Comparative effects of 3,5-diiodo-L-thyronine and 3,5,3'-triiodo-L-thyronine on mitochondrial damage and cGAS/STING-driven inflammation in liver of hypothyroid rats.

Maintaining a well-functioning mitochondrial network through the mitochondria quality control (MQC) mechanisms, including biogenesis, dynamics and mitophagy, is crucial for overall health. Mitochondrial dysfunction caused by oxidative stress and further exacerbated by impaired quality control can trigger inflammation through the release of the damage-associated molecular patterns (mtDAMPs). mtDAMPs act by stimulating the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway. Recently, aberrant signalling of the cGAS-STING axis has been recognised to be closely associated with several sterile inflammatory diseases (e.g. non-alcoholic fatty liver disease, obesity). This may fit the pathophysiology of hypothyroidism, an endocrine disorder characterised by the reduction of thyroid hormone production associated with impaired metabolic fluxes, oxidative balance and inflammatory status. Both 3,5,3'-triiodo-L-tyronine (T3) and its derivative 3,5-diiodo-L-thyronine (3,5-T2), are known to mitigate processes targeting mitochondria, albeit the underlying mechanisms are not yet fully understood. Therefore, we used a chemically induced hypothyroidism rat model to investigate the effect of 3,5-T2 or T3 administration on inflammation-related factors (inflammatory cytokines, hepatic cGAS-STING pathway), oxidative stress, antioxidant defence enzymes, mitochondrial DNA (mtDNA) damage, release and repair, and the MQC system in the liver. Hypothyroid rats showed: i) increased oxidative stress, ii) accumulation of mtDNA damage, iii) high levels of circulating cytokines, iv) hepatic activation of cGAS-STING pathways and v) impairment of MQC mechanisms and autophagy. Both iodothyronines restored oxidative balance by enhancing antioxidant defence, preventing mtDNA damage through the activation of mtDNA repair mechanisms (OGG1, APE1, and POLγ) and promoting autophagy progression. Concerning MQC, both iodothyronines stimulated mitophagy and dynamics, with 3,5-T2 activating fusion and T3 modulating both fusion and fission processes. Moreover, only T3 enhanced mitochondrial biogenesis. Notably, 3,5-T2, but not T3, reversed the hypothyroidism-induced activation of the cGAS-STING inflammatory cascade. In addition, it is noteworthy that 3,5-T2 seems more effective than T3 in reducing circulating pro-inflammatory cytokines IL-6 and IL-1B and in stimulating the release of IL-10, a known anti-inflammatory cytokine. These findings reveal novel molecular mechanisms of hepatic signalling pathways involved in hypothyroidism, which could be targeted by natural iodothyronines, particularly 3,5-T2, paving the way for the development of new treatment strategies for inflammatory diseases.

A novel risk score predicting 30-day hospital re-admission of patients with acute stroke by machine learning model.

BACKGROUND: The 30-day hospital re-admission rate is a quality measure of hospital care to monitor the efficiency of the healthcare system. The hospital re-admission of acute stroke (AS) patients is often associated with higher mortality rates, greater levels of disability and increased healthcare costs. The aim of our study was to identify predictors of unplanned 30-day hospital re-admissions after discharge of AS patients and define an early re-admission risk score (RRS). METHODS: This observational, retrospective study was performed on AS patients who were discharged between 2014 and 2019. Early re-admission predictors were identified by machine learning models. The performances of these models were assessed by receiver operating characteristic curve analysis. RESULTS: Of 7599 patients with AS, 3699 patients met the inclusion criteria, and 304 patients (8.22%) were re-admitted within 30 days from discharge. After identifying the predictors of early re-admission by logistic regression analysis, RRS was obtained and consisted of seven variables: hemoglobin level, atrial fibrillation, brain hemorrhage, discharge home, chronic obstructive pulmonary disease, one and more than one hospitalization in the previous year. The cohort of patients was then stratified into three risk categories: low (RRS = 0-1), medium (RRS = 2-3) and high (RRS >3) with re-admission rates of 5%, 8% and 14%, respectively. CONCLUSIONS: The identification of risk factors for early re-admission after AS and the elaboration of a score to stratify at discharge time the risk of re-admission can provide a tool for clinicians to plan a personalized follow-up and contain healthcare costs.

Ultrasound based tip location of femorally inserted central catheters into the inferior vena cava: A comparison between the transhepatic and the subcostal view.

BACKGROUND: Intraprocedural catheter tip location is currently recommended. Intracavitary EGC and ultrasound are the preferred methods of tip location for catheters with their tip in the superior vena cava or in the right atrium. Though, the best method of intraprocedural tip location for catheters with their tip in the inferior vena cava is still uncertain. One possibility is to visualize the subdiaphragmatic inferior vena cava by ultrasound, using either the transhepatic or the subxiphoid view. METHODS: In this prospective study, we compared two different ultrasound windows for the visualization of the inferior vena cava (transhepatic vs subxiphoid) for the purpose of localizing the catheter tip during the insertion of femorally inserted central catheters. RESULTS: We studied 249 consecutive insertions of central catheters via the superficial femoral vein. Intraprocedural location of the catheter tip was performed by ultrasound, using both transhepatic and subxiphoid view. Visualization of the inferior vena cava was possible only in 81 cases (32.5%) with the subxiphoid view, but it was always possible in all 249 cases with the transhepatic view. The catheter tip was localized in 15 patients out of 81 with the subxiphoid view (18.5%); the transhepatic view allowed the visualization of the tip in all 249 patients. CONCLUSIONS: The applicability of the subxiphoid window has several limitations, both in terms of visualization of the inferior vena cava and localization of the catheter tip. The transhepatic view should be the preferred method for intraprocedural ultrasound localization of the catheter tip in the inferior vena cava.

Machine Learning and Antibiotic Management.

Machine learning and cluster analysis applied to the clinical setting of an intensive care unit can be a valuable aid for clinical management, especially with the increasing complexity of clinical monitoring. Providing a method to measure clinical experience, a proxy for that automatic gestalt evaluation that an experienced clinician sometimes effortlessly, but often only after long, hard consideration and consultation with colleagues, relies upon for decision making, is what we wanted to achieve with the application of machine learning to antibiotic therapy and clinical monitoring in the present work. This is a single-center retrospective analysis proposing methods for evaluation of vitals and antimicrobial therapy in intensive care patients. For each patient included in the present study, duration of antibiotic therapy, consecutive days of treatment and type and combination of antimicrobial agents have been assessed and considered as single unique daily record for analysis. Each parameter, composing a record was normalized using a fuzzy logic approach and assigned to five descriptive categories (fuzzy domain sub-sets ranging from "very low" to "very high"). Clustering of these normalized therapy records was performed, and each patient/day was considered to be a pertaining cluster. The same methodology was used for hourly bed-side monitoring. Changes in patient conditions (monitoring) can lead to a shift of clusters. This can provide an additional tool for assessing progress of complex patients. We used Fuzzy logic normalization to descriptive categories of parameters as a form nearer to human language than raw numbers.

Pax8 and Nkx2-1 haploinsufficiencies differentially affect liver metabolic pathways.

Thyroid dysfunctions are associated with liver diseases ranging, in severity, from insulin resistance (IR) to hepatocellular carcinoma. The pathogenic mechanisms appear complex and are not attributable, exclusively, to the impaired thyroid hormone (TH) signalling. Using a mouse model of human congenital hypothyroidism, young double heterozygote for both NK2 homeobox 1 (Nkx2-1)- and Paired box 8 (Pax8)-null mutations (DHTP) mice, and single heterozygous Pax8+/- and Nkx2-1+/- mice, we studied the liver pathways, the endocrine and metabolic factors affected in conditions of different dysthyroidisms. Young Nkx2-1+/- females displayed a slight hyperthyroidism and, in liver, increased TH signalling (i.e. increased expression of Dio1 and Trß1) and lipogenic gene expression, with triglycerides accumulation. Hypothyroid DHTP and euthyroid Pax8+/- females shared liver and skeletal muscle IR and hepatic hypothyroidism (i.e. reduced expression of Mct8, Dio1 and TRß1), activation of AKT and increased expression of glutathione peroxidase 4. Oxidative stress and reduced mitochondrial COX activity were observed in DHTP mice only. Pax8+/- females, but, unexpectedly, not DHTP ones, displayed transcriptional activation of the hepatic (and renal) gluconeogenic pathway, hypercortisolemia, fasting hyperglycaemia and hyperinsulinemia, reduced serum ß-hydroxybutyrate, associated with hepatic AMPK activation. DHTP mice showed hypercholesterolemia and activation of mTOR. Collectively, the data indicate that heterozygote mutations of Pax8 and Nkx2-1 genes may produce multiple dysmetabolisms, even under systemic euthyroidism. Differential liver pathways and multiple hormonal axes are affected with implications for energy and nutrient homeostasis. The identified players may be specific target in the management of thyroid dysfunction-associated dysmetabolisms in terms of prevention/counteraction of IR, type 2 diabetes and related comorbidities.

Gas conditioning during helmet noninvasive ventilation: effect on comfort, gas exchange, inspiratory effort, transpulmonary pressure and patient-ventilator interaction.

BACKGROUND: There is growing interest towards the use of helmet noninvasive ventilation (NIV) for the management of acute hypoxemic respiratory failure. Gas conditioning through heat and moisture exchangers (HME) or heated humidifiers (HHs) is needed during facemask NIV to provide a minimum level of humidity in the inspired gas (15 mg H2O/L). The optimal gas conditioning strategy during helmet NIV remains to be established. METHODS: Twenty patients with acute hypoxemic respiratory failure (PaO2/FiO2 < 300 mmHg) underwent consecutive 1-h periods of helmet NIV (PEEP 12 cmH2O, pressure support 12 cmH2O) with four humidification settings, applied in a random order: double-tube circuit with HHs and temperature set at 34 °C (HH34) and 37 °C (HH37); Y-piece circuit with HME; double-tube circuit with no humidification (NoH). Temperature and humidity of inhaled gas were measured through a capacitive hygrometer. Arterial blood gases, discomfort and dyspnea through visual analog scales (VAS), esophageal pressure swings (ΔPES) and simplified pressure-time product (PTPES), dynamic transpulmonary driving pressure (ΔPL) and asynchrony index were measured in each step. RESULTS: Median [IqR] absolute humidity, temperature and VAS discomfort were significantly lower during NoH vs. HME, HH34 and HH37: absolute humidity (mgH2O/L) 16 [12-19] vs. 28 [23-31] vs. 28 [24-31] vs. 33 [29-38], p < 0.001; temperature (°C) 29 [28-30] vs. 30 [29-31] vs. 31 [29-32] vs 32. [31-33], p < 0.001; VAS discomfort 4 [2-6] vs. 6 [2-7] vs. 7 [4-8] vs. 8 [4-10], p = 0.03. VAS discomfort increased with higher absolute humidity (p < 0.01) and temperature (p = 0.007). Higher VAS discomfort was associated with increased VAS dyspnea (p = 0.001). Arterial blood gases, respiratory rate, ΔPES, PTPES and ΔPL were similar in all conditions. Overall asynchrony index was similar in all steps, but autotriggering rate was lower during NoH and HME (p = 0.03). CONCLUSIONS: During 1-h sessions of helmet NIV in patients with hypoxemic respiratory failure, a double-tube circuit with no humidification allowed adequate conditioning of inspired gas, optimized comfort and improved patient-ventilator interaction. Use of HHs or HME in this setting resulted in increased discomfort due to excessive heat and humidity in the interface, which was associated with more intense dyspnea. Trail Registration Registered on clinicaltrials.gov (NCT02875379) on August 23rd, 2016.

Diaphragm thickening fraction predicts noninvasive ventilation outcome: a preliminary physiological study.

BACKGROUND: A correlation between unsuccessful noninvasive ventilation (NIV) and poor outcome has been suggested in de-novo Acute Respiratory Failure (ARF) patients. Consequently, it is of paramount importance to identify accurate predictors of NIV outcome. The aim of our preliminary study is to evaluate the Diaphragmatic Thickening Fraction (DTF) and the respiratory rate/DTF ratio as predictors of NIV outcome in de-novo ARF patients. METHODS: Over 36 months, we studied patients admitted to the emergency department with a diagnosis of de-novo ARF and requiring NIV treatment. DTF and respiratory rate/DTF ratio were measured by 2 trained operators at baseline, at 1, 4, 12, 24, 48, 72 and 96 h of NIV treatment and/or until NIV discontinuation or intubation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of DTF and respiratory rate/DTF ratio to distinguish between patients who were successfully weaned and those who failed. RESULTS: Eighteen patients were included. We found overall good repeatability of DTF assessment, with Intra-class Correlation Coefficient (ICC) of 0.82 (95% confidence interval 0.72-0.88). The cut-off values of DTF for prediction of NIV failure were < 36.3% and < 37.1% for the operator 1 and 2 (p < 0.0001), respectively. The cut-off value of respiratory rate/DTF ratio for prediction of NIV failure was > 0.6 for both operators (p < 0.0001). CONCLUSION: DTF and respiratory rate/DTF ratio may both represent valid, feasible and noninvasive tools to predict NIV outcome in patients with de-novo ARF. Trial registration ClinicalTrials.gov Identifier: NCT02976233, registered 26 November 2016.

Physiological Comparison of High-Flow Nasal Cannula and Helmet Noninvasive Ventilation in Acute Hypoxemic Respiratory Failure.

Rationale: High-flow nasal cannula (HFNC) and helmet noninvasive ventilation (NIV) are used for the management of acute hypoxemic respiratory failure.Objectives: Physiological comparison of HFNC and helmet NIV in patients with hypoxemia.Methods: Fifteen patients with hypoxemia with PaO2/FiO2 < 200 mm Hg received helmet NIV (positive end-expiratory pressure ≥ 10 cm H2O, pressure support = 10-15 cm H2O) and HFNC (50 L/min) in randomized crossover order. Arterial blood gases, dyspnea, and comfort were recorded. Inspiratory effort was estimated by esophageal pressure (Pes) swings. Pes-simplified pressure-time product and transpulmonary pressure swings were measured.Measurements and Main Results: As compared with HFNC, helmet NIV increased PaO2/FiO2 (median [interquartile range]: 255 mm Hg [140-299] vs. 138 [101-172]; P = 0.001) and lowered inspiratory effort (7 cm H2O [4-11] vs. 15 [8-19]; P = 0.001) in all patients. Inspiratory effort reduction by NIV was linearly related to inspiratory effort during HFNC (r = 0.84; P < 0.001). Helmet NIV reduced respiratory rate (24 breaths/min [23-31] vs. 29 [26-32]; P = 0.027), Pes-simplified pressure-time product (93 cm H2O ⋅ s ⋅ min-1 [43-138] vs. 200 [168-335]; P = 0.001), and dyspnea (visual analog scale 3 [2-5] vs. 8 [6-9]; P = 0.002), without affecting PaCO2 (P = 0.80) and comfort (P = 0.50). In the overall cohort, transpulmonary pressure swings were not different between treatments (NIV = 18 cm H2O [14-21] vs. HFNC = 15 [8-19]; P = 0.11), but patients exhibiting lower inspiratory effort on HFNC experienced increases in transpulmonary pressure swings with helmet NIV. Higher transpulmonary pressure swings during NIV were associated with subsequent need for intubation.Conclusions: As compared with HFNC in hypoxemic respiratory failure, helmet NIV improves oxygenation, reduces dyspnea, inspiratory effort, and simplified pressure-time product, with similar transpulmonary pressure swings, PaCO2, and comfort.

Early coagulation support protocol: A valid approach in real-life management of major trauma patients. Results from two Italian centres.

INTRODUCTION: Early coagulation support (ECS) includes prompt infusion of tranexamic acid, fibrinogen concentrate, and packed red blood cells for initial resuscitation of major trauma patients. The aim of this study was to determine the effects, in terms of blood product consumption, length of stay, and in-hospital mortality, of the ECS protocol, compared to the massive transfusion protocol (MTP) in the treatment of major trauma patients. PATIENTS AND METHODS: A retrospective analysis was conducted using the registry data of two Italian trauma centres. Adult major trauma patients with, or at risk of, active bleeding who were managed according to the MTP during the years 2011-2012, or the ECS protocol during the years 2013-2014 and were considered at risk of multiple transfusions, were enrolled. The primary endpoint was to determine whether the ECS protocol reduces the use of blood products in the acute management of trauma patients. Secondary endpoints were the outcome measures of length of stay in ICU, length of stay in hospital, and mortality at 24-hours and 28-days after hospital admission. RESULTS: Among the 518 major trauma patients admitted to the trauma centres during the study period, 235 patients (118 in the pre-ECS period and 117 in the ECS period) matched one of the inclusion criteria and were enrolled in the study. Compared with the pre-ECS period, the ECS period showed a reduction in the average consumption of packed red blood cells (-1.87 units, 95% confidence interval [CI], -2.40, -1.34), platelets (-1.28 units; 95% CI, -1.64, -0.91), and fresh frozen plasma (-1.69; 95% CI, -2.14, -1.25) in the first 24-hours. Furthermore, during the ECS period, we recorded a 10-day reduction in the hospital length of stay (-10 days, 95% CI, -11.6, -8.4) and a non-significant 28-day mortality increase. CONCLUSIONS: The ECS protocol was effective in reducing blood product consumption compared to the MTP and confirmed the importance of early fibrinogen administration as a strategy of rapid coagulation. This novel approach may be adopted in real-life management of major trauma patients.

Data on the application of early coagulation support protocol in the management of major trauma patients.

This article provides additional data on the application of early coagulation support protocol in the management of major trauma patients. Data come from a retrospective analysis reported in the article "Early coagulation support protocol: a valid approach in real-life management of major trauma patients. Results from two Italian centres" [1]. Data contain information about the relationship between differences in resource use and mortality outcomes, and patient demographic and clinical features at presentation. Furthermore, a comparison between resource consumption, the probability of multiple transfusions and the mortality outcomes among propensity-score matched patients is reported.

Comparisons of two diaphragm ultrasound-teaching programs: a multicenter randomized controlled educational study.

BACKGROUND: This study aims to ascertain whether (1) an educational program is sufficient to achieve adequate Diaphragm Ultrasound (DUS) assessments on healthy volunteers and (2) combining a video tutorial with a practical session is more effective in making learners capable to obtain accurate DUS measurements, as opposed to sole video tutorial. RESULTS: We enrolledstep 1: 172 volunteers naïve to ultrasound. After watching a video tutorial, a questionnaire was administered and considered to be passed when at least 70% of the questions were correctly answered. Course participants who passed the theoretical test were randomized to either intervention or control group. Learners randomized to the interventional group underwent to a practical training, tutored by an expert, before accessing DUS examination. Participants randomized to the control group directly accessed DUS examination, without any practical training. DUS measurements by learners and tutors were recorded and checked for accuracy, according to predefined criteria. Detection of both acoustic windows and accurate DUS assessment was achieved by 83.7% learners of the intervention group while 3.5% only among controls (p < 0.0001). The subcostal view of the diaphragm was correctly identified by 92% and 65% learners in the intervention and control groups, respectively (p < 0.0001) while the apposition zone by 86% and 71% learners, respectively (p = 0.026). An accurate diaphragm displacement (DD) measurement was obtained by 91% and 45% learners in the intervention and control groups, respectively (p < 0.0001) while an accurate thickening fraction (TF) measurement by 99% and 21%, respectively (p < 0.0001). DD measurements by both groups of learners were significantly correlated with those assessed by expert tutors; however, a significant improvement of measurement accuracy was found in learners randomized to receive also the practical training, compared to controls. CONCLUSIONS: A combined approach consisting of a theoretical module followed by a practical training is more effective in managing acoustic windows and performing accurate measurements when compared to an exclusively theoretical course. Trial registration prospectively registered on clinicaltrials.gov (Identifier: NCT03704129; release date 17th October 2018).

Randomized, multicenter trial of lateral Trendelenburg versus semirecumbent body position for the prevention of ventilator-associated pneumonia.

PURPOSE: The lateral Trendelenburg position (LTP) may hinder the primary pathophysiologic mechanism of ventilator-associated pneumonia (VAP). We investigated whether placing patients in the LTP would reduce the incidence of VAP in comparison with the semirecumbent position (SRP). METHODS: This was a randomized, multicenter, controlled study in invasively ventilated critically ill patients. Two preplanned interim analyses were performed. Patients were randomized to be placed in the LTP or the SRP. The primary outcome, assessed by intention-to-treat analysis, was incidence of microbiologically confirmed VAP. Major secondary outcomes included mortality, duration of mechanical ventilation, and intensive care unit length of stay. RESULTS: At the second interim analysis, the trial was stopped because of low incidence of VAP, lack of benefit in secondary outcomes, and occurrence of adverse events. A total of 194 patients in the LTP group and 201 in the SRP group were included in the final intention-to-treat analysis. The incidence of microbiologically confirmed VAP was 0.5% (1/194) and 4.0% (8/201) in LTP and SRP patients, respectively (relative risk 0.13, 95% CI 0.02-1.03, p = 0.04). The 28-day mortality was 30.9% (60/194) and 26.4% (53/201) in LTP and SRP patients, respectively (relative risk 1.17, 95% CI 0.86-1.60, p = 0.32). Likewise, no differences were found in other secondary outcomes. Six serious adverse events were described in LTP patients (p = 0.01 vs. SRP). CONCLUSIONS: The LTP slightly decreased the incidence of microbiologically confirmed VAP. Nevertheless, given the early termination of the trial, the low incidence of VAP, and the adverse events associated with the LTP, the study failed to prove any significant benefit. Further clinical investigation is strongly warranted; however, at this time, the LTP cannot be recommended as a VAP preventive measure. CLINICALTRIALS. GOV IDENTIFIER: NCT01138540.

Ultrasound assessment of rectus femoris and anterior tibialis muscles in young trauma patients.

PURPOSE: Quantitative and qualitative changes of skeletal muscle are typical and early findings in trauma patients, being possibly associated with functional impairment. Early assessment of muscle changes-as evaluated by muscle ultrasonography-could yield important information about patient's outcome. METHODS: In this prospective observational study, we used ultrasonography to evaluate the morphological changes of rectus femoris (RF) and anterior tibialis (AT) muscles in a group of young, previously healthy trauma patients on enteral feeding. RESULTS: We studied 38 severely injured patients (median Injury Severity Score = 34; median age = 40 y.o.) over the course of the ICU stay up to 3 weeks after trauma. We found a progressive loss of muscle mass from day 0 to day 20, that was more relevant for the RF (45%) than for the AT (22%); this was accompanied by an increase in echogenicity (up to 2.5 by the Heckmatt Scale, where normal echogenicity = 1), which is an indicator of myofibers depletion. CONCLUSIONS: Ultrasound evaluation of skeletal muscles is inexpensive, noninvasive, simple and easily repeatable. By this method, we were able to quantify the morphological changes of skeletal muscle in trauma patients. Further studies may rely on this technicque to evaluate the impact of different therapeutic strategies on muscle wasting.

Clinical impact of pulmonary sampling site in the diagnosis of ventilator-associated pneumonia: A prospective study using bronchoscopic bronchoalveolar lavage.

PURPOSE: It is unclear whether ventilator-associated pneumonia (VAP) is actually a bilateral and multifocal process. In addition, the diagnostic role of chest x-ray is under debate. Assuming a low microbiologic concordance between the left and right lungs, the reliability of a single pulmonary sampling becomes questionable. The purpose of this study was to determine whether the choice of the pulmonary sampling area is clinically relevant in the management of VAP. METHODS: In 79 patients admitted to a university general intensive care unit with clinically suspected VAP, right- and left-lung bronchoalveolar lavage (BAL) samples were taken with separate bronchoscopes and quantitatively cultured. Primary end-point variable was microbiologic concordance rate between right- and left-lung BAL cultures. Secondary outcomes included predictors of microbiologic concordance, rates of appropriate antibiotic treatment, and diagnostic accuracy of chest x-ray. RESULTS: BAL cultures were bilaterally negative in 21 (27%) of 79 patients, bilaterally positive in 36 (46%), and unilaterally positive (right in 12, left in 10) in 22 (28%). Intra-patient concordance was observed in 47 (59.5%) of 79 cases and independently associated with purulent secretions and bilateral infiltrates on chest x-ray. In simulated prescribing experiments, treatments chosen based on right or left cultures alone were as appropriate as those based on bilateral data in >90% of cases. The presence of a radiographic infiltrate in the sampling area predicted BAL culture positivity with a positive predictive value of only 61%. CONCLUSIONS: In patients with clinically suspected VAP (especially those without purulent secretions or without radiographically documented bilateral infiltrates), quantitative culture of a single BAL sample may provide an incomplete assessment of lung microbiology, without having a relevant impact on the appropriateness of antimicrobial treatment. These findings suggest that single sampling of respiratory secretions, regardless radiographic opacity, seems to be a reliable diagnostic method in the management of VAP.

Risk factors and outcome of Acinetobacter baumanii infection in severe trauma patients.

OBJECTIVE: To investigate incidence, risk factors and outcome of Acinetobacter baumanii infection in trauma patients. DESIGN AND SETTING: A retrospective analysis of prospectively collected data of all trauma patients admitted to a general intensive care unit (ICU) of a 1,500-bed university hospital over 3 years. PATIENTS: Three hundred thirty trauma patients were included in the study. RESULTS: Thirty-six (10.9%) cases of A. baumanii infection were observed; 29 of them were late onset pneumonia. Patients with A. baumanii infection had a significantly higher Injury Severity Score (ISS) (p = 0.02), a lower Glasgow Coma Scale (GCS) on ICU admission (p = 0.03), stayed longer in the ICU (p = 0.00001), were mechanically ventilated for a longer period of time (p = 0.00001), were more frequently admitted to the emergency department with hypotension (p = 0.02), and had trans-skeletal traction for more than 3 days (p = 0.003) in comparison to the 294 patients who did not develop A. baumanii infection. At multivariate analysis the time spent on mechanical ventilation (p = 0.02) and the presence of long-term trans-skeletal traction (p = 0.04) were the only independent risk factors for A. baumanii infection. Patients with A. baumanii infection had a high mortality rate (9 out of 36; 25.0%). ISS (p = 0.003), GCS (p = 0.001) and older age (p = 0.00001), but not A. baumanii infection (p = 0.15), were independently correlated with mortality. CONCLUSIONS: In trauma patients prolonged mechanical ventilation and delayed fracture fixation with the persistence of trans-skeletal traction were major risk factors for A. baumanii infection. The presence of this infection was not correlated with mortality.

Reporting, access, and transparency: better infrastructure of clinical trials.

Open access to information in medical science and adequate reporting of clinical trials may allow investigators and editors to recognize bias in study designs and avoid unnecessary duplication of efforts. Unfortunately, most of clinical trials are very expensive and are often supported by industries that may have financial reasons to hide or partially disclose results. However, investigators and editors have a greater interest in publishing results that can immediately change clinical practice rather than negative results, thus contributing to facilitate publication biases. Several years ago, legislation in several countries mandated the registration of clinical trials as an effective means of promoting information access and full transparency in medical research. However, comprehensive registers have not been adequately supported by law, particularly in Europe, where legislation has ironically contributed to fragmented research, and dampened its competitiveness and productivity. In this context, appropriate strategies help to protect the independence of academic research and ensure full transparency in medical science.