Nebulized Amikacin and Fosfomycin for Severe Pseudomonas aeruginosa Pneumonia: An Experimental Study.

OBJECTIVES: Latest trials failed to confirm merits of nebulized amikacin for critically ill patients with nosocomial pneumonia. We studied various nebulized and IV antibiotic regimens in a porcine model of severe Pseudomonas aeruginosa pneumonia, resistant to amikacin, fosfomycin, and susceptible to meropenem. DESIGN: Prospective randomized animal study. SETTING: Animal Research, University of Barcelona, Spain. SUBJECTS: Thirty female pigs. INTERVENTIONS: The animals were randomized to receive nebulized saline solution (CONTROL); nebulized amikacin every 6 hours; nebulized fosfomycin every 6 hours; IV meropenem alone every 8 hours; nebulized amikacin and fosfomycin every 6 hours; amikacin and fosfomycin every 6 hours, with IV meropenem every 8 hours. Nebulization was performed through a vibrating mesh nebulizer. The primary outcome was lung tissue bacterial concentration. Secondary outcomes were tracheal secretions P. aeruginosa concentration, clinical variables, lung histology, and development of meropenem resistance. MEASUREMENTS AND MAIN RESULTS: We included five animals into each group. Lung P. aeruginosa burden varied among groups (p < 0.001). In particular, IV meropenem and amikacin and fosfomycin + IV meropenem groups presented lower P. aeruginosa concentrations versus amikacin and fosfomycin, amikacin, CONTROL, and fosfomycin groups (p < 0.05), without significant difference between these two groups undergoing IV meropenem treatment. The sole use of nebulized antibiotics resulted in dense P. aeruginosa accumulation at the edges of the interlobular septa. Amikacin, amikacin and fosfomycin, and amikacin and fosfomycin + IV meropenem effectively reduced P. aeruginosa in tracheal secretions (p < 0.001). Pathognomonic clinical variables of respiratory infection did not differ among groups. Resistance to meropenem increased in IV meropenem group versus amikacin and fosfomycin + meropenem (p = 0.004). CONCLUSIONS: Our findings corroborate that amikacin and fosfomycin alone efficiently reduced P. aeruginosa in tracheal secretions, with negligible effects in pulmonary tissue. Combination of amikacin and fosfomycin with IV meropenem does not increase antipseudomonal pulmonary tissue activity, but it does reduce development of meropenem-resistant P. aeruginosa, in comparison with the sole use of IV meropenem. Our findings imply potential merits for preemptive use of nebulized antibiotics in order to reduce resistance to IV meropenem.

Context-Dependent Effect of Glucocorticoids on the Proliferation, Differentiation, and Apoptosis of Regulatory T Cells: A Review of the Empirical Evidence and Clinical Applications.

Glucocorticoids (GCs) are widely used to treat several diseases because of their powerful anti-inflammatory and immunomodulatory effects on immune cells and non-lymphoid tissues. The effects of GCs on T cells are the most relevant in this regard. In this review, we analyze how GCs modulate the survival, maturation, and differentiation of regulatory T (Treg) cell subsets into both murine models and humans. In this way, GCs change the Treg cell number with an impact on the mid-term and long-term efficacy of GC treatment. In vitro studies suggest that the GC-dependent expansion of Treg cells is relevant when they are activated. In agreement with this observation, the GC treatment of patients with established autoimmune, allergic, or (auto)inflammatory diseases causes an expansion of Treg cells. An exception to this appears to be the local GC treatment of psoriatic lesions. Moreover, the effects on Treg number in patients with multiple sclerosis are uncertain. The effects of GCs on Treg cell number in healthy/diseased subjects treated with or exposed to allergens/antigens appear to be context-dependent. Considering the relevance of this effect in the maturation of the immune system (tolerogenic response to antigens), the success of vaccination (including desensitization), and the tolerance to xenografts, the findings must be considered when planning GC treatment.

Identification of 15 T Cell Restricted Genes Evaluates T Cell Infiltration of Human Healthy Tissues and Cancers and Shows Prognostic and Predictive Potential.

T cell gene signatures are used to evaluate T cell infiltration of non-lymphoid tissues and cancers in both experimental and clinical settings. However, some genes included in the available T cell signatures are not T cell-restricted. Herein, we propose a new human T cell signature that has been developed via a six-step procedure and comprises 15 T cell restricted genes. We demonstrate the new T cell signature, named signature-H, that differs from other gene signatures since it shows higher sensitivity and better predictivity in the evaluation of T cell infiltration in healthy tissues as well as 32 cancers. Further, results from signature-H are highly concordant with the immunohistochemistry methods currently used for assessing the prognosis of neuroblastoma, as demonstrated by the Kaplan-Meier curves of patients ranked by tumor T cell infiltration. Moreover, T cell infiltration levels calculated using signature-H correlate with the risk groups determined by the staging of the neuroblastoma. Finally, multiparametric analysis of tumor-infiltrating T cells based on signature-H let us favorably predict the response of melanoma to the anti-PD-1 antibody nivolumab. These findings suggest that signature-H evaluates T cell infiltration levels of tissues and may be used as a prognostic tool in the precision medicine perspective after appropriate clinical validation.

Brain 3D-echographic early predictors of neuro-behavioral disorders in infants: a prospective observational study.

BACKGROUND: Prematurity, low birth weight (LBW), very low birth weight (VLBW), and intrauterine growth restriction (IUGR) are risk factors of long-term poor neuro-development outcomes and associate with reduction of regional brain volumes. OBJECTIVE: To evaluate the possible role of 3D ultrasound sonography (3DUS) regional brain volumes, measured at 30-40 days of postnatal period, as early predictors of long-term risk of neuro-behavioral disorders. METHODS: A highly selected population, which included: full-term, preterm, IUGR, and preterm-IUGR born individuals, was followed longitudinally from 30 to 40 days of postnatal period to the second year of life. The population was mostly composed of bichorionic twins to ensure a, theoretically, major intracategory homogeneity. Preterm and IUGR subjects were characterized by a gestational age (GA) and birth weight (BW)>32 weeks and >1500 g, respectively, whereas the full-term neonates were of 37 weeks GA. At enrollment, the assessment of the volumetric measurements was performed using the 3DUS. The evaluation of neuro-development was performed at 2 years using the Griffiths Mental Development Scales. RESULTS: The 3DUS measurements of whole brain, thalamus, frontal cortex, and cerebellum volumes, assessed at 30-40 days of postnatal period, were significantly reduced in infants characterized by negative outcome. In addition, the respective areas of the ROC curves, made by comparing values of normal and abnormal neuro-development groups, were indicative of a strong diagnostic accuracy. CONCLUSION: Data found suggest that the 3DUS regional brain volumes may assume a significant role as early indicators of neonates at major risk of neuro-behavioral disorders in later life. Further and larger studies in this direction are needed to validate this significant perspective.

Urinary Nerve Growth Factor in full-term, preterm and intra uterine growth restriction neonates: Association with brain growth at 30-40 days of postnatal period and with neuro-development outcome at two years. A pilot study.

Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) are crucial for the peripheral and central nervous system development, respectively, and differential brain and blood levels in Intra Uterine Growth Restriction (IUGR) and prematurity have been found. As reduced growth of brain regions, measured at 30-40 days of postnatal period, has been demonstrated in preterm and IUGR neonates who showed impaired neuro-development at two years of age, in this study, the levels of NGF and BDNF were evaluated in the urine samples of 30-40 day-old subjects who were full-term, preterm and IUGR and showed a normal or an abnormal neuro-development at follow up after two years. Neurotrophins were measured concurrently with volumes of whole brain, thalamus, frontal cortex and cerebellum. Values were then correlated with later neuro-developmental outcome. Biochemical parameters and cerebral volumes were assessed using colorimetric ELISA kits and three-dimensional ultra-sonography (3DUS), respectively. Neuro-development was estimated using the Griffiths-II test. Urinary NGF and brain volumes significantly correlated and were lower in preterm and IUGR subjects characterized by poor neuro-development. No differences were seen in the case of BDNF. The present investigation demonstrates, for the first time, the strong and direct association of NGF with brain growth at the initial phase of the postnatal period and with neuro-developmental outcome in later life. Remarkably, urinary NGF may be suggested as an early prognostic indicator of high long-term risk of motor and cognitive impairment in IUGR and preterm neonates.

3-D Echo Brain Volumes to Predict Neurodevelopmental Outcome in Infants: A Prospective Observational Follow-up Study.

Prematurity and intra-uterine growth restriction (IUGR) are risk factors for long-term poor neurodevelopmental outcomes and are associated with reductions in regional brain volumes. In this study, the aim was to determine the possible role of 3-D ultrasonography (3-DUS) volumes of whole brain, thalamus, frontal cortex and cerebellum, measured at postnatal days 30-40, as early predictors of long-term risk for neurobehavioral disorders. To this purpose, a heterogeneous population of full-term, preterm, IUGR and preterm IUGR (pre-IUGR) born individuals (n = 334), characterized by gestational age and birth weight in the ranges 24-41 wk and 860-4000 g, respectively, was followed from postnatal days 30-40 to the second year of life. At enrollment, brain volumes were measured using 3-DUS, whereas neurodevelopment was assessed at 2 y using the Griffiths III test. Cerebral volumes were strictly and significantly lower in infants characterized by a negative outcome and had excellent diagnostic accuracy. The 3-DUS volume of whole brain, thalamus, frontal cortex or cerebellum may be an early predictor of neonates at major risk for neurobehavioral disorders in later life.

Development and characterization of a new swine model of invasive pneumococcal pneumonia.

Streptococcus pneumoniae is the most common microbial cause of community-acquired pneumonia. Currently, there are no available models of severe pneumococcal pneumonia in mechanically ventilated animals to mimic clinical conditions of critically ill patients. We studied endogenous pulmonary flora in 4 healthy pigs and in an additional 10 pigs in which we intra-bronchially instilled S. pneumoniae serotype 19 A, characterized by its resistance to penicillin, macrolides and tetracyclines. The pigs underwent ventilation for 72 h. All pigs that were not challenged with S. pneumoniae completed the 72-h study, whereas 30% of infected pigs did not. At 24 h, we clinically confirmed pneumonia in the infected pigs; upon necropsy, we sampled lung tissue for microbiological/histological confirmation of pneumococcal pneumonia. In control pigs, Streptococcus suis and Staphylococcus aureus were the most commonly encountered pathogens, and their lung tissue mean ± s.e.m. concentration was 7.94 ± 20 c.f.u./g. In infected pigs, S. pneumoniae was found in the lungs of all pigs (mean ± s.e.m. pulmonary concentration of 1.26 × 105 ± 2 × 102 c.f.u./g). Bacteremia was found in 50% of infected pigs. Pneumococcal pneumonia was confirmed in all infected pigs at 24 h. Pneumonia was associated with thrombocytopenia, an increase in prothrombin time, cardiac output and vasopressor dependency index and a decrease in systemic vascular resistance. Upon necropsy, microbiological/histological pneumococcal pneumonia was confirmed in 8 of 10 pigs. We have therefore developed a novel model of penicillin- and macrolide-resistant pneumococcal pneumonia in mechanically ventilated pigs with bacteremia and severe hemodynamic compromise. The model could prove valuable for appraising the pathogenesis of pneumococcal pneumonia, the effects associated with macrolide resistance and the outcomes related to the use of new diagnostic strategies and antibiotic or complementary therapies.

Behavioral responses in people affected by alcohol use disorder and psychiatric comorbidity: correlations with addiction severity.

AIM: In this study, we investigated in people suffering from alcohol use disorder (AUD) with or without dual diagnosis (concomitant psychiatric disability) how they feel their dependence condition. We predicted that AUD people with a dual diagnosis could feel potentiated their addiction. METHODS: Alcohol habits and psychiatric conditions of 183 AUD men and 62 AUD women were measured by using the DSM-5, the severity of alcohol dependence questionnaire (SADQ), the alcohol anamnesis and psychiatric examination by the symptom check list 90-R (SCL-90-R). RESULTS: We have shown that alcohol drinking does not correlate with both psychiatric examination and self-reported psychopathology. SADQ shows that severe alcohol dependence correlates with highest psychiatric symptoms and with the levels of alcohol consumption. CONCLUSIONS: This finding suggests that high SADQ scores may represent a tool to early disclose only patients with dual diagnosis. SADQ may provide information to address pharmacological interventions because revealing aspects of the dark side of addiction potentiated by AUD associated psychopathology.

Short-Term Appraisal of the Effects and Safety of Manual Versus Ventilator Hyperinflation in an Animal Model of Severe Pneumonia.

BACKGROUND: In patients on mechanical ventilation, lung hyperinflation is often performed to reverse atelectasis and clear retained mucus. We evaluated the effects of manual hyperinflation and ventilator hyperinflation on mucus clearance, gas exchange, pulmonary mechanics, and hemodynamics. METHODS: Six mechanically ventilated pigs with severe Pseudomonas aeruginosa pneumonia randomly received either 12 manual hyperinflation breaths over a period of 2 min (through a gradual manual compression of a resuscitation bag within 4 s to achieve 40 cm H2O of airway pressure), or 12 ventilator hyperinflation over 2 min to achieve the same ventilatory end points as in manual hyperinflation. Mucus clearance rate was measured through fluoroscopic tracking of tracheal markers. Prior to each maneuver and 15 min thereafter, we assessed arterial and mixed gas exchange, pulmonary mechanics, and hemodynamics. RESULTS: Both manual hyperinflation and ventilator hyperinflation significantly decreased inspiratory flow by approximately 16 L/min (P < .001) and increased peak expiratory flow by roughly 44 L/min (P < .001). The median (interquartile range) mucus clearance rate was 1.31 (0.84-2.30) prior to the interventions, and 0.70 (0.00-2.58) and 0.65 (0.45-1.47) during manual hyperinflation and ventilator hyperinflation, respectively (P = .09). Hyperinflations, whether delivered manually or through the ventilator, did not significantly modify pulmonary or hemodynamic parameters. CONCLUSIONS: In an animal model of severe P. aeruginosa pneumonia, neither manual hyperinflation nor ventilator hyperinflation improved mucus clearance. If confirmed in comprehensive clinical experimentations, these findings should promote reappraisal of indications for both manual hyperinflation and ventilator hyperinflation as a therapeutic technique for mucus clearance and atelectasis reversal.

Treatment of alcohol dependence. Alcohol and homelessness: social point of view.

The phenomenon of homeless people is eliciting a devastating social impact with an estimated prevalence in the USA and in Europe between 5.6% and 13.9%. These persons have a poor quality of life, a limited or no social life. They are often unemployed or work only occasionally. They are at risk for problems with the law and often suffering from addiction to other drugs, psychiatric and other medical diseases. Alcohol is often not the cause of their social status, but only the result of other discomforts thus contributing to their bio-psycho-social degradation. In 2009 the US Department of Housing and Urban Development's Homelessness Assistance Programs and in 2010 the European Consensus Conference on Homelessness discussed about the social rehabilitation of these people, using the concept of case management. In particular, the Standard Case Management was able to improve the housing stability, to reduce the use of drugs and to remove the working barriers. The Assertive Community Treatment was able to improve the housing stability and had a better efficacy for patients suffering from double diagnosis.

Treatment of alcohol dependence. Alcohol and the young: social point of view.

Adolescents are the most vulnerable group for alcohol-related diseases, as starting to drink at a young age is associated with an increased risk of alcohol dependence in adulthood. Young people tend to drink large amounts of alcohol to seek out strong emotions and for reaching fun at all costs through the psychotropic properties of alcohol. The behavioural motivations of this kind of drinking (binge drinking) depend on the lack of awareness of the harmful effects of alcohol, in the rite of social conviviality (a condition for which alcohol is attributed to the function of facilitating the aggregation among young people), in the absence of personal interests, lack of controls and family habits. Actions to be taken to limit or stop harmful alcohol consumption in young people should be based on interventions aimed at delaying the age of first contact with alcoholic beverages through the implementation of educational campaigns aimed at young people, their families and the whole society.

Treatment of alcohol use disorder from a psychological point of view.

The development of a treatment for alcohol use disorder (AUD) is a crucial and complex moment. Indeed, the information gathered by a team of professionals (physicians, psychologists and social workers) (bio-psycho-social model of AUD) interact to choose the most appropriate cure. As for AUD psychological treatment, it is of considerable importance to avoid clinical treatments leading to drop-out for improving the patients quality of life. Psychoanalytic and behavioral techniques were early utilized as psychological treatment of AUD, however, evidence-based approaches as motivational interviewing (MI) and cognitive behavioral therapy (CBT) are recently used in AUD. In this work we review the more effective and appropriate AUD psychological treatments.

Intensive care unit-acquired pneumonia due to Pseudomonas aeruginosa with and without multidrug resistance.

OBJECTIVE: Pseudomonas aeruginosa often presents multi-drug resistance (MDR) in intensive care unit (ICU)-acquired pneumonia (ICUAP), possibly resulting in inappropriate empiric treatment and worse outcomes. We aimed to identify patients with ICUAP at risk for these pathogens in order to improve treatment selection and outcomes. METHODS: We prospectively assessed 222 consecutive immunocompetent ICUAP patients confirmed microbiologically. We determined the characteristics, risk factors, systemic inflammatory response and outcomes of P. aeruginosa pneumonia (Pa-ICUAP), compared to other aetiologies. We also compared patients with MDR vs. non-MDR Pa-ICUAP. RESULTS: Pseudomonas aeruginosa was the most frequent aetiology (64, 29%); 22 (34%) cases had MDR. Independent predictors for Pa-ICUAP were prior airway colonization by P. aeruginosa, previous antibiotic treatment, solid cancer and shock; alcohol abuse and pleural effusion were independently associated to lower risk for Pa-ICUAP. Chronic liver disease independently predicted MDR among Pa-ICUAP. The inflammatory biomarkers were similar between all groups. Patients with Pa-ICUAP had lower unadjusted 90-day survival (p = 0.049). However, the 90-day survival adjusted for confounding factors using a propensity score did not differ between all groups. CONCLUSION: Pseudomonas aeruginosa remains the most frequent aetiology of ICUAP, with high prevalence of MDR. These risk factors should be taken into account to avoid inappropriate empiric antibiotics for Pa-ICUAP. Pseudomonas aeruginosa, regardless multidrug resistance, was not associated with different propensity-adjusted survival.

The effects of direct hemoperfusion using a polymyxin B-immobilized column in a pig model of severe Pseudomonas aeruginosa pneumonia.

BACKGROUND: Hemoperfusion through a column containing polymyxin B-immobilized fiber (PMX-HP) is beneficial in abdominal sepsis. We assessed the effects of PMX-HP in a model of severe Pseudomonas aeruginosa pneumonia. METHODS: Eighteen pigs with severe P. aeruginosa pneumonia were mechanically ventilated for 76 h. Pigs were randomized to receive standard treatment with fluids and vasoactive drugs, or standard treatment with two 3-h PMX-HP sessions. Antibiotics against P. aeruginosa were never administered. We assessed endotoxemia through the endotoxin activity assay (EA). We measured the static lung elastance, ratio of arterial partial pressure per inspiratory fraction of oxygen (PaO2/FIO2), mean arterial pressure, cardiac output, systemic vascular resistance and inotropic score. Finally, every 24 h, we assessed complete blood count. RESULTS: In comparison with the control group, PMX-HP decreased percentage of circulating neutrophils from 47.4 ± 13.8 to 40.8 ± 11.5 % (p = 0.009). In a subgroup of animals with the worst hemodynamic impairment, EA in the control and PMX-HP groups was 0.50 ± 0.29 and 0.29 ± 0.14, respectively (p = 0.018). Additionally, in the control and PMX-HP groups, static lung elastance was 26.9 ± 8.7 and 25.3 ± 7.5 cm H2O/L (p = 0.558), PaO2/FIO2 was 347.3 ± 61.9 and 356.4 ± 84.0 mmHg (p = 0.118), mean arterial pressure was 81.2 ± 10.3 and 81.6 ± 13.1 mmHg (p = 0.960), cardiac output was 3.30 ± 1.11 and 3.28 ± 1.19 L/min (p = 0.535), systemic vascular resistance was 1982.6 ± 608.4 and 2011.8 ± 750.0 dyne/s/cm(-5) (p = 0.939), and inotropic score was 0.25 ± 0.10 and 0.26 ± 0.18 (p = 0.864). CONCLUSIONS: In mechanically ventilated pigs with severe P. aeruginosa pneumonia, PMX-HP does not have any valuable clinical benefit, and studies are warranted to fully evaluate a potential role of PMX-HP in septic shock associated with severe pulmonary infections.

Resistance patterns and outcomes in intensive care unit (ICU)-acquired pneumonia. Validation of European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) classification of multidrug resistant organisms.

INTRODUCTION: Bacterial resistance has become a major public health problem. OBJECTIVE: To validate the definition of multidrug-resistant organisms (MDRO) based on the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) classification. MATERIAL: Prospective, observational study in six medical and surgical Intensive-Care-Units (ICU) of a University hospital. RESULTS: Three-hundred-and-forty-three patients with ICU-acquired pneumonia (ICUAP) were prospectively enrolled, 140 patients had no microbiological confirmation (41%), 82 patients (24%) developed ICUAP for non-MDRO, whereas 121 (35%) were MDROs. Non-MDRO, MDRO and no microbiological confirmation patients did not present either a significant different previous antibiotic use (p 0.18) or previous hospital admission (p 0.17). Appropriate antibiotic therapy was associated with better ICU survival (105 [92.9%] vs. 74 [82.2%]; p = 0.03). An adjusted multivariate regression logistic analysis identified that only MDRO had a higher ICU-mortality than non-MDRO and no microbiological confirmation patients (OR 2.89; p < 0.05; 95% CI for Exp [ß]. 1.02-8.21); Patients with MDRO ICUAP remained in ICU for a longer period than MDRO and no microbiological confirmation respectively (p < 0.01) however no microbiological confirmation patients had more often antibiotic consumption than culture positive ones. CONCLUSIONS: Patients who developed ICUAP due to MDRO showed a higher ICU-mortality than non-MDRO ones and use of ICU resources. No microbiological confirmation patients had more often antibiotic consumption than culture positive patients. Risk factors for MDRO may be important for the selection of initial antimicrobial therapy, in addition to local epidemiology.

Impact of COPD in the outcome of ICU-acquired pneumonia with and without previous intubation.

BACKGROUND: COPD seems related to poor outcome in patients with ventilator-associated pneumonia (VAP). However, many patients in the ICU with COPD do not require intubation but can also develop pneumonia in the ICU. We, therefore, compared the characteristics and outcomes of patients with ICU-acquired pneumonia (ICUAP) with and without underlying COPD. METHODS: We prospectively assessed the characteristics, microbiology, systemic inflammatory response, and survival of 279 consecutive patients with ICUAP clustered according to underlying COPD or not. The primary end point was 90-day survival. RESULTS: Seventy-one patients (25%) had COPD. The proportion of VAP was less frequent in patients with COPD: 30 (42%) compared with 126 (61%) in patients without COPD (P = .011). Patients with COPD were older; were more frequently men, smokers, and alcohol abusers; and more frequently had previous use of noninvasive ventilation. The rate of microbiologic diagnosis was similar between groups, with a higher rate of Aspergillus species and a lower rate of Enterobacteriaceae in patients with COPD. We found lower levels of IL-6 and IL-8 in patients with COPD without previous intubation. The 90-day mortality was higher in patients with COPD (40 [57%] vs 74 [37%] in patients without COPD, P = .003). Among others, COPD was independently associated with decreased 90-day survival in the overall population (adjusted hazard ratio, 1.94; 95% CI, 1.11-3.40; P = .020); this association was observed only in patients with VAP but not in those without previous intubation. CONCLUSIONS: COPD was independently associated with decreased 90-day survival in patients with VAP but not in those without previous intubation.

Endotracheal tubes for critically ill patients: an in vivo analysis of associated tracheal injury, mucociliary clearance, and sealing efficacy.

BACKGROUND: Improvements in the design of the endotracheal tube (ETT) have been achieved in recent years. We evaluated tracheal injury associated with ETTs with novel high-volume low-pressure (HVLP) cuffs and subglottic secretions aspiration (SSA) and the effects on mucociliary clearance (MCC). METHODS: Twenty-nine pigs were intubated with ETTs comprising cylindrical or tapered cuffs and made of polyvinylchloride (PVC) or polyurethane. In specific ETTs, SSA was performed every 2 h. Following 76 h of mechanical ventilation, pigs were weaned and extubated. Images of the tracheal wall were recorded before intubation, at extubation, and 24 and 96 h thereafter through a fluorescence bronchoscope. We calculated the red-to-green intensity ratio (R/G), an index of tracheal injury, and the green-plus-blue (G+B) intensity, an index of normalcy, of the most injured tracheal regions. MCC was assessed through fluoroscopic tracking of radiopaque markers. After 96 h from extubation, pigs were killed, and a pathologist scored injury. RESULTS: Cylindrical cuffs presented a smaller increase in R/G vs tapered cuffs (P = .011). Additionally, cuffs made of polyurethane produced a minor increase in R/G (P = .012) and less G+B intensity decline (P = .022) vs PVC cuffs. Particularly, a cuff made of polyurethane and with a smaller outer diameter outperformed all cuffs. SSA-related histologic injury ranged from cilia loss to subepithelial inflammation. MCC was 0.9 ± 1.8 and 0.4 ± 0.9 mm/min for polyurethane and PVC cuffs, respectively (P < .001). CONCLUSIONS: HVLP cuffs and SSA produce tracheal injury, and the recovery is incomplete up to 96 h following extubation. Small, cylindrical-shaped cuffs made of polyurethane cause less injury. MCC decline is reduced with polyurethane cuffs.

Avoidance coping strategies, alexithymia and alcohol abuse: a mediation analysis.

Alexithymia and avoidance coping strategies are both associated with alcohol abuse, but their effects have been seldom studied simultaneously. The present study investigated the interplay between alexithymia and avoidance coping strategies in predicting the severity of alcohol abuse in an alcohol-dependent sample. The TAS-20 and COPE-NVI questionnaires were administered to 110 alcoholic inpatients enrolled into a recovery program at the Center for Alcohol Abuse of the Department of Clinical Medicine, Sapienza University of Rome, Italy. The alcohol abuse index consisted of the mean alcohol units consumed by participants and days of abstinence before being enrolled into the recovery program. Results showed that alexithymic alcoholics consumed significantly more alcohol and were less abstinent than non-alexithymic alcoholics. Concerning the relationship among alexithymia, coping strategies and alcohol abuse, data showed that alexithymia completely mediated the effects of avoidance coping strategies on alcohol abuse, suggesting that avoidance strategies have therefore an indirect effect on alcohol abuse among alcoholics. Theoretical and clinical implications of the results are discussed.