Significant Difference In 30-day Mortality Research Articles

Anisodamine hydrobromide in the treatment of critically ill patients with septic shock: a multicenter randomized controlled trial

Background Septic shock is the development of sepsis to refractory circulatory collapse and metabolic derangements, characterized by persistent hypotension and increased lactate levels. Anisodamine hydrobromide (Ani HBr) is a Chinese medicine used to improve blood flow in circulatory disorders. The purpose of this study was to determine the therapeutic efficacy of Ani HBr in the treatment of patients with septic shock. Methods This was a prospective, multicenter, randomized controlled trial focusing on patients with septic shock in 16 hospitals in China. Patients were randomly assigned in a 1:1 ratio to either the treatment group or the control group. The primary endpoint was 28-day mortality. The secondary outcomes included 7-day mortality, hospital mortality, hospital length of stay, vasopressor-free days within 7 days, etc. These indicators were measured and collected at 0, 6h, 24h, 48h, 72h and 7d after the diagnosis. Results Between September 2017 and March 2021, 404 subjects were enrolled. 203 subjects received Ani HBr and 201 subjects were assigned to the control group. The treated group showed lower 28-day mortality than the control group. Stratified analysis further showed significant differences in 28-day mortality between the two groups for patients with a high level of illness severity. We also observed significant differences in 7-day mortality, hospital mortality and some other clinical indicators between the two groups. Conclusion Ani HBr might be an important adjuvant to conventional treatment to reduce 28-day mortality in patients with septic shock. A large-scale prospective randomized multicenter trial is warranted to confirm our results.

Mortality and length of hospital stay after bloodstream infections caused by ESBL-producing compared to non-ESBL-producing E. coli

Objective To compare mortality and length of hospital stay between patients with ESBL-producing E. coli bloodstream infections (BSIs) and patients with non-ESBL E. coli BSIs. We also aimed at describing risk factors for ESBL-producing E. coli BSIs and time to effective antibiotic treatment for the two groups. Methods A retrospective case-control study among adults admitted between 2014 and 2021 to a Norwegian University Hospital. Results A total of 468 E. coli BSI episodes from 441 patients were included (234 BSIs each in the ESBL- and non-ESBL group). Among the ESBL-producing E. coli BSIs, 10.9% (25/230) deaths occurred within 30 days compared to 9.0% (21/234) in the non-ESBL group. The adjusted 30-day mortality OR was 1.6 (95% CI 0.7–3.7, p = 0.248). Effective antibiotic treatment was administered within 24 hours to 55.2% (129/234) in the ESBL-group compared to 86.8% (203/234) in the non-ESBL group. Among BSIs of urinary tract origin (n = 317), the median length of hospital stay increased by two days in the ESBL group (six versus four days, p < 0.001). No significant difference in the length of hospital stay was found for other sources of infection (n = 151), with a median of seven versus six days (p = 0.550) in the ESBL- and non-ESBL groups, respectively. Conclusion There was no statistically significant difference in 30-day mortality in ESBL-producing E. coli compared to non-ESBL E. coli BSI, despite a delay in the administration of an effective antibiotic in the former group. ESBL-production was associated with an increased length of stay in BSIs of urinary tract origin.

Is hepatectomy feasible for hepatocellular carcinoma patients with clinically significant portal hypertension and beyond the Milan criteria?

BackgroundHepatocellular carcinoma (HCC) patients with clinically significant portal hypertension (CSPH) and beyond the Milan criteria undergoing hepatectomy were previously considered to be at high risk and to have a poor prognosis, especially for major hepatectomy. The aim of this study was to investigate the safety and efficacy of hepatectomy in those patients. MethodsData were collected on HCC patients with CSPH treated at a single centre from January 2010 to October 2021. Propensity score-matched (PSM) analysis was used to balance the bias between groups. ResultsOf the included patients, 556 underwent hepatectomy and 172 underwent transcatheter arterial chemoembolization (TACE). Comparison of patients beyond the Milan criteria and those with Milan criteria underwent hepatectomy, the 90-day mortality and complication rates were similar in the two groups. However, the overall survival (OS) and recurrence-free survival (RFS) of patients within the Milan criteria were significantly better than those beyond the Milan criteria (p < 0.001). In HCC patients beyond the Milan criteria, OS of performing hepatectomy was significantly longer than TACE (p < 0.001). Within HCC patients beyond the Milan criteria underwent hepatectomy, there was no significant difference in 90-day mortality and complications between minor and major hepatectomy in patients beyond the Milan criteria and no significant difference in RFS and OS after PSM. ConclusionsHepatectomy for HCC patients with CSPH and beyond the Milan criteria is safe and feasible, with an acceptable prognosis and no significant difference between minor and major hepatectomy.

Effect of closed incision negative pressure wound treatment in vascular surgery: A meta-analysis.

The meta-analysis aimed to assess and compare the effect of closed-incision negative pressure wound (NPW) treatment in vascular surgery. Using dichotomous or contentious random or fixed effect models, the outcomes of this meta-analysis were examined, and the odds Ratio (OR) and the mean difference (MD) with 95% confidence intervals (CIs) were computed. Ten examinations from 2017 to 2022 were enrolled for the present meta-analysis, including 2082 personals with vascular surgery. Closed-incision NPW treatment had significantly lower infection rates (OR, 0.39; 95% CI, 0.30-0.51, p < 0.001), grade I infection rates (OR, 0.33; 95% CI, 0.20-0.52, p < 0.001), grade II infection rates (OR, 0.39; 95% CI, 0.21-0.71, p = 0.002), and grade III infection rates (OR, 0.31; 95% CI, 0.13-0.73, p = 0.007), and surgical re-intervention (OR, 0.49; 95% CI, 0.25-0.97, p = 0.04) compared to control in personal with vascular surgery. However, no significant differences were found between closed-incision NPW treatment and control in the 30-day mortality (OR, 0.54; 95% CI, 0.29-1.00, p = 0.05), antibiotic treatment (OR, 0.53; 95% CI, 0.24-1.19, p = 0.12), and length of hospital stay (MD, -0.02; 95% CI, -0.24-0.19, p = 0.83) in personnel with vascular surgery. The examined data revealed that closed-incision NPW treatment had significantly lower infection rates, grade I infection rates, grade II infection rates, and grade III infection rates, surgical re-intervention, however, there were no significant differences in 30-day mortality, antibiotic treatment, or length of hospital stay compared to control group with vascular surgery. Yet, attention should be paid to its values since some comparisons had a low number of selected studies.

Use of polymyxin B with different administration methods in the critically ill patients with ventilation associated pneumonia: a single-center experience.

Background: Whether nebulized polymyxin B should be used as an adjunctive therapy or substitution strategy to intravenous polymyxin B for the treatment of ventilator-associated pneumonia (VAP) remains controversial. This study's aim is to evaluate the efficacy and safety of different administration ways of polymyxin B in the treatment of ventilator-associated pneumonia caused by extensively drug-resistant Gram-negative bacteria(XDR-GNB). Methods: This retrospective cohort study enrolled ventilator-associated pneumonia patients caused by XDR-GNB treated with polymyxin B in the intensive care unit. Patients were categorized by the administration methods as intravenous (IV) group, inhaled (IH) group, and the intravenous combined with inhaled (IV + IH) group. Microbiological outcome and clinical outcome were compared in each group. The side effects were also explored. Results: A total of 111 patients were enrolled and there was no difference in demographic and clinical characteristics among the three groups. In terms of efficacy, clinical cure or improvement was achieved in 21 patients (55.3%) in the intravenous group, 19 patients (50%) in the IH group, and 20 patients (57.1%) in IV + IH group (p = 0.815). All three groups showed high success rates in microbiological eradication, as 29 patients with negative cultures after medication in inhaled group. Among all the patients who had negative bacterial cultures after polymyxin B, the inhaled group had significantly shorter clearance time than the intravenous group (p = 0.002), but with no significant difference in 28-day mortality. Compared with intravenous group, a trend towards a lower risk of acute kidney injury was observed in inhaled group (p = 0.025). Conclusion: From the perspective of minimal systemic renal toxicity, nebulized polymyxin B as a substitution strategy to intravenous polymyxin B for the treatment of ventilator-associated pneumonia caused by XDR-GNB is feasible.

Differences in Cholecystectomy Outcomes and Operating Time Between Male and Female Surgeons in Sweden

Female surgeons are still in the minority worldwide, and highlighting gender differences in surgery is important in understanding and reducing inequities within the surgical specialty. Studies on different surgical procedures indicate equal results, or safer outcomes, for female surgeons, but it is still unclear whether surgical outcomes of gallstone surgery differ between female and male surgeons. To examine the association of the surgeon's gender with surgical outcomes and operating time in elective and acute care cholecystectomies. A population-based cohort study based on data from the Swedish Registry of Gallstone Surgery was performed from January 1, 2006, to December 31, 2019. The sample included all registered patients undergoing cholecystectomy in Sweden during the study period. The follow-up time was 30 days. Data analysis was performed from September 1 to September 7, 2022, and updated March 24, 2023. The surgeon's gender. The association between the surgeon's gender and surgical outcomes for elective and acute care cholecystectomies was calculated with generalized estimating equations. Differences in operating time were calculated with mixed linear model analysis. A total of 150 509 patients, with 97 755 (64.9%) undergoing elective cholecystectomies and 52 754 (35.1%) undergoing acute care cholecystectomies, were operated on by 2553 surgeons, including 849 (33.3%) female surgeons and 1704 (67.7%) male surgeons. Female surgeons performed fewer cholecystectomies per year and were somewhat better represented at universities and private clinics. Patients operated on by male surgeons had more surgical complications (odds ratio [OR], 1.29; 95% CI, 1.19-1.40) and total complications (OR, 1.12; 95% CI, 1.06-1.19). Male surgeons had more bile duct injuries in elective surgery (OR, 1.69; 95% CI, 1.22-2.34), but no significant difference was apparent in acute care operations. Female surgeons had significantly longer operation times. Male surgeons converted to open surgery more often than female surgeons in acute care surgery (OR, 1.22; 95% CI, 1.04-1.43), and their patients had longer hospital stays (OR, 1.21; 95% CI, 1.11-1.31). No significant difference in 30-day mortality could be demonstrated. The results of this cohort study indicate that female surgeons have more favorable outcomes and operate more slowly than male surgeons in elective and acute care cholecystectomies. These findings may contribute to an increased understanding of gender differences within this surgical specialty.

FTP3.1 Impact of Covid-19 on Emergency Laparotomies due to Cancer

Abstract Aim To study the effect of the COVID-19 pandemic on the number of emergency laparotomies for bowel cancer. Methods Emergency laparotomies undertaken at St Peter’s Hospital (SPH) from August 2018 to August 2021 were identified. Pre-Covid era (PCE) was defined as August 2018 to January 2020; Covid-19 era (CE) was defined as February 2020 to August 2021. Electronic records were examined to identify the indication for surgery (cancer vs non cancer), length of stay and mortality. Patients undergoing multiple laparotomies in a single admission were only counted once. Results The total number of emergency laparotomies was 473 (PCE= 233, CE = 240). Emergency cancer laparotomy numbers in CE were significantly increased compared to PCE (68 vs. 44, p-value &amp;lt;0.05). CE emergency cancer laparotomy patients had a longer median length of stay. There was no significant difference in 30-day mortality (PCE 9 vs. CE 8 days). Conclusion There were an increased number of emergency laparotomies for cancer during CE. Possible causes include not presenting due to national lockdown and concerns regarding COVID-19. Further regional and nationwide data needs to be studied to establish whether this finding has been replicated on a wider scale or whether it is a local issue. Further analysis of data to determine the TNM staging will be useful to see the level of disease pathology.

Low-Dose vs Conventional-Dose Trimethoprim-Sulfamethoxazole Treatment for Pneumocystis Pneumonia in Patients Not Infected With HIV: A Multicenter, Retrospective Observational Cohort Study

Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV infection; however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared with conventional-dose TMP-SMX after adjusting for patient background characteristics? In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-dose (TMP< 12.5mg/kg/d) and conventional-dose (TMP 12.5-20mg/kg/d) groups. The primary end point was 30-day mortality, and the secondary end points were 180-day mortality, adverse events grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates. Background characteristics were adjusted using the overlap weighting method with propensity scores. Fifty-five patients in the low-dose group and 81 in the conventional-dose group were evaluated. In the overall cohort, the average age was 70.7 years, and the proportion of women was 55.1%. The average dose of TMP-SMX was 8.71mg/kg/d in the low-dose group and 17.78mg/kg/d in the conventional-dose group. There was no significant difference in 30-day mortality (6.7%vs18.4%, respectively; P= .080) or 180-day mortality (14.6%vs26.1%, respectively; P= .141) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (29.8%vs59.0%, respectively; P= .005). The initial treatment completion rates were 43.3%and 29.6%in the low-dose and conventional-dose groups (P= .158), respectively. Survival was similar between the low-dose and conventional-dose TMP-SMX groups, and low-dose TMP-SMX was associated with reduced adverse events in patients with non-HIV PCP.

Mini-Aortic Valve Replacement versus Transcatheter Aortic Valve Implantation: A Propensity-Matched Study

Background. Total sternotomy for aortic valve replacement has been superseded by less invasive approaches such as mini-sternotomy or transcatheter procedures. There has been an exponential uptake in transcatheter aortic valve implantation (TAVI) in younger and lower risk patients following recent randomized trials. This study aims to compare the outcomes of patients with aortic stenosis treated with minimally invasive approaches: mini-sternotomy for aortic valve replacement (mini-AVR) and TAVI implantation. Methods. Between January 2015 and December 2021, a total of 1437 TAVI and 176 mini-AVR patients from 2 tertiary centers fulfilled the criteria and were included in the propensity matching model. Results. A total of 256 TAVIs and 146 mini-AVR were included in the matched cohort. There was no significant difference in 30-day mortality in the two groups (TAVI vs. mini-AVR 2.7% vs. 2.8%, p = 0.935 ). TAVI confers slightly lower gradients in the follow-up echo when compared with mini-AVR (peak gradient 20 ± 8.7 mmHg vs. 24.5 ± 10 mmHg, p &lt; 0.001 ; mean gradient 10.9 ± 5.6 mmHg vs. 13.2 ± 5.7 mmHg, p &lt; 0.001 ). On the other hand, mini-AVR exhibits remarkably lower rates of paravalvular leak (mild leak 8% vs. 41.5%, p &lt; 0.001 ; moderate leak 2.8% vs. 0%, p &lt; 0.001 ) and of need for permanent pacemaker implantation (2% vs. 12.2%, p &lt; 0.001 ). Unsurprisingly, TAVI has lower in-hospital stay 3 (2 to 6) days vs. 10 (8 to 13) days, p &lt; 0.001 ). Conclusions. For eligible aortic stenosis patients in the 7th decade of life, mini-AVR remains an excellent therapeutic option.

Prehospital times and outcomes of patients transported using an ambulance trauma transport protocol: A data linkage analysis from New South Wales Australia

IntroductionPrehospital trauma systems are designed to ensure optimal survival from critical injuries by triaging and transporting such patients to the most appropriate hospital in a timely manner. ObjectivesWe sought to evaluate whether prehospital time and location (metropolitan versus non-metropolitan) were associated with 30-day mortality in a cohort of patients transported by road ambulance using a trauma transport protocol. MethodsData linkage analysis of routinely collected ambulance and hospital data across all public hospitals in New South Wales (NSW). The data linkage cohort included adult patients (age ≥ 16years) transported by NSW Ambulance, where a T1 Major Trauma Transport Protocol was documented by paramedic crews and transported by road to a public hospital emergency department in NSW for two years between January 2019 and December 2020. The outcomes of interest were prehospital times (response time, scene time and transport time) and 30-day mortality due to injury. Results9012 cases were identified who were transported to an emergency department with T1 protocol indication. Median prehospital transport times were longer in non-metropolitan road transports [n = 3,071, 98 min (71–126)] compared to metropolitan transports [n = 5,941, 65 min (53–80), p < 0.001]. There was no significant difference in 30-day mortality between the two groups (1.24% vs 1.65%, p = 0.13). In the subgroup of patients with abnormal vital signs, the only predictors of mortality were increasing age, presence of severe injury (OR 24.87, 95%CI 11.02, 56.15, p < 0.001), and arrival at a non-trauma facility (OR 3.01, 95%CI 1.26, 7.20, p < 0.05). Increasing transport times were not found to increase the odds of 30-day mortality. DiscussionIn the context of an inclusive trauma system and an established prehospital major trauma protocol, increasing prehospital transport times and scene location were not associated with increased mortality.

Prognostic implication of downregulated exosomal miRNAs in patients with sepsis: a cross-sectional study with bioinformatics analysis

BackgroundDespite the understanding of sepsis-induced extracellular vesicles (EVs), such as exosomes, and their role in intercellular communication during sepsis, little is known about EV contents such as microRNA (miRNA), which modulate important cellular processes contributing to sepsis in body fluids. This study aimed to analyze the differential expression of exosomal miRNAs in plasma samples collected from sepsis patients and healthy controls, and to identify potential miRNA regulatory pathways contributing to sepsis pathogenesis.MethodsQuantitative real-time PCR-based microarrays were used to profile plasma exosomal miRNA expression levels in 135 patients with sepsis and 11 healthy controls from an ongoing prospective registry of critically ill adult patients admitted to the intensive care unit. The identified exosomal miRNAs were tested in an external validation cohort (35 sepsis patients and 10 healthy controls). And then, functional enrichment analyses of gene ontology, KEGG pathway analysis, and protein–protein interaction network and cluster analyses were performed based on the potential target genes of the grouped miRNAs. Finally, to evaluate the performance of the identified exosomal miRNAs in predicting in-hospital and 90-day mortalities of sepsis patients, receiver operating characteristic curve (ROC) and Kaplan–Meier analyses were performed.ResultsCompared with healthy controls, plasma exosomes from sepsis patients showed significant changes in 25 miRNAs; eight miRNAs were upregulated and 17 downregulated. Additionally, the levels of hsa-let-7f-5p, miR-331-3p miR-301a-3p, and miR-335-5p were significantly lower in sepsis patients than in healthy controls (p < 0.0001). These four miRNAs were confirmed in an external validation cohort. In addition, the most common pathway for these four miRNAs were PI3K-Akt and mitogen-activated protein kinase (MAPK) signaling pathways based on the KEGG analysis. The area under the ROC of hsa-let-7f-5p, miR-331-3p, miR-301a-3p, and miR-335-5p level for in-hospital mortality was 0.913, 0.931, 0.929, and 0.957, respectively (p < 0.001), as confirmed in an external validation cohort. Also, the Kaplan–Meier analysis showed a significant difference in 90-day mortality between sepsis patients with high and low miR-335-5p, miR-301a-3p, hsa-let-7f-5p, and miR-331-3p levels (p < 0.001, log-rank test).ConclusionAmong the differentially-expressed miRNAs detected in microarrays, the top four downregulated exosomal miRNAs (hsa-let-7f-5p, miR-331-3p miR-301a-3p, and miR-335-5p) were identified as independent prognostic factors for in-hospital and 90-day mortalities among sepsis patients. Bioinformatics analysis demonstrated that these four microRNAs might provide a significant contribution to sepsis pathogenesis through PI3K-Akt and MAPK signaling pathway.

The Impact of COVID-19 on the Epidemiology and Outcomes of Candidemia: A Retrospective Study from a Tertiary Care Center in Lebanon.

Invasive fungal infections, notably candidemia, have been associated with COVID-19. The epidemiology of candidemia has significantly changed during the COVID-19 pandemic. We aim to identify the microbiological profile, resistance rates, and outcomes of COVID-19-associated candidemia (CAC) compared to patients with candidemia not associated with COVID-19. We retrospectively collected data on patients with candidemia admitted to the American University of Beirut Medical Center between 2004 and 2022. We compared the epidemiology of candidemia during and prior to the COVID-19 pandemic. Additionally, we compared the outcomes of critically ill patients with CAC to those with candidemia without COVID-19 from March 2020 till March 2022. Among 245 candidemia episodes, 156 occurred prior to the pandemic and 89 during the pandemic. Of the latter, 39 (43.8%) were CAC, most of which (82%) were reported from intensive care units (ICU). Non-albicans Candida (NAC) spp. were predominant throughout the study period (67.7%). Candida auris infection was the most common cause of NAC spp. in CAC. C. glabrata had decreased susceptibility rates to fluconazole and caspofungin during the pandemic period (46.1% and 38.4%, respectively). The mortality rate in the overall ICU population during the pandemic was 76.6%, much higher than the previously reported candidemia mortality rate observed in studies involving ICU patients. There was no significant difference in 30-day mortality between CAC and non-CAC (75.0% vs. 78.1%; p = 0.76). Performing ophthalmic examination (p = 0.002), CVC removal during the 48 h following the candidemia (p = 0.008) and speciation (p = 0.028) were significantly associated with a lower case-fatality rate. The epidemiology of candidemia has been significantly affected by the COVID-19 pandemic at our center. Rigorous infection control measures and proper antifungal stewardship are essential to combat highly resistant species such as C. auris.

Impact of the SARS-CoV-2 Pandemic on Treatment Pathways and Outcomes of Esophagogastric Cancer: A Pre- Versus Post-Pandemic Comparison of International Prospective Cohort Data

Introduction: This study aimed to characterize the outcomes of esophagogastric (OG) cancer patients and compare perioperative outcomes with pre-pandemic data. Methods: Three international prospective cohort studies were included in this analysis. First, COVIDSurg-Cancer (n = 1999) included patients with an OG cancer planned for surgery from the start of the pandemic up to 14th April 2020 with follow-up until 31st August 2020. Treatment pathways and outcomes were compared against patients undergoing treatment for OG cancers before the pandemic, Oesophagogastric Anastomosis Audit (OGAA, n = 2246) and GlobalSurg 3 (n = 1256) study. The surgical composite outcome was defined as in patients achieving margin negative resection, resectability and no postoperative mortality. Results: This study included 1999 patients during the COVID-19 pandemic, of which 32.4% had a change from standard pre-pandemic management. Patients with delay to surgery had significantly higher rates of no surgery (24.7%vs 7.5%, P &lt; .001) and less likely to have achieve a composite outcome (57.8%vs 73.4%, P &lt; .001) than those without any delay in surgery. There was no significant difference in 30-day mortality (3.5% vs 3.4%; OR: 0.98, CI95%: 0.69-1.37) or anastomotic leak rate (10.9% vs 10.2%%; OR: 1.11, CI95%: 0.90-1.37) but higher reoperation rates (13.6% vs 10.4%; OR: 1.59, CI95%: 1.30-1.92) in patients between pre-pandemic and pandemic cohorts. Conclusion: The pandemic appears to have led to widespread changes in management pathways affecting one-third of patients. Developing elective surgical pathways resilient to periods of system “stress” are key to minimizing future harm from treatment delay for OG cancer patients.

Cefiderocol-containing regimens for the treatment of carbapenem-resistant A. baumannii ventilator-associated pneumonia: a propensity-weighted cohort study.

Cefiderocol is a novel β-lactam with activity against carbapenem-resistant Acinetobacter baumannii (CRAB), but its role in CRAB pulmonary infections is controversial due to limited evidence. To assess the association between cefiderocol-containing regimens treatment and 28-day mortality in carbapenem-resistant A. baumannii ventilator-associated pneumonia (VAP). An observational cohort study including critically ill COVID-19 patients with CRAB-VAP admitted to two ICUs of a large academic hospital in Rome between September 2020 and December 2022. The primary outcome was 28-day all-cause mortality. A propensity score was created to balance the cefiderocol- and non-cefiderocol-containing groups. A propensity-weighted multiple logistic regression model was calculated to evaluate risk factors for 28-day mortality. Survival curves were calculated using the Kaplan-Meier method. 121 patients were enrolled, 55 were treated with cefiderocol- and 66 with non-cefiderocol-containing regimens. The 28-day all-cause mortality was 56% (68/121). A statistically significant difference in 28-day mortality was found between cefiderocol- and non-cefiderocol- containing regimens groups (44% versus 67%, P = 0.011). In the propensity-adjusted multiple logistic regression, cefiderocol (OR 0.35 95% CI 0.14, 0.83) was a predictor of 28-day survival, Charlson comorbidity index (OR 1.36 95% CI 1.16, 1.78), SOFA score (OR 1.24 95% CI 1.09, 1.57) and septic shock (OR 3.71 95% CI 1.44, 12.73) were all associated with increased 28-day mortality. Cefiderocol-containing regimens were associated with reduced 28-day mortality in CRAB-VAP. The sample size and the observational design limit the study's conclusions. Future RCTs are needed to establish cefiderocol's definite role in these infections.

#3153 HEMOPERFUSION WITH CYTOSORB AND RENAL REPLACEMENT THERAPY IN PATIENTS WITH ACUTE KIDNEY INJURY IN THE INTENSIVE CARE UNIT

Abstract Background and Aims Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious clinical disorder in the intensive care unit (ICU), occurring in a substantial proportion of critically ill patients. The aim of our single centre retrospective observational study was to analyse the outcomes of patients admitted to a non-surgical ICU and treated with RRT and with/without continuous hemoperfusion with Cytosorb. Method One hundred critically ill patients (mean age, 64.3 years; 69 men) admitted to the ICU and requiring RRT for AKI were analysed. Patient demographics, concomitant diseases, type of RRT, and survival were obtained from the medical record. APACHE II and Sofa Scores on admission were calculated. 30-day mortality was assessed using Kaplan-Meyer or Cox proportional hazards models. Results Reasons for ICU admission were acute respiratory failure (39%), cardiopulmonary resuscitation (14%), shock (13%), acute coronary syndrome (9%), sepsis (3%), acute pancreatitis (3%), and other (19%). Prior comorbidities were hypertension (70%), diabetes (43%), heart failure (32%), chronic kidney disease (CKD) (30%), coronary artery disease (CAD) (27%), chronic obstructive pulmonary disease (COPD) (15%), malignancies (12%). Eighty-six patients were treated with continuous RRT (CRRT) and 14 with intermittent hemodialysis (IHD). Twenty-four (24%) of patients treated with CRRT were also treated with hemoperfusion with Cytosorb. Using an independent-samples T test, we compared the two groups of patients with respect to the use of Cytosorb (Table 1). 30-day mortality was 82% in all patients and 87.5% in patients treated with CRRT and Cytosorb. Among concomitant diseases, only patients with previous heart failure had worse survival (p = 0.032), previous CKD, CAD, COPD, malignancy had no statistically significant impact. We found no statistically significant differences in 30-day mortality between patients treated with CRRT+Cytosorb and patients treated with CRRT or IHD alone. Multivariate Cox proportional hazard regression showed that of all the variables in the statistical model (age, sex, body mass index, previous diabetes, C-reactive protein, lactate, procalcitonin, serum creatinine, mean arterial pressure, APACHE II, ultrafiltration between CRRT), only lactate levels on admission (p = 0.002; 95%CI 1.08-1.38) were significant predictor of survival. Conclusion The use of hemoperfusion with Cytosorb in ICU patients with AKI did not reduce 30-day mortality. Patients with prior heart failure had a worse outcome. Serum lactate levels at ICU admission were an independent highly prognostic factor for death within 30 days of admission.

#2808 REMDESIVIR FOR MODERATE-TO-SEVERE COVID-19 PNEUMONIA IN MAINTENANCE DIALYSIS PATIENTS: A RETROSPECTIVE COHORT STUDY

Abstract Background and Aims Remdesivir has shown better patient outcomes and shorter time to recovery among hospitalized patients with moderate to severe COVID-19 pneumonia. However, data on its safety and efficacy in dialysis patients is lacking. Method Dialysis patients with moderate to severe COVID-19 pneumonia who were given remdesivir were matched 1:2 to those who received standard-of-care (SOC) based on age, sex, COVID-19 severity and CKD etiology. Results The final cohort comprised 201 patients and 67 were given remdesivir. Median age was 52 years, majority were male (51.7%), 94% were on hemodialysis (94%) and 48% had diabetic nephropathy. The 28-day probability of survival among moderate COVID-19 cases was 100% for both remdesivir and SOC group. In severe cases, the survival probability for remdesivir recipients was lower compared to SOC (67.63% vs 87.72%), but this was not statistically significant. Overall, median length of stay (LOS) was significantly shorter by 17 days (QR: 11-24) in the remdesivir group, compared to 21 days [IQR: 16-24] in the SOC group (p = 0.0485). Median LOS in the remdesivir group was only significantly shorter in those with moderate COVID-19 pneumonia but not in severe cases. Early administration of remdesivir resulted in a significantly shorter LOS with a median of 10 days [IQR: 7-15] compared to18 days [IQR: 13-25] in the SOC group (p = 0.0240). When stratified by severity, there was no significant difference whether remdesivir was given early or late. Conclusion Remdesivir administration within 48 hours of admission in maintenance dialysis patients with moderate COVID-19 pneumonia resulted in a significantly shorter LOS. However, there was no significant difference in 28-day mortality in early or late administration of remdesivir in both moderate and severe COVID-19 pneumonia among HD patients. Thus, survival was similar to SOC. Our study showed that it is safe to use in dialysis patients.

Vitamin C in critical illness: end of the story or still a place?

Critical illness is associated with decreased micronutrient levels, including vitamin C, an essential antioxidant for systemic inflammation. This review discusses the most recent evidence of high-dose vitamin C monotherapy in critically ill adults. Three randomized-controlled trials (RCTs) were published in 2022. A pilot study including 40 patients with septic shock could not detect significant differences in outcome parameters after administering vitamin C. A multicenter study with 124 septic patients showed no significant difference in 28-day mortality, while vitamin C was associated with an increased risk of acute kidney dysfunction. The LOVIT trial, an international prospective RCT in 872 septic patients, revealed an increased risk of the composite endpoint persistent organ dysfunction plus death at day 28 in the high-dose vitamin C group. Six systematic reviews and meta-analyses (SRMA), including up to 4740 patients published before and 2 SRMA publications including these RCTs showed divergent results on clinical endpoints including mortality. The use of high-dose intravenous vitamin C cannot be recommended for the septic critically ill in clinical practice since the LOVIT trial. Further research is needed to evaluate its potential role in other critically ill patients.

Treatment patterns and outcomes of diffuse alveolar hemorrhage: Findings from a single-center retrospective study.

e19063 Background: Diffuse alveolar hemorrhage (DAH) is a life-threatening complication seen in patients with malignancy most commonly after a hematopoietic stem cell transplant (HSCT). Systemic therapy with corticosteroids to reduce inflammation and control bleeding is the mainstay of treatment for DAH, however ideal dosing strategies are not known. Methods: This single-center, retrospective study reviewed patients presenting to Roswell Park Comprehensive Cancer Center (RPCCC) from January 2010 through November 2022. Patients were included in this review if they were &gt;18 years and were actively treated at RPCCC for presumed or definite DAH. The bone marrow transplant database, ICD-9, and ICD-10 codes were used to screen patients for inclusion. Upon meeting inclusion criteria, patients were stratified based on daily methylprednisolone dosing equivalents [low-dose: &lt; 250 mg, intermediate-dose: &gt;250 mg or &lt; 1000 mg, high-dose: &gt;1000 mg, or no steroid]. The primary endpoint was 30-day mortality. Secondary endpoints included ICU mortality, ICU length of stay (LOS), overall LOS, hemorrhage recurrence, steroid complications, and utilization of other DAH treatments. Steroid complications, including hyperglycemia, infection, and uremia were evaluated as safety endpoints. Results: Thirty-seven patients met inclusion criteria; 23 HSCT and 14 non-transplant patients. Analysis included 20 patients in the low-dose, 2 patients in the intermediate-dose, 12 patients in the high-dose, and 3 patients in the no steroid group. The median duration of steroids was 15, 4, and 14 days in the low, intermediate, and high groups, respectively. There was no statistically significant difference in 30-day mortality across treatment groups (p = 0.76). The overall 30-day mortality rate was 24.3%, with 25%, 50%, and 17% in the low, intermediate, and high-dose groups, respectively. A 30-day mortality rate of 33% was seen in patients who did not receive steroids. Hemorrhage recurrence occurred in 9 patients (24.3%), most commonly in the high-dose treatment group. Utilization of additional agents including aminocaproic acid, etanercept, and inhaled factor VIIa was most common in the intermediate-dose group. Conclusions: Despite variable steroid dosing, 30-day mortality was not found to be statistically significant among patients treated for DAH. Based on our findings of similar efficacy between dosing strategies, yet increased rates of steroid complications and hemorrhage recurrence in the high-dose group, lower steroid doses for the treatment of DAH can be considered. [Table: see text]

Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure

Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n= 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n= 30). There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p= 0.018) and CLIF-C ACLF scores (p= 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p= 0.036). Biomarkers of systemic inflammation such as IL-8 (p= 0.006), cell death [cytokeratin-18: M30 (p= 0.005) and M65 (p= 0.029)], endothelial function [asymmetric dimethylarginine (p= 0.002)] and, ligands for Toll-like receptor 4 (p= 0.030) and inflammasome (p= 0.002) improved significantly in the DIALIVE group. These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. NCT03065699.

The Impact of Midodrine Tapering Versus Nontapering Regimens on the Clinical Outcomes of Critically Ill Patients: A Retrospective Cohort Study.

Midodrine has been used in the intensive care unit (ICU) setting to reduce the time to vasopressor discontinuation. The limited data supporting midodrine use have led to variability in the pattern of initiation and discontinuation of midodrine. To compare the effectiveness and safety of 2 midodrine discontinuation regimens during weaning vasopressors in critically ill patients. A retrospective cohort study was conducted at King Abdulaziz Medical City. Included patients were adults admitted to ICU who received midodrine after being unable to be weaned from intravenous vasopressors for more than 24 hours. Patients were categorized into two subgroups depending on the pattern of midodrine discontinuation (tapered dosing regimen vs. nontapered regimen). The primary endpoint was the incidence of inotropes and vasopressors re-initiation after midodrine discontinuation. The incidence of inotropes or vasopressors' re-initiation after discontinuation of midodrine was lower in the tapering group (15.4%) compared with the non-tapering group (40.7%) in the crude analysis as well as regression analysis (odd ratio [OR] = 0.15; 95% CI = 0.03, 0.73, P = 0.02). The time required for the antihypertensive medication(s) initiation after midodrine discontinuation was longer in patients who had dose tapering (beta coefficient (95% CI): 3.11 (0.95, 5.28), P = 0.005). Moreover, inotrope or vasopressor requirement was lower 24 hours post midodrine initiation. In contrast, the two groups had no statistically significant differences in 30-day mortality, in-hospital mortality, or ICU length of stay. These real-life data showed that tapering midodrine dosage before discontinuation in critically ill patients during weaning from vasopressor aids in reducing the frequency of inotrope or vasopressor re-initiation. Application of such a strategy might be a reasonable approach among ICU patients unless contraindicated.