The beneficial effects of TAVI in mitral insufficiency.

Background Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization. Methods This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion, pleural effusion needing drainage, and renal insufficiency events (estimated glomerular filtration rate ≤30/mL/min per 1.73 m2) in de novo HTx recipients receiving immediate everolimus (EVR-I) (≤144 hours post-HTx) or delayed everolimus (EVR-D) (4-6 weeks post-HTx with mycophenolate mofetil as a bridge) with reduced-dose cyclosporine A. Cumulative incidence of biopsy-proven rejection ≥ 2R, rejection with hemodynamic compromise, graft loss, or death was the secondary composite efficacy endpoint. Results Overall, 181 patients were randomized to the EVR-I (n = 89) or EVR-D (n = 92) arms. Incidence of primary safety endpoint was higher for EVR-I than EVR-D arm (44.9% vs 32.6%; P = 0.191), mainly driven by a higher rate of pericardial effusion (33.7% vs 19.6%; P = 0.04); wound healing delays, acute renal insufficiency events, and pleural effusion occurred at similar frequencies in the study arms. Efficacy failure was not significantly different in EVR-I arm versus EVR-D arm (37.1% vs 28.3%; P = 0.191). Three patients in the EVR-I arm and 1 in the EVR-D arm died. Incidence of clinically significant adverse events leading to discontinuation was higher in EVR-I arm versus EVR-D arm (P = 0.02). Conclusions Compared with immediate initiation, delayed everolimus initiation appeared to provide a clinically relevant early safety benefit in de novo HTx recipients, without compromising efficacy. © 2017 The Author(s). Published by Wolters Kluwer Health, Inc

Antibiotic therapy, supportive treatment and management of immunomodulation-inflammation response in community acquired pneumonia: review of recommendations

Community-acquired pneumonia is a common and serious disease, with high rates of morbidity and mortality. Management and treatment of community-acquired pneumonia are described in three main documents: the 2007 American Thoracic Society guidelines, the 2011 European Respiratory Society guidelines, and the 2009 British Thoracic Society guidelines, updated by the NICE in 2015. Despite the validity of current guidelines in improving prognosis and management of patients with community-acquired pneumonia, not all recommendations have high levels of evidence and there are still some controversial issues. In particular, there are some areas of low evidence such as the efficacy of an antibiotic molecule or scheme in patients with same risk factors; duration of antibiotic treatment, supportive therapy for acute respiratory failure and immunomodulation molecules. This review will summarize the main recommendations with high level of evidence and discuss the recommendations with lower evidence, analyzing the studies published after the guidelines' release

Staphylococcus haemolyticus superinfection of Legionella pneumonia during infliximab therapy

We present the case of a 42-year-old man affected by psoriasis with Staphylococcus Haemolyticus superinfection of Legionella pneumonia during infliximab therapy. The introduction of compounds that block TNF-\u3b1 has yielded great benefits for patients affected by selected autoimmune diseases that fail to respond to classic anti-inflammatory agents, but, on the other hand, has led to an increased susceptibility to infections, in particular of those caused by intracellular pathogens, such as L. Pneumophila. Emerging evidence suggests that legionellosis can be complicated by superinfection with other agents, including saprophytic microorganisms, among which coagulasenegative staphylococci. To our knowledge, this is the first report of systemic legionellosis with superinfection by S. haemolyticus, an emerging nosocomial multi-resistant pathogen that commonly causes septicemia, osteomyelitis or endocarditis, but has not so far been associated with necrotizing pneumonia. Despite the optimal antimicrobial therapy for Staphylococcus spp. Pneumonia is still controversial, evidence suggests that in patients with confirmed positivity for methicillin resistant strains, particularly if sensitivity to vancomycin is suboptimal, linezolid should be the first choice therapy, being superior to vancomycin and teicoplanin

Bronchoalveolar Lavage-microRNAs Are Potential Novel Biomarkers of Outcome after Lung Transplantation

Background. Primary graft dysfunction, infections, and acute rejection (AR) worsen lung transplantation (LTx) outcome and patient survival. Despite significant efforts, reliable biomarkers of acute lung allograft dysfunction are lacking. To address this issue, we profiled the bronchoalveolar lavage (BAL) miRNome in LTx patients. Methods. BAL-microRNAs (miRNAs) from 16 patients were collected 7 days (T0), 15 days (T1), and 3 months (T2) after bilateral LTx and profiled on low-density array. Unsupervised and supervised analyses were used to identify miRNAs associated with clinical features, pneumonia, or AR. Prognostic markers were identified using the Cox model. Targeted signaling pathways were predicted in silico. A second series of 11 patients were used to validate AR-associated miRNAs. Results. Variation in BAL-miRNAs was associated with acute lung allograft dysfunction. Increased levels of miR-23b-3p at T2 were detected in patients with pneumonia, whereas let-7f-5p, miR-146b-3p, miR-22-5p, miR-29c-5p, miR-362-5p, and miR-452-5p were upregulated at T2 in patients with AR. miR-148b-5p and miR-744-3p distinguished LTx patients with AR in both cohorts. Low miR-148b-5p and high miR-744-3p expression levels were significantly associated with a shorter time to AR either within the first year after LTx or during follow-up. Combination of the 2 miRNAs identified LTx patients with higher AR risk independently of clinical variables. Conclusions. Our data provide new insights into the roles of BAL-miRNAs in regulating the pulmonary environment after transplantation and suggest that these miRNAs could serve as biomarkers of early- or mid-stage events. If validated, these findings could pave the way to a personalized clinical approach in LTx patients

Non-invasive continuous positive airway pressure in monolateral lung transplant patient with pneumonia and IPF

Patients who undergo lung transplantation are prone to develop lower respiratory tract infections, leading to severe acute respiratory failure (ARF). Endotracheal intubation may not be indicated in these patients in light of a higher rate of mortality due to infections. The application of non-invasive ventilation could play a role in bridging these patients through the episode of ARF waiting for medical treatment to have effect. We report the evidence of morphological and physiological effects of the application of non-invasive continuous positive airway pressure during ARF sustained by pneumonia in a patient who underwent left lung transplantation because of idiopathic pulmonary fibrosis (IPF). We studied the effects of the application of positive end-expiratory pressure on both the right native lung affected by IPF and the transplanted lung affected by pneumonia

Sympatho-Vagal Dysfunction in Patients with End-Stage Lung Disease Awaiting Lung Transplantation

Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx; 19 men, age 38 \ub1 15 years) and 49 healthy non-smoking controls (HC; 22 men, age 40 \ub1 16 years) were enrolled in a case-control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients

Reliability of computed tomography (CT) quantitative analysis in lung transplantation follow-up

Functional analysis of CT imaging in lung-transplanted patients is an emerging tool for the interpretation of parenchymal (patterns) evolution after lung transplantation (LT). Aim of this study was to determine the trends of pulmonary function (PFT) indices and quantitative CT parameters within 1-year followup. We prospectively collected PFT parameters (FEV1, FVC) and inspiration/expiration CT scans of LT patients at standard time-points (3-6-12 months). Specific gas volume (SV , ml/g) was measured on CT images as previously described (Salito et al, Radiology 2009; Aliverti et al, ERJ 2013). Selected quantitative indexes were lung volume at inspiration (V ) and the difference between inspiration and expiration SV normalized on expiration SV : \u394SV /SV EXP. Patients who experienced uneventful 12 months postoperative course after bilateral LT were included. Fifteen patients completed the trial. As expected, FEV1 and FVC values significantly improved at each time-point until the 12-month check. Correspondingly, V and \u394SV / SV EXP increased in the same fashion with a trend toward healthy values (Fig1, bottom panels). This preliminary trial evidenced the reliability of specific gas volume analysis as an attractive quantitative CT parameter of lung function after LT. Future studies are requested to verify the accuracy of specific gas volume analysis in the evaluation of patients with lung allograft dysfunction

Non-invasive continuous positive airway pressure in monolateral lung transplant patient with pneumonia and IPF

Patients who undergo lung transplantation are prone to develop lower respiratory tract infections, leading to severe acute respiratory failure (ARF). Endotracheal intubation may not be indicated in these patients in light of a higher rate of mortality due to infections. The application of non-invasive ventilation could play a role in bridging these patients through the episode of ARF waiting for medical treatment to have effect. We report the evidence of morphological and physiological effects of the application of non-invasive continuous positive airway pressure during ARF sustained by pneumonia in a patient who underwent left lung transplantation because of idiopathic pulmonary fibrosis (IPF). We studied the effects of the application of positive end-expiratory pressure on both the right native lung affected by IPF and the transplanted lung affected by pneumonia

Regional analysis with quantitative computed tomography after lung transplantation

Regional analysis with quantitative computed tomography (CT) of graft could be an attractive technique to interpret lung patterns after transplantation. Aim of this study was the definition of lung regional patterns in the early post-transplantation period. We prospectively collected the CT scans at end-expiration (EXP) and full-inspiration (INSP) of patients at 3 months after lung transplantation (LT). Lungs were segmented from both scans. INSP images were registered to EXP by optical flow to obtain maps of density variation (\u394HU) with pixel-by-pixel subtraction. We evaluated a classification of the pixels from maps of \u394HU in low ventilation (LV), consolidation (C), air trapping (AT) and healthy parenchyma (H). Patients who experienced uneventful early postoperative course after bilateral LT were enrolled. The figure shows the resulted composition of the parenchyma in 20 patients: LV=59.6\ub15.4%, C=1.7\ub10.4%, AT=0.06\ub10.05%, H=38.7\ub15.6%. To note that low ventilation pattern still affected the majority of lung tissue while consolidation and air trapping were negligible. Quantitative CT regional analysis may provide a significant advance in the interpretation of ventilation abnormalities after LT

The effect of primary graft dysfunction after lung transplantation on parenchymal remodeling detected by quantitative computed tomography

Background: Regional analysis by computed tomography (CT) is an attractive technique to interpret lung patterns after transplantation (LTx). We evaluated the application of CT functional mask derived parameters to determine whether development of primary graft dysfunction (PGD) is associated with short and/or long-term postoperative evidences of pulmonary function alterations. Methods: A total of 38 patients who underwent bilateral LTx were evaluated at 24, 48 and 72 hours after the end of surgery to establish PGD occurrence and grading. CT scans at 3 and 12 months after LTx were analyzed to measure specific gas volume (SV g ) changes normalized on expiratory SVgEXP of the whole lung (\u394SV g /SV gEXP ) and to obtain functional masks of density variation, namely maps of low ventilation (LV), consolidation (C), air trapping (AT) and healthy parenchyma (H). Results: Our main result was the evidence of a marked decrease in \u394SV g /SV gEXP in all subjects, irrespectively on PGD, at each time point after LTx, indicating a high degree of ventilation defects versus healthy. High percentages of LV were found in all subjects while percentages of AT and C were negligible. Conclusions: We demonstrate that quantification of ventilation defects by CT functional mask offers insights into the correlation between PGD and pulmonary function after LTx at short and mid-term