30-day Survival Research Articles

A multistage drug delivery approach for colorectal primary tumors and lymph node metastases

The presence of lymph node (LN) metastases guides cancer staging and worsens prognoses. Incomplete lymphadenectomy of metastatic LNs may end up with disease recurrence, while excessive resection can result in increased postoperative complications with even no survival benefit. Thus, effective non-invasive methods to treat metastatic LNs would be highly desirable. Here, we develop an enzyme-responsive formulation of small-sized doxorubicin-loaded mesoporous silica nanoparticles (DMSN, 40 nm) encapsulated in nanoliposomes (DMSN@Pla-Lipo, 160 nm). The liposomal membrane contains 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), two phospholipids sensitive to secreted phospholipase A2 in human colorectal tumors. In an orthotopic colorectal murine tumor model, phospholipase-induced membrane permeabilization triggers the liberation of DMSN from liposomes for enhanced tumor penetration, conferring an enhanced suppression for the primary tumor. Furthermore, through translocation into metastatic LNs via tumor lymphatics, metastatic tumor cells in LNs are eradicated. Metastases to other major organs are also suppressed, which can be ascribed to the inhibition of colorectal cancer metastasis-associated TGF-β, Wnt, and Hippo signaling pathways in metastatic LNs. The treatment confers an 80% 90-day survival rate in this aggressive tumor model. Taken together, this study demonstrates a deliberate treatment approach for management of both primary tumors and metastatic LNs through multistage drug delivery.

Radio-protective effects of ultra-fine bubble hydrogen water and serum protein responses in whole-body radiation-exposed mice

Many studies have demonstrated hydrogen’s therapeutic and preventive effects on various diseases. Its selective antioxidant properties against hydroxyl radicals, which are responsible for the indirect effects of ionizing radiation, may make it worthy of attention as a new radio-protector. We recently developed new hydrogen water that is more stable and has higher antioxidant activity by using ultra-fine bubbles. In this study, female C57BL/6J mice given ad libitum access to ultra-fine bubble hydrogen water (UBHW) were subjected to whole-body irradiation (WBI) with X-rays, and the radio-protective effect of UBHW was evaluated. WBI with 6.0 Gy (sub-lethal dose) resulted in a 30-day survival rate of 100% in UBHW-fed mice, compared with 37% in control mice. In the case of WBI with 6.5 Gy (lethal dose), while the control mice died out in about 3 weeks, the 30-day survival rate improved to 40% by UBHW due to the high scavenging activity of hydroxy radicals. Twenty-six serum proteins involved in inflammatory and immune responses were significantly identified in UBHW-fed mice by proteomics, and UBHW may enhance and regulate these functions, resulting in reduced damage in mice exposed to WBI. We conclude that UBHW has good potential in radio-protection, with evidence that warrants further research efforts in this field.

Oseltamivir Reduces 30-Day Mortality in Older Adults with Influenza: A Pooled Analysis from the 2012-2019 Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN)

Abstract Background Oseltamivir is recommended for the treatment of adults hospitalized with influenza, but adherence is often suboptimal. This may be due to doubts about the reliability of the evidence supporting its benefits, particularly when initiation is delayed. We aimed to assess the effectiveness of oseltamivir in reducing mortality in older adults hospitalized with influenza, with a focus on the timing of initiation. Methods The CIRN-SOS Network gathered data on severe respiratory illnesses across five Canadian provinces during the influenza seasons 2012-2019. Individuals aged 65+ years with confirmed influenza and available antiviral prescription data were included. We compared the 30-day survival rates of hospitalized patients based on oseltamivir prescription status. Kaplan-Meier estimated survival probability and IPT-weighted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for mortality. The analyses considered the time to antiviral initiation (>48 vs.≤48 h). Results Among the 8,135 influenza patients studied, 2,126 did not receive antiviral treatment, whereas 6,009 were treated with oseltamivir. A total of 395 patients were hospitalized for more than 30 days. The overall mortality rate was 8.32 per 1,000 person-days, with 53.9% of the deaths occurring within the first week. Oseltamivir recipients had a 18% lower risk of 30-day mortality (IPT-weighted HR=0.82, 95% CI: 0.69-0.98). The benefit was significant for influenza A (IPT-weighted HR=0.74, 95% CI: 0.61-0.91) but not for influenza B (IPT-weighted HR=1.12, 95% CI: 0.81-1.56). Oseltamivir remained effective even when initiated after 48 hours (IPT-weighted HR=0.66, 95% CI: 0.49-0.90). Influenza vaccination did not mediate the effectiveness of oseltamivir in reducing mortality. Conclusions Oseltamivir significantly reduces mortality risk in older adults hospitalized with influenza, even when administered after 48 h, independent of vaccination status.

A new prognostic model based on serum apolipoprotein AI in patients with HBV-ACLF and acutely decompensated liver cirrhosis

Background/AimTo investigate the prognostic value of circulating apolipoprotein AI (apoAI) levels and develop a new prognostic model in individuals with acute-on-chronic liver failure (ACLF) and acute decompensation (AD) of liver cirrhosis caused by hepatitis B virus (HBV) infection.MethodsBaseline levels of serum lipids were measured, and data concerning the presence of complications were collected from 561 HBV-ACLF and AD patients. Survival analysis was conducted by log-rank test. Proportional hazards model was used to perform multivariate analysis. The dynamics of serum apoAI levels were also explored in 37 HBV-ACLF patients.ResultsIn the cohort, the negatively correlation was found between the Model for End-Stage Liver Disease (MELD) score and serum apoAI levels (r = -0.7946, P < 0.001). Circulating apoAI concentration was an independent risk factor for 90-day survival according to Cox multivariate analysis. A new prognostic score-integrated serum lipid profile for ACLF patients (Lip-ACLF score = 0.86×International Normalized Ratio (INR) + 0.0034×total bilirubin (TBIL) (µmol/L) + 0.99× hepatorenal syndrome (HRS) (HRS: no/1; with/2) + 0.50×hepatic encephalopathy (HE) (grade/ponint: no/1; 1–2/2; 3–4/3) − 2.97×apoAI (g/L) + 5.2) was subsequently designed for the derivation cohort. Compared to MELD score, Child-Turcotte-Pugh (CTP) score or apoAI, Lip-ACLFs was superior for the prediction of 90-day outcomes (receiver operating characteristic curve (ROC): 0.930 vs. 0.885, 0.833 or 0.856, all P < 0.01), as was the validation cohort (ROC 0.906 vs. 0.839, 0.857 or 0.837, all P < 0.05). In Kaplan‒Meier survival analysis, low apoAI levels (< 0.42 g/L) at baseline indicated poor prognosis in ACLF and AD patients. Among the 37 patients, the deceased individuals were characterised with significantly decreased serum apoAI levels during the follow-up test compared with those at baseline (P < 0.05), whereas in patients with a good prognosis, the serum apoAI levels remained stable during the follow-up.ConclusionIn HBV-ACLF and AD patients, lower serum apoAI levels suggest greater disease severity and 90-day mortality risk. For predicting the short-term prognosis of these patients, the new Lip-ACLF score might serve as a potential model.

Urine Output and Development of Acute Kidney Injury in Sepsis: A Multicenter Observational Study.

Acute kidney injury (AKI) is common in sepsis and a urine output <0.5 mL/kg/h associated with increased mortality is incorporated into AKI diagnosis. We aimed to identify the urine-output threshold associated with increased AKI incidence and hypothesized that a higher urine output than a specified threshold, which differs from the predominantly used 0.5 mL/kg/h threshold, would be associated with an increased AKI incidence. This was a post-hoc analysis of a nationwide prospective observational study. This study included adult patients newly diagnosed with sepsis and requiring intensive care. Urine output on the day of sepsis diagnosis was categorized as low, moderate, or high (<0.5, 0.5-1.0, and >1.0 mL/kg/h, respectively), and we compared AKI incidence, renal replacement therapy (RRT) requirement, and 28-day survival by category. Estimated probabilities for these outcomes were also compared after adjusting for patient background and hourly fluid administration. Among 172 eligible patients, AKI occurred in 46.3%, 48.3%, and 53.1% of those with high, moderate, and low urine output, respectively. The probability of AKI was lower in patients with high urine output than in those with low output (43.6% vs 56.5%; P = .028), whereas RRT requirement was lower in patients with high and moderate urine output (11.7% and 12.8% vs 49.1%; P < .001). Patients with low urine output demonstrated significantly lower survival (87.7% vs 82.8% and 67.8%; P = .018). Cubic spline curves for AKI, RRT, and survival prediction indicated different urine-output thresholds, including <1.2 to 1.3 mL/kg/h for AKI and <0.6 to 0.8 mL/kg/h for RRT and mortality risk. Urine output >1.0 mL/kg/h on the day of sepsis diagnosis was associated with lower AKI incidence. The urine-output threshold was higher for developing AKI than for RRT requirement or mortality.

Textbook Outcomes as a Novel Patient-Centric Metric to Inform Carotid Revascularization.

The recent National Coverage Decision surrounding carotid stenting and shared decision-making (SDM) has ushered in an era of patient-centric carotid care. However, historical carotid intervention endpoints have lacked patient-centered nuances to inform clinical decisions. Accordingly, we aimed to create a comprehensive novel, patient-centric textbook outcome (TO) to inform treatment paradigms. We developed a novel composite TO for patients who underwent carotid revascularization reflecting a combination of patient centric outcomes derived from previous patient interviews and the published literature. We defined a TO to include freedom from postprocedural neurologic events, myocardial infarction, cranial nerve injury, return to the OR, reperfusion syndrome, or access site complications. The endpoint also included discharge on postprocedural day 1, home discharge, and 30-day survival. We measured the risk of a TO versus non-TO among asymptomatic patients undergoing carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), or transfemoral carotid artery stenting (TF-CAS) in the VQI from 2016-2023. We studied 72,778 patients who underwent carotid revascularization, 70.3% CEA, 21.0% TCAR, and 8.7% TF-CAS. The mean age across all patients was 71.6±8.4 years, 39.9% were female, and 91.7% were white. A TO was achieved in 76.9% of patients, and was 76.7% after CEA, 76.5% after TCAR, and 79.1% after TF-CAS (p<.001). postprocedural length of stay was 2 days or more in 21.0% of patients, and was 21.1% after CEA, 21.6% after TCAR, and 18.4% after TF-CAS (p<.001). Postprocedural neurologic events occurred in 1.0% of patients after CEA, 1.3% after TCAR, and 1.4% after TF-CAS (p=.037). A sensitivity analysis of the TO that did not include postprocedural length of stay demonstrated a non-TO in 5.9% of patients after CEA, 5.5% after TCAR, and 6.3% after TF-CAS (p=.070). Patients who did not achieve a TO had inferior 5-year survival compared to patients who did have a TO across all three cohorts (log-rank P<.001). This novel patient-centric endpoint demonstrated that a substantial percentage of patients fail to achieve a TO in current practice, and that failure to achieve a TO was associated with inferior 5-year survival. These findings are particularly important in light of the recent Medicare mandate for a SDM approach to carotid care delivery and may help to best align patient preferences with procedure type.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Cytoreductive Surgery (CRS): Age-Related Outcomes and a Look into the Future

Introduction: Peritoneal carcinomatosis presents significant treatment challenges. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) offers a promising therapeutic approach. Patient selection remains critical, and the role of age as an exclusion criterion requires further investigation. This study evaluates whether age influences postoperative outcomes in CRS-HIPEC patients. Methods: A retrospective review of a prospective comprehensive database of 271 CRS-HIPEC procedures performed between 2018 and 2023 was conducted. Logistic regression assessed the relationship between age and postoperative outcomes. Age groups (18–44, 45–69, ≥70 years) were compared based on demographic data, primary tumor site, Peritoneal Cancer Index scores, and key outcome measures. Results: Across the different age groups, there were no significant differences in PCI scores, recurrence, disease-free survival, 30-day morbidity, or mortality. Length of stay was longer in older patients (p = 0.009). Patients aged ≥70 had higher readmission rates (p = 0.041) and were more often discharged to transitional care facilities (p = 0.001). Older patients were also more likely to experience Clavien–Dindo grade III or higher complications (p = 0.008). Logistic regression confirmed these findings. Continuous age analysis yielded similar results and revealed significant differences in race and primary organ involvement. Conclusions: Age is not a significant predictor of 30-day morbidity, mortality, or survival outcomes in patients undergoing CRS-HIPEC. However, older patients require closer attention to discharge planning and readmission risk management. This study highlights the importance of comprehensive patient assessment beyond age and underscores the need for further research to better understand factors influencing outcomes in this population.

Safety and Efficacy of Coil Embolization for Endoleak Prevention as an Adjunct to Endovascular Repair of Abdominal Aortic Aneurysm or Subsequently for Repair of Endoleak

This study assessed the real-world safety and efficacy of coil embolization during endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) for prophylactic endoleak prevention or as a reintervention for endoleak repair, using the Cerenovus family of coils (Cerenovus, Irvine, CA, USA). This was a multicenter, retrospective cohort study of consecutive patients who underwent embolization of branching arteries during EVAR of an AAA or as a reintervention for endoleak repair, using Cerenovus coils between January 2017 and December 2021 in Japan. The primary outcome was 30-day reintervention-free survival, defined as cardiovascular mortality or any complication requiring reintervention within 30days post procedure. Secondary outcomes included conversion to open surgical repair, length of hospitalization, and the following outcomes through 30days and 1-year post procedure: occurrence of endoleak (Type I-V), reintervention, complications not requiring reintervention, aneurysm-related mortality, coil migration, and all-cause mortality. A total of 306 patients (mean age 76.7±7.8; 16.7% [51/306] female) were included in the study. Infrarenal AAA were most common (175/306; 57.2%), and the mean aneurysm size was 52.1±10.9mm. At 30days, reintervention-free survival was achieved in 96.4% (295/306) of the patients; 9 (2.9%) patients required reintervention, and 2 (0.7%) died from cardiovascular causes through 30days. One (1/305; 0.3%) patient underwent conversion to open repair. The mean length of hospitalization was 8.6±7.2days. Complications not requiring reintervention occurred in 3.9% (12/306) of the patients through 30-days and 12.4% (38/306) through 1-year. Endoleak occurred in 2.9% (9/306) of the patients at 30days and 9.5% (29/306) at 1year. Coil migration and aneurysm rupture were not reported for any patient. Aneurysm-related mortalities occurred in 0.0% (0/305) at 30days and 0.3% (1/303) at 1year. All-cause mortalities occurred in 0.7% (2/306) at 30days and 3.3% (10/304) at 1year. This study demonstrated that the use of Cerenovus coils yielded a high rate of 30-day-reintervention-free survival and low rates of type II endoleak occurrence and recurrence at the target vessel through 30days and 1year in patients following EVAR of an AAA with coil embolization, either for prophylactic endoleak prevention during EVAR or as a reintervention to repair an endoleak.

Long-term outcomes after postponing surgery to optimise patients with acute right-sided obstructing colon cancer.

To retrospectively analyse the short- and long-term oncological, morbidity and mortality outcomes in patients diagnosed with acute right-sided obstructing colon cancer. Patients who underwent pre-optimisation prior to the oncological resection were compared to patients who did not undergo pre-optimisation. All consecutive patients with right-sided obstructing colon cancer, either with a high clinical suspicion or confirmed diagnosis by histological analysis, who underwent curative-intent treatment between March 2013 and December 2020 were included. Patients were divided into two groups: an optimised group and a non-optimised group. Preoperative optimisation included additional nutrition, physiotherapy, and, if needed, bowel decompression. Data about disease-free survival and mortality were collected up to three years after surgery. Sixty-two patients were included. Thirty patients underwent the optimisation protocol before postponed surgery, and 32 patients received emergency surgery, without optimisation (surgery performed with a median of 9.6 days versus 22h after admission). The postoperative complication rate was significantly lower in the optimisation group (50% vs 78%, p=0.033). No significant differences were found in the 90-day mortality rate (7% vs 13%, p=0.672) and three-year overall survival rate (43% vs 56%, p=0.49). After three years, sixteen (53%) patients in the optimised group and twenty (63%) in the non-optimised were deceased (p=0.672). Postponing the surgery with preoperative optimisation in patients with obstructing right-sided colon cancer results in a significantly lower 90-day complication rate and suggests no negative effect on survival rates compared to an acute resection. Although, further research with a larger sample size is needed.

Safety and Efficacy of DPMAS in Patients With Acute-on-Chronic Liver Failure Based on Different Platelet Count Levels.

To investigate the effect of different platelet (PLT) counts on the safety and efficacy of the double-plasma molecular absorption system (DPMAS) in patients with acute-on-chronic liver failure (ACLF). A total of 156 patients with ACLF receiving DPMAS were divided into the observed group (40 × 109/L ≤ PLT < 50 × 109/L) and the control group (PLT ≥ 50 × 109/L) according to PLT count level. The safety and efficacy indices of bleeding-related complications, PLT reduction rate, total bilirubin (TBIL) reduction rate, and 28-days survival rate after DPMAS were analyzed and compared between the two groups. The incidence of bleeding complications during and after DPMAS in the observed and control groups (14.3% vs. 14.9%, p = 0.922), the decline rate of PLT immediately and 24 h after treatment (0.13 vs. 0.11/0.05 vs. 0.09, p = 0.256/0.161), and the 28-days survival rate after treatment (76.2% vs. 75.4%, p = 0.923) were not significantly different. The thromboelastogram before DPMAS showed no significant difference in PLT function between the two groups (p > 0.05). Although the TBIL level of the two groups rebounded 24 h after treatment compared with immediately after treatment, it decreased significantly immediately and 24 h after treatment compared with pre-treatment levels (p < 0.05). There was no significant difference in the rate of decline of serum TBIL immediately after treatment and 24 h after treatment between the two groups (0.33 vs. 0.35/0.14 vs. 0.16, p = 0.193 and 0.653, respectively). DPMAS is safe and effective in patients with ACLF with 40 × 109/L ≤ PLT count < 50 × 109/L.

Expedited conveyance of out-of-hospital-cardiac arrest patients with STEMI and shockable rhythms to Cardiac Arrest Centres - A feasibility pilot study of the British Cardiovascular Intervention Society conveyance algorithm.

Guidelines suggest non-traumatic out-of-hospital cardiac arrest (OHCA) be conveyed to cardiac arrest centres (CAC). We hypothesised that (a) a pre-hospital conveyance algorithm based on initial presenting rhythm following OHCA is feasible and (b) that would demonstrate survival advantage. This observational pilot study included all consecutive patients with OHCA from suspected cardiac aetiology from the county of Essex, United Kingdom from April 2022-April 2023. For the first 6months, OHCA patients had conveyance as standard of care. For the next 6months, consecutive OHCA patients with STEMI or initial shockable rhythm were directly conveyed to the CAC, initial non-shockable rhythm without STEMI continued to be taken to the nearest Emergency Department (BCIS protocol). Primary outcome was death from any cause at 30days. Secondary outcome was survival with favourable neurological outcome. Of 330 patients (mean age 67.5±13.1, 66% male), 162 patients were in the standard care group and 168 in the BCIS conveyance group. Algorithm implementation was associated with numerically lower all cause 30-day mortality [(81% vs 73%, RR 1.10 (95% CI 0.98-1.24) p=0.10] and numerically higher 30-day survival with favourable neurological outcome [15% vs 19%, RR 1.05 (0.95-1.15), p=0.38]. Post hoc analysis showed that the BCIS conveyance algorithm was associated with lower 30day mortality in those with an initial shockable rhythm [(61% vs 41%, RR 1.5 (95% CI 1.05-2.13) p=0.02 and in those with a MIRACLE2 score≤5 [(63%% vs 38%, RR 0.59 (95% CI 0.61-0.86) p=0.005]. The BCIS algorithm is feasible and did not impact overall mortality, but there is signal that direct conveyance of OHCA patients with an initial shockable rhythm and low MIRACLE2 score, to a dedicated CAC may improve survival.

Trends and Outcomes Over Time with Fenestrated and Branched Endovascular Aortic Repair in the United States Aortic Research Consortium.

To characterize trends and outcomes with fenestrated and branched endovascular aortic repair (F/B-EVAR) performed at centers participating in the United States Aortic Research Consortium. F/B-EVARs performed in 10 prospective, non-randomized, physician-sponsored investigative device exemption studies from 2015-2023 were retrospectively studied. Outcomes included 30-day major adverse event (MAE) and 1-year secondary reintervention. Outcome determinants were modeled with mixed-effects multivariable regression. Adjusted observed-minus-expected cumulative sum analysis was used to evaluate outcomes achieved over time. In the study period, 2,377 patients underwent F/B-EVAR. Median[IQR] follow-up was 2.3 years [0.7-3.5]. The proportion of thoracoabdominal aneurysms (p = 0.01) and aortic dissections (p = 0.001) increased over the study period while technical failure rates (p = 0.6) and length of hospital stay (p = 0.1) remained stable. Fusion imaging (p = 0.0005), low-profile devices (p < 0.0001), and completely transfemoral repair (p = 0.0005) were increasingly adopted over time. There were decreases in fluoroscopy time, procedure time, radiation dosage, and blood loss throughout the study (all p < 0.0001). Adjusted 30-day survival was 99.6% [99.3-99.8] and MAE occurred in 240 (10%). MAE determinants included age (OR[95%CI]: 1.3 per 10-years [1.1-1.6]; p = 0.005), eGFR (0.9 per 10-mL/min/1.73m2 [0.82-0.95]; p = 0.001), thoracoabdominal aneurysm (1.8 [1.3-2.6]; p = 0.002), operative time (1.04 per 10-minutes [1.03-1.06]; p < 0.0001), and technical failure (3.0 [1.7-5.1]; p = 0.0001). The cumulative rate of 30-day MAE remained stable, reflecting expected outcomes rates. The 1-year reintervention rate was 18% (n=435). Secondary intervention determinates included patient-specific device usage (0.4 [0.28-0.65]; p = 0.045) technical failure (3.1 [1.9-5.3]; p < 0.0001), total target vessels (1.3 per vessel [1.05-1.6]; p = 0.002), and prior aortic dissection (1.9 [1.3-2.6]; p = 0.0005). The cumulative rate of 1-year reintervention remained stable during the study period. Data from multiple U.S. centers demonstrate that F/B-EVAR can be performed safely and with acceptable outcomes. Despite increasing repair extent and complexity, the rates of technical failure, adverse events, and reintervention remained stable, likely driven, in part, by evolutions in minimally-invasive technique.

Risk Factors for Gastrointestinal Bleeding in Patients With Acute Myocardial Infarction: Multicenter Retrospective Cohort Study.

Gastrointestinal bleeding (GIB) is a severe and potentially life-threatening complication in patients with acute myocardial infarction (AMI), significantly affecting prognosis during hospitalization. Early identification of high-risk patients is essential to reduce complications, improve outcomes, and guide clinical decision-making. This study aimed to develop and validate a machine learning (ML)-based model for predicting in-hospital GIB in patients with AMI, identify key risk factors, and evaluate the clinical applicability of the model for risk stratification and decision support. A multicenter retrospective cohort study was conducted, including 1910 patients with AMI from the Affiliated Hospital of Guangdong Medical University (2005-2024). Patients were divided into training (n=1575) and testing (n=335) cohorts based on admission dates. For external validation, 1746 patients with AMI were included in the publicly available MIMIC-IV (Medical Information Mart for Intensive Care IV) database. Propensity score matching was adjusted for demographics, and the Boruta algorithm identified key predictors. A total of 7 ML algorithms-logistic regression, k-nearest neighbors, support vector machine, decision tree, random forest (RF), extreme gradient boosting, and neural networks-were trained using 10-fold cross-validation. The models were evaluated for the area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, recall, F1-score, and decision curve analysis. Shapley additive explanations analysis ranked variable importance. Kaplan-Meier survival analysis evaluated the impact of GIB on short-term survival. Multivariate logistic regression assessed the relationship between coronary heart disease (CHD) and in-hospital GIB after adjusting for clinical variables. The RF model outperformed other ML models, achieving an area under the receiver operating characteristic curve of 0.77 in the training cohort, 0.77 in the testing cohort, and 0.75 in the validation cohort. Key predictors included red blood cell count, hemoglobin, maximal myoglobin, hematocrit, CHD, and other variables, all of which were strongly associated with GIB risk. Decision curve analysis demonstrated the clinical use of the RF model for early risk stratification. Kaplan-Meier survival analysis showed no significant differences in 7- and 15-day survival rates between patients with AMI with and without GIB (P=.83 for 7-day survival and P=.87 for 15-day survival). Multivariate logistic regression showed that CHD was an independent risk factor for in-hospital GIB (odds ratio 2.79, 95% CI 2.09-3.74). Stratified analyses by sex, age, occupation, marital status, and other subgroups consistently showed that the association between CHD and GIB remained robust across all subgroups. The ML-based RF model provides a robust and clinically applicable tool for predicting in-hospital GIB in patients with AMI. By leveraging routinely available clinical and laboratory data, the model supports early risk stratification and personalized preventive strategies.

P-2295. Risk Factors for and Impact of Enteric Gram-negative Infections on Lung Transplant Clinical Outcomes

Abstract Background Bacterial infections such as Pseudomonas aeruginosa (PsA) and S. aureus lead to increased morbidity post-lung transplant. Less is known about the impact of enteric gram-negative (GNR) infections. This study’s aim was to assess risk factors for developing GNR infections within 6-months of transplant and associated 1-year outcomes compared to lung transplant recipients (LTR) with other bacterial infections or uninfected LTR. Table 1 Characteristics and Outcomes of LTR with post-transplant GNR infections, other bacterial infections, and no infection Methods A single-center retrospective study of LTR between January 2017 and October 2023 was performed. Donor/recipient characteristics, microbiologic data, and 1-year clinical outcomes were analyzed. Results During the study period, 327 patients had a lung transplant with a greater than 30-day survival. 77 (23%) had GNR infections, 64 (20%) had either PsA, S. aureus, or Streptococcal infections (infect), and 186 (57%) did not have a bacterial infection within 6-months post-transplant. The GNR infections were: 18% Enterobacter cloacae complex, 16% E.coli, 25% Klebsiella sp., 7% Acinetobacter sp., 1% Serratia sp., 1% Citrobacter sp., 7% Burkholderia sp., 19% Stenotrophomonas sp., 6% others. Infections included: 19% bacteremia, 91% pneumonia, 5% empyema, 4% mediastinitis, 1% other. Donor, recipient, and perioperative characteristics were similar amongst the cohorts. A similar proportion of LTR donors were colonized with GNR, PsA, and S. aureus in the 3 cohorts pre-transplant. A greater proportion of the GNR cohort had delayed chest closure, required dialysis, mechanical ventilation, and/or ECMO for &amp;gt;48 hours, and had a longer ICU and index hospitalization compared to the other cohorts [Table 1]. The median time to infection was similar for the GNR and infect cohorts (52 and 51 days), but a greater proportion of the GNR cohort developed chronic kidney disease or respiratory failure. 6-month and 1-year survival were less in the GNR cohort but not statistically significant. Conclusion LTR with more complicated post-operative courses were more likely to develop enteric GNR infections which led to increased post-transplant morbidities. Pre-transplant GNR colonization was not a risk factor for GNR infection post-transplant. Strategies to minimize post-transplant enteric GNR infections need further study. Disclosures All Authors: No reported disclosures

P-2247. Comparison of a Cellular Host-Response Test to Blood Culture Results for Risk Stratification and Diagnosis of Sepsis

Abstract Background Sepsis is a life-threatening syndrome that requires urgent intervention to achieve optimal outcomes[1-3]. While considered the gold standard for bacteremia and sepsis diagnosis, blood cultures (BCX) require long turnaround and offer low sensitivity [4], with only 18-25% of patients with sepsis returning positive BCXs [5]. In this study, we compared a cellular host response test to BCX in performance for diagnosing and risk-stratifying patients suspected of sepsis in the ED. Figure 1 Rate of sepsis status, per Sepsis-3 definition, across HR interpretation bands (A) and blood culture results (B). 28-day survival probability for in-hospital infection associated mortality for (C) HR interpretation bands and (D) blood culture results. * and **** represent p &amp;lt; 0.05 and p &amp;lt; 0.0001, respectively. Methods A semi-quantitative in-vitro cellular host-response test (HR) uses deformability cytometry to assess leukocyte biophysical properties from whole blood in &amp;lt; 10 min. The test generates an Index based on increasing WBC deformability, stratified into 3 interpretation bands (Band 1, Band 2, Band 3) of increasing sepsis likelihood [6]. Adult patients presenting to the ED with signs or suspicion of infection were prospectively enrolled at multiple US sites (02/2016–10/2021). EDTA-anticoagulated blood was assayed 5 hours from draw using the test, and patients were followed by retrospective chart review. Infection and sepsis status was determined via retrospective physician adjudication per Sepsis-3, during which adjudicators were blinded to HR results but had BCX results visible. Table 1 Sepsis-3 receiver operator characteristic diagnostic performance for HR compared to blood culture results. Results Our cohort of 490 patients for whom BCXs were ordered was stratified into 175 Band 1, 129 Band 2, and 186 Band 3 patients for HR versus 385 BCX+ and 105 BCX- patients. When evaluated for diagnostic performance for Sepsis-3, HR, compared to BCX, yielded higher AUC (0.82 [0.78 - 0.86 95% CI] HR vs. 0.7 [0.66 - 0.74] BCX), higher sensitivity (93.2% HR vs 46.9% BCX), and higher negative predictive value (93.1% HR vs 75.6% BCX) with similar specificity (82.1% [75.4 - 87.3%] HR vs 93.0% [87.8 - 96.0%] BCX) and positive predictive value (68.5% [61.0 - 75.1%] HR vs 79.0% [71.4 - 84.3%] BCX,Fig. 1 A/B, Tab. 1). For infection-associated mortality, survival rates of 100% (N = 35 surv. /35 inf.) and 87.1% (N = 122 surv. /140 inf.) were found for Bands 1 &amp; 3, respectively (p &amp;lt; 0.05) compared 93.1% (N = 135 surv. / 145 inf.) and 89.1% (N = 82 survived /92 infected) for BCX - &amp; +, respectively (p &amp;gt; 0.05). References Conclusion These findings indicate that the HR test may provide more accurate and timely results for sepsis diagnosis and risk stratification when compared to BCX. Disclosures Matt Sorrells, PhD, Cytovale Inc.: Employee Roya Sheybani, PhD, Cytovale Inc.: Employee Ajay M. Shah, PhD, Cytovale Inc.: CEO Robert Scoggins, MD, PhD, Cytovale Inc.: Employee, CMO

P-892. Impact of early continuous renal replacement therapy in patients with septic acute kidney injury: an analysis of the MIMIC-IV database

Abstract Background Renal replacement therapy (RRT) is an important treatment option for septic acute kidney injury (AKI); however, the optimal timing for its initiation remains controversial. Here, we aimed to investigate the clinical outcomes of early continuous renal replacement therapy (CRRT), which was defined as CRRT initiation within 6 hours of the onset of septic AKI, which is earlier than the time of initiation defined in previous studies.Figure 1.Study flowchart. Methods We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. This study included patients aged ≥18 years who met the sepsis diagnostic criteria and received CRRT because of stage 2 or 3 AKI. Early and late CRRT were defined as CRRT initiation within 6 hours and after 6 hours of the development of septic AKI, respectively.Table 1.Clinical characteristics of patients with sepsis after propensity matching Results Of the 33,236 patients diagnosed with sepsis, 553 underwent CRRT for septic AKI. After excluding cases of early mortality and patients with a history of dialysis, 45 and 334 patients were included in the early and late CRRT groups, respectively. After propensity score matching, the 28-day mortality rate was significantly lower in the early CRRT group than that in the late CRRT group (26.7% vs. 43.9%, P=0.035). The early CRRT group also had a significantly greater number of days free of mechanical ventilation (median days, 19; interquartile range [IQR] 3–25) and vasopressor administration (median days, 21, IQR 5–26) than did the late CRRT group (median days, 10.5; IQR, 0–23; P=0.037 and median days, 13.5; IQR, 0–25; P=0.028, respectively). The Kaplan–Meier curve also showed that early CRRT initiation was associated with an improved 28-day mortality rate (log-rank test, P=0.040). In contrast, there was no significant difference in the 28-day mortality between patients who started CRRT within 12 h and those who did not (log-rank test, P=0.237).Table 2.Clinical outcomes of patients with sepsis after propensity score matching Conclusion Early CRRT initiation can improve the survival of patients with septic AKI. CRRT must be initiated as early as possible after the onset of septic AKI, preferably within 6 hours.Figure 2.Kaplan-Meier survival curves of patients with septic acute kidney injury after propensity score matching.A. Comparison of 28-day survival and B. 90-day mortality among patients with sepsis between continuous renal replacement therapy initiation &amp;lt; 6 hours and ≥ 6 hours. C. Comparison of 28-day survival and D. 90-day mortality among patients with sepsis between continuous renal replacement therapy initiation &amp;lt; 12 hours and ≥ 12 hours. Disclosures All Authors: No reported disclosures

P-1943. Risk Factors for Coronavirus disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis (CAPA) in Critically Ill Patients: The Predictive Value of KL-6 for CAPA and Mortality

Abstract Background Coronavirus Disease 2019 (COVID-19) is an acute respiratory viral illness that can be complicated by secondary invasive fungal infections, such as COVID-19-Associated Pulmonary Aspergillosis (CAPA). Krebs von den Lungen-6 (KL-6), a mucinous high-molecular-weight glycoprotein found on the surface of type II alveolar epithelial cells, has been known as a biomarker indicative of respiratory epithelial damage. This study aims to evaluate the risk factors for CAPA in critically ill COVID-19 patients, with a focus on the predictive value of KL-6. Overall 30-day survival rates between patients with and without CAPA Methods This single-center retrospective cohort study included critically ill COVID-19 patients (those requiring high-flow respiratory support or mechanical ventilation) admitted from January 2021 through June 2023. CAPA diagnosis was established based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. The study investigated factors associated with CAPA and compared overall 30-day mortality for patients with and without CAPA. Results Among 238 critically ill COVID-19 patients, 25 (10.5%) were diagnosed with CAPA. Notably, patients with CAPA exhibited significantly higher median serum peak levels of KL-6 (787.4 vs. 290.2 U/mL, P&amp;lt; 0.001), with a cutoff value of 392.9 U/mL determined by the Youden index. Multivariable analysis revealed that a peak KL-6 level ≥ 392.9 U/mL was strongly associated with CAPA (adjusted odds ratio 8.62, 95% confidence interval [CI] 2.43-31.69). Additionally, inotropics/vasopressor support, diabetes mellitus, and tocilizumab were identified as factors associated with the development of CAPA. The overall 30-day mortality was significantly higher in patients with CAPA (60.8%) compared to those without (45.2%) (P=0.020), with the difference persisting after adjustment (adjusted hazard ratio 2.06, 95% CI 1.05-4.03). Furthermore, along with older age, lacticemia, and diabetes mellitus, elevated KL-6 was also associated with increased mortality. Conclusion Our study suggests that KL-6 may be a significant predictor of both the development of CAPA and mortality among critically ill patients with COVID-19. Disclosures All Authors: No reported disclosures

Survival of Patients with Solid Tumours and Sepsis Admitted to Intensive Care in a Tertiary Oncology Centre: A Retrospective Analysis.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Patients with cancer are at risk of developing sepsis and requiring intensive care unit (ICU) admission. We aimed to assess survival of patients with a solid tumour admitted to ICU as an emergency with sepsis, and to identify predictors of 90-day survival at admission. We conducted a retrospective cohort survival analysis. We identified adults with a solid tumour admitted to ICU with sepsis between 01/01/2011 and 31/12/2020 at a tertiary oncology centre with two hospitals (London and Surrey, UK). We defined sepsis using the Sepsis-3 definition. The primary outcome was 90-day survival. We used the parametric accelerated failure time model for multivariate analysis to generate acceleration factors (AF). 625 patients were identified and the 90-day survival rate was 59.5%(353/593).Multivariate analysis identified the presence of localized (AF 0.13, 95% CI 0.06-0.25) or regionalized disease (AF 0.21, 95% CI 0.12-0.36) compared to distant metastatic disease, unplanned surgery on the day of admission (AF 0.15, 95% CI 0.07-0.31), lactate (AF 1.25 95% CI 1.15-1.35), Sequential Organ Failure Assessment Score (AF 1.19, 95% CI 1.12-1.27), previous radiotherapy (AF 1.89, 95% CI 1.14-3.125), previous systemic anti-cancer treatment (excluding hormonal therapy) (AF 1.49, 95% CI 0.93-2.38), bacteraemia (AF 0.47, 95% CI 0.27-0.81) and serum albumin (AF 0.94, 95% CI 0.91-0.98) as independent predictors of 90-day survival. This study of solid tumour patients admitted to ICU is one of the largest providing survival data to inform clinicians and patients. This data provides information on factors that should be considered when deliberating the possible outcome of ICU admission for a patient with solid malignancy and sepsis and highlights that the presence of cancer itself should not limit ICU admission for sepsis.

Early achievement of hemostasis defined by transfusion velocity: A possible mechanism for whole blood survival benefit.

Whole blood resuscitation is associated with survival benefits in observational cohort studies. The mechanisms responsible for outcome benefits have not been adequately determined. We sought to characterize the achievement of hemostasis across patients receiving early whole blood versus component resuscitation. We hypothesized that achieving hemostasis would be associated with outcome benefits and patients receiving whole blood would be more likely to achieve hemostasis. We performed a post hoc retrospective secondary analysis of data from a recent prospective observational cohort study comparing early whole blood and component resuscitation in patients at risk of hemorrhagic shock. Achievement of hemostasis was defined by receiving a single unit of blood or less, including whole blood or red cells, in any 60-minute period, over the first 4 hours from the time of arrival. Time-to-event analysis with log-rank comparison and regression modeling were used to determine the independent benefits of achieving hemostasis and whether achieving hemostasis was associated with whole blood resuscitation. For the current analysis, 1,047 patients met the inclusion criteria for the study. When we compared patients who achieved hemostasis versus those who did not, achievement of hemostasis had significantly more hemostatic coagulation parameters, had lower transfusion requirements, and was independently associated with 4-hour, 24-hour and 28-day survival. Whole blood patients were significantly more likely to achieve hemostasis (88.9% vs. 81.1%, p < 0.001). Whole blood patients achieved hemostasis earlier (log-rank χ2 = 8.2, p < 0.01) and were independently associated with over twofold greater odds of achieving hemostasis (odds ratio, 2.4; 95% confidence interval, 1.6-3.7; p < 0.001). Achievement of hemostasis is associated with significant outcome benefits. Early whole blood resuscitation is associated with a greater independent odds of achieving hemostasis and at an earlier time point. Reaching a nadir transfusion rate early following injury represents a possible mechanism of whole blood resuscitation and its attributable outcome benefits. Secondary Analysis; Level III.

Extracorporeal membrane oxygenation in trauma: a single-center retrospective observational study

PurposeGlobally, trauma is a leading cause of death in young adults. The use of extracorporeal membrane oxygenation (ECMO) in the trauma population remains controversial due to the limited published research. This study aimed to analyze 30-day survival of all the trauma ECMO patients at our center, with respect to injury severity score (ISS) and new injury severity score (NISS).MethodsWe performed a retrospective analysis of all trauma patients receiving ECMO support at a Level 1 trauma center in Sweden between 1997 and 2019.ResultsA total of 53 trauma patients received ECMO support. 85% were male; the median age was 24, with interquartile range (IQR) 17–44 years. More than 70% were multi-trauma patients. The mean NISS and ISS were 50 (IQR:34–57) and 42 (IQR:33–57), respectively. 62% were supported on veno-arterial ECMO with a survival benefit for veno-venous ECMO (75% vs. 36%, respectively (p = 0.01)). There was no association between severity in terms of trauma-score and survival. Sixteen patients (30%) were cannulated at referring hospitals and transported to our unit on ECMO with a survival of 69%, similar to those cannulated in-house. 60% of patients survived ECMO, and 51% survived to hospital discharge.ConclusionsThis study indicates that trauma patients may benefit from ECMO, independent of severity. Furthermore, our results support ECMO transport as feasible in trauma patients. We recommend larger multi-center studies to determine which trauma patients would have the greatest benefit of ECMO.