the curve [AUC] 0.75, p &amp;lt; 0.001). Cumulative survival free from events was lower in patients with RASr ≤ 12% as compared to those with RASr &amp;gt; 12% in the whole population (52% vs 84%; Log rank p &amp;lt; 0.001) and in both ASTR and VSTR (Figure 1 and Figure 2). Conclusions Right atrial reservoir strain is an useful and reliable tool to identify patients with STR at high risk of death and hospitalization for heart failure and it offers the best prognostic performance in patients with ASTR. ASTR patients survival according to RASr VSTR patients survival according to RASr

163. Novel Factors Predicting Mortality in Allogeneic Hematopoietic Cell Transplantation Recipients with Viral Upper Respiratory Tract Infection

Abstract Background We previously identified novel risk factors for progression to lower respiratory tract disease (LRTD) among allogeneic hematopoietic cell transplant (HCT) recipients presenting with upper respiratory tract infection (URTI) with 12 viruses in the PCR era and proposed a simple prediction model by a number of risk factors (BMT Ogimi C, et al. Bone Marrow Transplant 2022; 57(4):649-657). We aimed to investigate whether the presence of these risk factors at the time of URTI diagnosis also predicts overall mortality and pulmonary death.Figure 1.Kaplan-Meier plot of overall death and cumulative incidence plot of pulmonary death by day 90 among patients with any viral URTI (N=947) Methods We retrospectively analyzed patients with the first respiratory virus detected by multiplex PCR after allogeneic HCT (4/2008-9/2018). We created Kaplan-Meier plots for overall mortality and cumulative incidence plots for pulmonary death within 90 days among patients presenting with URTI by a single virus. Candidate risk factors were age &amp;gt;=40 years, a history of multiple HCT, early timing post-HCT (&amp;lt; =30 days), albumin &amp;lt; =3 g/dL, monocytopenia (&amp;lt; =100 cells/µL), highest glucose value &amp;gt;200 mg/dl, and systemic steroid use within 14 days.Figure 2.Kaplan-Meier plot of overall death by day 90 among patients with viral URTI Results A total of 947 patients (199 children and 748 adults) presented with URTI only as follows: 407 human rhinoviruses (HRV), 174 parainfluenza viruses (PIV) 1–4, 140 common cold coronaviruses, 84 respiratory syncytial virus (RSV), 58 influenza A/B, 43 human metapneumovirus (MPV), and 41 adenoviruses. Among these, 81 (18%) died with 44 pulmonary deaths within 90 days from URTI. No patients with any viral URTI without risk factors died (Figure 1). Patients with 3 or more risk factors appear to have high overall mortality, and pulmonary death accounted for more than half of cases as a cause of death (Figure 1). These trends were seen across viruses evaluated (Figure 2). Conclusion Established risk factors for progression from viral URTI to LRTD also predict overall mortality and pulmonary death. Patients without any risk factors appeared to be completely protected from death, while patients with &amp;gt;3 risk factors were at the highest risk for death, suggesting an intervention opportunity and close monitoring. These trends were observed across several viruses and future studies are needed to validate our findings in different cohorts. Disclosures Chikara Ogimi, MD, PhD, AstraZeneca: Honoraria|bioMerieux Japan Ltd.: Honoraria|ELSEVIER: Honoraria|KYORIN: Honoraria|Miyarisan: Honoraria|MSD: Honoraria|NOVARTIS: Honoraria|Pfizer: Honoraria Alpana waghmare, MD, Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|GlaxoKlineSmith: Advisor/Consultant|GlaxoKlineSmith: Grant/Research Support|Pfizer: Grant/Research Support|Vir: Advisor/Consultant Janet A. Englund, MD, Abbvie: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Speaker at meeting|SanofiPasteur: Advisor/Consultant|Shinogi: Advisor/Consultant Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Symbio: Advisor/Consultant

Artificial intelligence-enhanced electrocardiogram left ventricular diastolic function assessment for prognostic assessment in mitral annulus calcification

Abstract Background Moderate-severe mitral annulus calcification (MAC) and left ventricular (LV) diastolic dysfunction are both linked to increased risks of heart failure and mortality. Assessing LV diastolic function (LVDF) in moderate-severe-MAC by echocardiography is frequently challenging and unreliable. We recently validated an AI-ECG model for LVDF. We aimed to determine if this tool can predict long-term mortality in patients with moderate-severe-MAC and whether it can help establish MAC-specific echocardiographic LVDF parameter cutoffs. Methods This retrospective study included all patients from the AI-ECG LVDF study test cohort who underwent comprehensive transthoracic echocardiography confirming moderate-severe-MAC and ECG within fourteen days of each other at Mayo Clinic between 09/2001 and 06/2022. AI-ECG LVDF was determined based on the index ECG. Patients were categorized based on AI-ECG into groups representing normal/grade-1 LVDF, grade-2 LVDF, or grade-3 LVDG (DF-1, DF-2, and DF-3, respectively). Results Of 2,506 patients with moderate-severe-MAC [mean age 77, 64.1% females], 709 (28.3%), 1,510 (60.3%), and 287 (11.5%) were classified as DF-1, DF-2, and DF-3, respectively. Worse LVDF grade was associated with older age, male sex, lower LV ejection fraction, and higher rates of noncardiovascular and cardiovascular comorbidities. Over a median follow-up of 2.8 years, 1,059 (42.3%) patients died. In multivariable survival analysis, DF-2 [adjusted hazard ratio (aHR) 1.43, 95% confidence interval (95%CI) 1.21-1.68] and DF-3 (aHR 1.54, 95%CI 1.22-1.93) were independently associated with a higher risk of death (figure). Findings were also consistent after adjusting to mitral inflow gradients. When comparing LVDF echocardiographic parameters in controls without MAC matched by age, sex, left ventricular ejection fraction, and AI-ECG DF grade, significant differences were observed. Patients with moderate to severe MAC generally exhibited lower e' velocities, higher TR velocities, elevated E/e' ratios, and increased LAVi. Interestingly, the E/A ratio between MAC patients and their matched controls across AI-ECG LVDF grades remained consistent. Conclusion AI-ECG LVDF predicts mortality risk in patients with moderate-severe-MAC, regardless of mitral inflow gradients. Utilizing AI-ECG LVDF might aid in the risk stratification of patients with significant MAC.

Frequency, course and prognostic yield of valvular heart disease in the general population- Results from the STAAB cohort study

Abstract Background Valvular heart disease (VHD) is a major burden to public health. The complexity and the long asymptomatic phase of VHD pose significant challenges to its recognition and monitoring. Assuming gradual disease progression, the ACC/AHA define consecutive stages of VHD from "at risk" through "progressive stage" to "severe symptomatic VHD". Purpose To determine the frequency and course of VHD stages in the general population and to estimate their respective prognostic value regarding all-cause mortality. Methods The STAAB study recruited a representative sample of inhabitants of a medium-sized town in Germany stratified for sex (1:1) and age decades (30-79 years), who had no preceding diagnosis of heart failure. All participants underwent standardized transthoracic echocardiography (TTE). VHD was graded into stages A to D: stage A = at risk for valve dysfunction: valve deformity, sclerosis, mild mitral or tricuspid regurgitation (MR/TR); stage B = progressive valve dysfunction: mild or moderate aortic regurgitation or stenosis, mild mitral stenosis, moderate MR and TR; stage C/D VHD = asymptomatic/symptomatic severe valve dysfunction: severe valvular regurgitation or stenosis. The relevance of baseline markers with respect to VHD progression and all-cause mortality was analysed using multivariable model and Cox proportional hazards regression model, respectively. Results N=4943 STAAB participants (mean age 55±12 years, 52% women) with valid TTE entered our baseline analysis, and 24% of them were free from VHD. Stage A VHD was present in n=2694 (54%) participants, stage B in n=1056 (21%), and stage C/D in n=16 (0.3%). Participants with stage C/D VHD were older, more frequently male, and showed higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin (Table). Over a median follow-up of 34 months (quartiles 30–41), 35 participants died. Stage C/D VHD (HR, 6.23 [95% CI, 1.24 – 31.34], p=0.026) was associated with all-cause mortality after adjusting for age and sex. N=3833 participants (mean age 58 ±11 years, 52% women) underwent a repeat echocardiography at follow-up. In this sample, 10% of stage A and 1.3% of stage B had progressed from baseline to higher VHD stages, respectively (Figure). Determinants of disease progression were E/e´ (stage A, OR 1.14 [95% CI, 1.03 –1.26], p=0.01) and NT-proBNP (stage B, OR 7.48 [95% CI, 1.38 –40.4], p=0.019) at baseline, respectively. Conclusions In this well-characterized population-based sample, we found a high prevalence of VHD stages A and B. Stage C/D VHD was associated with higher levels of cardiac injury indicators such as troponin and NT-proBNP as well as with a higher risk of death. The majority of individuals with stage A and B VHD was asymptomatic, but a sizable fraction showed VHD progression in the subsequent three years. Elevated E/e´ and NT-proBNP might be helpful in identifying patients at higher risk for disease progression. Baseline characteristics Distribution of VHD stages

Pulmonary artery effective elastance in patients with tricuspid valve regurgitation: a simple effective echo marker for risk stratification

Abstract Background/Introduction Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle (RV) in patients with TR and to investigate their association with outcomes. Various echo parameters have emerged that assess RV-PA coupling, including the ratio of TAPSE to RV systolic pressure (RVSP) and the PA pulsatility index (PAPi). The effective PA elastance (PA Ea) is a composite measure of RV afterload that refers to the measure of the pulmonary vascular load that the RV must overcome to eject blood into the PA. PA Ea is simple to estimate by echo and found to be an independent haemodynamic risk measure in various left heart and pulmonary hypertension (PH) diseases. Whether PA Ea discriminates risk in unselected patients with significant TR and how it compares to other measures of RV-PA coupling is untested. Purpose To ascertain the prognostic value of PA Ea in patients with TR. Methods In consecutive patients with a first diagnosis of ≥ moderate TR (regardless of aetiology), we compared all-cause mortality at five years based on the PA Ea (defined as the RVSP/stroke volume as measured by transthoracic echocardiography). As stroke volume was measured by Doppler at the left ventricular (LV) outflow tract, patients with &amp;gt; moderate aortic valve regurgitation were excluded. The Tricuspid Regurgitation Impact on Outcomes (TRIO) score was calculated as previously described. PA Ea was separated into 4 groups for comparison based on the separation of quartiles of PA Ea rounded to one decimal place. Results In the 13,608 patients studied, PA Ea could be calculated in 12,682 patients (94.4%). The median PA Ea was 0.68 mmHg/mL (IQR 0.50, 0.92). Increasing levels of PA Ea were associated with clinical comorbidities including heart failure, liver and kidney disease and clinical markers of risk such as the TRIO score. Increasing levels of PA Ea were also associated with larger RVs, worse RV systolic function, higher NT-pro BNP levels, and greater degrees of right heart failure (Table). Each quartile of PA Ea was associated with a significant increase in all-cause mortality (Figure). After adjusting for age and sex, PA Ea was associated with higher risk of death (HR 2.41 (2.28-2.56); p&amp;lt;.0001). While worsening degrees of PA Ea correlated with both declining levels of TAPSE/PASP and PAPi (Table), PA Ea was independently predictive of outcome in a combined model: PA Ea HR 1.65 (1.51-1.80, Chi-squ 120, p&amp;lt;.0001); PAPi HR 0.84 (0.80-0.89, Chi-squ 48, p&amp;lt;.0001) and TAPSE/PASP HR 0.32 (017-0.60, Chi-squ 12, p=.0004). Conclusion(s) In patients with significant TR, PA Ea is highly feasible and higher PA Ea is progressively associated with RV dysfunction, right heart failure, and worse survival. Incorporating PA Ea into the routine echo assessment may help stratify disease severity in patients with significant TR. Table Assoc. of PA Ea with mortality in TR

Circumstantial risk factors for death after intensive care unit-to-unit inter-hospital transfer—a Swedish registry study

BackgroundUnit-to-unit transfer of critically ill patients infers hazards that may cause adverse events. Circumstantial factors associated with mortality after intensive care include days in the ICU, night-time or weekend discharge and capacity transfer as compared to other reasons for transfer. Distance travelled may also constitute an indirect risk. The aim of this study was to assess potential associations between these circumstantial factors and the risk of death 30 days after transfer.MethodsData from 2015 to 2019 was retrieved from the Swedish Intensive Care Registry. Logistic regression was used for risk analysis.ResultsAmong 4,327 patients, 965 (22%) were deceased 30 days after transfer. 1351 patients undergoing capacity transfer had a higher morbidity than patients transferred for other reasons. Using univariable logistic regression, days spent in the referring ICU before transfer, capacity transfer as compared to clinical transfer and repatriation as well as SAPS3 in the receiving ICU were associated with a higher risk of death at 30 days. However, after multivariable regression with adjustment for ICD-10 diagnosis and Standardised Mortality Rate in the receiving ICU, these associations were lost.ConclusionOur results suggest that inter-hospital transfer is safe to carry out at any time of day and over shorter as well as longer distances.

Peak atrial longitudinal strain identifies patients with acute decompensated heart failure at high risk of cardiac death

Abstract Background Heart failure (HF) is an increasing health problem with high morbidity and mortality. Left atrial function has prognostic relevance in long-term survival of patients with HF. However, its prognostic value in patients with acute decompensated heart failure (ADHF) is less well studied. Objective The main objective of this study was to assess the association between PALS (peak atrial longitudinal strain) and cardiovascular (CV) death in patients ADHF. Methods A prospective single center study was performed. We enrolled patients admitted with ADHF according to the current European guidelines criteria. Clinical and biochemical data were collected. Echocardiography was performed during the first 24 hours of admission including quantification of left ventricular, right ventricular and left atrial function. Patients were followed up during hospitalization and at discharge. PALS was quantified by a single vendor equipment, using four and two chamber dedicated left atrial views and semi-automated software. The primary outcome was cardiovascular death at 3 years of follow-up. Variables were compared between patients with and without cardiovascular death. A ROC curve was constructed to define the best cut-off point, sensitivity, and specificity of PALS to predict the primary outcome. Results Sixty patients were included. The median age was 58 (24-90) years, 26% were female. Median NT-PRO BNP 5168 (186-70000) pg/mL, Creatinine clearance 70.6 ± 31.1 ml/min, hemoglobin 14.6 (1.5-19.3) g/dL. Left ventricular indexed end-diastolic volume 74.8 (26.8-181) ml/m2, left ventricular indexed end-systolic volume 51.4 (6.7-170.6) ml/m2, left ventricle ejection fraction 62.2 ± 13.6 %. Patients with cardiovascular death during follow-up, had lower LVEF 24 ± 8.3 vs 33.9 ± 13.8 % (p&amp;lt;0.033) and lower PALS 7.2 (4-14) vs (17 (3-39) %;(p&amp;lt; 0.002). In the ROC curve analysis, in the best-case scenario, an atrial strain value lower than 12% had a sensitivity of 72% and 90% of specificity for predicting cardiovascular death. Survival analysis demonstrated better survival in patients with PALS higher than 12%. Conclusions Left atrial strain is useful in patients with ADHF to identify patients at higher risk of cardiac death. According to our results, patients with PALS lower than 12% constitute a high-risk group in whom a closer follow-up and intensive treatment might be needed. Future studies are needed to confirm our findings. Survival according to PALS in ADHF

Acute Kidney Injury, Renal Replacement Therapy, and Extracorporeal Membrane Oxygenation Treatment During the COVID-19 Pandemic: Single-Center Experience

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) was described in December 2019 for the first time, and it was responsible for a global pandemic. An alarming number of patients with coronavirus disease 2019 (COVID-19) also developed acute kidney injury (AKI), especially those who required extracorporeal membrane oxygenation (ECMO) therapy for acute respiratory distress syndrome (ARDS). The aim of our retrospective observational study was to assess the prognostic significance of AKI in these patients. This study observed, in COVID-19 patients admitted to an intensive care unit (ICU), AKI stages and the need for renal replacement therapy (RRT), assessing the risk factors and outcomes. Moreover, we evaluated the mortality rate of patients treated by ECMO. Materials and Methods: Between November 2020 and December 2022, among 396 patients admitted to our intensive care unit (ICU) diagnosed with SARS-CoV-2 infection, we selected patients with severe ARDS requiring veno-venous (vv) ECMO support and AKI. Results: The 30-day mortality after ECMO positioning was 85.7%. A Cox regression revealed a significant advantage for RRT with a high cut-off (HCO) hemofilter both for ICU mortality (HR 0.17 [95% CI: 0.031–0.935], p = 0.035) and 15 day-mortality after the start of vv-ECMO (HR 0.13 [95%CI: 0.024–0.741], p= 0.021), whereas the early onset of vasoplegic shock after ECMO implantation indicated a higher risk of death (HR 11.55 [95% CI: 1.117–119.567], p = 0.04) during the ICU stay. Conclusions: COVID-19 induces a high risk of AKI and RRT. In our cohort, hypertension, pre-existing renal disease, and mechanical ventilation represented independent risk factors for AKI. Patients requiring ECMO support had a high mortality rate. The early implementation of RRT reduced the risk of death during the ICU stay.

Incident heart failure and recurrent coronary events following acute myocardial infarction.

Recurrent myocardial infarction (MI) and incident heart failure (HF) are major post-MI complications. Herein, contemporary post-MI risks for recurrent MI and HF are described. A total of 6804 patients with a primary discharge diagnosis of MI at 28 Baylor Scott & White Health hospitals (January 2015 to December 2021) were studied. Patient characteristics, treatment, and outcomes, including incident HF, recurrent MI, all-cause death, and all-cause and cardiovascular rehospitalizations, were assessed. Landmark approach anchored at 3 months post-discharge was used to assess 1-year outcomes. Median age was 69 years, 59.7% were male, and 76.7% had non-ST-elevation MI. Comorbidities included hypertension (89%), dyslipidaemia (87%), Type 2 diabetes (48%), and chronic kidney disease (34%); 17% had a history of MI and 23% of HF; 63% underwent percutaneous/surgical revascularization. In landmark-anchored 1-year outcomes (N = 6210), 413 (6.7%) patients died, 1730 (27.9%) had all-cause and 735 (11.8%) cardiovascular hospitalizations, 234 (3.8%) had recurrent MI. Of patients without history of HF, 1160 (23.8%) developed incident HF [42.2%, 26.7%, and 31.1% with ejection fraction (EF) < 40%, 41-49%, and >50%, respectively) within 3 months of discharge. Patients who developed HF had higher risk of death and hospitalizations (all P < .001), irrespective of EF. Of 2179 patients with EF > 50% without prevalent HF or HF during index hospitalization, 257 (11.8%) developed HF and 77 (3.5%) recurrent MI within 1 year. In a contemporary post-MI cohort, the risk for incident HF was greater than recurrent MI, even among those with normal EF and no HF at discharge.

Validation of mortality risk scores after esophagectomy

PurposeOncological esophagectomy is the mainstay in esophageal cancer treatment, but perioperative mortality remains a significant concern. Various scoring systems exist to identify patients at high risk for postoperative complications and death. In the following, we aim to evaluate and compare these different scoring systems.MethodsWe analyzed data from 714 patients who underwent esophagectomy between 2002 and 2021. Each patient’s risk was calculated using three models: the International Esodata Study Group (IESG) 90-day mortality risk prediction, the Steyerberg 30-day mortality score, and the Fuchs et al. preoperative in-hospital mortality score (Fuchs score). The diagnostic performance of these models was assessed using the area under the receiver operating characteristic (ROC) curves.ResultsOf the 714 patients, the majority (87.67%) underwent abdomino-thoracic esophagectomy with intrathoracic anastomosis. The IESG score classified 52.1% as very low, 26.6% low, 17.5% middle, 2.8% high, and 1% as very high risk, while the Fuchs score identified 94.5% as low-risk and 5.5% as high-risk patients. Mortality rates were 6.9% at 90 days, 3.4% at 30 days, and 6.7% in-hospital. The area under the ROC curve was 0.634 (95%CI: 0.557–0.712) for the IESG model, 0.637 (95%CI: 0.526–0.747) for the Steyerberg score, and 0.686 (95%CI: 0.611–0.760) for the Fuchs score.ConclusionsExisting risk score systems provide a possibility for preoperative risk stratification, particularly for identifying high-risk patients. However, due to their limited predictive ability, improvements are needed to apply these strategies effectively in clinical practice.

Empiric antibiotic therapy resistance and mortality in emergency department patients with bloodstream infection: a retrospective cohort study

BackgroundTimely management of sepsis in the emergency department, including the use of appropriate antimicrobials, is crucial for improving patient outcomes. Inadequate empiric antimicrobial treatment is associated with potential changes in patient outcomes. We aimed to pinpoint risk factors, characterize antibiotic resistance trends, and investigate the association between antibiotic resistance and mortality among patients with bacteremia admitted to the emergency department.MethodsWe conducted a retrospective analysis of emergency department patients admitted between 15/06/2016 and 30/09/2022. Patients with a positive blood culture receiving emergency department-initiated antibiotic therapy were included. Antibiotic administration, resistance, and survival data were collected. Descriptive statistics, survival analysis, and Cox proportional hazards models were performed.ResultsOf 157,884 emergency department visits, 1,136 patients had a positive blood culture and received antibiotic therapy initiated in the emergency department. Resistance against empiric antibiotics was 14.5%. The overall 30-day and one-year mortality was 38.6% and 61.8%, respectively. In adjusted Cox models, patients with Escherichia coli or Staphylococcus aureus infection had 36% lower and 44% higher risk of death, respectively. Although resistance to emergency department-administered antibiotic therapy was not associated with overall mortality, one-year mortality of patients with Escherichia coli bacteremia was higher in those with antibiotic resistance (69.0% vs. 49.4%, p = 0.011); these patients had a 1.5-fold increased risk of death in an adjusted Cox model.ConclusionThe mortality of patients with bloodstream infection is high. The association of mortality with empiric emergency department-initiated antibiotic adequacy is pathogen-dependent.

Myocardial Inflammation in Cardiac Transthyretin Amyloidosis: Prevalence and Potential Prognostic Implications.

Despite previous histopathologic evidence for its presence, the role of myocardial inflammation in the development and progression of cardiac transthyretin amyloidosis (ATTR-CA) remains insufficiently understood. Thus, this study sought to characterize the prevalence and potential prognostic implications of myocardial inflammation in ATTR-CA. A retrospective observational study including patients with ATTR-CA diagnosed by endomyocardial biopsy was conducted. Myocardial inflammation was diagnosed through a review of routine endomyocardial biopsy reports. Baseline characteristics were compared using the Mann-Whitney U test and the Pearson χ2 test. Clinical outcomes were monitored via follow-up visits or telephone calls. Primary outcomes were all-cause death and a composite end point of all-cause death or heart failure hospitalization. Kaplan-Meier analyses, as well as univariable and age- and sex-adjusted multivariable Cox regression analyses, were used to assess differences in overall and composite end point-free survival between patients with ATTR-CA with and without myocardial inflammation. A total of 103 patients with ATTR-CA (100 wild type; 3 variant) were enrolled. Median follow-up was 18.2 (8.0-31.1) months. Myocardial inflammation was prevalent in 32% (n=33/103) of patients with ATTR-CA. Among evaluable patients with myocardial inflammation, 96% (n=26/27) and 31% (n=9/29) had elevated CD68 (clusters of differentiation 68)-positive macrophage and CD3 (clusters of differentiation 3)-positive T-cell counts, respectively. Overall survival (P=0.017) and composite end point-free survival (P=0.014) were significantly impaired in patients with ATTR-CA with myocardial inflammation (n=33) compared with those without (n=70). Statistical significance for both associations was sustained after adjustment for age and sex, yielding adjusted hazard ratios of 4.72 (95% CI, 1.33-16.71; P=0.016) and 2.30 (95% CI, 1.04-5.11; P=0.041) for all-cause death and the composite end point, respectively. Our findings affirm previous evidence that myocardial inflammation is present in approximately one-third of all patients with ATTR-CA. Moreover, we provide first data indicating that myocardial inflammation may be associated with a higher risk of death and heart failure hospitalizations in ATTR-CA.

Hematopoietic stem cell transplantation in inborn errors of metabolism-a retrospective analysis on behalf of the pediatric disease working party from the Brazilian Society of Bone Marrow Transplantation and Cellular Therapy.

Hematopoietic stem cell transplantation (HSCT) is an established treatment for selected patients with inborn errors of metabolism. In this first report from the PDWP-SBTMO, we included 105 patients transplanted between 1988 and 2021 across six Brazilian HSCT centers. The most prevalent diseases were X-linked adrenoleukodystrophy (n = 61) and mucopolysaccharidosis (type I n = 20; type II n = 10), with a median age at HSCT of 8.7 years and 2.1 years, respectively. Most conditioning regimens were myeloablative and busulfan-based. With a median follow-up of 6.7 years, the 5-years overall survival (OS) was 75% (95% CI, 0.65-0.82) with a superior 5-years OS for those transplanted after 2010 (87% vs. 63%, p = 0.01). Higher risk of death was associated with the use of haploidentical donor (HR8.86, p 0.021), unrelated cord blood (HR 8.76, p 0.005), unrelated donor (HR 5.91, p 0.02), and for HSCT performed before 2010(HR 4.16, p = 0.0015). The CI of acute GVHD was 24.8%, while chronic GVHD was 9.5%. Major causes of death were infections (n = 8), GVHD (n = 6), and neurologic progression (n = 3). Despite improvements in transplant outcomes since 2011, challenges persist, emphasizing the need for early diagnosis, timely transplantation and expanding HSCT centers with expertise in the field.

Abstract A008: Imaging response to induction PD-1 and PARP inhibition in patients with locally advanced head and neck squamous cell carcinoma

Abstract Introduction: Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have high risk of disease progression and death after standard concurrent chemoradiotherapy (CCRT). We are conducting a prospective trial to investigate the efficacy of combining immune checkpoint blockade (ICB) with PARP inhibition prior to and following CCRT. Here we report the feasibility of utilizing pre- and post-induction CT simulations to assess early imaging response in patients treated on trial. Methods: NCT05366166 is an ongoing multi-institution, phase II trial. Patients with HPV negative or high-risk HPV positive LA-HNSCC were eligible. All received induction pembrolizumab 400mg IV and olaparib 150mg BID for 3 weeks followed by CCRT to 70Gy with weekly cisplatin (40mg/m2) followed by one year of maintenance pembrolizumab 400mg every 6 weeks and olaparib 150mg BID. Per protocol, all patients underwent CT simulation in the radiation treatment position with intravenous contrast pre- and post-induction. Dedicated post-induction imaging by radiology was not obtained. Gross tumor volumes of the primary (GTVp) and nodal (GTVn) disease were contoured on the pre- and post-induction simulation CTs by the treating physician in RayStation (RaySearch Laboratories). Pre- and post-induction simulation CTs were evaluated by two neuroradiologists independently using the RECIST criteria (v1.1). Statistical analyses were conducted in Microsoft Excel. Results: We evaluated the first 9 patients treated on-study at our center only. Median age was 67 years (range 59-76) and 78% were male. Location of primary site was oropharynx (N=6; 4 were HPV-positive), oral cavity (N=2), and larynx (N=1). 78% were T3-T4 and 89% had N2-N3 nodal disease. The median duration from the start of induction therapy to post-induction simulation was 22 days (range 7-51). Following induction, all patients experienced symptomatic benefit and had stable disease without progression per RECIST. Comparing pre- and post-induction GTVp and GTVn, overall mean volumes were not statistically different (mean±standard deviation -- 34.0±17.9 vs 35.6±19.5 cm3 for GTVp and 38.7±51.8 vs 39.5±54.2 cm3 for GTVn, respectively). At the individual patient level, the percent volume change after induction ranged from -21.9 to +16.5% (GTVp) and -48.7 to +53.2% (GTVn). Two patients (22%) had a decrease in GTVp, while five (56%) had a decrease in GTVn. There was a positive correlation (Pearson coefficient 0.77) between the percent volume changes in GTVp and GTVn (p=0.016). No differences in response by TNM stage or HPV status were observed. Conclusion: Favorable clinical and radiographic responses to three weeks of induction pembrolizumab and olaparib suggest anti-tumor activity. Performing pre- and post-induction radiation CT simulations is necessary to ensure adequate and accurate assessment of tumor extent for radiation planning. Therefore, omitting conventional post-induction scans by radiology to assess tumor response may be feasible. Formal cost-effective analysis will be conducted. Citation Format: Xuguang S. Chen, Colette J. Shen, Benjamin Y. Huang, Valerie L. Jewells, Michael C. Repka, Travis P. Schrank, Christopher B. Sullivan, Wendell G. Yarbrough, Trevor G. Hackman, Catherine Lumley, Jeffrey M. Blumberg, Shetal A. Patel, Sumita Trivedi, Jared Weiss, Bhisham Chera, Siddharth Sheth. Imaging response to induction PD-1 and PARP inhibition in patients with locally advanced head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A008.

Clinical Case of a Patient with Acute Tricuspid Valve Infective Endocarditis and A Multiplex Approach to Evaluation of The Complication Risk

Infective endocarditis (IE) is characterized by the difficulty of diagnosis, treatment and risk assessment of an unfavorable prognosis. Currently there are no approved scales and calculators for the risk of complications and death that help the practitioner make decisions, especially in patients with isolated right-sided IE. For right-sided IE, the timing of successful surgical treatment remains uncertain. Previously developed risk calculators (Italian Rizzi calculator and French Hubert) are poorly validated in a wide population of patients with IE, especially for right-sided IE. One of the required parameters of calculators is the determination of etiological affiliation. However, with negative results of microbiological studies reaching 56-83 %, this parameter becomes uninformative. Moreover, existing risk assessment tools do not take into account the activity of the disease (including laboratory activity), which intuitively is an important guideline for every doctor in decision-making. At the moment, there is a great need for the introduction of molecular biological methods to improve the quality of etiological diagnosis and in-depth study of possible biomarkers from simple (neutrophil/lymphocytic, platelet/lymphocytic and systemic immuno-inflammatory index) to more complex (neutrophil extracellular traps, cytokine profile). We present a clinical case of a young patient with acute tricuspid valve IE with giant vegetation (28 mm), complicated by severe valvular insufficiency without signs of heart failure, recurrent embolic syndrome in the pulmonary artery system with the formation of pulmonary hypertension, determining indications for cardiac surgical treatment. The etiological affiliation of IE to Staphylococcus aureus was established only by PCR. The urgent timing of intervention was determined based on an increase in new markers — neutrophil/lymphocytic index ≥20.0, systemic immuno-inflammatory index ≥2314.0 and neutrophil extracellular traps ≥14.2, indicating an extremely high risk of death. A fundamental pathohistological study of the tissue material revealed a low content of intact CD86+ proinflammatory macrophages, probably associated with their excessive destruction and uncontrolled release of copious amounts of proinflammatory cytokines, which led to rapid and severe damage to the tricuspid valve. Thus, modern management of patients with IE should be multiplex using current methods of etiological and imaging diagnostics, and aimed at early detection of patients at adverse risk for a timely differentiated approach to conservative or cardiac surgical treatment tactics.

Clinical burden of obstructive hypertrophic cardiomyopathy in France

BackgroundHypertrophic cardiomyopathy (HCM) can be genetic and occurs as obstructive and non-obstructive 21 subtypes. Little is known about the clinical burden of the obstructive subtype of HCM at a national 22 level, and how it may differ by New York Heart Association (NYHA) class. Therefore, this study 23 aimed to describe the clinical burden of patients hospitalized with obstructive HCM from a 24 nationwide study in France.MethodsThis retrospective, longitudinal, observational study was performed using data from the French National Health Data System. All adult patients (≥ 18 years old) with a hospitalization related to obstructive HCM [International Classification of Diseases, Tenth Revision (ICD-10) code I42.1], or at least one hospitalization with ICD-10 code I42.2 or I42.9 and at least one code for septal reduction therapy between 2012 and 2018 were included. Patients were followed up for a minimum of 1 year. NYHA class was assigned using an algorithm based on treatment and symptom codes. Treatment patterns and clinical outcomes by NYHA class over time were examined.ResultsOverall, 6,823 patients with obstructive HCM were included (54.7% male, mean [standard deviation (SD)] age 66.2 [16.7] years). At inclusion, the proportion of patients in NYHA classes I, II, III, and IV were 4%, 32%, 60%, and 4%, respectively. Over the follow-up [mean (SD) follow-up: 4.4 (2.5) years; cumulative patient follow-up: 30,021 patient-years], 73% of patients remained in the same NYHA class, 14% of patients worsened, and 13% improved. At inclusion, 22% of patients had no HCM-related treatment, 56% were receiving β-blockers, 12% calcium-channel blockers, and 11% a combination of both. The incidence of cardiovascular-related hospitalization was high (35,436 hospitalizations; 117,229 per 100,000 patient-years) and this risk increased with NYHA class (from 81,247 per 100,000 patient-years for NYHA class I/II patients to 140,790 per 100,000 patient-years for NYHA class III/IV patients, p &amp;lt; 0.0001).ConclusionsPatients with obstructive HCM are at high risk of death and cardiovascular outcomes, especially those in higher NYHA classes. Despite current therapeutics, the clinical burden of symptomatic obstructive HCM remains high, supporting the need for additional therapies.