Interim-analysis of the COSA (COVID-19 patients treated with the Seraph® 100 Microbind® Affinity filter) registry

Abstract Background The Seraph®100 Microbind Affinity Blood Filter® is a hemoperfusion device that is licensed for the reduction of pathogens, including several viruses, in the blood. It received Emergency Use Authorization (EUA) for the treatment of severe coronavirus disease 2019 (COVID-19) by the FDA. Several studies have shown that the blood viral load of SARS-CoV-2 correlates with adverse outcomes and removal of the nucleocapsid of the SARS-CoV-2 virus by the Seraph®100 has been recently demonstrated. The aim of this registry was to evaluate safety and efficacy of Seraph®100 treatment for COVID-19 patients. Methods Twelve hospitals from six countries representing two continents documented patient and treatment characteristics as well as outcome parameters without reimbursement. Additionally, mortality and safety results of the device were reported. One hundred-and-two treatment sessions in 82 patients were documented in the registry. Four patients were excluded from mortality analysis due to incomplete outcome data, which were available in the other 78 patients. Results Overall, a 30-day mortality rate of 46.2% in the 78 patients with complete follow up was reported. Median treatment time was 5.00 [4.00–13.42] h. and 43.1% of the treatments were performed as hemoperfusion only. Adverse events of the Seraph®100 treatment were reported in 8.8% of the 102 treatments and represented premature end of treatment due to circuit failure. Patients that died were treated later in their ICU stay and onset of COVID symptoms. They also had higher ferritin levels. Multivariate Cox regression revealed that delayed Seraph®100 treatment after ICU admission (>60 hours) as well as bacterial superinfection were associated with mortality. While average predicted mortality rate according to SOFA score in ICU patients was 56.7% the observed mortality was 50.7%. In non-ICU patients 4C-Score average predicted a mortality rate of 38.0% while the observed mortality rate was 11.1% Conclusions The treatment of COVID-19 patients with Seraph®100 is well tolerated and the circuit failure rate was lower than previously reported for KRT in COVID-19 patients. Mortality corelated with late initiation of Seraph treatment after ICU admission and bacterial superinfection infection. Compared to predicted mortality according to 4C-Score and SOFA Score, mortality of Seraph®100 treated patients reported in the registry was lower.

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Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study

Annals of Intensive Care ◽

10.1186/s13613-020-00652-0 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Rene A. Posma ◽

Trine Frøslev ◽

Bente Jespersen ◽

Iwan C. C. van der Horst ◽

Daan J. Touw ◽

...

Keyword(s):

Cohort Study ◽

Mortality Rate ◽

Critically Ill ◽

Critically Ill Patients ◽

Cox Regression ◽

Lower Mortality ◽

Prognostic Impact ◽

Icu Admission ◽

Lactate Levels ◽

Restricted Cubic Splines

Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.

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Comparison of Cefepime-Cefpirome and Carbapenem Therapy for Acinetobacter Bloodstream Infection in a Multicenter Study

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02392-19 ◽

2020 ◽

Vol 64 (6) ◽

Author(s):

Yea-Yuan Chang ◽

Ya-Sung Yang ◽

Shang-Liang Wu ◽

Yung-Chih Wang ◽

Te-Li Chen ◽

...

Keyword(s):

Mortality Rate ◽

Bloodstream Infection ◽

Antimicrobial Therapy ◽

Sofa Score ◽

Cox Regression ◽

Content Type ◽

Cox Regression Analysis ◽

Medical Centers ◽

Acinetobacter Pittii ◽

Underlying Diseases

ABSTRACT Carbapenems are currently the preferred agents for the treatment of serious Acinetobacter infections. However, whether cefepime-cefpirome can be used to treat an Acinetobacter bloodstream infection (BSI) if it is active against the causative pathogen(s) is not clear. This study aimed to compare the efficacy of cefepime-cefpirome and carbapenem monotherapy in patients with Acinetobacter BSI. The population included 360 patients with monomicrobial Acinetobacter BSI receiving appropriate antimicrobial therapy admitted to four medical centers in Taiwan in 2012 to 2017. The predictors of 30-day mortality were determined by Cox regression analysis. The overall 30-day mortality rate in the appropriate antibiotic treatment group was 25.0% (90/360 patients). The crude 30-day mortality rates for cefepime-cefpirome and carbapenem therapy were 11.5% (7/61 patients) and 26.3% (21/80 patients), respectively. The patients receiving cefepime-cefpirome or carbapenem therapy were infected by Acinetobacter nosocomialis (51.8%), Acinetobacter baumannii (18.4%), and Acinetobacter pittii (12.1%). After adjusting for age, Sequential Organ Failure Assessment (SOFA) score, invasive procedures, and underlying diseases, cefepime-cefpirome therapy was not independently associated with a higher or lower 30-day mortality rate compared to that with the carbapenem therapy. SOFA score (hazard ratio [HR], 1.324; 95% confidence interval [CI], 1.137 to 1.543; P < 0.001) and neutropenia (HR, 7.060; 95% CI, 1.607 to 31.019; P = 0.010) were independent risk factors for 30-day mortality of patients receiving cefepime-cefpirome or carbapenem monotherapy. The incidence densities of 30-day mortality for cefepime-cefpirome versus carbapenem therapy were 0.40% versus 1.04%, respectively. The therapeutic response of cefepime-cefpirome therapy was comparable to that with carbapenems among patients with Acinetobacter BSI receiving appropriate antimicrobial therapy.

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Influence of Chemotherapy Within 30 Days Before ICU Admission on Mortality in Critically Ill Medical Patients With Cancer

Journal of Intensive Care Medicine ◽

10.1177/0885066617711894 ◽

2017 ◽

Vol 34 (9) ◽

pp. 732-739

Author(s):

Ricardo Calderón-Pelayo ◽

Pilar León ◽

Pablo Monedero ◽

Pilar Calderón-Breñosa ◽

Marc Vives ◽

...

Keyword(s):

Multivariate Analysis ◽

Mortality Rate ◽

Organ Failure ◽

Cox Regression ◽

Group Versus ◽

Rank Test ◽

Control Group ◽

Medical Patients ◽

Icu Admission ◽

Patients With Cancer

Background: The main objective was to determine whether the administration of chemotherapy (CT) during the month before intensive care unit (ICU) admission of medical patients with cancer influences the survival rate. The design was a single-institution observational cohort study in an ICU of a tertiary university hospital. Methods: Our cohort included 248 oncology patients admitted to the ICU from 2005 to 2014 due to nonsurgical problems. Seventy-six (30.6%) patients had received CT in the month before admission (CT group) and 172 did not receive CT (control group). The main outcome measures were ICU, hospital, 30-day, 90-day, and 1-year mortalities. We performed survival analysis using the Kaplan-Meier estimator, comparing both groups using the log-rank test, and multivariate analysis using Cox regression adjusted for gender, age, maximum Sequential Organ Failure Assessment (SOFA), and delta maximum SOFA to calculate the hazard ratios (HRs) and their respective 95% confidence intervals. This association was also evaluated by a graphic representation of survival. Results: The CT group presented an ICU mortality rate of 27.6% versus 25.5% in the control group. The multivariate analysis adjusted for age, sex, and delta maximum SOFA showed significant differences between the groups (HR: 2.12; P = .009). The hospital mortality rate was 55.3% in the CT group compared to 45.4% in the control group (adjusted HR: 1.81; P = .003). At 30 days, the mortality rate was 56.6% in the CT group compared to 46.5% in the control group (adjusted HR: 1.69; P = .008). Mortality at 90 days was 65.8% in the CT group versus 59.9% in the control group (adjusted HR: 1.47; P = .03). One-year mortality was also higher in the CT group (79% vs 72.7%, adjusted HR: 1.44; P = .02). Conclusion: The administration of CT in the month before ICU admission in patients with cancer was associated with higher mortality in the ICU, in the hospital, and 30 and 90 days after admission when adjusted for the increase in organ failure measured by delta maximum SOFA. We provide useful new information for decision-making about ICU management of patients with cancer.

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Antibiotic Pressure Is a Major Risk Factor for Rectal Colonization by Multidrug-Resistant Pseudomonas aeruginosa in Critically Ill Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03419-14 ◽

2014 ◽

Vol 58 (10) ◽

pp. 5863-5870 ◽

Cited By ~ 32

Author(s):

Silvia Gómez-Zorrilla ◽

Mariana Camoez ◽

Fe Tubau ◽

Elisabet Periche ◽

Rosario Cañizares ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Cox Regression ◽

Multidrug Resistant ◽

Intestinal Colonization ◽

Icu Patients ◽

Content Type ◽

Cox Regression Analysis ◽

Icu Admission ◽

Rectal Colonization ◽

The Impact

ABSTRACTThe intestinal reservoir is central to the epidemiology ofPseudomonas aeruginosa, but the dynamics of intestinal colonization by different phenotypes have been poorly described. To determine the impact of antimicrobial exposure on intestinal colonization by multidrug-resistant (MDR) and extensively drug-resistant (XDR)P. aeruginosa, we screened intensive care unit (ICU) patients for rectal colonization on admission and at weekly intervals. During an 18-month study period, 414 ICU patients were enrolled, of whom 179 (43%) were colonized; 112 (63%) of these were identified at ICU admission and 67 (37%) during their ICU stay. At 10 days after ICU admission, the probabilities of carriage were 44%, 24%, and 24% for non-MDR, MDR-non-XDR, and XDRP. aeruginosastrains, respectively (log rank, 0.02). Pulsed-field gel electrophoresis showed 10 pairs of non-MDRP. aeruginosaand subsequent MDR-non-XDR strains isolated from the same patients to be clonally identical and another 13 pairs (8 MDR-non-XDR and 5 XDR) to be unrelated. There was one specific clone between the 8 MDR-non-XDR strains and an identical genotype in the 5 XDR isolates. The Cox regression analysis identified MDRP. aeruginosaacquisition as associated with the underlying disease severity (adjusted hazard ratio [aHR], 1.97; 95% confidence interval [CI], 1.22 to 3.18;P= 0.006) and prior use of fluoroquinolones (aHR, 1.02; 95% CI, 1.00 to 1.04;P= 0.039), group 2 carbapenems (aHR, 1.03; 95% CI, 1.00 to 1.07;P= 0.041), and ertapenem (aHR, 1.08; 95% CI, 1.02 to 1.14;P= 0.004). The epidemiology of MDRP. aeruginosais complex, and different clusters may coexist. Interestingly, ertapenem was found to be associated with the emergence of MDR isolates.

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Epidemiology, outcomes, and utilization of intensive care unit resources for critically ill COVID-19 patients in Libya: A prospective multi-center cohort study

PLoS ONE ◽

10.1371/journal.pone.0251085 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0251085

Author(s):

Muhammed Elhadi ◽

Ahmed Alsoufi ◽

Abdurraouf Abusalama ◽

Akram Alkaseek ◽

Saedah Abdeewi ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Mortality Rate ◽

Critically Ill ◽

Sofa Score ◽

Critically Ill Patients ◽

Univariate Analysis ◽

The Body ◽

Icu Admission ◽

Risk Of Mortality

Background The coronavirus disease (COVID-19) pandemic has severely affected African countries, specifically the countries, such as Libya, that are in constant conflict. Clinical and laboratory information, including mortality and associated risk factors in relation to hospital settings and available resources, about critically ill patients with COVID-19 in Africa is not available. This study aimed to determine the mortality and morbidity of COVID-19 patients in intensive care units (ICU) following 60 days after ICU admission, and explore the factors that influence in‐ICU mortality rate. Methods This is a multicenter prospective observational study among COVID-19 critical care patients in 11 ICUs in Libya from May 29th to December 30th 2020. Basic demographic data, clinical characteristics, laboratory values, admission Sequential Organ Failure Assessment (SOFA) score, quick SOFA, and clinical management were analyzed. Result We included 465 consecutive COVID-19 critically ill patients. The majority (67.1%) of the patients were older than 60 years, with a median (IQR) age of 69 (56.5–75); 240 (51.6%) were male. At 60 days of follow-up, 184 (39.6%) were discharged alive, while 281 (60.4%) died in the intensive care unit. The median (IQR) ICU length of stay was 7 days (4–10) and non-survivors had significantly shorter stay, 6 (3–10) days. The body mass index was 27.9 (24.1–31.6) kg/m2. At admission to the intensive care unit, quick SOFA median (IQR) score was 1 (1–2), whereas total SOFA score was 6 (4–7). In univariate analysis, the following parameters were significantly associated with increased/decreased hazard of mortality: increased age, BMI, white cell count, neutrophils, procalcitonin, cardiac troponin, C-reactive protein, ferritin, fibrinogen, prothrombin, and d-dimer levels were associated with higher risk of mortality. Decreased lymphocytes, and platelet count were associated with higher risk of mortality. Quick SOFA and total SOFA scores increase, emergency intubation, inotrope use, stress myocardiopathy, acute kidney injury, arrythmia, and seizure were associated with higher mortality. Conclusion Our study reported the highest mortality rate (60.4%) among critically ill patients with COVID-19 60 days post-ICU admission. Several factors were found to be predictive of mortality, which may help to identify patients at risk of mortality during the ongoing COVID-19 pandemic.

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Characteristics and prognosis of bloodstream infection in patients with COVID-19 admitted in the ICU: an ancillary study of the COVID-ICU study

Annals of Intensive Care ◽

10.1186/s13613-021-00971-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nicolas Massart ◽

Virginie Maxime ◽

Pierre Fillatre ◽

Keyvan Razazi ◽

Alexis Ferré ◽

...

Keyword(s):

Risk Factors ◽

Mortality Rate ◽

Propensity Score ◽

Risk Model ◽

Antiviral Drug ◽

Data Set ◽

Icu Patients ◽

Icu Admission ◽

Increased Risk ◽

Hospital Acquired

Abstract Background Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients. Patients and methods We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching. Results Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05–1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population. Conclusion COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate.

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Interim-analysis of the COSA (COVID-19 Patients Treated With the Seraph® 100 Microbind® Affinity Filter) Registry

10.21203/rs.3.rs-557453/v1 ◽

2021 ◽

Author(s):

Julius J. Schmidt ◽

Dan Nicolae Borchina ◽

Mariet van´t Klooster ◽

Khalida Soki ◽

Reuben Okioma ◽

...

Keyword(s):

Survival Rate ◽

Bacterial Infections ◽

Treatment Time ◽

Adverse Outcome ◽

Intermittent Hemodialysis ◽

Icu Patients ◽

Blood Filter ◽

Laboratory Markers ◽

Pathogen Reduction ◽

Bacterial Superinfection

Abstract Background: The Seraph®100 Microbind Affinity Blood Filter® is a hemofiltration device that is licensed for pathogen reduction in the blood. This includes several viruses. Removal of the nucleocapsid of the SARS-CoV-2 virus by the Seraph®100 has been recently demonstrated. As viral load has repeatedly been shown to correlate with adverse outcome in severe coronavirus disease 2019 (COVID-19), the aim of this registry was to evaluate safety and efficacy of Seraph®100 treatment for COVID-19.Methods: An online registry in which main patient charcteristics, treatment coordinates and outcome parameters was documented without reimbursement. So far 12 hospitals in 4 countries on 2 continents took part in the registry. 75 treatment sessions in 60 patients were documented in the registry. Results: Adverse effects of the Seraph® 100 treatment were reported in 2 (2.6 %) of the 75 treatments. Eight (10.6 %) of all the procedures ended prematurely due to circuit failure / clotting. Half of the treatments (47.6 %) were performed as hemoperfusion only. 21.6 % of the treatments were performed in conjuction with intermittent hemodialysis. Median treatment time was 4.21 [4.00 - 8.06] h. Anticoagulation was performed using citrate in 20.6 % of treatments. Patients that died despite treatment with the Seraph® 100 filter had a higher rate of bacterial superinfection, higher level of inflammatory laboratory markers (procalcitonin and ferritin) and higher d-dimer levels. While predicted survival rate in ICU patients was >80 %, the observed survival rate was 47.6 %. In non-ICU patients, 4 C score predicted a survival rate of 31.4-34.9 % while the observed survival rate was 22.2 %.Conclusion: Seraph® 100 treatment was well tolerated and circuit failure rate was significantly lower than reported for KRT in COVID-19 patients. All patients that died despite of Seraph® 100 treatment had serious pre-existing medical conditions, coexisting bacterial infections and more pronounced systemic signs of inflammation. Compared to the calculated mortality using established scores, the observed mortality in the Seraph® 100 treated patients was lower.Trial registration:ClinicalTrials.gov Identifier: NCT04361500

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Thoracic Skeletal Muscle Quantification Using Computed Tomography And Prognosis Of Elderly ICU Patients

10.21203/rs.3.rs-144315/v1 ◽

2021 ◽

Author(s):

Sung Woo Moon ◽

Song Yee Kim ◽

Ji Soo Choi ◽

Ah Young Leem ◽

Su Hwan Lee ◽

...

Keyword(s):

Computed Tomography ◽

Skeletal Muscle ◽

Muscle Mass ◽

Sofa Score ◽

Pectoralis Muscle ◽

Muscle Loss ◽

Icu Patients ◽

Icu Admission ◽

Prolonged Ventilation ◽

Skeletal Muscle Loss

Abstract Background: In elderly ICU patients, the prevalence of skeletal muscle loss is high. And the consequences of skeletal muscle loss can be severe in elderly. Correlations have been found between the muscle cross-sectional area (CSA) at a single thoracic level on chest computed tomography (CT). Correlation between thoracic muscle mass and mortality has been found in ICU patients. But longitudinal effect of thoracic muscles especially in elderly ICU patients are unclear although skeletal muscle loss is related with the short- and long-term outcomes. Objective: This study aimed to evaluate whether pectoralis muscle mass could be a predictor of prognosis in elderly ICU patients.Methods: We retrospectively evaluated 190 elderly patients admitted in the ICU between January 2010 and December 2015 in one tertiary care hospital in South Korea. We measured the CSA of the pectoralis muscle area (PMCSA) at the fourth vertebral region. CT scans within two days before ICU admission were used for analysis. Mortality, prolonged mechanical ventilation, and longitudinal change in Sequential Organ Failure Assessment (SOFA) scores were examined. Multivariate logistic regression, linear mixed, and multivariate Cox proportional hazards models were used.Results: PMCSA below median was significantly related with prolonged ventilation. (odds ratio 2.92, 95% CI: 1.02-1.42, P=0.06) and a higher SOFA score during the ICU stay (estimated mean = 0.94, P = 0.03). PMCSA below median was a significant risk for all-cause mortality (HR: 2.06, 95% CI: 1.23-3.47, P=0.01)Conclusions: In elderly ICU patients, low ICU admission PMCSA was associated with prolonged ventilation, a higher SOFA score during the ICU stay and higher mortality. Adding thoracic skeletal muscle CSA at the time of ICU admission into consideration in deciding therapeutic intensity in elderly ICU patients may help in making medical decisions.

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Disseminated Cryptococcus neoformans var. grubii infections in intensive care units

Epidemiology and Infection ◽

10.1017/s0950268809990926 ◽

2009 ◽

Vol 138 (7) ◽

pp. 1036-1043 ◽

Cited By ~ 7

Author(s):

Y.-M. CHUANG ◽

S. C. KU ◽

S. J. LIAW ◽

S. C. WU ◽

Y. C. HO ◽

...

Keyword(s):

Intensive Care ◽

Mortality Rate ◽

Hiv Infection ◽

Cryptococcus Neoformans ◽

Intensive Care Units ◽

Cox Regression ◽

Total Mortality ◽

Icu Admission ◽

Cell Counts ◽

White Blood Cell Counts

SUMMARYA retrospective study of clinical characteristics, outcome and prognostic factors of patients with cryptococcosis was undertaken in intensive care units (ICUs) of a medical centre for the period 2000–2005. Twenty-six patients with Cryptococcus neoformans var. grubii infection were identified (16 males, median age 58 years). The most frequent underlying diseases were liver cirrhosis (38·5%), diabetes mellitus (26·9%) and HIV infection (19·2%). The most frequently identified sites of infection were blood (61·5%), cerebrospinal fluid (38·5%) and airways (34·6%). The mean Acute Physiologic and Chronic Health Evaluation II score at ICU admission was 22·46. The ICU mortality rate in these patients was 73·1% (19/26) and there were a further two mortalities recorded after discharge from ICU, reaching a total mortality rate of 80·8% (21/26). Patients with ICU survival >2 weeks had lower rates of HIV infection (P=0·004), less use of inotropic agents during ICU stay (P<0·001) and lower white blood cell counts (P=0·01). After adjusting for clinical variables in the multivariate Cox regression model, diabetes and cryptococcal infection after ICU admission were independent predictors of good long-term prognosis (P=0·015) and HIV infectious status was associated with poor outcome (P=0·012).

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