Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

The prevalence of sleep impairments and predictors of sleep quality among patients with asthma.

BACKGROUND: Sleep is a significant dimension of daily life. However, only a few studies have examined the sleep quality of asthmatics in a real-world clinical settings. OBJECTIVE: This study is aimed to estimate the prevalence of sleep impairments among asthmatic patients and examine the relationship between sleep quality, asthma control, rhinitis symptoms, and sociodemographic characteristics. METHODS: The present study adopted the observational cross-sectional research design that has been designed by the Italian Respiratory Society and used valid assessments to measure the study variables. RESULTS: Data from 1150 asthmatic patients (mean age 51.01 years ± 16.03) were subjected to analysis. 58.3% of the patients had impaired sleep quality (Pittsburgh Sleep Quality Index [PSQI] total scores > 5), and their mean PSQI score was 5.68 (SD = 3.4). A significant correlation emerged between sleep quality and asthma control (p = 0.0001) and a significant albeit weak correlation emerged between PSQI total scores and Total 5 Symptoms Score (r = 0.24, p = 0.0001). Sleep quality was significantly associated health-related quality of life [HRQoL]. (r = 0.50, p < 0.001). After exclusion of patients at risk for Obstructive Sleep Apnea Syndrome (OSAS) and Gastro Esophageal Reflux Disease (GERD), the most important determinants of PSQI score were HRQoL, In the entire sample asthma control is the strongest predictor of both sleep quality and HRQoL. CONCLUSIONS: The results of this real-world study highlight the prevalence, impact and predictors of sleep disturbances in asthmatic patients and suggest the need for physicians to detect poor sleep quality.

Pulmonary hypertension in COPD and lung transplantation: timing and procedures.

The prevalence of pulmonary hypertension (PH) in the general chronic obstructive pulmonary disease (COPD) population is undefined because stable COPD patients do not routinely undergo screening echocardiogram and right heart catheterization. Most studies published on this topic are focused on a highly selected group of patients with moderate to severe disease awaiting lung transplantation, since hemodynamic data from cardiac catheterization are part of the standard transplant evaluation. In a very recent article, Hurdman et al. studied the characteristics and outcomes, with a particular focus on mortality, of extensively phenotyped, consecutive patients with PH-COPD over a 9-year period. This article offers the opportunity to update the role of PH in COPD as a timer to propose lung transplantation, based on solid literature data on survival, and to select the best procedure (single or double lung transplant), since the outcome indexes based on the old GOLD classification according to FEV1 (1-4) and the new GOLD classification (A-D) have failed in purpose to define the correct timing, due to the lack of functional (6 minutes walking test) and nutritional (Body Mass Index) data. After a revision of available literature including the recent paper of Hurdman et al. we conclude that the timing for lung transplantation is easy to manage in case of severe PH-COPD. On the other hand mild and moderate PH-COPD are still object of debate for therapy, procedure timing and choice and rehabilitation. In other words, we have some confirms for a little percentage of patients, whilst many doubts still exist for the rest.

TB drug susceptibility testing in high fluoroquinolone resistance settings.

BACKGROUND: The insurgence of resistance to key drugs of the BPaLM (bedaquiline + pretomanid + moxifloxacin) regimen is a major concern. In settings with widespread resistance to fluoroquinolones (FQs), like Pakistan, new technologies, such as Xpert® MTB/XDR, may ensure drug resistance upfront screening. This study aims to assess MTB/XDR's performance in detecting FQs and isoniazid resistance, proposing a renewed diagnostic algorithm for drug-resistant TB (DR-TB). METHODS: This cross-sectional prospective study, approved by the local ethical committee, collected samples from people newly and previously diagnosed with TB over 6 months. Xpert® MTB/RIF Ultra, MTB/XDR, Genotype® MTBDRplus, Genotype® MTBDRsl, culture, and phenotypic drug susceptibility testing (pDST) for relevant drugs (including bedaquiline and levofloxacin) were performed. Next-generation sequencing (NGS) resolved discordances between MTB/XDR and pDST results. RESULTS: The analysis showed that MTB/XDR has 91.5% and 88.2% sensitivity and 99.5% and 97.7% specificity in detecting respectively isoniazid (INH) and resistance to FQs, demonstrating that MTB/XDR meets the WHO targets for INH resistance detection at the peripheral level. NGS effectively resolved discordances between MTB/XDR and pDST results. CONCLUSIONS: The obtained results allowed designing the proposed diagnostic algorithm for rapid identification of DR-TB, ensuring rapid and equitable access to drug susceptibility testing for TB, ultimately improving TB care and control.

CONTEXTE: La recrudescence de la résistance aux médicaments clés du régime BPaLM (bédaquiline + prétomanide + moxifloxacine) est une préoccupation majeure. Dans les contextes où la résistance aux fluoroquinolones (FQ) est répandue, comme le Pakistan, de nouvelles technologies, telles que Xpert® MTB/XDR, peuvent assurer un dépistage initial de la résistance aux médicaments. Cette étude vise à évaluer la performance de MTB/XDR dans la détection des FQ et de la résistance à l'isoniazide, en proposant un algorithme de diagnostic renouvelé pour la TB pharmacorésistante (DR-TB, pour l'anglais «drug-resistant TB ¼ ). MÉTHODES: Cette étude prospective transversale, approuvée par le comité d'éthique local, a recueilli des échantillons de personnes nouvellement diagnostiquées et précédemment diagnostiquées avec la TB pendant 6 mois. Xpert® MTB/RIF Ultra, MTB/XDR, le GenoType® MTBDRplus, le GenoType® MTBDRsl, la culture et des tests phénotypiques de sensibilité aux médicaments (pDST, pour l'anglais «phenotypic drug susceptibility testing ¼ ) pour les médicaments pertinents (y compris la bédaquiline et la lévofloxacine) ont été effectués. Le séquençage de nouvelle génération (NGS, pour l'anglais «next-generation sequencing ¼ ) a résolu les discordances entre les résultats MTB/XDR et pDST. RÉSULTATS: L'analyse a montré que le MTB/XDR a une sensibilité de 91,5% et 88,2% et une spécificité de 99,5% et 97,7% dans la détection respectivement de l'isoniazide et de la résistance aux FQ, démontrant que le MTB/XDR répond aux objectifs de l'OMS pour la détection de la résistance à l'isoniazide au niveau périphérique. NGS a efficacement résolu les discordances entre les résultats MTB/XDR et pDST. CONCLUSIONS: Les résultats obtenus ont permis de concevoir l'algorithme de diagnostic proposé pour l'identification rapide de la DR-TB, garantissant un accès rapide et équitable aux tests de sensibilité aux médicaments pour la TB, améliorant ainsi la prise en charge et le contrôle de la TB.

COPD classification methods and informativeness on mortality: contrasting evidences.

Understanding whether the ABCD GOLD classification method is informative with respect to the spirometric classification of severity in predicting mortality of patients with chronic obstructive pulmonary disease (COPD) is subject of debate. The results of a study performed on a sample of the Norwegian population (HUNT2) were recently published. Such data showed the inferiority of ABCD classification in predicting mortality compared to the spirometric classification, which was considered the gold standard up to the 2011 version of GOLD guidelines. This result is not in line with the results of other studies that have shown the equivalence of the two classifications. The new GOLD classification seemed to be a step forward for what concerns understanding patient's needs, but it seems clear that the insertion of a single clinical variable to the spirometric data may not be exhaustive in describing all the phenomena related to a heterogeneous disease such as COPD. The publication of the HUNT study provides an opportunity to analyze how the evidence has been produced, which scientific speculations it offers, what considerations could be drawn and what further research would be appropriate.

Where are we with the use of N-acetylcysteine as a preventive and adjuvant treatment for COVID-19?

OBJECTIVE: As N-acetylcysteine (NAC) is promising as a re-purposed drug for the adjunctive or supportive treatment of serious COVID-19, this article aimed to describe current evidence. MATERIALS AND METHODS: A search was performed in PubMed/Medline for "NAC", "viral Infection", COVID-19", oxidative stress", "inflammation", retrieving preclinical and clinical studies. RESULTS: NAC is a pleiotropic molecule with a dual antioxidant mechanism; it may neutralize free radicals and acts as a donor of cysteine, restoring the physiological pool of GSH. Serious COVID-19 patients have increased levels of reactive oxygen species (ROS) and free radicals and often present with glutathione depletion, which prompts a cytokine storm. NAC, which acts as a precursor of GSH inside cells, has been currently used in many conditions to restore or protect against GSH depletion and has a wide safety margin. In addition, NAC has anti-inflammatory activity independently of its antioxidant activity. CONCLUSIONS: Clinical and experimental data suggest that NAC may act on the mechanisms leading to the prothrombotic state observed in severe COVID-19.

The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor.

The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2), which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor. CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome 21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By approximately 12 wk of age, the majority of mutant mice raised in a conventional facility developed a chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10-deficient mice. These findings suggest that CRF2-4 is essential for IL-10-mediated effects and is a subunit of the IL-10 receptor.

Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.

What drives inhaler prescription for asthma patients? Results from a real-life retrospective analysis.

BACKGROUND: The choice of inhaler device for asthma patients depends upon multiple attributes. We investigated factors that may drive general practitioners (GPs) and respiratory specialists in the prescription of inhaler devices for asthma patients who initiated inhalation therapy. METHODS: We retrospectively analysed prescriptions by GPs and respiratory specialists to asthma patients commencing inhaled corticosteroid/long-acting ß2-agonist combination therapy available as both pressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Patient characteristics were compared by device and multivariate analysis was used to model the likelihood of receiving a pMDI as opposed to a DPI in order to identify drivers for prescription. A sample of the respiratory specialists completed an ad-hoc survey of their perceived success in achieving asthma control in their patients and barriers to attaining full control. RESULTS: Prescription of a particular inhaler device was unrelated to the characteristics of the patients. Multivariate analysis revealed that the main driver for the choice of inhaler device was the medication (Odds Ratio and 95% Confidence Interval, respectively for GPs and specialists: 0.19 [0.16-0.23]; 0.17 [0.08-0.37]). Specialists perceived asthma as being inadequately controlled in 41% of their patients, and considered patients' difficulties in using DPIs and pMDIs as instrumental in this, citing a need for a novel, more effective inhaler technology. CONCLUSION: Physicians choose inhaler devices according to the prescribed drugs and not to the characteristics of the individual patient. This may reflect a lack of confidence in existing inhaler devices and underlines the need for technologies, which are more reliable and easier to use by patients.

Stromelysin-1 polymorphism as a new potential risk factor in progression of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive lung disease (COPD) is characterised by partially reversible usually progressive airflow limitation caused by inflammation and remodelling. Stromelysin-1 (MMP-3) has regulatory activity on other matrix-metalloproteinases. Altered MMP-3 activity has been described in different diseases. We investigated the role of a promoter MMP-3 polymorphism in determining susceptibility and severity of COPD. METHODS: We studied 147 patients with COPD in stable conditions and distinguished two groups based on FEV1 values. In 100 patients functional modifications across a two-year period were noted. 133 healthy subjects were used as controls. Genotyping for the -1171 5A/6A MMP-3 polymorphism was performed using nucleotide sequencing. RESULTS: No difference was noted in the genotype distribution between COPD patients and controls. However, among patients with severe disease 6A/6A genotype and 6A allelic frequency were significantly more represented than among mild-moderate patients (p < 0.05). The 6A/6A genotype was also associated with a higher FEV1 decline over time. CONCLUSIONS: Our data suggests that -1171 6A allele does not represent a risk factor for the development of COPD while it is associated with more severe disease and different functional decline. We hypothesis that a disregulation of MMP-3, possibly caused by the -1171 5A/6A polymorphism or other linked variants, may lead to different progression in COPD.

Effects of a structured educational intervention in moderate-to-severe elderly asthmatic subjects.

BACKGROUND: Adherence to inhaled drugs is linked to patients' satisfaction with their device, and an incorrect use can negatively affect the outcomes of asthma treatment. We speculated that this is particularly true in elderly asthmatic subjects. AIM: We performed a national pre-post interventional multicentre study, enrolling moderate-to-severe asthmatic subjects aged ≥65 â€‹years treated with fixed inhaled combination drugs by dry powder inhaler (DPI) or pressurized metered dose inhaler (pMDI). Adherence and critical errors were evaluated by means of validated questionnaires at first visit (V1) and after 3-6 months (V2). At V1, subjects underwent intensive training on the correct use of their device by physical demonstration. RESULTS: A total of 411 asthmatics (F/M: 238/173, mean age±SD: 72 â€‹± â€‹5 â€‹years) participated to the study. At V1, 50% of the study subjects showed an Asthma Control Test (ACT) score ≤19 despite GINA step 3 and 4 treatment, and 40% had experienced at least one severe asthma exacerbation in the previous year. Poor adherence to treatment was recorded in 43% of subjects, and at least one error in using the device was registered in 56% of subjects. At V2, available for 318 patients, both the percentage of individuals with poor adherence and with at least one critical error significantly decreased (from 46% to 25%, and from 49% to 25%, respectively; p â€‹< â€‹0.001 for both comparisons) with a significant increase of the ACT score (from 19 â€‹± â€‹4.9 to 20 â€‹± â€‹4.0, p â€‹< â€‹0.001). CONCLUSIONS: Asthma in the elderly is characterized by low levels of symptom control. Educational interventions are strongly advocated in this age group in order to increase adherence to treatment and inhaler techniques.

Comparison of the acute effect of tiotropium versus a combination therapy with single inhaler budesonide/formoterol on the degree of resting pulmonary hyperinflation.

In 20 COPD patients (FEV(1) < or =65% predicted, IC<80% predicted), we evaluated changes in the degree of pulmonary hyperinflation after acute administration of tiotropium 18 microg or budesonide/formoterol 320/9 microg. The study consisted of a screening visit and two study days separated by at least one week. Functional parameters were measured before and 30, and 120 min after inhalation of single study drug. Both tiotropium and budesonide/formoterol induced significant changes in functional parameters after 30 and 120 min. However, the impact of tiotropium on the degree of pulmonary hyperinflation was larger than that of budesonide/formoterol, although only differences in IC and TGV between the two treatments were significant (P<0.05), at least after 120 min, whereas those in RV were not significant. The documentation that tiotropium is able to modify IC even after an acute administration indicates its capacity of influencing expiratory flow limitation in a very fast manner and this is an important finding. In fact, changes in IC after bronchodilators in patients with COPD with expiratory flow limitation at rest may represent an objective tool for prescribing these drugs to attain symptomatic improvement and better quality of life, even in the absence of a significant increase in FEV(1).

Effect of inhaled combination therapy on asthma management.

The growing use of guidelines to manage asthmatic patients prompted us to evaluate their impact on clinical practice. This study was performed in two similar groups of asthmatic patients. A retrospective and prospective review of medical records in an asthmatic population was performed. The patients were followed up for a mean period of 2 years before (group 1 [G1]) and after the publication of the Guideline for Asthma Treatment (group 2 [G2]). After evaluation of objective/clinical measurements we noticed a significant difference between both groups. There were 23 and 40 patients who did not complain of any respiratory symptoms in G1 and G2, respectively. The total number of visits to the emergency department decreased by more than 75%, from 26 (G1) to six (G2). The forced expiratory volume in 1 sec improved by a mean of 4% in G1 and 9% in G2. After application of the guidelines there was a redistribution of the degree of disease severity. In G2, there was a 12% increase in the use of long-acting beta2-stimulating sprays; 40% of the patients were using a combination of a long-acting beta2-stimulating drug and an inhaled steroid. In our experience, the use of the Global Initiative for Asthma (GINA) guidelines leads to better management of asthma patients with different degrees of severity. These findings suggest the need to perform a similar analysis in a broader setting such as a national multicenter survey in order to collect information on the challenges of putting these theoretical difficulties into practice and to compare their implementation in distinct centers.

Anxiety and depression in cystic fibrosis.

Cystic fibrosis (CF) is the most common genetic disorders in the Caucasian population, with estimated between 70,000 and 100,000 patients worldwide. Even if improved diagnostics and clinical management have led to an increased life expectancy, CF still remains a disease that significantly impacts patients' life in terms of symptoms, daily functioning, psychological morbidity and health related quality of life. Available data suggest that symptoms of anxiety and depression, such as in other chronic conditions, are common features in CF patients and in their caregivers, with a significant impact on disease outcomes. In this review we analyze and discuss the findings of The International Depression and Anxiety Epidemiological Study (TIDES), recently published on Thorax. This study was aimed to determine the prevalence of symptoms of depression and anxiety in a large population of adolescents and adults with CF and in parents of children with CF, across eight European countries and the USA. The TIDES provides useful insights about the psychological/psychiatric comorbidities in CF and its conclusions are absolutely shareable. Nevertheless some doubts remain on the methods and the tools. Further investigation and understanding of anxiety and depression in CF (in terms of prevalence, association with clinical, psychological and socio-cultural factors) is necessary and evidence is crescent that a global and multidisciplinary approach is wanted.

Anxiety and depression in cystic fibrosis.

Cystic fibrosis (CF) is the most common genetic disorders in the Caucasian population, with estimated between 70,000 and 100,000 patients worldwide. Even if improved diagnostics and clinical management have led to an increased life expectancy, CF still remains a disease that significantly impacts patients' life in terms of symptoms, daily functioning, psychological morbidity and health related quality of life. Available data suggest that symptoms of anxiety and depression, such as in other chronic conditions, are common features in CF patients and in their caregivers, with a significant impact on disease outcomes. In this review we analyze and discuss the findings of The International Depression and Anxiety Epidemiological Study (TIDES), recently published on Thorax. This study was aimed to determine the prevalence of symptoms of depression and anxiety in a large population of adolescents and adults with CF and in parents of children with CF, across eight European countries and the USA. The TIDES provides useful insights about the psychological/psychiatric comorbidities in CF and its conclusions are absolutely shareable. Nevertheless some doubts remain on the methods and the tools. Further investigation and understanding of anxiety and depression in CF (in terms of prevalence, association with clinical, psychological and sociocultural factors) is necessary and evidence is crescent that a global and multidisciplinary approach is wanted.

Choose the best route: ultrasound-guided transbronchial and transesophageal needle aspiration with echobronchoscope in the diagnosis of mediastinal and pulmonary lesions.

Nodal mediastinal staging is a crucial part of the diagnostic workup of patients with non-small-cell lung cancer (NSCLC) for planning optimal treatment. Transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and real-time endobronchial ultrasounds transbronchial needle aspiration (EBUS-TBNA) are accurate, minimally invasive and safe diagnostic techniques for mediastinal staging. Because of the different accessibility to the mediastinum, they are considered complementary and their combination increases the diagnostic yield as compared with the either alone. Recent studies have shown that endosonography represents the best initial test for invasive mediastinal evaluation in NSCLC. Endoscopic ultrasound (with bronchoscope)-guided fine needle aspiration (EUS-B-FNA) is a recently introduced procedure consisting of a transesophageal needle aspiration using an ultrasound bronchoscope. It allows to perform both transbronchial and transesophageal needle sampling with the same instrument, in the same session and by one operator only, thus maximizing time and costs savings. In a recent study Oki et al. randomized 110 patients with hilar/mediastinal adenopathies or lung abnormalities adjoining both the esophagus and the bronchi, to undergo EBUS-TBNA or EUS-FNA performed by pulmonologists with an echobronchoscope. The Authors demonstrated that both procedures provide a high diagnostic yield, without any difference in the number of adverse events and a good comparable tolerance. Nevertheless, the transesophageal approach guaranteed a significantly lower dose of anesthetics and sedatives, a shorter procedural time, fewer oxygen desaturations, a significantly lower cough score and a higher operator satisfaction. In this review our aim was to discuss the findings by Oki et al. in the context of medical literature, highlighting the importance of the EUS-B needle aspiration technique in diagnosing mediastinal and lung lesions, when EBUS-TBNA is deemed less suitable. Finally, we pointed out the importance of interventional pulmonologists being trained to perform mediastinal sampling by the esophageal route, to choose the best solution in every technical and clinical occurence.

Choose the best route: ultrasound-guided transbronchial and transesophageal needle aspiration with echobronchoscope in the diagnosis of mediastinal and pulmonary lesions.

Nodal mediastinal staging is a crucial part of the diagnostic workup of patients with nonsmall- cell lung cancer (NSCLC) for planning optimal treatment. Transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and real-time endobronchial ultrasounds transbronchial needle aspiration (EBUS-TBNA) are accurate, minimally invasive and safe diagnostic techniques for mediastinal staging. Because of the different accessibility to the mediastinum, they are considered complementary and their combination increases the diagnostic yield as compared with the either alone. Recent studies have shown that endosonography represents the best initial test for invasive mediastinal evaluation in NSCLC. Endoscopic ultrasound (with bronchoscope)-guided fine needle aspiration (EUS-B-FNA) is a recently introduced procedure consisting of a transesophageal needle aspiration using an ultrasound bronchoscope. It allows to perform both transbronchial and transesophageal needle sampling with the same instrument, in the same session and by one operator only, thus maximizing time and costs savings. In a recent study Oki et al. randomized 110 patients with hilar/mediastinal adenopathies or lung abnormalities adjoining both the esophagus and the bronchi, to undergo EBUSTBNA or EUS-FNA performed by pulmonologists with an echobronchoscope. The Authors demonstrated that both procedures provide a high diagnostic yield, without any difference in the number of adverse events and a good comparable tolerance. Nevertheless, the transesophageal approach guaranteed a significantly lower dose of anesthetics and sedatives, a shorter procedural time, fewer oxygen desaturations, a significantly lower cough score and a higher operator satisfaction. In this review our aim was to discuss the findings by Oki et al. in the context of medical literature, highlighting the importance of the EUS-B needle aspiration technique in diagnosing mediastinal and lung lesions, when EBUS-TBNA is deemed less suitable. Finally, we pointed out the importance of interventional pulmonologists being trained to perform mediastinal sampling by the esophageal route, to choose the best solution in every technical and clinical occurence.

Rescue therapy with polymyxin B hemoperfusion in high-dose vasopressor therapy refractory septic shock.

BACKGROUND: Refractory septic shock (RSS) requiring major vasopressor support is associated with high mortality, especially in Gram-negative infections. The study aim was to describe hemodynamics, organ failure, and clinical outcomes in high-dose vasopressor therapy (HDVT) RSS patients treated with Polymyxin B hemoperfusion (PMX-HP) as rescue therapy. METHODS: We retrospectively analyzed 52 patients, unresponsive to conventional therapy, treated with two sessions of PMX-HP requiring HDVT (norepinephrine and/or epinephrine requirement (NEP+EP) ≥ 0.5 µg/kg/min), ≥ 2 organ failures, and suspected/confirmed Gram-negative infection from any source. RESULTS: At baseline, mean arterial pressure (MAP) was 80 ± 13 mmHg and NEP + EP requirement was 1.11 ± 0.56 µg/kg/min. After two PMX-HP sessions, at 72 h, MAP significantly increased and NEP + EP requirement decreased respectively by 12% and 76%. Pulmonary and renal function also improved significantly. Thirty patients (58%) showed a ≥ 50% reduction in NEP + EP dose within only 24 h after the first PMX-HP session (early responders), and 22 did not or died from irreversible shock in the same time frame (early non-responders). The 30-day hospital mortality was 29%; it was 16% in early responders and 45% in early non-responders. On multivariate analysis, SAPS II score, vasopressin, and central venous pressure significantly affected 30-day hospital mortality. CONCLUSION: This is the first study describing the use of PMX-HP as a rescue therapy in RSS patients with HDVT and MOF. Our results suggest a possible role for PMX-HP in improving hemodynamics, organ function, and mortality in RSS, with a 30-day survival of up to 70%.