6-month Mortality Research Articles

Abstract 17853: Efficacy of Grace Score for Prediction of Mortality in Patients of Acute Coronary Syndrome: A Meta-Analysis

Introduction: The Global Registry of Acute Coronary Syndrome (GRACE) is a validated risk prediction model for acute coronary syndromes (ACS). However, discrimination ability of this model for predicting mortality in ACS remains unclear. The aim of this meta-analysis is to determine the predictive accuracy of GRACE score for mortality in ACS patients. Methods: A comprehensive literature search was conducted across MEDLINE, Embase & the Cochrane Library from inception till May 2023. All studies that reported the C-statistic for predicting in-hospital, 6-month, 1 year & 2-year mortality in ACS patients were included. The generic inverse variance weighted random effects method was used to pool C-statistics & corresponding standard errors (SEs) from each study. Subgroup analysis was conducted based on whether the patients required percutaneous coronary intervention (PCI) or not. Results: A total of 22 studies with a patient population of 132856 were included. For in-hospital mortality (n=99774), the GRACE score showed a good discrimination ability to predict mortality (summary C-statistic 0.86 [0.85-0.87], I 2 =58%). The pooled C-statistic for 6-month mortality (n=24174) was 0.80 (0.70-0.84; I 2 =93%). For 1-year mortality (n=13517), the predictive accuracy of the GRACE score was moderate (summary estimate= 0.77 [0.70-0.83]; I 2 =94%). The GRACE score proved to be moderately accurate in predicting 2-year mortality (n=4972) in ACS patients [0.75 (0.66-0.83); I 2 =66%]. All the findings were consistent across the two subgroups of PCI vs no PCI (p for interaction >0.05). Conclusion: The GRACE score is a simple scoring system that demonstrated good predictive ability for in hospital mortality, & at 6-months while moderate predictive ability for the risk of death at 1-year, & 2-year in patients of ACS with & without PCI.

Association of blood pressure parameters post mechanical thrombectomy in anemic versus non-anemic patients and clinical outcomes

IntroductionHigher blood pressure (BP) is considered to be detrimental in patients who undergo mechanical thrombectomy (MT), however, the impact of BP post-MT based on comorbidities like anemia has not been well studied. We aim to determine the association of 24-h post-MT BP parameters with clinical outcomes depending on their anemia status. MethodsWe conducted a retrospective chart review of patients who underwent MT at a comprehensive stroke center from 1/2015 to 12/2020. Patients were dichotomized into anemic and non-anemic groups based on the World Health Organization’s definition of anemia [hemoglobin < 12.0 g/dL in women and < 13.0 g/dL in men]. We performed a multivariable analysis with binary logistic regression with the 24-h post-MT BP parameters as predictors. The outcomes were functional dependence (3-month mRS 3–6), mortality, and an early neurological improvement. Results220 patients met the inclusion criteria. 158 (71.82 %) patients had functional dependence at 3-months. In the multivariable analysis, the parameters of a higher mean SBP (132.9 ± 11.94 vs.126.52 ± 13.3; OR, 1.05; 95 % CI, 1.02–1.09; P 0.011), a higher mean MAP (93.35 ± 8.44 vs.89.69 ± 10.03; OR,1.06; 95 % CI, 1.01–1.11; P 0.029) and a higher maximum MAP (115.26 ± 11.73 vs.109.37 ± 12.51; OR,1.05; 95 % CI, 1.01–1.08; P 0.023)were significantly associated with functional dependence in non-anemic patients, while a lower mean DBP (65.53 ± 9.73 vs. 71.94 ± 10.16; OR, 0.92; 95 % CI, 0.86–0.98; P 0.007), lower mean MAP (85.7 ± 8.65 vs. 91.38 ± 10; OR, 0.93; 95 % CI, 0.86–0.99; P 0.02), a lower minimum DBP (49.27 ± 10.51 vs. 55.1 ± 11.23; OR, 0.93; 95 % CI, 0.88–0.99; P 0.019), a lower minimum MAP (68.96 ± 9.54 vs. 74.73 ± 10.47; OR, 0.93; 95 % CI, 0.87–0.99; P 0.023) were significantly associated with mortality in patients with anemia, and a lower minimum DBP (54.75 ± 10.42 vs. 59.69 ± 8.87; OR, 0.95; 95 % CI, 0.91–0.99; P 0.012) and a lower minimum MAP (71.92 ± 14.7 vs.75.67 ± 14.17; OR, 0.97; 95 % CI, 0.94–0.99; P 0.047) were significantly associated with an early neurological improvement in non-anemic patients. For patients with anemia, there was no association between 24-hour BP Parameters post-MT and functional dependence and early neurological improvement, and between 24-hour BP Parameters post-MT and mortality in non-anemic patients. ConclusionIn our study, higher BP parameters were associated with worse outcomes in patients without anemia, however, this effect was not found in patients with anemia. Certain lower BP parameters were associated with higher 3-month mortality in anemic patients; however, this effect was not found in non-anemic patients. Higher BP post-MT can potentially promote perfusion and thus is not associated with worse outcomes in anemic patients post-MT, whereas in non-anemic patients it may potentially lead to reperfusion injury While our study is limited because of size and its retrospective nature, the findings suggest that an individualized approach to tailor the target BP post-MT to a patient's risk factor profile and associated co-morbid conditions to achieve optimization of medical care post-MT and associated co-morbid conditions to achieve optimization of medical care post-MT.

Retrospective evaluation of an intervention bundle on OPAT implementation in a large non-university hospital

ABSTRACT Objectives Optimization of outpatient parenteral antimicrobial therapy (OPAT) requires interdisciplinarity and an operational algorithm. This report retrospectively assesses the impact of a multimodal quality-enhancement intervention bundle on the implementation rate, efficacy, and safety of a home OPAT program in a Belgian large community-based hospital. Methods OPAT recipients between 1 March 2019 and 30 June 2022 were included. The OPAT trajectories were divided into pre-intervention (from 1 March 2019 to 31 October 2020) and post-intervention (from 1 November 2020 to 30 June 2022) groups. The quality-enhancement intervention bundle consisted of the involvement of an infectious disease specialist, revision and implementation of a state-of-the-art prosthetic joint infection diagnosis and treatment protocol, weekly multidisciplinary discussion of all prosthetic joint infections, revision of the OPAT algorithm, and the introduction of teicoplanin as an OPAT-convenient antimicrobial. Results Eighty-five patients were included in a total of 96 OPAT trajectories (n = 33 pre-intervention; n = 63 post-intervention). After the intervention, the number of OPAT trajectories nearly doubled. The number of patients with a recurrent infection within 6 months after OPAT completion decreased 15%. The overall 6-month mortality and readmission rates during OPAT treatment decreased 8% and 10%, respectively. Mortality during OPAT treatment did not change. These differences between pre- and post-intervention did not achieve statistical significance, despite the higher risk for complications in the post-intervention group because of increased infection complexity and required treatment duration. Conclusion Within a Belgian, single, large community-based hospital, a multimodal intervention bundle resulted in increases in OPAT implementation, infection complexity, and required treatment durations without statistically significant differences in outcomes.

Transcatheter Palliation With Pulmonary Artery Flow Restrictors in Neonates With Congenital Heart Disease: Feasibility, Outcomes, and Comparison With a Historical Hybrid Stage 1 Cohort.

Neonates with complex congenital heart disease and pulmonary overcirculation have been historically treated surgically. However, subcohorts may benefit from less invasive procedures. Data on transcatheter palliation are limited. We present our experience with pulmonary flow restrictors (PFRs) for palliation of neonates with congenital heart disease, including procedural feasibility, technical details, and outcomes. We then compared our subcohort of high-risk single ventricle neonates palliated with PFRs with a similar historical cohort who underwent a hybrid Stage 1. Cox regression was used to evaluate the association between palliation strategy and 6-month mortality. From 2021 to 2023, 17 patients (median age, 4 days; interquartile range [IQR], 2-8; median weight, 2.5 kilograms [IQR, 2.1-3.3]) underwent a PFR procedure; 15 (88%) had single ventricle physiology; 15 (88%) were high-risk surgical candidates. All procedures were technically successful. At a median follow-up of 6.2 months (IQR, 4.0-10.8), 13 patients (76%) were successfully bridged to surgery (median time since PFR procedure, 2.6 months [IQR, 1.1-4.4]; median weight, 4.9 kilograms [IQR, 3.4-5.8]). Pulmonary arteries grew adequately for age, and devices were easily removed without complications. The all-cause mortality rate before target surgery was 24% (n=4). Compared with the historical hybrid stage 1 cohort (n=23), after adjustment for main confounding (age, weight, intact/severely restrictive atrial septum or left ventricle to coronary fistulae), the PFR procedure was associated with a significantly lower all-cause 6-month mortality risk (adjusted hazard ratio, 0.26 [95% CI, 0.08-0.82]). Transcatheter palliation with PFR is feasible, safe, and represents an effective strategy for bridging high-risk neonates with congenital heart disease to surgical palliation, complete repair, or transplant while allowing for clinical stabilization and somatic growth.

Infectious Complications and Mortality in Post-Transplant Lymphoproliferative Disorder Following Solid Organ Transplantation: Experiences of 10 Years in a Single Center

Introduction: An estimated 2 to 20% of patients with solid organ transplants (SOT) are later diagnosed with post-transplant lymphoproliferative disorder (PTLD). These patients receive immunosuppression therapy for SOT, however, there is a paucity of research examining the infection complications and morbidity in those diagnosed with PTLD. Our single center study examined infections following a PTLD diagnosis and the potential risk of morbidity. Methods: We reviewed the Cleveland Clinic electronic medical record (EMR) of SOT patients who were diagnosed with PTLD between 2010 and 2020. 98 patients met the inclusion criteria. These were further stratified by transplant type: 26 liver, 24 renal, 22 lung, 19 heart, and 2 combined heart and lung transplant patients. All data were analyzed using R software. Results: The mean onset of biopsy confirmed PTLD following transplant was 7.13 ± 7.28 years,. Abdominal pain was the most common presenting symptom prompting further work up, seen in 29% of patients. Patients were also diagnosed based on other chief complaints, including fatigue (n = 20), weight loss (n = 16), and fever (n = 14). Additionally, a smaller subset of patients were diagnosed incidentally on imaging. The most frequent primary site of PTLD was the lymphoid tissue / enlarged lymph nodes (34% of patients) and followed by gastrointestinal tract (29%). Elevated lactate dehydrogenase was present in 42% of patients, diagnostic criteria for acute kidney injury in 23%, and hyperuricemia was noted in 16%. Diffuse large B-lymphoma was the most common subtype diagnosed in 72 of 98 patients followed by EBV related. After diagnosis, 60% of PTLD patients presented to the hospital due to infections, with a mean of 49.9 ± 55.3 days following PTLD diagnosis. Of those patients, bacterial infections were the most common (49.3%), followed by viral infections (34.5%), fungal infections (14.9%), and parasitic infections (1.15%). The bacterial infections were predominantly encapsulated organisms including Pseudomonas aeruginosa (33%), Escherichia coli (19%), and Streptococcus pneumoniae (14%). Rituximab was used in 40% of patients following diagnosis while rituximab, cyclophosphamide, doxorubicin, and vincristine (R-CHOP) was used in 41% of patients. There was no significant difference in infection risk in the first 100-days, following initiation of rituximab infections were seen in 33%, while the infection risk with R-CHOP was 35% (p = 0.31). Moreover, the most common cause of death was infection seen in 39% of patients, while PTLD itself with progressive disease was the second most common cause of death in 27%. The 6-month mortality following PTLD was 16% with 56% of those deaths being attributed to infection. The one-year mortality rate following PTLD was 25% with 48% of those being attributed to infection. Conclusions: In patients with PTLD diagnosis, the most common cause of death was infection (39%), followed by complications related to PTLD such as progressive disease with multi-organ failure. High serious infection risk may be due to aberrant monoclonal B-cell proliferation which paradoxically leads to decreased cellular immunity. The increased risk of B-cell PTLD in patients with SOT is likely due to the chronic immunosuppression, where patients gain acquired somatic driver mutations leading to a malignant state yet with an increased infection risk. Additionally, there was no difference in infection at 100 days between rituximab chemotherapy compared to R-CHOP. This necessitates the question of initiating viral, bacterial and fungal infection prophylaxis, similar to that following splenectomy or post BMT, should be implemented in patients diagnosed with PTLD. Further larger prospective studies are needed to further analyze the potential need and benefit of prophylactic vaccinations at the time of diagnosis in the PTLD patient population.

Impact of Patient Selection and Management over Different Time Periods on the Outcome of Patients with Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy

Introduction. Autologous chimeric antigen receptor (CAR) T-cell therapy targeting CD19 is an effective treatment for relapsed or refractory large B-cell lymphoma (LBCL). Real-world studies have reported improved outcomes in terms of safety and efficacy in comparison with pivotal trials. These differences have been associated to a learning curve in patient selection and adverse event control, but this hypothesis has not been proven. The aim of this study was to analyze patient selection and CAR T-cell management across different time periods and assess its impact on treatment outcomes Methods. This retrospective analysis included all consecutive LBCL patients receiving CAR-T cell therapy (axicabtagene-ciloleucel [axi-cel] and tisagenlecleucel) in the third line setting from approval in 2019 to 2023 and reported in the Spanish Registry. Patients were categorized in 3 consecutive time periods of 18 months each according to infusion date. Baseline characteristics, manufacturing times and production failures as well as efficacy and safety outcomes were compared across periods. An additional safety and efficacy analysis was conducted in patients receiving axi-cel. Results. The study included 458 patients: 117 (26%), 194 (42%) and 147 (32%) in the early (EP) (January 2019-June 2020), intermediate (IP) (July 2020-December 2021) and recent period (RP) (January 2022-June 2023), respectively. In terms of patient profile, baseline characteristics evolved overtime as patients in the RP had received less number of prior therapies, had less primary refractory disease, less bulky disease and had lower LDH at lymphodepletion. On the contrary, the RP had more patients with ECOG performance status ³2 and higher comorbidity burden. Regarding the product, the use of axi-cel increased overtime, from 45% in the EP to 83% in the RP (Table). The time from apheresis to infusion improved overtime, moving from 48 days in the EP to 38 days in the RP. Manufacturing failures (5%) and use of bridging therapy (81%) remained stable overtime. Regarding efficacy, overall (complete) response rates improved overtime (from 66% [25%] in the EP to 78% [52%] in the RP [p&amp;lt;0.001], respectively). Median PFS and OS for the whole cohort were 3.9 months (95% CI 3.23-5.83) and 18.5 months (95% CI 13.53 - 27.67) without differences across periods. In terms of toxicity, patients in the RP had more grade &amp;gt; or = 3 CRS and ICANS, received more tocilizumab and corticosteroids and required more ICU admission compared with the EP. These results were driven by the higher use of axi-cel in the RP. When focusing exclusively on axi-cel patients (n=301), the CR rate also improved overtime (32% in the EP; 37% in the IP and 55% in the RP, p=0.016) (Figure) while median PFS (6.63 months, 95%CI 3.90 - 11.43) and OS (25.73 months, 95%CI 18.57 - NA) remained stable. In the multivariable analysis, ECOG PS &amp;gt; 1 (HR 2.68, 95% CI 1.35-5.09, p=0.005) and LDH ³ 500 UI/L (HR 1.54, 95% CI 1.02-2.31, p=0.04) but not treatment period were associated with a shorter PFS. In terms of toxicity, the time to CRS onset (median of 3 vs. 1 days, p=0.001) and ICANS (median of 8 vs. 6 days, p=0.06) was later in the EP compared with the RP. The incidence of grade &amp;gt; or = 3 CRS and ICANS (ranging from 10% to 7% and 36% to 41%, respectively), the use of tocilizumab, corticosteroids, and anakinra as well as ICU admission rate and 12-month non-relapse mortality (2% vs 5%) remained stable across periods. Conclusion. The criteria for selecting patients for CAR T-cell therapy have evolved overtime towards a less aggressive disease profile and allowing less fit patients for therapy in recent times. Patients treated in the RP were more likely to respond to these therapies but this did not translate into prolonged survival or an improved safety profile.

Non-atherosclerotic acute cardiac syndromes: spontaneous coronary artery dissection and Takotsubo syndrome. Comparison of long-term clinical outcomes.

Spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS) constitute two common causes of nonatherosclerotic acute cardiac syndrome particularly frequent in women. Currently, there is no information comparing long-term clinical outcomes in unselected patients with these conditions. We compared the baseline characteristics, in-hospital outcomes, and the 12-month and long-term clinical outcomes of two large prospective registries on SCAD and TTS. A total of 289 SCAD and 150 TTS patients were included; 89% were women. TTS patients were older with a higher prevalence of cardiovascular risk factors. Precipitating triggers were more frequent in TTS patients, while emotional triggers and depressive disorders were more common in the SCAD group. Left ventricular ejection fraction was lower in TTS patients, but SCAD patients showed higher cardiac biomarkers. In-hospital events (43.3% vs. 5.2%, P<0.01) occurred more frequently in TTS patients. TTS patients also presented more frequent major adverse events at 12-month (14.7% vs. 7.1%, HR 5.3, 95% CI: 2.4-11.7, P<0.01) and long-term (median 36 vs. 31 months, P=0.41) follow-up (25.8% vs. 9.6%, HR 4.5, 95% CI: 2.5-8.2, P<0.01). Atrial fibrillation was also more frequent in TTS patients. Moreover, TTS patients presented a higher 12-month and long-term mortality (5.6% vs. 0.7%, P=0.01; and 12.6% vs. 0.7%, P<0.01) mainly driven by noncardiovascular deaths. Compared to SCAD, TTS patients are older and present more cardiovascular risk factors but less frequent depressive disorder or emotional triggers. TTS patients have a worse in-hospital, mid-term, and long-term prognosis with higher noncardiac mortality than SCAD patients.

Predictors of Cytokine Release Syndrome and Neurotoxicity in Patients with Large B-Cell Lymphoma and Their Impact on Survival

Background: Autologous CAR-T therapy targeting CD19 is an effective treatment for relapsed or refractory large B-cell lymphoma (LBCL). However, morbidity and mortality related to CAR-T toxicity remain significant concerns. This study aims to evaluate the patterns, risk factors, and implications of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) following CD19-CAR-T therapy in LBCL. Methods: This retrospective analysis includes 1916 LBCL patients treated with CD19-CAR-T cell therapy (axicabtagene-ciloleucel [axi-cel] 75% and tisagenlecleucel 25%) between 2018 and 2020 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Patient demographics, baseline characteristics, treatment-related variables, and clinical outcomes were collected. The incidence, severity and timing of onset of CRS and ICANS (according to median time to onset) were analyzed, factors associated with these outcomes and their impact on overall survival as time dependent covariates were done using Cox Regression multivariate analyses. Results: The median age of the patients was 64 years, with a majority having a Karnofsky performance status (KPS) below 90% (61%) and not receiving bridging therapy (67%). CRS was observed in 75.1% of patients, with 9% experiencing severe CRS (grades ≥ 3). Similarly, 43% of patients experienced ICANS, with 20% having severe ICANS (grade ≥ 3). The median time to toxicity was shorter for CRS (4 days) compared to ICANS (7 days). Nearly all the patients who developed ICANS also experienced CRS (98%; ), and the correlation between these two events and respective severities are shown in the Figure 1a. In the multivariate analyses, factors associated with development of CRS were gender (women, Odds ratio [OR] 1.39, 95% confidence interval [CI] 1.10- 1.76, p=0.006), high LDH at time of infusion (OR 1.56; 95% CI 1.22 - 2.00, p=0.002) and product (axi-cel OR 4.60, 95% CI 3.56 -5.81, p&amp;lt;0.001). Factors associated with the development of ICANS included age (&amp;gt; 65 years, OR 1.83; 1.50-2.24, p&amp;lt;0.001), KPS (&amp;lt;80%, OR 2.48; 1.88-3.27, p&amp;lt;0.001), disease status at infusion (treatment resistant disease, OR 1.98; 1.09-3.58, p=0.024; and untreated relapse OR 2.62, 1.35-5.10, p=0.004) and product (axi-cel, OR 5.85; 4.47-7.64, p&amp;lt;0.0001). Factors associated with severe and early onset CRS and ICANS are listed in the table below. The median follow-up of 14.2 months, the estimated 12-month overall survival, progression-free survival (PFS), and treatment-related mortality were 61.6% (95% CI: 59.4-63.9), 42.2% (39.9-44.5), and 4.3% (3.4-5.3), respectively. Overall CRS, early onset CRS and overall ICANS were not associated with higher mortality, however grade &amp;gt;3 CRS (HR 1.79; 1.41-2.28, p&amp;lt;0.001), grade &amp;gt;3 ICANS (hazard ratio [HR] 1.34; 95% CI 1.13-1.59, p=0.002) and early onset ICANS (&amp;lt;7 days, HR 1.23; 1.05-1.44, p=0.01) were associated with higher mortality. The impact of severe CRS on survival are shown in the landmark analysis at 30 days from infusion in the figure 1B. Conclusion: In the largest analysis of CD19-CAR-T cell therapy toxicities to date, we observed a high burden of CRS and ICANS among LBCL patients. The CAR T cell product type was consistently associated with higher incidence, shorter onset and higher severity of both toxicities. High LDH, older age and low performance score also influence the severity and onset of these outcomes. Additionally, patients who developed higher grades of CRS/ICANS and earlier onset ICANS had a higher mortality, stressing the need to develop novel strategies to mitigate the incidence and optimize management of these patients to improve their outcomes.

Clinical Characteristics and Risk Factors for Bloodstream Infections in Children with Cancer: A Report from a Pediatric Hematology Oncology Unit.

Infections are a major cause of morbidity and mortality in children with haematologic malignancies and solid tumors as well as those undergoing hematopoietic stem cell transplantation (HSCT). The purpose of our study was to record the epidemiological characteristics and outcomes of bacteremias, focusing on pathogens, as well as risk factors and mortality rates in patients of a pediatric hematology-oncology unit from Northern Greece. A retrospective analysis was conducted, which included all positive blood cultures from pediatric hematology oncology patients aged from 1 to 16 years old admitted to the Pediatric and Adolescent Hematology Oncology Unit of AHEPA University Hospital of Thessaloniki between January 2014 and December 2018. Data were collected from patients' printed and electronic medical records. 73 episodes of bacteremias were identified (41% male and 32% female with a ratio of 1.28:1; median age 6.5 years; 13.7% solid tumor, 72.6% acute lymphoblastic leukemia, 13.7% acute myeloid leukemia, and 95.8% with an indwelling permanent catheter). 49.3% of the isolates were Gram-positive bacteria and 50.7% Gram-negative, and the ratio of Gram-negative to Grampositive was 1.02. Coagulase-negative staphylococci were most frequent (39.7%), followed by E. coli (17.8%) and Klebsiella pneumoniae (17.8%). Out of all Gram-negatives, 13.5% carbapenemase producers and 8.1% ESBL-producers were found. In relation to Gram-positive, 79.3% were identified as methicillin-resistant CoNS. During the study period, 10.9% of indwelling catheters were removed, and 2.73% of episodes resulted in ICU transfer. The 3-month mortality rate was 8.2%. This study demonstrated an almost equal distribution of Gram-positive and Gramnegative bacteremias in total in this population but with an increase in the isolation of Grampositive bacteria over the last years, which is consistent with other similar studies in this patient group. Knowledge of the local epidemiology and bacterial antimicrobial resistance is important to prevent and timely treat these life-threatening infections in immunocompromised pediatric oncology patients.

Characteristics and outcome of critically ill patients with systemic rheumatic diseases referred to the intensive care unit

ObjectivesPatients with systemic rheumatic diseases (SRDs) are at risk of admission to the intensive care unit (ICU). Data concerning these critically ill patients are limited to few retrospective studies.MethodsThis is...

Sociodemographic differences in treatment and survival for patients who receive genomic tumor testing in a rural state.

170 Background: New cancer technologies like genomic tumor testing (GTT) make targeted treatments and improved outcomes possible. However, access to technologies like GTT is often inequitably skewed such that it is most available to urban and socially advantaged individuals, which may contribute to cancer disparities in disadvantaged groups. This study aims to assess the impact of differential resource allocation by examining whether patient rurality, education, or income are associated with whether patients receive genome matched treatment (GMT) and their survival. Methods: Patients with cancer ( n=1,258) enrolled in the Maine Cancer Genomics Initiative, which provided free GTT across a rural state Demographic and clinical data was collected from surveys and electronic medical records. We used multivariable logistic regression models to examine whether receipt of GMT differs by patient rurality, education, and income. Kaplan-Meier survival (KM) curves and multivariable Cox proportional hazards regression were conducted to explore the relationship between 12-month mortality and rurality, education, and income. We fit both unadjusted and adjusted (age, gender, physical quality of life, cancer stage and type) models. Results: After completing GTT, ~16% of patients received at least one GMT. Rurality, education, or income did not predict receipt of GMT. 41.4% of the lower educational level group versus 32.2% of the higher education group died within 365 days of enrollment (unadjusted HR: 1.37; 95% CI: 1.12 to 1.68; p=0.002). This difference was driven by patients who did not receive GMT, where those in the lower education group had increased mortality (unadjusted HR: 1.43, 95% CI: 1.15 to 1.78, p=0.001). For patients who received GMT, there was no difference in mortality between the education groups (unadjusted HR: 1.03, 95% CI: 0.58 to 1.83, p=0.9). No significant differences in mortality were observed for rurality or income. Conclusions: Lower educational attainment was associated with worse survival for patients who did not receive GMT. Education and specialized health care are differentially available to those in urban and rural areas and can cause health disparities. Sustaining initiatives that provide access to novel technologies is critical to address cancer disparities. To account for the intersection of social and psychological factors on cancer disparities, future analyses will include patients’ perceptions of GTT.

The Clinical Frailty Scale is a Strong Predictor of 1-Year Mortality in Surgically Managed Hip Periprosthetic Fracture: An Analysis From a High-Volume Institution

BackgroundHip periprosthetic fractures (PPFs) after primary total hip arthroplasty are increasing with the number of primary implants and aging population. Mortality has been reported up to 34% at 1-year. The aim of this study was to evaluate the association of Clinical Frailty Scale (CFS) and 1-year mortality, complication rate, and length of stay (LOS) in surgically managed hip PPFs. MethodsThis was a retrospective study of prospectively collected data from January 2008 to January 2021. A total of 282 surgically managed hip PPFs were identified. Mean age was 79 years (range, 42 to 106). Preoperative scores were analyzed through linear regression to identify significant association with mortality, complication and LOS. Receiver operating characteristic curve and Area Under the Curve (AUC) were generated to evaluate the quality of the models and the discriminatory ability of each clinical score. Significance was considered at P values < .05. ResultsMortality was 7.8% at 3-months and 15.7% at 1-year. Complication rate requiring surgery was 19.5% and mean LOS was 8.9 ± 7 days. The CFS was significantly associated with 3-month (odds ratio 2.23, P < .001) and 1-year mortality (odds ratio 2.01, P < .001). The receiver operating characteristic curve test for 1-year mortality showed a greater AUC for the CFS when compared with American Society for Anesthesiologists score and age-adjusted Charlson Comorbidity Index (AUC 0.80 versus 0.68 versus 0.72, respectively). ConclusionsFrailty is a syndrome with increased risk of mortality after surgically managed PPF. The CFS can be easily assessed at the time of admission and could be considered as a strong and reliable predictor of 1-year mortality with a greater AUC than the conventionally used American Society for Anesthesiologists score.

Association between hospital onset of infection and outcomes in sepsis patients – A propensity score matched cohort study based on health claims data in Germany

BackgroundHospital-acquired infections are a common source of sepsis. Hospital onset of sepsis was found to be associated with higher acute mortality and hospital costs, yet its impact on long-term patient-relevant outcomes and costs is unknown. ObjectiveWe aimed to assess the association between sepsis origin and acute and long-term outcomes based on a nationwide population-based cohort of sepsis patients in Germany. MethodsThis retrospective cohort study used nationwide health claims data from 23 million health insurance beneficiaries. Sepsis patients with hospital-acquired infections (HAI) were identified by ICD-10-codes in a cohort of adult patients with hospital-treated sepsis between 2013 and 2014. Cases without these ICD-10-codes were considered as sepsis cases with community-acquired infection (CAI) and were matched with HAI sepsis patients by propensity score matching. Outcomes included in-hospital/12-month mortality and costs, as well as readmissions and nursing care dependency until 12 months postsepsis. ResultsWe matched 33,110 HAI sepsis patients with 28,614 CAI sepsis patients and 22,234 HAI sepsis hospital survivors with 19,364 CAI sepsis hospital survivors. HAI sepsis patients had a higher hospital mortality than CAI sepsis patients (32.8% vs. 25.4%, RR 1.3, p < .001). Similarly, 12-months postacute mortality was higher (37.2% vs. 30.1%, RR=1.2, p < .001). Hospital and 12-month health care costs were 178% and 22% higher in HAI patients than in CAI patients, respectively. Twelve months postsepsis, HAI sepsis survivors were more often newly dependent on nursing care (33.4% vs. 24.0%, RR=1.4, p < .001) and experienced 5% more hospital readmissions (mean number of readmissions: 2.1 vs. 2.0, p < .001). ConclusionsHAI sepsis patients face an increased risk of adverse outcomes both during the acute sepsis episode and in the long-term. Measures to prevent HAI and its progression into sepsis may be an opportunity to mitigate the burden of long-term impairments and costs of sepsis, e.g., by early detection of HAI progressing into sepsis, particularly in normal wards; adequate sepsis management and adherence to sepsis bundles in hospital-acquired sepsis; and an improved infection prevention and control.

Advanced Metrics and Early Predictors of Cardiogenic Shock.

Cardiogenic shock (CS) can be defined as a range of illnesses that describes a state where cardiac output, which is the blood volume ejected from the left ventricle every minute that leads to tissue perfusion of nutrients, is insufficient in providing adequate oxygenation to the systemic circulation. The incidence of CS on admission has increased in recent years, with the six- and 12-month mortality rates remaining unchanged. The purpose of this literature review is to bring forth several parameters that have been utilized in the past 10 years to predict CS mortality. Further studies to implement these parameters in management algorithms, along with early screenings and advanced treatment options such as mechanical cardiac assist devices, can improve the mortality associated with CS. This literature-based review was conducted by evaluating current research focusing on the clinical presentation of CS and predictors of CS. PubMed served as the primary database for article retrieval due to access. Two searches were conducted: One for clinical presentations and advanced metrics for CS and another for early predictors for CS. Thirteen articles regarding clinical presentation and seven articles regarding early predictors were selected. Three tools/scores and five laboratory tests were identified that allowed clinicians to prognosticate outcomes in patients suffering from CS based on clinical and laboratory presentations. Examining these predictors will allow earlier intervention in the development of CS and potentially help lower the mortality rate of CS. The eventual creation of a scoring system that incorporates multiple metrics discussed in this review can provide the most accurate prognosis of CS, which can lead to more targeted interventions.

Feasibility of using red cell distribution width for prediction of postoperative mortality in severe burn patients: an association with acute kidney injury after surgery.

Severe burns cause pathophysiological processes that result in mortality. A laboratory biomarker, red cell distribution width (RDW), is known as a predictor of mortality in critically-ill patients. We examined the association between RDW and postoperative mortality in severe burn patients. We retrospectively analyzed medical data of 731 severely burned patients who underwent surgery under general anesthesia. We evaluated whether preoperative RDW value can predict 3-month mortality after burn surgery using receiver operating characteristic (ROC) curve analysis, logistic regression, and Cox proportional-hazards regression analysis. Mortality was also analyzed according to preoperative RDW values and incidence of postoperative acute kidney injury (AKI). The 3-month mortality rate after burn surgery was 27.1% (198/731). The area under the ROC curve of preoperative RDW to predict mortality after burn surgery was 0.701 (95% confidence interval [CI], 0.667-0.734; P < 0.001) with a cut-off point of 12.9. The adjusted hazard ratio in patients with RDW > 12.9 was 1.238 (95% CI, 1.138-1.347; P < 0.001). Subgroup analysis showed that the survival rate was 88.8% for the non-AKI group with RDW ≤ 12.9 and 17.6% for the AKI group with RDW > 12.9. Preoperative RDW was considered an independent risk factor for mortality (odds ratio, 1.679; 95% CI, 1.378- 2.046; P < 0.001). Preoperative RDW may predict 3-month postoperative mortality in patients with severe burns, while preoperative RDW > 12.9 and postoperative AKI may further increase mortality after burn surgery.

Machine learning based readmission and mortality prediction in heart failure patients

This study intends to predict in-hospital and 6-month mortality, as well as 30-day and 90-day hospital readmission, using Machine Learning (ML) approach via conventional features. A total of 737 patients remained after applying the exclusion criteria to 1101 heart failure patients. Thirty-four conventional features were collected for each patient. First, the data were divided into train and test cohorts with a 70–30% ratio. Then train data were normalized using the Z-score method, and its mean and standard deviation were applied to the test data. Subsequently, Boruta, RFE, and MRMR feature selection methods were utilized to select more important features in the training set. In the next step, eight ML approaches were used for modeling. Next, hyperparameters were optimized using tenfold cross-validation and grid search in the train dataset. All model development steps (normalization, feature selection, and hyperparameter optimization) were performed on a train set without touching the hold-out test set. Then, bootstrapping was done 1000 times on the hold-out test data. Finally, the obtained results were evaluated using four metrics: area under the ROC curve (AUC), accuracy (ACC), specificity (SPE), and sensitivity (SEN). The RFE-LR (AUC: 0.91, ACC: 0.84, SPE: 0.84, SEN: 0.83) and Boruta-LR (AUC: 0.90, ACC: 0.85, SPE: 0.85, SEN: 0.83) models generated the best results in terms of in-hospital mortality. In terms of 30-day rehospitalization, Boruta-SVM (AUC: 0.73, ACC: 0.81, SPE: 0.85, SEN: 0.50) and MRMR-LR (AUC: 0.71, ACC: 0.68, SPE: 0.69, SEN: 0.63) models performed the best. The best model for 3-month rehospitalization was MRMR-KNN (AUC: 0.60, ACC: 0.63, SPE: 0.66, SEN: 0.53) and regarding 6-month mortality, the MRMR-LR (AUC: 0.61, ACC: 0.63, SPE: 0.44, SEN: 0.66) and MRMR-NB (AUC: 0.59, ACC: 0.61, SPE: 0.48, SEN: 0.63) models outperformed the others. Reliable models were developed in 30-day rehospitalization and in-hospital mortality using conventional features and ML techniques. Such models can effectively personalize treatment, decision-making, and wiser budget allocation. Obtained results in 3-month rehospitalization and 6-month mortality endpoints were not astonishing and further experiments with additional information are needed to fetch promising results in these endpoints.

Minimally invasive ultrasound-assisted evacuation of Spontaneous Supratentorial Intracerebral hemorrhages: Retrospective observational single-cohort study

OBJECTIVETo assess safety and efficacy of minimally invasive evacuation of Spontaneous Supratentorial Intracerebral Hemorrhage (SSICH) by means of tailored minicraniotomies and intraoperative ultrasound (iUS) assistance. METHODSRetrospective analysis of 55 patients who underwent microsurgical evacuation of SSICH using minicraniotomy and iUS assistance, between January 2015 and January 2022. Surgical complications, mortality rate, recurrent bleeding, percentage of hematoma evacuation and reliability of iUS were collected and investigated. The clinical outcomes were measured by the modified Rankin Scale (mRS) at 6 months. Subgroup analysis was performed to assess the differences between the pre-operative GCS (3-9 versus 10-14), the residual hematoma volume (<10ml versus >10ml) and the location (deep versus lobar). RESULTS3 patients had an unfavourable outcome owing to surgery. The 6-month overall mortality accounted for 10,9%. Symptomatic recurrent bleeding occurred in 3 cases. 2 patients (3.6%) developed brain swelling treated with decompressive hemicraniectomy. With reference to clinical outcome, 39 patients (70,9%) had a good functional outcome (GFO) and the average 6-month mRS was 2,75±1,97. Hematoma volume decreased from 54,2±12,8mL pre-evacuation (range 30-95mL) to 11,1±12,5mL post-evacuation (range 0-35mL), with an average reduction of 78,15%±16,4% (P < 0.001). iUS was reliable to correctly check hematoma evacuation during the procedure in 46 patients (83.6%). Pre-operative GCS>9 and residual hematoma <10ml were found to be associated with higher probability to have GFO (P < 0.01). CONCLUSIONSEvacuation of SSICH using minicraniotomy with iUS assistance is a straightforward, affordable, and reproducible technique. Its safety and efficacy profiles appear consistent with other published studies.

The Impacts of Antiretroviral and Antifungal Treatments, and Tuberculosis Co-infection on Mortality and Relapse in Patients with Talaromyces Marneffei Infection

To date, clinical data on long-term clinical outcomes, including 6-month mortality and relapse in talaromycosis (Tm) patients and impacts of ART and secondary antifungal prophylaxis are still lacking. We conducted a secondary data analysis from 6-month prospective observation of patients with culture-confirmed talaromycosis who participated in the Itraconazole versus Amphotericin B for HIV-associated Talaromycosis (IVAP) trial. The primary outcome was 6-month Tm mortality, while the secondary outcome was relapse. Multivariable Cox proportional hazard models were used to identify predictors of outcomes of interest. The median patient age was 34 years (IQR:30 – 38). The median pre-ART CD4 counts at baseline were 10 (IQR: 5-21) cells/µL. The cumulative 76/435 (17.4%) patients died, and Tm relapse was observed in 18/435 (4.1%) patients. The multivariable analyses showed that strong independent predictors of 6-month Tm mortality included ineffective ART (either absence of ART or ART failure) (HR = 6.26, 95% CI: 3.95 – 9.92, P &lt; 0.001), and TB co-infection (HR =1.98, 95% CI: 1.23 – 3.17; P &lt; 0.01). Induction antifungal treatment with itraconazole versus amphotericin B deoxycholate was significantly associated with Tm death in the univariable model, however, it became insignificant in the multivariable model. In addition, the significant risk factors for Tm relapse were ineffective ART, induction antifungal treatment with itraconazole than intravenous amphotericin B, and shorter duration of itraconazole secondary prophylaxis after completing induction therapy in-hospital (all with significant P-values). Antiretroviral therapy, antifungal treatment and tuberculosis co-infection were main predictors for 6-month Tm fatality as well as relapse. Keywords: Invasive fungal infections, Mortality, Relapse, Talaromyces marneffei, Vietnam.

The Association of Endothelin-1 with Early and Long-Term Mortality in COVID-19.

(1) Background: Endothelial dysfunction is a key mechanism in the pathogenesis of COVID-19. High endothelin-1 during COVID-19 is associated with severe complications and increased mortality rates during hospitalization. This study is aimed to investigate the association of endothelin-1 levels with the risk of 30-day and 12-month all-cause mortality in patients with prior COVID-19. (2) Methods: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The level of endothelin-1 in the blood serum was evaluated by ELISA. Univariate and multivariate Cox regression was used to determine factors and significance of endothelin-1 associated with the risk of mortality within 30 and 365 days from hospitalization. (3) Results: The median endothelin-1 was higher in the group of patients who passed away within 30 days. The group showed statistically significant differences when compared to healthy volunteers from the control group (p = 0.0001), surviving patients (p = 0.001), and those who passed away within a year (p = 0.002). (4) Conclusions: Endothelin-1 levels are associated with increased mortality risk during the acute period of COVID-19, while plasma endothelin-1 level association with COVID-19 survivor mortality risk does not persist after 12 months.

Cytokine absorption in critically ill old COVID-19 patients with renal failure: A retrospective analysis of 503 intensive care unit patients.

COVID-19 is associated with cytokine release in critical disease states. Thus, cytokine absorption has been proposed as a therapeutic option. This study investigated the influence of cytokine absorption on mortality in old critical patients with COVID-19 and renal failure admitted to intensive care units (ICU). This retrospective analysis of a prospective international observation study (the COVIP study) analysed ICU patients≥70 years with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, clinical frailty scale (CFS), ICU therapy details including renal replacement therapy (RRT) with/without cytokine absorption were collected. The cytokine absorption group was compared to patients receiving RRT without cytokine absorptionRESULTS:Among 3927 patients, 503 received RRT; among them 47 patients were treated with cytokine absorption. Mortality rates were high in both groups with increased rates in the cytokine group for ICU mortality and 30-day mortality, but not for 3-month mortality. Logistic regression analysis indicated that SOFA-score, but not cytokine absorption was associated with mortality. Critical COVID-19 patients with renal failure treated with cytokine absorption showed higher short term mortality rates when compared to patients with renal replacement therapy alone. Mortality is associated with disease severity, but not cytokine absorption in a multivariate analysis.