Adding vortexing to the Maki technique provides no benefit for the diagnosis of catheter colonization or catheter-related bacteremia.

BACKGROUND: A previous study compared vortexing and Maki techniques for the diagnosis of catheter-related bloodstream infection (CRBSI), and concluded that vortexing was not superior to Maki method. AIM: To determine whether the combined use of vortexing and Maki techniques provides profitability versus the Maki technique for the diagnosis of catheter tip colonization (CTC) and CRBSI. METHODS: Observational and prospective study carried out in an Intensive Care Unit. Patients with suspected catheter-related infection (CRI) and with one central venous catheter for at least 7 days were included. The area under the curve (AUC) of the Maki technique, the vortexing technique and the combination of both techniques for the diagnosis of CTC and CRBSI were compared. RESULTS: We included 136 episodes of suspected CRI. We found 21 cases of CTC of which 10 were also CRBSI cases. Of the 21 CTC episodes, 18 (85.7%) were diagnosed by Maki technique and vortexing technique, 3 (14.3%) only by the technique of Maki, and none only by technique of vortexing. Of the 10 CRBSI episodes, 9 (90.0%) were diagnosed by the techniques of Maki and vortexing, 1 (10.0%) was diagnosed only by the technique of Maki, and none only by the technique of vortexing. We no found differences in the comparison of AUC between the technique of Maki and the combination of Maki and vortexing techniques for the diagnosis of CTC (P = 0.99) and CRBSI (P = 0.99). CONCLUSION: The novel finding of our study was that the combined use of vortexing and Maki techniques did not provide profitability to the technique of Maki alone to CRBSI diagnosis of.

Surveillance and prevention of healthcare-associated infections: best practices to prevent ventilator-associated events.

INTRODUCTION: Ventilator associated pneumonia (VAP) leads to an increase in morbidity, mortality, and healthcare costs. In addition to increased evidence from the latest European and American guidelines (published in 2017 and 2022, respectively), in the last two years, several important clinical experiences have added new prevention tools to be included to improve the management of VAP. AREAS COVERED: This paper is a narrative review of new evidence on VAP prevention. We divided VAP prevention measures into pharmacological, non-pharmacological, and ventilator care bundles. EXPERT OPINION: Most of the effective strategies that have been shown to decrease the incidence of complications are easy to implement and inexpensive. The implementation of care bundles, accompanied by educational measures and a multidisciplinary team should be part of optimal management. In addition to ventilator care bundles for the prevention of VAP, it could possibly be beneficial to use ventilator care bundles for the prevention of noninfectious ventilator associated events.

Parthanatos type programmed cell death and septic patient mortality.

OBJECTIVE: Parthanatos is a form of programmed cell death mediated by apoptosis-inducing factor (AIF). However, there are not data on parthanatos in septic patients. The objective of the current study was to explore whether parthanatos is associated with mortality of septic patients. DESIGN: Observational and prospective study. SETTING: Three Spanish Intensive Care Units during 2017. PATIENTS: Patients with sepsis according to Sepsis-3 Consensus criteria. INTERVENTIONS: Serum AIF concentrations were determined at moment of sepsis diagnosis. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: There were included 195 septic patients, and non-surviving (n=72) had serum AIF levels (p<0.001), lactic acid (p<0.001) and APACHE-II (p<0.001) that surviving (n=123). Multiple logistic regression analysis showed that patients with serum AIF levels>55.6ng/mL had higher mortality risk (OR=3.290; 95% CI=1.551-6.979; p=0.002) controlling for age, SOFA and lactic acid. CONCLUSIONS: Parthanatos is associated with mortality of septic patients.

Elevated soluble fas blood concentrations in patients dying from spontaneous intracerebral hemorrhage.

BACKGROUND: Several studies of spontaneous intracerebral hemorrhage (SICH) patients have shown apoptotic changes in brain samples after hematoma evacuation. However, there have been no data on the association between blood concentrations of soluble fas (sFas) (the main surface death receptor of the extrinsic apoptosis pathway) and the prognosis of spontaneous intracranial hypotension (SIH) patients. AIM: To determine whether there is an association between blood sFas concentrations and SICH patient mortality. METHODS: We included patients with severe and supratentorial SIH. Severe was defined as having Glasgow Coma Scale < 9. We determined serum sFas concentrations at the time of severe SICH diagnosis. RESULTS: We found that non-surviving patients (n = 36) compared to surviving patients (n = 39) had higher ICH score (P = 0.001), higher midline shift (P = 0.004), higher serum sFas concentrations (P < 0.001), and lower rate of early hematoma evacuation (P = 0.04). Multiple logistic regression analysis showed an association between serum sFas concentrations and 30-d mortality (odds ratio = 1.070; 95% confidence interval = 1.014-1.129; P = 0.01) controlling for ICH score, midline shift, and early hematoma evacuation. CONCLUSION: The association of blood sFas concentrations and SICH patient mortality is a novel finding in our study.

Patients with hepatocellular carcinoma that die during the first year of liver transplantation have high blood sFasL concentrations.

BACKGROUND: Fas ligand (FasL) is one ligand that activates extrinsic apoptosis pathway. High expression in lymphocytes of FasL have been found in patients with acute rejection of liver transplantation (LT). No high blood concentrations of soluble FasL (sFasL) have been found in patients with acute LT rejection; however, the samples size of those studies was small. AIM: To determine whether patients with hepatocellular carcinoma (HCC) that dead during the first year of LT have higher blood sFasL concentrations previously to LT that those who that remain alive in a study of higher sample size. METHODS: Patients underwent LT due to HCC were included in this retrospective study. Serum sFasL levels prior to LT were measured and one-year LT mortality was registered. RESULTS: Non-surviving patients (n = 14) showed higher serum sFasL levels [477 (269-496) vs 85 (44-382) pg/mL; P < 0.001] than surviving patients (n = 113). Serum sFasL levels (pg/mL) were associated with mortality (OR = 1.006; 95%CI = 1.003-1.010; P = 0.001) independently of age of LT donor in the logistic regression analysis. CONCLUSION: We report for the first time that HCC patients who die within the first year of HT have higher blood sFasL concentrations prior to HT than those who remain alive.

Serum Fas levels during first week of sepsis are associated with severity and mortality.

INTRODUCTION: The aim of our study was to explore whether there is an association of serum sFas (cell death apoptosis receptor) concentrations during the first week of sepsis with sepsis severity and sepsis mortality. METHODS: In this observational study, septic patients were recruited. Serum sFas concentrations were determined on days 1, 4, and 8 of sepsis diagnosis. Thirty-day mortality was the outcome variable. RESULTS: Surviving patients (n = 181) compared to non-survivors (n = 101) presented lower serum sFas levels on day 1 (p < 0.001), day 4 (p < 0.001) and day 8 (p < 0.001), and lower SOFA on day 1 (p < 0.001), day 4 (p < 0.001) and day 8 (p < 0.001). Logistic regression analyses showed associations between 30-day mortality and serum sFas levels controlling for SOFA on day 1 (OR = 1.005; 95% CI = 1.003-1.007; p < 0.001), day 4 (OR = 1.044; 95% CI = 1.029-1.060; p < 0.001) and day 8 (OR = 1.012; 95% CI = 1.002-1.022; p = 0.02). CONCLUSIONS: The association of serum sFas concentrations during the first week of sepsis with sepsis severity and sepsis mortality were our new findings.

Association between blood caspase-9 concentrations and septic patient prognosis.

BACKGROUND: There are few data on caspase­9 (intrinsic apoptosis pathway initiating caspase) in septic patients. Higher serum caspase­9 levels in septic patients than in healthy subjects have been found. However, there are no data on the prognosis of septic patients and blood caspase­9 concentrations. Therefore, the objective of this study was to analyze the potential association between blood caspase­9 concentrations and prognosis in septic patients. METHODS: Three Spanish hospitals participated in the recruitment of septic patients admitted to intensive care units in this observational and prospective study. Serum caspase­9 concentrations were determined at the time of sepsis diagnosis. The 30-day mortality was the outcome variable. RESULTS: Higher Acute Phisiology and Chronic Health Evaluation(APACHE)-II (p < 0.001), Sepsis-related Organ Failure Assessment score (SOFA) (p < 0.001), serum lactic acid levels (p = 0.001), serum caspase­9 levels (p < 0.001), age (p < 0.001), International normalized ratio (INR) (p = 0.001), rate of septic shock (p = 0.001), Activated partial thromboplastin time (aPTT) (p = 0.03), rate of diabetes mellitus (p = 0.04), and lower platelet counts (p = 0.01) were found in non-surviving (n = 80) than in surviving patients (n = 134). Multiple logistic regression analysis showed an association between serum caspase­9 concentrations and mortality (Odds Ratio (OR) = 1.985; 95% Confidence Interval (CI) = 1.359-2.900; p < 0.001) regardless of age, SOFA, lactic acid and septic shock and history of diabetes mellitus. No significant differences were found when we compared area under ROC curves of serum caspase­9 with SOFA (p = 0.92) and with lactic acid (p = 0.59). CONCLUSIONS: The main novel finding of our study was the association between blood caspase­9 concentrations and septic patient prognosis. However, our study showed some limitations (for example, the absence of data in respect to execution of Surviving Sepsis Campaign bundles); thus, more research could be interesting to confirm our preliminary findings.

A genome-wide association study of survival in patients with sepsis.

BACKGROUND: Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis. METHODS: This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10-8. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants. FINDINGS: We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37-6.78], p = 4.92 × 10-8). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury. INTERPRETATION: We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.

DNA and RNA oxidative damage in hepatocellular carcinoma patients and mortality during the first year of liver transplantation.

BACKGROUND: Oxidative damage of DNA and RNA has been associated with mortality of patients with different diseases. However, there is no published data on the potential use of DNA and RNA oxidative damage to predict the prognosis of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). AIM: To determine whether patients with increased DNA and RNA oxidative damage prior to LT for HCC have a poor LT prognosis. METHODS: Patients with HCC who underwent LT were included in this observational and retrospective study. Serum levels of all three oxidized guanine species (OGS) were measured prior to LT since guanine is the nucleobase that forms DNA and RNA most prone to oxidation. LT mortality at 1 year was the end-point study. RESULTS: Surviving patients (n = 101) showed lower serum OGS levels (P = 0.01) and lower age of the liver donor (P = 0.03) than non-surviving patients (n = 13). An association between serum OGS levels prior to LT and 1-year LT (odds ratio = 2.079; 95% confidence interval = 1.356-3.189; P = 0.001) was found in the logistic regression analysis. CONCLUSION: The main new finding was that high serum OGS concentration prior to LT was associated with the mortality 1 year after LT in HCC patients.

High blood Fas concentrations in non-survivor patients with traumatic brain injury.

Fas is one of the main death receptors of the extrinsic pathway of apoptosis. A study has reported higher Fas expression in brain samples of non-surviving TBI patients than in survivors. The objective of our current study was to determine whether there is an association between Fas concentrations in blood and mortality of isolated TBI patients. Patients with severe TBI [< 9 points in Glasgow Coma Scale (GCS)] and isolated TBI (< 10 non-cranial aspects points on the Injury Severity Score) were included from 5 Intensive Care Units. We measured serum Fas concentrations on the day of TBI. Non-surviving (n = 23) compared to surviving patients (n = 57) had higher age (p = 0.01), lower GCS (p = 0.001), higher APACHE-II score (p < 0.001), higher ICP (p = 0.01), higher CT findings with high risk of death (p = 0.02) and higher serum Fas concentrations (p < 0.001). We found in regression analyses an association between serum Fas levels and mortality of TBI patients after controlling for CT findings, age and CGS (OR = 1.006; 95% CI 1.001-1.011; p = 0.02), and after controlling for CT findings, ICP and APACHE-II (OR = 1.007; 95% CI 1.001-1.012; p = 0.02). Thus, the most interesting and novel finding in this study is the association between high blood Fas concentrations and mortality in TBI patients.

Association between neutrophil-to-lymphocyte ratio in the first seven days of sepsis and mortality.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of sepsis has been found to be higher in non-survivors than in survivors, and that is associated with mortality. A higher NLR in non-survivors than in survivors has been reported in two studies during patient follow-up; however, NLR was not controlled for sepsis severity. Thus, the objective of this study was to determine whether there is an association between NLR in the first seven days and mortality controlling for sepsis severity. METHODS: This observational study, which included septic patients, was conducted in the Intensive Care Units of 3 Spanish hospitals. NLR was recorded on the first, fourth, and eighth day of sepsis. Multiple logistic regression analyses were carried out to determine the association between NLR during the first 7 days of sepsis diagnosis and mortality controlling for sepsis severity. RESULTS: Thirty-day non-surviving patients (n=68) compared to surviving patients (n=135) showed higher NLR on the first (p<0.001), fourth (p<0.001), and eighth (p<0.001) day of sepsis diagnosis. Multiple logistic regression analysis found an association between NLR at days first (p<0.001), fourth (p=0.004), and eighth (p=0.01) of sepsis diagnosis and mortality controlling for SOFA and lactic acid in those days. CONCLUSIONS: The new finding of our study was the association between NLR in the first seven days of sepsis and mortality controlling for sepsis severity.

High mortality rate of septic patients with high blood granzyme B concentrations.

Granzyme B could be released from cytotoxic T lymphocytes producing apoptosis activation. The objective of our study was to determine whether an association between septic patient mortality and blood granzyme B concentrations exist. We recruited septic patients admitted in 3 Intensive Care Units. We recorded mortality at 30 days and we determined serum granzyme B concentrations at moment of sepsis diagnosis. We found higher rate of history of diabetes mellitus (P = 0.02), serum granzyme B concentrations (P < 0.001), age (P = 0.001), serum lactic acid levels (P = 0.001) and sepsis-related organ failure assessment (P < 0.001) exhibited non-surviving patients (n = 67) than surviving ones (n = 110). We found in multiple logistic regression analysis an association of serum granzyme B concentrations with mortality (odds ratio = 1.223; 95% confidence interval = 1.104-1.355; P < 0.001) controlling for diabetes mellitus, sepsis-related organ failure assessment, lactic acid and age. That we know, our study is the first reporting the existence of an association of high serum granzyme B concentrations with high septic patients mortality.

Blood Bcl-2 levels to predict the mortality of septic patients.

Aim: To determine whether blood concentrations of Bcl-2 during the 1st week of sepsis could help predict mortality. Methods: Serum Bcl-2 concentrations were determined at the 1st, 4th and 8th days of sepsis diagnosis. Results: Thirty-day surviving patients (n = 168) showed higher serum Bcl-2 levels at the 1st (p = 0.002), 4th (p < 0.001) and 8th days (p < 0.001) of sepsis diagnosis than non-surviving patients (n = 91). An association between serum Bcl-2 concentrations at the 1st (p = 0.003), 4th (p < 0.001) and 8th days (p = 0.01) and 30-day mortality after controlling for diabetes mellitus, Sepsis-related Organ Failure Assessment, lactic acid and age was found in the multiple logistic regression analysis. Conclusions: The novel finding is that blood Bcl-2 concentrations at any time in the 1st week of sepsis are associated with mortality.

Mortality prediction of septic patients by blood caspase-8 levels.

We have not found data about blood caspase-8 concentrations (initiator caspase in the extrinsic pathway of apoptosis) during follow-up of sepsis and this was the objective of our study. We included septic patients. Serum caspase-8 concentrations were determined at days 1, 4, and 8 of sepsis diagnosis. We registered mortality at 30 days. Nonsurviving patients (n = 89) in respect to surviving patients (n = 160) showed higher serum caspase-8 levels at days 1 (P < 0.001), 4 (P <0.001), and 8 (P <0.001) of sepsis diagnosis. Serum caspase-8 levels on day 1, day 4, and day 8 had an area under curve for the prediction of 30-day mortality of 68% (60%-75%, P<0.001), 72% (62%-82%, P<0.001), and 81% (73%-90%, P<0.001). Thus, that blood caspase-8 concentrations at any time during the first week of sepsis were higher in non-survivor than in survivor patients and that were able to predict mortality were new findings in our study.

Blood soluble Fas concentrations and ischemic stroke patient mortality.

BACKGROUND: Fas is a major receptor for cell death by apoptosis. Higher blood concentrations of soluble Fas (sFas) have been reported in patients with ischemic stroke compared to control subjects. The aim of this study was to explore the existence or not of an association between blood sFas concentrations and mortality in patients with ischemic stroke. METHODS: This study included patients admitted to Intensive Care Units with severe and malignant middle cerebral artery infarction (MCAI), defined as acute infarction, in more than 50% of this territory on computed tomography and less than 9 points on the Glasgow Coma Scale (GCS). Serum sFas levels were determined at the time of diagnosis of MMCAI. RESULTS: Non-surviving severe MMCAI patients (n = 27) showed lower platelet count (p = 0.004), higher serum sFas (p < 0.001), and lower GCS (p = 0.001) compared to surviving patients (n = 27). Multiple logistic regression found an association of serum sFas levels and mortality at 30 days (OR = 1.015; 95% CI = 1.002-1.027; p = 0.02) after control for CGS and platelet count. CONCLUSIONS: The main novelty of our study was the existence of an association between high blood sFas concentrations and mortality in patients with ischemic stroke.

Skin insertion site culture for the prediction of primary bloodstream infection.

PURPOSE: Previous studies have analyzed the capability of skin insertion site culture to predict catheter-related bloodstream infection (CRBSI). However, there has been not analyzed its capability to predict primary bloodstream infection (PBSI), that include CRBSI and bloodstream infection of unknown origin (BSIUO). The novel objective of our study was to determine the capability of insertion skin site culture to predict CRBSI and primary bloodstream infection (PBSI), that include CRBSI and bloodstream infection of unknown origin (BSIUO). MATERIAL AND METHODS: Observational and prospective study in one Intensive Care Unit. Patients with some central venous catheter (CVC) at least during 7 days and suspected catheter-related infection (CRI) (new episode of fever or sepsis) were included. Cultures of insertion skin site, paired blood samples, catheter-tip, and other clinical samples were taken. Capability of insertion skin site culture to predict CRBSI and PBSI was determined. RESULTS: We included 108 CVC from 96 CRI suspicion episodes. The causes that motivated CRI suspicion were 20 (18.5%) PBSI, 44 (40.7%) other infections, and 44 (40.7%) unknown. Among the 20 PBSI, 11 (55%) were CRBSI and 9 (45%) were BSIUO. Negative predictive value of insertion skin site culture to predict CRBSI was 95% (87-98%) and to predict PBSI was 85% (76-91%). CONCLUSIONS: The new finding of our study was that skin insertion site culture had a good negative predicted valued for the prediction of CRBSI and PBSI.

Association between serum concentrations of anti-apoptotic B-cell lymphoma-2 protein and traumatic brain injury mortality.

BACKGROUND: There are scarce and contradictory data existing about B-cell lymphoma 2 (Bcl2), one of the Bcl2 family of anti-apoptotic proteins, in traumatic brain injury (TBI) patients. Thus, the objective of this study was to analyze whether blood concentrations of Bcl2 are associated with mortality. METHODS: Patients with isolated and severe TBI, defined as <10 points of the Injury Severity Score (ISS) in non-cranial aspects and <9 points in Glasgow Coma Scale (GCS), were included. This was an observational and prospective study carried out in five Intensive Care Units. Serum Bcl2 concentrations on day 1 of TBI were determined. RESULTS: Serum Bcl2 concentrations were lower (p < 0.001) in surviving patients (n = 59) compared to non-survivors (n = 24). We found an association between serum Bcl2 levels and mortality controlling for age and GCS (OR = 1.149; 95% CI = 1.056-1.251; p = 0.001) and controlling for computer tomography findings (OR = 1.147; 95% CI = 1.056-1.246; p = 0.001). CONCLUSIONS: This study reports for the first time an association between serum Bcl2 levels and 30-day mortality in TBI patients.

Mortality prediction of patients with spontaneous intracerebral hemorrhage by serum soluble Fas ligand concentrations.

BACKGROUND: A study of patients with spontaneous intracerebral hemorrhage (SIH) found a higher content of Fas ligand in the perihematomic brain area compared to healthy brain areas. The objective of this study was to analyze whether blood soluble Fas ligand (sFasL) concentrations could be used to estimate the prognosis of SIH patients. METHODS: Observational and prospective study performed in five Spanish Intensive Care Units. Patients with severe supratentorial SIH, defined as Glasgow Coma Scale (GCS) <9, were included. Serum sFasL levels were determined at the time of diagnosis of severe SIH. Mortality at 30 days was the end-point study. RESULTS: Surviving SIH patients (n = 41) compared to nonsurvivors (n = 38) showed lower serum sFasL levels (p < 0.001). The area under curve of mortality prediction for serum sFasL levels was 0.79 (95% CI = 0.70-0.89; p < 0.001). Multiple logistic regression analysis found an association of serum sFasL concentrations with 30-day mortality (ORo = 1,034; 95% CI = 1,010-1,058; p = 0,006) after controlling for midline shift, early hematoma evacuation, and intracerebral hemorrhage score. CONCLUSIONS: The capability of serum sFasL to predict SIH patient mortality is the main novel finding of our study. ABBREVIATIONS: APACHE II: Acute Physiology and Chronic Health Evaluation; aPTT: activated partial thromboplastin time; FIO2: fraction of inspired oxygen; GCS: Glasgow Coma Scale; ICU: Intensive Care Unit; INR: international normalized ratio; PaO2: pressure of arterial oxygen.

Mortality prediction by serum melatonin levels of patients with spontaneous intracerebral hemorrhage.

OBJECTIVE: In one study, higher serum melatonin levels have been reported at diagnosis of spontaneous intracerebral hemorrhage (ICH) in non-surviving than in surviving patients. Now, we carried out this study with the aims to explore whether blood melatonin concentrations in the first 7 days of ICH are different in survivor and non-survivor patients and whether are useful in the prediction of mortality. METHODS: Six Spanish hospitals participated in this observational study of patients with severe supratentorial ICH (defining severe as Glasgow Coma Scale < 9). We determined serum melatonin levels during the first, fourth, and eighth day of severe ICH. RESULTS: Surviving (n = 64) compared to non-surviving (n = 53) patients showed lower serum melatonin levels during the first (p < 0.001), fourth (p < 0.001), and eighth day (p < 0.001) of severe ICH. We found in multiple logistic regression analysis an association between serum melatonin levels and 30-day mortality (odds ratio = 8.932; 95% CI = 2.442-32.665; p = 0.001) controlling for midline shift, ICH score, early evacuation of ICH, and glycemia. We found an AUC (95% CI) for the mortality prediction of 0.90 (0.83-0.95; p < 0.001), 0.94 (0.87-0.98; p < 0.001), and 0.90 (0.81-0.96; p < 0.001) by serum melatonin concentrations during the first, fourth, and eighth day. CONCLUSIONS: In our current study, it appears that novel findings of serum melatonin levels recollected at any moment during the first 7 days of a severe ICH were higher in non-survivor than in survivor patients and could help in mortality prediction.