The Diagnostic Accuracy of Procalcitonin and Its Combination with Other Biomarkers for Candidemia in Critically Ill Patients.

Background: The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their combination, in distinguishing candidemia from bacteremia in intensive care unit (ICU) patients. Methods: This is a retrospective study in ICU patients with documented bloodstream infections (BSIs) and with both serum PCT and CRP measurements on the day of the positive blood sample. Illness severity was assessed by sequential organ failure assessment (SOFA) score on both admission and BSI day. Demographic, clinical, and laboratory data, including PCT and CRP levels and NLR on the day of the BSI, were recorded. Results: A total of 63 patients were included in the analysis, of whom 32 had bacteremia and 31 had candidemia. PCT, CRP, and NLR values were all significantly lower in candidemia compared with bacteremia (0.29 (0.14-0.69) vs. 1.73 (0.5-6.9) ng/mL, p < 0.001, 6.3 (2.4-11.8) vs. 19 (10.7-24.8) mg/dl, p < 0.001 and 6 (3.7-8.6) vs. 9.8 (5.3-16.3), p = 0.001, respectively). PCT was an independent risk factor for candidemia diagnosis (OR 0.153, 95%CI: 0.04-0.58, p = 0.006). A multivariable model consisting of the above three variables had better predictive ability (AUC-ROC = 0.88, p < 0.001), for candidemia diagnosis, as compared to that of PCT, CRP, and NLR, whose AUC-ROCs were all lower (0.81, p < 0.001, 0.78, p < 0.001, and 0.68, p = 0.015, respectively). Conclusions: A combination of routinely available laboratory tests, such as PCT, CRP, and NLR, could prove useful for the early identification of ICU patients with candidemia.

Temporal trends in laboratory parameters in survivors and non­survivors of critical COVID­19 illness and the effect of dexamethasone treatment.

Although coronavirus disease 2019 (COVID-19)-induced changes in laboratory parameters in patients upon admission have been well-documented, information on their temporal changes is limited. The present study describes the laboratory trends and the effect of dexamethasone treatment on these parameters, in patients with COVID-19 in the intensive care unit (ICU). Routine laboratory parameters, namely white blood cell (WBC), neutrophil, lymphocyte and platelet (PLT) counts, fibrinogen, C-reactive protein (CRP), lactate dehydrogenase (LDH) and albumin concentrations, were recorded upon admission to the ICU and, thereafter, on days 3, 5, 10, 15 and 21; these values were compared between survivors and non-survivors, as well as between those who were treated with dexamethasone and those who were not. Among the 733 patients in the ICU, (mean age, 65±13 years; 68% males; ICU mortality rate 45%; 76% of patients treated with dexamethasone), the WBC and neutrophil counts were persistently high in all patients, without significant differences over the first 15 days. Initially, low lymphocyte counts exhibited increasing trends, but remained higher in survivors compared to non-survivors (P=0.01). The neutrophil-to-lymphocyte ratio (NLR) was persistently elevated in all patients, although it was significantly higher in non-survivors compared to survivors (P<0.001). The PLT count was initially increased in all patients, although it was significantly decreased in non-survivors over time. The fibrinogen and LDH values remained similarly elevated in all patients. However, the increased levels of CRP, which did not differ between patients upon admission, further increased in non-survivors compared to survivors after day 10 (P=0.001). Declining trends in albumin levels over time, overall, with a significant decrease in non-survivors compared to survivors, were observed. Dexamethasone treatment significantly affected the temporal progression of fibrinogen and CRP in survivors and that of NLR in non-survivors. On the whole, the present study demonstrates that patients in the ICU with COVID-19 present persistently abnormal laboratory findings and significant differences in laboratory trends of NLR, CRP, PLT and albumin, but not in WBC and neutrophil count, and fibrinogen and LDH levels, between survivors and non-survivors. The temporal progression of fibrinogen, CRP and NLR is affected by dexamethasone treatment.

Serum inflammatory and brain injury biomarkers in COVID-19 patients admitted to intensive care unit: A pilot study.

Background: The aim of this study was to measure serum brain injury biomarkers in patients with COVID-19 admitted to intensive care unit (ICU), without evidence of brain impairment, and to determine potential correlations with systemic inflammatory markers, illness severity, and outcome. Methods: In patients admitted to the ICU with COVID-19, without clinical evidence of brain injury, blood S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE) and interleukin-6 (IL-6) were measured on admission. Clinical, routine laboratory data and illness severity were recorded. Comparisons between 28-day survivors and non-survivors and correlations of neurological biomarkers to other laboratory data and illness severity, were analyzed. Results: We included 50 patients, median age 64 [IQR 58-78] years, 39 (78%) males, 39 (78%) mechanically ventilated and 11 (22%) under high flow nasal oxygen treatment. S100B and NSE were increased in 19 (38%) and 45 (90%) patients, respectively. S100B was significantly elevated in non-survivors compared to survivors: 0.15 [0.10-0.29] versus 0.11 [0.07-0.17] µg/L, respectively, (p = 0.03), and significantly correlated with age, IL-6, arterial lactate, noradrenaline dose, illness severity and lymphocyte count. IL-6 was significantly correlated with C-reactive protein, noradrenaline dose and organ failure severity. NSE was correlated only with lactate dehydrogenase. Conclusion: Brain injury biomarkers were frequently elevated in COVID-19 ICU patients, in the absence of clinical evidence of brain injury. S100B was significantly correlated with IL-6, low lymphocyte count, hypoperfusion indices, illness severity, and short-term outcome. These findings indicate a possible brain astrocytes and neurons involvement, also suggesting a broader role of S100B in systemic inflammatory response.

Older adults with severe coronavirus disease 2019 admitted to intensive care unit: prevalence, characteristics and risk factors for mortality.

BACKGROUND: Although older adults are at high risk for severe coronavirus disease 2019 (COVID-19) requiring intensive care unit (ICU) admission, age is often used as a selection criterion in case of ICU beds scarcity. We sought to compare the proportion, clinical features and mortality between patients ≥70 years old and younger ICU patients with COVID-19. METHODS: All patients, consecutively admitted to our COVID ICU, where age was not used as an admission criterion, from March 2020 through April 2021, were included. Demographics, clinical and laboratory characteristics were recorded. Illness severity and Charlson comorbidity Index (CCI) were calculated. Patients≥70 years old were compared to youngers. RESULTS: Of 458 patients (68 [59-76] years, 70% males), 206 (45%) were ≥70 years old. Compared to younger, older patients had higher illness severity scores (APACHE II 18 [14-23] versus 12 [9-16], P<0.001, SOFA 8 [6-10] versus 6 [2-8], P<0.001, CCI 5 [4-6] versus 2 [1-3], P<0.001), increased need for mechanical ventilation (92% vs. 72%, P<0.001) and ICU mortality (74% versus. 29%, P<0.001). Age (HR: 1.045, CI: 1.02-1.07, P=0.001), CCI (HR: 1.135, CI: 1.037-1.243, P=0.006) and APACHE II (HR: 1.070, CI: 1.013-1.130, P=0.015) were independently associated with mortality. Among comorbidities, obesity, chronic pulmonary disease and chronic kidney disease were independent risk factors for death. CONCLUSIONS: When age is not used as criterion for admission to COVID ICU, patients ≥70 years old represent a considerable proportion and, compared to younger ones, they have higher mortality. Age, severity of illness and CCI, and certain comorbidities are independent risk factors for mortality.

Effect of Early vs. Delayed or No Intubation on Clinical Outcomes of Patients With COVID-19: An Observational Study.

Background: Optimal timing of initiation of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure due to COVID-19 is unknown. Thanks to early flattening of the epidemiological curve, ventilator demand in Greece was kept lower than supply throughout the pandemic, allowing for unbiased comparison of the outcomes of patients undergoing early intubation vs. delayed or no intubation. Methods: We conducted an observational study including all adult patients with laboratory-confirmed COVID-19 consecutively admitted in Evangelismos Hospital, Athens, Greece between March 11, 2020 and April 15, 2020. Patients subsequently admitted in the intensive care unit (ICU) were categorized into the "early intubation" vs. the "delayed or no intubation" group. The "delayed or no intubation" group included patients receiving non-rebreather mask for equal to or more than 24 h or high-flow nasal oxygen for any period of time or non-invasive mechanical ventilation for any period of time in an attempt to avoid intubation. The remaining intubated patients comprised the "early intubation" group. Results: During the study period, a total of 101 patients (37% female, median age 65 years) were admitted in the hospital. Fifty-nine patients (58% of the entire cohort) were exclusively hospitalized in general wards with a mortality of 3% and median length of stay of 7 days. Forty-two patients (19% female, median age 65 years) were admitted in the ICU; all with acute hypoxemic respiratory failure. Of those admitted in the ICU, 62% had at least one comorbidity and 14% were never intubated. Early intubation was not associated with higher ICU-mortality (21 vs. 33%), fewer ventilator-free days (3 vs. 2 days) or fewer ICU-free days than delayed or no intubation. Conclusions: A strategy of early intubation was not associated with worse clinical outcomes compared to delayed or no intubation. Given that early intubation may presumably reduce virus aerosolization, these results may justify further research with a randomized controlled trial.

Effect of early versus late or no tracheostomy on mortality and pneumonia of critically ill patients receiving mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Delay of tracheostomy for roughly 2 weeks after translaryngeal intubation of critically ill patients is the presently recommended practice and is supported by findings from large trials. However, these trials were suboptimally powered to detect small but clinically important effects on mortality. We aimed to assess the benefit of early versus late or no tracheostomy on mortality and pneumonia in critically ill patients who need mechanical ventilation. METHODS: We systematically searched PubMed, CINAHL, Embase, Web of Science, DOAJ, the Cochrane Library, references of relevant articles, scientific conference proceedings, and grey literature up to Aug 31, 2013, to identify randomised controlled trials comparing early tracheostomy (done within 1 week after translaryngeal intubation) with late (done any time after the first week of mechanical ventilation) or no tracheostomy and reporting on mortality or incidence of pneumonia in critically ill patients under mechanical ventilation. Our primary outcomes were all-cause mortality during the stay in the intensive-care unit and incidence of ventilator-associated pneumonia. Mortality during the stay in the intensive-care unit was a composite endpoint of definite intensive-care-unit mortality, presumed intensive-care-unit mortality, and 28-day mortality. We calculated pooled odds ratios (OR), pooled risk ratios (RR), and 95% CIs with a random-effects model. All but complications analyses were done on an intention-to-treat basis. FINDINGS: Analyses of 13 trials (2434 patients, 648 deaths) showed that all-cause mortality in the intensive-care unit was not significantly lower in patients assigned to the early versus the late or no tracheostomy group (OR 0·80, 95% CI 0·59-1·09; p=0·16). This result persisted when we considered only trials with a low risk of bias (511 deaths; OR 0·80, 95% CI 0·59-1·09; p=0·16; eight trials with 1934 patients). Incidence of ventilator-associated pneumonia was lower in mechanically ventilated patients assigned to the early versus the late or no tracheostomy group (691 cases; OR 0·60, 95% CI 0·41-0·90; p=0·01; 13 trials with 1599 patients). There was no evidence of a difference between the compared groups for 1-year mortality (788 deaths; RR 0·93, 95% CI 0·85-1·02; p=0·14; three trials with 1529 patients). INTERPRETATION: The synthesised evidence suggests that early tracheostomy is not associated with lower mortality in the intensive-care unit than late or no tracheostomy. However, early, compared with late or no, tracheostomy might be associated with a lower incidence of pneumonia; a finding that could question the present practice of delaying tracheostomy beyond the first week after translaryngeal intubation in mechanically ventilated patients. Nevertheless, the scarcity of a beneficial effect on long-term mortality and the potential complications associated with tracheostomy need careful consideration; thus, further studies focusing on long-term outcomes are warranted. FUNDING: None.

The art of providing resuscitation in Greek mythology.

BACKGROUND: We reviewed Greek mythology to accumulate tales of resuscitation and we explored whether these tales could be viewed as indirect evidence that ancient Greeks considered resuscitation strategies similar to those currently used. METHODS: Three compendia of Greek mythology: The Routledge Handbook of Greek Mythology, The Greek Myths by Robert Graves, and Greek Mythology by Ioannis Kakridis were used to find potentially relevant narratives. RESULTS: Thirteen myths that may suggest resuscitation (including 1 case of autoresuscitation) were identified. Methods to attempt mythological resuscitation included use of hands (which may correlate with basic life support procedures), a kiss on the mouth (similar to mouth-to-mouth resuscitation), application of burning torches (which might recall contemporary use of external defibrillators), and administration of drugs (a possible analogy to advanced life support procedures). A careful assessment of relevant myths demonstrated that interpretations other than medical might be more credible. CONCLUSIONS: Although several narratives of Greek mythology might suggest modern resuscitation techniques, they do not clearly indicate that ancient Greeks presaged scientific methods of resuscitation. Nevertheless, these elegant tales reflect humankind's optimism that a dying human might be restored to life if the appropriate procedures were implemented. Without this optimism, scientific improvement in the field of resuscitation might not have been achieved.

RETRACTED: Effect of early versus late or no tracheostomy on mortality of critically ill patients receiving mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Delay of tracheostomy for roughly 2 weeks after translaryngeal intubation of critically ill patients is the presently recommended practice and is supported by findings from large trials. However, these trials were suboptimally powered to detect small but clinically important effects on mortality. We aimed to assess the mortality benefit of early versus late or no tracheostomy in critically ill patients who need mechanical ventilation. METHODS: We systematically searched PubMed, CINAHL, Embase, Web of Science, DOAJ, the Cochrane Library, references of relevant articles, scientific conference proceedings, and grey literature up to Aug 31, 2013, to identify randomised controlled trials comparing early tracheostomy (done within 1 week after translaryngeal intubation) with late (done any time after the first week of mechanical ventilation) or no tracheostomy and reporting on mortality or incidence of pneumonia in critically ill patients under mechanical ventilation. Our primary outcomes were all-cause mortality during the stay in the intensive-care unit and incidence of ventilator-associated pneumonia. We calculated pooled odds ratios (OR), pooled risk ratios (RR), and 95% CIs with a random-effects model. All but complications analyses were done on an intention-to-treat basis. FINDINGS: Analyses of 13 trials (2434 patients, 800 deaths) showed that all-cause mortality in the intensive-care unit was significantly lower in patients assigned to the early versus the late or no tracheostomy group (OR 0·72, 95% CI 0·53-0·98; p=0·04). This finding represents an 18% reduction in the relative risk of death, translating to a 5% absolute improvement in survival (from 65% to 70%). This result persisted when we considered only trials with a low risk of bias (663 deaths; OR 0·68, 95% CI 0·49-0·95; p=0·02; eight trials with 1934 patients). There was no evidence of a difference between the compared groups for 1-year mortality (788 deaths; RR 0·93, 95% CI 0·85-1·02; p=0·14; three trials with 1529 patients). INTERPRETATION: The synthesised evidence suggests that early tracheostomy is associated with lower mortality in the intensive-care unit than late or no tracheostomy; a finding that might question the present practice of delaying tracheostomy beyond the first week after translaryngeal intubation in mechanically ventilated patients. However, the scarcity of a beneficial effect on long-term mortality and the potential complications associated with tracheostomy need careful consideration; thus, further studies focusing on long-term outcomes are warranted. FUNDING: None.

Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial.

IMPORTANCE: Among patients with cardiac arrest, preliminary data have shown improved return of spontaneous circulation and survival to hospital discharge with the vasopressin-steroids-epinephrine (VSE) combination. OBJECTIVE: To determine whether combined vasopressin-epinephrine during cardiopulmonary resuscitation (CPR) and corticosteroid supplementation during and after CPR improve survival to hospital discharge with a Cerebral Performance Category (CPC) score of 1 or 2 in vasopressor-requiring, in-hospital cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, parallel-group trial performed from September 1, 2008, to October 1, 2010, in 3 Greek tertiary care centers (2400 beds) with 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines (from 364 patients assessed for eligibility). INTERVENTIONS: Patients received either vasopressin (20 IU/CPR cycle) plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (VSE group, n = 130) or saline placebo plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (control group, n = 138) for the first 5 CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the VSE group received methylprednisolone (40 mg) and patients in the control group received saline placebo. Shock after resuscitation was treated with stress-dose hydrocortisone (300 mg daily for 7 days maximum and gradual taper) (VSE group, n = 76) or saline placebo (control group, n = 73). MAIN OUTCOMES AND MEASURES: Return of spontaneous circulation (ROSC) for 20 minutes or longer and survival to hospital discharge with a CPC score of 1 or 2. RESULTS: Follow-up was completed in all resuscitated patients. Patients in the VSE group vs patients in the control group had higher probability for ROSC of 20 minutes or longer (109/130 [83.9%] vs 91/138 [65.9%]; odds ratio [OR], 2.98; 95% CI, 1.39-6.40; P = .005) and survival to hospital discharge with CPC score of 1 or 2 (18/130 [13.9%] vs 7/138 [5.1%]; OR, 3.28; 95% CI, 1.17-9.20; P = .02). Patients in the VSE group with postresuscitation shock vs corresponding patients in the control group had higher probability for survival to hospital discharge with CPC scores of 1 or 2 (16/76 [21.1%] vs 6/73 [8.2%]; OR, 3.74; 95% CI, 1.20-11.62; P = .02), improved hemodynamics and central venous oxygen saturation, and less organ dysfunction. Adverse event rates were similar in the 2 groups. CONCLUSION AND RELEVANCE: Among patients with cardiac arrest requiring vasopressors, combined vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in postresuscitation shock, compared with epinephrine/saline placebo, resulted in improved survival to hospital discharge with favorable neurological status. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00729794.

Impact of the administration of probiotics on the incidence of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials.

BACKGROUND: Previous reviews showed no benefit for the administration of probiotics in critically ill patients, but they did not focus on ventilator-associated pneumonia. DESIGN: Meta-analysis of randomized controlled trials comparing probiotics and control in patients undergoing mechanical ventilation and reporting on incidence of ventilator-associated pneumonia. METHODS: PubMed, Scopus, Current Contents, Cochrane Central Register of Controlled Trials, and reference lists were searched. Weighted mean differences, pooled odds ratios, and 95% confidence intervals were calculated, implementing both the Mantel-Haenszel fixed effect and the DerSimonian-Laird random effects model. RESULTS: Five randomized controlled trials were included. Administration of probiotics, compared with control, was beneficial in terms of incidence of ventilator-associated pneumonia (689 patients; fixed effect model: odds ratio, 0.61; 95% confidence interval, 0.41-0.91; random effects model: odds ratio, 0.55, 95% confidence interval, 0.31-0.98), length of intensive care unit stay (fixed effect model: weighted mean difference, -0.99 days; 95% confidence interval, -1.37--0.61), and colonization of the respiratory tract with Pseudomonas aeruginosa (odds ratio, 0.35; 95% confidence interval, 0.13-0.93). However, no difference was revealed between comparators regarding intensive care unit mortality (odds ratio, 0.75; 95% confidence interval, 0.47-1.21), in-hospital mortality (odds ratio, 0.75; 95% confidence interval, 0.46-1.24), duration of mechanical ventilation (weighted mean difference, -0.01 days; 95% confidence interval, -0.31--0.29), and diarrhea (odds ratio, 0.61; 95% confidence interval, 0.28-1.34). CONCLUSION: Administration of probiotics is associated with lower incidence of ventilator-associated pneumonia than control. Given the increasing antimicrobial resistance, this promising strategy deserves consideration in future studies, which should have active surveillance for probiotic-induced diseases.

Predictors of mortality in adult patients with ventilator-associated pneumonia: a meta-analysis.

Studies exploring predictors of mortality in patients with ventilator-associated pneumonia (VAP) produced conflicting results. The present work is a meta-analysis of studies that enrolled only patients with microbiologically confirmed VAP and reported on mortality. Potentially eligible reports were searched in PubMed, EMBASE, CINAHL, and HEALTHSTAR with no language restrictions. Twenty-six reports were included. Factors associated with mortality were malignancy (odds ratio [OR], 2.20; 95% confidence interval [CI], 1.10-4.40) at intensive care unit admission as well as inappropriate initial treatment (i.e., treatment either in vitro inactive against the causative bacteria or administered later than 24 h after diagnosis of VAP) (OR, 2.92; 95% CI, 2.01-4.22), bacteremia (OR, 2.07; 95% CI, 1.16-3.71), acute respiratory distress syndrome/acute lung injury (OR, 2.28; 95% CI, 1.24-4.21), shock (OR, 3.90; 95% CI, 2.31-6.61), sepsis (OR, 4.77; 95% CI, 2.22-10.25), disease severity, and sepsis-related organ failure score at the day of diagnosis of VAP. Isolation of nonfermenting gram-negative bacteria in general (OR, 1.71; 95% CI, 1.09-2.68) and Acinetobacter baumannii in specific (OR, 1.74; 95% CI, 1.02-2.96) was also associated with higher fatality. Intensive care unit admission caused by trauma, as opposed to other reasons, was linked to lower mortality (OR, 0.35; 95% CI, 0.22-0.57). These findings may help investigators to formulate appropriate predicting scores for patients with VAP and may further motivate clinicians to provide appropriate initial treatment and to manage sepsis and shock optimally in such patients.