Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.

Quality metrics in the management of acute stroke in Greece during the first 5 years of Registry of Stroke Care Quality (RES-Q) implementation.

Introduction: Establishment of a prospective stroke registry may promote the documentation and improvement of acute stroke care. We present the status of stroke management in Greece using the Registry of Stroke Care Quality (RES-Q) dataset. Methods: Consecutive patients with acute stroke were prospectively registered in RES-Q registry by contributing sites in Greece during the years 2017-2021. Demographic and baseline characteristics, acute management, and clinical outcomes at discharge were recorded. Stroke quality metrics, with a specific interest in the association between acute reperfusion therapies and functional recovery in ischemic stroke patients are presented. Results: A total of 3590 acute stroke patients were treated in 20 Greek sites (61% men, median age 64 years; median baseline NIHSS 4; 74% ischemic stroke). Acute reperfusion therapies were administered in almost 20% of acute ischemic stroke patients, with a door to needle and door to groin puncture times of 40 and 64 min, respectively. After adjustment for contributing sites, the rates of acute reperfusion therapies were higher during the time epoch 2020-2021 compared to 2017-2019 (adjusted OR 1.31; 95% CI 1.04-1.64; p < 0.022; Cochran-Mantel-Haenszel test). After propensity-score-matching, acute reperfusion therapies administration was independently associated with higher odds of reduced disability (one point reduction across all mRS scores) at hospital discharge (common OR 1.93; 95% CI 1.45-2.58; p < 0.001). Conclusions: Implementation and maintenance of a nationwide stroke registry in Greece may guide the stroke management planning, so that prompt patient transportation, acute reperfusion therapies, and stroke unit hospitalization become more widely accessible, improving the functional outcomes of stroke patients.

Impact of secondary sepsis on mortality in adult intensive care unit patients.

RATIONALE: Septic patients admitted to the intensive care unit (ICU) suffer from immune dysregulation, potentially leading to a secondary sepsis episode. This study aims to (i) assess the secondary sepsis rate, (ii) compare the second with the first episodes in terms of demographics, clinical and laboratory characteristics, and outcomes, and iii) evaluate the outcome of secondary sepsis. METHODS: A single-center, retrospective study (2014-2017) was conducted in a Greek ICU, including consecutive cases of adult patients admitted to the ICU for at least 48 h with a principal admission diagnosis of sepsis and stayed for at least 48 h. We searched for a secondary episode of sepsis following the primary-one. We performed survival analyses with Cox proportional hazard, Fine-Gray, and multistate models. RESULTS: In this study, 121 patients that fulfilled the eligibility criteria were included. The secondary sepsis group included 28 (23.1 %) patients, with episode onset, median (interquartile range), 9.5 (7.7-16.2) days after ICU admission, who had less frequently had a medical admission diagnosis, a microbiologically confirmed first episode, and the C-reactive protein was lower. The overall ICU mortality of the cohort was 44.6 %. The group that developed secondary sepsis had higher mortality, but significance was lost in Cox regression [Hazard ratio (95 % CI) 0.59(0.31-1.16)]. However, after multistate modeling adjustment, the attributable mortality was estimated at 43.9 % (95 %CI ± 14.8 %). CONCLUSION: Secondary sepsis was evident in a quarter of the study participants and may be associated with an increased risk of death.

Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial.

BACKGROUND: Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. METHODS: EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe, Turkey, Israel, and the USA. Subjects ≥ 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose), or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. RESULTS: Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n = 16/87; placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n = 16/85; placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4% (n = 19/85) of MEDI3902 1500 mg recipients and in 18.1% (n = 15/83) of placebo recipients (relative risk reduction [RRR]: - 23.7%; 80% confidence interval [CI] - 83.8%, 16.8%; p = 0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) µg/mL, with 80.6% (n = 58/72) subjects achieving concentrations > 1.7 µg/mL, a level associated with improved outcome in animal models. Treatment-emergent adverse event incidence was similar between groups. CONCLUSIONS: The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects. Trial registration Registered on Clinicaltrials.gov ( NCT02696902 ) on 11th February 2016 and on EudraCT ( 2015-001706-34 ) on 7th March 2016.

Toward personalized immunotherapy in sepsis: The PROVIDE randomized clinical trial.

The state of immune activation may guide targeted immunotherapy in sepsis. In a double-blind, double-dummy randomized clinical study, 240 patients with sepsis due to lung infection, bacteremia, or acute cholangitis were subjected to measurements of serum ferritin and HLA-DR/CD14. Patients with macrophage activation-like syndrome (MALS) or immunoparalysis were randomized to treatment with anakinra or recombinant interferon-gamma or placebo. Twenty-eight-day mortality was the primary endpoint; sepsis immune classification was the secondary endpoint. Using ferritin >4,420 ng/mL and <5,000 HLA-DR receptors/monocytes as biomarkers, patients were classified into MALS (20.0%), immunoparalysis (42.9%), and intermediate (37.1%). Mortality was 79.1%, 66.9%, and 41.6%, respectively. Survival after 7 days with SOFA score decrease was achieved in 42.9% of patients of the immunotherapy arm and 10.0% of the placebo arm (p = 0.042). Three independent immune classification strata are recognized in sepsis. MALS and immunoparalysis are proposed as stratification for personalized adjuvant immunotherapy. Clinicaltrials.gov registration NCT03332225.

ICU-Associated Gram-Negative Bloodstream Infection: Risk Factors Affecting the Outcome Following the Emergence of Colistin-Resistant Isolates in a Regional Greek Hospital.

Intensive care unit patients may present infections by difficult-to-treat-resistant Gram-negative microorganisms. Colistin resurfaced as a last resort antibiotic for the treatment of multi-drug-resistant Gram-negative bacteria. However, colistin might not improve survival, particularly after the emergence of colistin-resistant isolates. We aimed to (1) examine the first Gram-negative-associated-bloodstream infection (GN-BSI) effect on 28-day mortality and (2) distinguish mortality risk factors. From 1 January 2018 to 31 December 2019, we retrospectively studied all adult patients admitted for more than 48 h in the critical care department of a regional Greek hospital, with prevalent difficult-to-treat Gram-negative pathogens. We examined the patient records for the first GN-BSI. The local laboratory used broth microdilution to evaluate bacterial susceptibility to colistin. Seventy-eight patients fulfilled the entry criteria: adult and first GN-BSI. They developed GN-BSI on day 10 (6-18), while the overall mortality was 26.9%. Thirty-two and 46 individuals comprised the respective colistin-resistant and colistin-sensitive groups. The admission Acute Physiology Assessment and Chronic Health Evaluation II score was associated with acquiring colistin-resistant GN-BSI in the multivariable logistic regression analysis (οdds ratio (CI), 1.11 (1.03-1.21)). Regarding mortality, the index day sequential organ failure assessment score was solely associated with the outcome (hazard-ratio (CI), 1.23 (1.03-1.48), Cox proportional hazard analysis). GN-BSI was often caused by colistin-resistant bacteria. Concerning our data, sepsis severity was the independent predictor of mortality regardless of the colistin-resistance phenotype or empirical colistin treatment.

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients.

BACKGROUND: Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. METHODS: In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin >4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28, serum biomarkers, and cytokine production by mononuclear cells were secondary endpoints. RESULTS: The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (p: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment. CONCLUSION: Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS.

Rapid Test Ag 2019-nCoV (PROGNOSIS, BIOTECH, Larissa, Greece); Performance Evaluation in Hospital Setting with Real Time RT-PCR.

INTRODUCTION: Rapid antigen tests (RATs) are convenient for SARS-CoV-2 detection because they are simpler and faster than nucleic acid amplification tests (NAATs). This study aimed to assess the accuracy of a locally manufactured test; Rapid Test Ag 2019-nCoV (PROGNOSIS, BIOTECH, Larissa, Greece) in a clinical setting and during mass screening. METHODS: Nasopharyngeal samples from 624 individuals were analyzed. The results of the rapid test were compared to real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR). At the end of the test's procedure, positive test strips were scanned in an S-Flow reader in order to roughly estimate the antigen concentration. RESULTS: The lower limit of detection of the test was 468.75 genome copies/mL. The PROGNOSIS rapid test displayed a sensitivity of 85.5% (141/165) (95%CI: 79.1-90.5) and a specificity of 99.8% (458/459) (95%CI: 98.8-100.0%). The general inter-rater agreement was 0.89 (95%CI: 85.1-93.3). The regression analysis between the S-flow reader measurements (viral antigen) and the viral load of the positive samples demonstrated a weak correlation (R2 = 0.288, p < 0.001). CONCLUSION: The Rapid Test Ag 2019-nCoV demonstrated sufficient sensitivity, excellent specificity and could be available to be used with low overall cost. Thus, it could be used as point of care test, but also for mass screening for rapid detection of infected persons (e.g., for travelers).

Gastroenterology and liver disease during COVID-19 and in anticipation of post-COVID-19 era: Current practice and future directions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global public health. The virus causes the clinical syndrome known as coronavirus disease 2019 (COVID-19), in which multiple organs can get affected. Apart from manifestations of the respiratory system, which predominate, its clinical presentation is frequently accompanied by symptoms of the gastro-intestinal (GI) tract and liver abnormalities. The correlation of symptoms and abnormalities with disease severity is discussed, leading to ambiguous results from international literature. Moreover, the disease infects patients with co-existing liver and GI disorders affecting both their health status and the availability of healthcare services provided to them. The risk of transmission of the disease during aerosol-generating procedures has changed the diagnostic approach and follow-up algorithms for liver and GI diseases. For the safety of both doctors and patients, telemedicine and distant evaluation have become everyday practice, whereas several routines and emergency visits at outpatient and emergency departments have been postponed or delayed. Vaccination against SARS-CoV-2 is underway, providing hope to humanity and the expectation that the post-COVID-19 era is near. This review aims to update knowledge about the manifestations of COVID-19 related to liver and GI diseases and the effect of the pandemic on the diagnostic and therapeutic procedures for these diseases with a special focus on how current practices have changed and what changes will possibly remain in the future.

Transmission Dynamics of SARS-CoV-2 during an Outbreak in a Roma Community in Thessaly, Greece-Control Measures and Lessons Learned.

A COVID-19 outbreak occurred among residents of a Roma settlement in Greece (8 April-4 June 2020). The aim of this study was to identify factors associated with an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to evaluate the effectiveness of control measures implemented. Data were analyzed from individuals that were tested for SARS-CoV-2 during contact tracing, population screening or hospital visits. RT-PCR was used for the detection of SARS-CoV-2 in oropharyngeal samples. Risk factors for household secondary attack rates (SAR) and hospitalization with COVID-19 were examined using chi-square tests, Fisher's exact tests and logistic regression analyses. During the outbreak, 142 cases, 20 hospitalizations and 1 death were recorded, with a total of 2273 individuals tested. The risk of hospitalization was associated with age (OR: 1.04, 95% CI: 1.02-1.07) and Cycle threshold (Ct) values (OR for a decrease in Ct values by 1: 1.18, 95% CI: 1.07-1.31). Household SAR was estimated at 38.62% (95% CI: 32.50-45.01%). After the designation of an isolation facility for cases, household SAR declined from 74.42% to 31.03%. Household size was associated with the risk of infection (OR: 2.65, 95% CI: 1.00-7.07). The presence of COVID-19 symptoms among index cases was correlated with higher transmission (OR: 23.68, 95% CI 2.21-253.74) in multivariate analysis, while age was found to be associated with SAR only in univariate analysis. Roma communities can be particularly vulnerable to the spread of SARS-CoV-2. In similar settings, symptomatic cases are more important transmitters of SARS-CoV-2. Within these communities, immediate measures should be implemented to mitigate disease spread.

Combination of thrombolytic and immunosuppressive therapy for coronavirus disease 2019: A case report.

In a proportion of patients, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multisystem syndrome characterized by hyperinflammation, acute respiratory distress syndrome (ARDS), and hypercoagulability. A 68-year-old man with coronavirus disease 2019 (COVID-19) was admitted to the intensive care unit with respiratory failure, cytokine release syndrome (CRS), and skin ischemia - microthrombosis. Specific coagulation and inflammatory markers (D-dimer, ferritin, and C-reactive protein), along with the clinical picture, triggered the trial of recombinant tissue plasminogen activator (rt-PA) and tocilizumab. This was followed by resolution of the skin ischemia and CRS, while respiratory parameters improved. No major complications associated with rt-PA or tocilizumab occurred. The combination of rt-PA with targeted anti-inflammatory treatment could be a new therapeutic option for patients with COVID-19, ARDS, hyperinflammation, and increased blood viscosity.

Favorable Anakinra Responses in Severe Covid-19 Patients with Secondary Hemophagocytic Lymphohistiocytosis.

Dysregulation of inflammation is hypothesized to play a crucial role in the severe complications of COVID-19, with the IL-1/IL-6 pathway being central. Here, we report on the treatment of eight severe COVID-19 pneumonia patients-seven hospitalized in intensive care units (ICUs) in Greece and one non-ICU patient in the Netherlands-with the interleukin-1 receptor antagonist Anakinra. All patients scored positive for the hemophagocytosis score (HScore) and were diagnosed with secondary hemophagocytic lymphohistocytosis (sHLH) characterized by pancytopenia, hyper-coagulation, acute kidney injury, and hepatobiliary dysfunction. At the end of treatment, ICU patients had less need for vasopressors, significantly improved respiratory function, and lower HScore. Although three patients died, the mortality was lower than historical series of patients with sHLH in sepsis. These data suggest that administration of Anakinra may be beneficial for treating severe COVID-19 patients with sHLH as determined by the HScore, and they support the need for larger clinical studies to validate this concept.

Inadvertent direct pulmonary artery catheterization complicating the effort for subclavian venous cannulation and central venous catheter placement: A case report and review of the literature.

Subclavian access is commonly used in the intensive care unit (ICU) for central venous catheterization. Many complications have been reported during the placement of central venous catheters including pneumothorax, hemothorax, hematoma, and bleeding. The direct, through the thoracic wall, catheterization of pulmonary artery is a very rare one with only three previous reports in the literature. We report a patient who was catheterized for subclavian venous catheter placement, but the imaging techniques (chest X-ray and computed tomography with reconstruction of the images) revealed the direct positioning of the catheter into the pulmonary trunk, fortunately without other adverse events for the patient. Our case report in accordance with recent review of the literature strongly emphasizes the benefits of performing ultrasound-guided interventions in ICU.

Effect of integrin AV and B8 gene polymorphisms in patients with traumatic brain injury.

Background: Α few genetic variants are associated with the outcome after traumatic brain injury (TBI). Integrins are glycoprotein receptors that play an important role in the integrity of microvasculature of the brain. Objective: To examine the role of integrin-AV (ITGAV) and integrin-B8 (ITGB8) tag single nucleotide polymorphisms (SNPs) on the outcome of patients with TBI. Methods: 363 participants were included and genotyped for 11 SNPs for ITGAV and 11 for ITGB8 gene. SNPs were tested for associations with the 6-month outcome after TBI, the presence of a hemorrhagic event after TBI, and the initial TBI severity after adjustment for TBI's main predictors. Results: The ITGAV rs3911239 CC and rs7596996 GG genotypes were associated with an unfavorable outcome after TBI, compared to the TT and AA genotypes, respectively. The ITGB8 rs10239099 CC and rs3757727 CC genotypes were associated with increased risk of any cerebral hemorrhagic event after TBI compared to GG and TT respectively. The ITGAV rs7589470 and rs7565633 were associated with the TBI's initial severity. Conclusions: ITGAV gene SNPs may be implicated in the outcome after TBI, as well as in the initial TBI severity, and also of ITGB8 gene SNPs in the risk of hemorrhagic event after a TBI.

Intravenous thrombolysis for acute ischemic stroke in Greece: the Safe Implementation of Thrombolysis in Stroke registry 15-year experience.

BACKGROUND: Intravenous thrombolysis (IVT) remains the only approved systemic reperfusion treatment for acute ischemic stroke (AIS), however there are scarce data regarding outcomes and complications of IVT in Greece. We evaluated safety and efficacy outcomes of IVT for AIS in Greece using the Safe Implementation of Thrombolysis in Stroke: International Stroke Thrombolysis Register (SITS-ISTR) dataset. METHODS: All AIS patients treated with IVT in Greece between December 2002 and July 2017 and recorded in the SITS-ISTR were evaluated. Demographics, risk factors, baseline stroke severity [defined using National Institutes of Health Stroke Scale (NIHSS)], and onset-to-treatment time (OTT) were recorded. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 3-month mortality rates. The efficacy outcomes evaluated a reduction in baseline NIHSS score at 2 and 24 h following IVT onset, 3-month favorable functional outcome [FFO; modified Rankin scale (mRS) scores of 0-1] and 3-month functional independence (FI; mRS-scores of 0-2). The safety and efficacy outcomes were assessed comparatively with previously published data from SITS national and international registries. RESULTS: A total of 523 AIS patients were treated with IVT in 12 Greek centers participating in the SITS-ISTR during the study period (mean age 62.4 ± 12.7; 34.6% women; median baseline NIHSS score: 11 points; median OTT: 150 min). The rates of sICH were 1.4%, 2.3%, and 3.8% according to the SIST-MOST, ECASS II, and NINDS criteria respectively. The median reduction in NIHSS score at 2 and 24 h was 3 [interquartile range (IQR): 1-5] and 5 (IQR: 2-8) points respectively. The 3-month FI, FFO and mortality were 66.5%, 55.6% and 7.9%. All safety and efficacy outcomes were comparable with available data from SITS-ISTR in other European countries. CONCLUSIONS: Our study underscores the safety and efficacy of IVT for AIS in Greece. Additional action is necessary in order to increase the availability of IVT in the Greek population and to include more centers in the SITS-ISTR.

Predictors of Need for Critical Care Support, Adverse Events, and Outcome after Stroke Thrombolysis.

BACKGROUND: Results from trials and international registries exhibit heterogeneity regarding safety, efficacy, markers of prognosis, and markers of the need for critical care support after intravenous thrombolysis (IVT) for strokes. The purpose of our study was to indentify such markers after performance of comparisons among patients who received thrombolysis in our intensive care unit. MATERIALS AND METHODS: Our study included 124 patients who received IVT in accordance with international criteria. Outcome measures of univariate and regression analyses resulted from comparisons between groups of patients with or without the need for critical care support (advanced life support and neurocritical care interventions), groups of patients developing or not developing primary adverse events (symptomatic intracranial hemorrhage [SICH] and/or Death and/or Serious systemic bleeding and/or New stroke) and groups of patients with different main outcome variables (mortality, functional independence at 3 months). RESULTS: Our results suggested that higher severity scores (Simplified Acute Physiology Score II, National Institutes of Health Stroke Scale) correlated with the need for critical care support, primary adverse events, and main outcome variables, whereas older age was significantly associated with fewer adverse events. Hyperlipidemia, symptom-to-needle time, and vascular disease were associated with functional capacity at 3 months, whereas diabetes mellitus and vascular disease correlated with the need for critical care support. CONCLUSION: Patients' age, hyperlipidemia, presence of vascular disease, Simplified Acute Physiology Score II (a novel marker), and National Institutes of Health Stroke Scale at 2 hours and at 7 days are independent predictors of the need for critical care support, adverse events, and clinical outcomes after thrombolysis.

Effect of angiotensin-converting enzyme tag single nucleotide polymorphisms on the outcome of patients with traumatic brain injury.

BACKGROUND: Genetic variants appear to influence, at least to some degree, the extent of brain injury and the clinical outcome of patients who have sustained a traumatic brain injury (TBI). Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that is implicated in the regulation of blood pressure and cerebral circulation. ACE gene polymorphisms were found to regulate serum ACE enzyme activity. OBJECTIVE: The present study aimed to investigate possible influence of ACE gene region variants on patients' outcome after TBI. PATIENTS AND METHODS: In total, 363 TBI patients prospectively enrolled in the study were genotyped for five tag single nucleotide polymorphisms (SNPs) across the ACE gene. Using logistic regression analyses, tag SNPs and their constructed haplotypes were tested for associations with 6-month Glasgow Outcome Scale scores, after adjustment for age, sex, Glasgow Coma Scale scores at admission, and the presence of a hemorrhagic event in the initial computed tomography scan. RESULTS: Significant effects on TBI outcome were found for three neighboring tag SNPs in the codominant (genotypic) model of inheritance [rs4461142: odds ratio (OR) 0.26, 95% confidence interval (CI) 0.12-0.57, P = 0.0001; rs7221780: OR 2.67, 95% CI 1.25-5.72, P = 0.0003; and rs8066276: OR 3.82, 95% CI 1.80-8.13, P = 0.0002; for the heterozygous variants compared with the common alleles]. None of the constructed common tag SNPs haplotypes was associated with TBI outcome. CONCLUSION: The present study provides evidence of the possible influence of genetic variations in a specific region of the ACE gene on the outcome of TBI patients. This association may have pharmacogenetic implications in identifying those TBI patients who may benefit from ACE inhibition.

AQP4 tag single nucleotide polymorphisms in patients with traumatic brain injury.

Accumulating evidence suggests that the extent of brain injury and the clinical outcome after traumatic brain injury (TBI) are modulated, to some degree, by genetic variants. Aquaporin-4 (AQP4) is the predominant water channel in the central nervous system and plays a critical role in controlling the water content of brain cells and the development of brain edema after TBI. We sought to investigate the influence of the AQP4 gene region on patient outcome after TBI by genotyping tag single nucleotide polymorphisms (SNPs) along AQP4 gene. A total of 363 patients with TBI (19.6% female) were prospectively evaluated. Data including the Glasgow Coma Scale (GCS) scores at admission, the presence of intracranial hemorrhage, and the 6-month Glasgow Outcome Scale (GOS) scores were collected. Seven tag SNPs across the AQP4 gene were identified based on the HapMap data. Using logistic regression analyses, SNPs and haplotypes were tested for associations with 6-month GOS after adjusting for age, GCS score, and sex. Significant associations with TBI outcome were detected for rs3763043 (OR [95% confidence interval (CI)]: 5.15 [1.60-16.5], p=0.006, for recessive model), rs3875089 (OR [95% CI]: 0.18 [0.07-0.50] p=0.0009, for allele difference model), and a common haplotype of AQP4 tag SNPs (OR [95% CI]: 2.94, [1.34-6.36], p=0.0065). AQP4 tag SNPs were not found to influence the initial severity of TBI or the presence of intracranial hemorrhages. In conclusion, the present study provides evidence for possible involvement of genetic variations in AQP4 gene in the functional outcome of patients with TBI.

Prevalence, risk factors, and mortality for ventilator-associated pneumonia in middle-aged, old, and very old critically ill patients*.

OBJECTIVE: We investigated the epidemiology of ventilator-associated pneumonia in elderly ICU patients. More precisely, we assessed prevalence, risk factors, signs and symptoms, causative bacterial pathogens, and associated outcomes. DESIGN: Secondary analysis of a multicenter prospective cohort (EU-VAP project). SETTING: Twenty-seven European ICUs. PATIENTS: Patients who were mechanically ventilated for greater than or equal to 48 hours. We compared middle-aged (45-64 yr; n = 670), old (65-74 yr; n = 549), and very old patients (≥ 75 yr; n= 516). MEASUREMENTS AND MAIN RESULTS: Ventilator-associated pneumonia occurred in 103 middle-aged (14.6%), 104 old (17.0%), and 73 very old patients (12.8%). The prevalence (n ventilator-associated pneumonia/1,000 ventilation days) was 13.7 in middle-aged patients, 16.6 in old patients, and 13.0 in very old patients. Logistic regression analysis could not demonstrate older age as a risk factor for ventilator-associated pneumonia. Ventilator-associated pneumonia in elderly patients was more frequently caused by Enterobacteriaceae (24% in middle-aged, 32% in old, and 43% in very old patients; p = 0.042). Regarding clinical signs and symptoms at ventilator-associated pneumonia onset, new temperature rise was less frequent among very old patients (59% vs 76% and 74% for middle-aged and old patients, respectively; p = 0.035). Mortality among patients with ventilator-associated pneumonia was higher among elderly patients: 35% in middle-aged patients versus 51% in old and very old patients (p = 0.036). Logistic regression analysis confirmed the importance of older age in the risk of death (adjusted odds ratio for old age, 2.1; 95% CI, 1.2-3.9 and adjusted odds ratio for very old age, 2.3; 95% CI, 1.2-4.4). Other risk factors for mortality in ventilator-associated pneumonia were diabetes mellitus, septic shock, and a high-risk pathogen as causative agent. CONCLUSIONS: In this multicenter cohort study, ventilator-associated pneumonia did not occur more frequently among elderly, but the associated mortality in these patients was higher. New temperature rise was less common in elderly patients with ventilator-associated pneumonia, whereas more episodes among elderly patients were caused by Enterobacteriaceae.

Nursing Activities Score as a predictor of family satisfaction in an adult intensive care unit in Greece.

AIM: To study family satisfaction with care in an Intensive Care Unit (ICU) and its association with nursing workload estimated by the Nursing Activities Score (NAS). BACKGROUND: Few previous studies have investigated the association between workload in ICUs and family satisfaction. METHODS: Family Satisfaction ICU 24 (FS ICU-24) questionnaires were distributed to 161 family members (106 respondents). Questionnaires' score, NAS measurements and Simplified Acute Physiology Score II (SAPS-II) data were analysed. RESULTS: The mean total level of family satisfaction was equal to 80.72% (± 9.59). Family members were more satisfied with the level of care compared with decision making. NAS values revealed a shortage of nurses in the morning shift. Moreover, there was a statistically significant positive correlation between NAS and total satisfaction after adjusting for age, length of stay and SAPS-II. CONCLUSIONS: Improvements in clinical practice require the measurement of care quality which particularly includes family satisfaction. Our results indicated that family members were less satisfied with decision making. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should plan for the successful involvement of family members in the decision-making process. Higher levels of nurse staffing might improve the care provided.