The bacterial lysate OM-85 engages Toll-like receptors 2 and 4 triggering an immunomodulatory gene signature in human myeloid cells.

OM-85 is a bacterial lysate used in clinical practice to reduce duration and frequency of recurrent respiratory tract infections. Whereas knowledge of its regulatory effects in vivo has substantially advanced, the mechanisms of OM-85 sensing remain inadequately addressed. Here, we show that the immune response to OM-85 in the mouse is largely mediated by myeloid immune cells through Toll-like receptor (TLR) 4 in vitro and in vivo. Instead, in human immune cells, TLR2 and TLR4 orchestrate the response to OM-85, which binds to both receptors as shown by surface plasmon resonance assay. Ribonucleic acid-sequencing analyses of human monocyte-derived dendritic cells reveal that OM-85 triggers a pro-inflammatory signature and a unique gene set, which is not induced by canonical agonists of TLR2 or TLR4 and comprises tolerogenic genes. A largely overlapping TLR2/4-dependent gene signature was observed in individual subsets of primary human airway myeloid cells, highlighting the robust effects of OM-85. Collectively, our results suggest caution should be taken when relating murine studies on bacterial lysates to humans. Furthermore, our data shed light on how a standardized bacterial lysate shapes the response through TLR2 and TLR4, which are crucial for immune response, trained immunity, and tolerance.

Endobronchial Papillomatosis of the Central Airways / Papillomatosis endobronquial de las vías aereas centrales

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Endobronchial coil spring fiducial markers for CyberKnife® stereotactic body radiation therapy.

BACKGROUND AND OBJECTIVE: SBRT is an alternative treatment for early-stage inoperable lung cancer. Metallic FM allow to increase tumour tracking precision by CyberKnife®. Currently used techniques for FM placement have many limitations; transthoracic insertion has a high risk for pneumothorax, endovascular insertion requires expertise and dedicated angiography infrastructure and endobronchial linear-gold FM dislocate frequently. This is the first study to assess the safety and efficacy of cs-FM endobronchial insertion under fluoroscopy with or without R-EBUS assessment. METHODS: We retrospectively evaluated all consecutive patients undergoing endobronchial cs-FM placement for at least one PPL <25 mm between 10.2015 and 12.2019. TBB of the PPL were performed in case of a typical R-EBUS signal. PPL tracking accuracy by CyberKnife, complications, cs-FM migration rate and procedure duration were analysed. RESULTS: A total of 52 patients were treated during 55 procedures and 207 cs-FM were placed in 70 PPL. Tracking was successful for 65 of 70 (93%) PPL. R-EBUS was performed for 33 (47%) PPL and TBB for 9 (13%) PPL. Bronchospasm occurred once and any other complications were observed. Migration of cs-FM occurred in 16 of 207 (8%) cs-FM. Migration was more frequent when the target was in a previously irradiated area (P = 0.022). The median bronchoscopy duration was 31.5 min (n = 48 procedures). CONCLUSION: Bronchoscopic cs-FM placement is a rapid and safe procedure. It is associated with a low migration rate and allows precise SBRT delivery. Previous irradiation of the PPL was associated with a higher migration rate.

Lung MRI assessment with high-frequency noninvasive ventilation at 3 T.

PURPOSE: To investigate three MR pulse sequences under high-frequency noninvasive ventilation (HF-NIV) at 3 T and determine which one is better-suited to visualize the lung parenchyma. METHODS: A 3D ultra-short echo time stack-of spirals Volumetric Interpolated Breath-hold Examination (UTE Spiral VIBE), without and with prospective gating, and a 3D double-echo UTE sequence with spiral phyllotaxis trajectory (3D radial UTE) were performed at 3 T in ten healthy volunteers under HF-NIV. Three experienced radiologists evaluated visibility and sharpness of normal anatomical structures, artifacts assessment, and signal and contrast ratio computation. The median of the three readers'scores was used for comparison, p < .05 was considered statistically significant. Incidental findings were recorded and reported. RESULTS: The 3D radial UTE resulted in less artifacts than the non-gated and gated UTE Spiral VIBE in inferior (score 3D radial UTE = 3, slight artifact without blurring vs. score UTE Spiral VIBE non-gated and gated = 2, moderate artifact with blurring of anatomical structure, p = .018 and p = .047, respectively) and superior lung regions (score 3D radial UTE = 3, vs. score UTE Spiral VIBE non-gated = 2.5, p = .48 and score UTE Spiral VIBE gated = 1, severe artifact with no normal structure recognizable, p = .014), and higher signal and contrast ratios (p = .002, p = .093). UTE Spiral VIBE sequences provided higher peripheral vasculature visibility than the 3D radial UTE (94.4% vs 80.6%, respectively, p < .001). The HF-NIV was well tolerated by healthy volunteers who reported on average minor discomfort. In three volunteers, 12 of 18 nodules confirmed with low-dose CT were identified with MRI (average size 2.6 ±â€¯1.2 mm). CONCLUSION: The 3D radial UTE provided higher image quality than the UTE Spiral VIBE. Nevertheless, a better nodule assessment was noticed with the UTE Spiral VIBE that might be due to better peripheral vasculature visibility, and requires confirmation in a larger cohort.

[Computer instruments for the management of isolated pulmonary nodule. Detectability and prediction of malignancy]. / Outils informatiques pour la prise en charge du nodule pulmonaire isolé - Détectabilité et prédiction de malignité.

Lung cancer remains the most common cause of cancer deaths in the world, but its mortality can be significantly reduced by diagnosis and early detection. Computerized resources were developed to assist radiologists in their management of the large volume of thoracic images to be analyzed. Their objective is the detection of pulmonary nodules with high sensitivity and a low rate of false-positives and the ability to differentiate benign and malignant nodules. The volume of a pulmonary nodule and its volume doubling time are essential to nodule management. Computer aided detection or diagnosis (CAD) software are not currently used in clinically settings on a routine basis . Significant advances are expected due to the implementation of the artificial intelligence systems who will probably be integrated into the multidisciplinary management of any pulmonary nodule.

Le cancer du poumon reste la principale cause de décès par cancer dans le monde. Sa mortalité peut être significativement réduite par un diagnostic et un dépistage précoce. Des outils informatiques ont été développés afin d'aider les radiologues à gérer la quantité d'images thoraciques à analyser. Ils ont pour objectif la détection des nodules pulmonaires avec une haute sensibilité et un taux faible de faux positifs, mais aussi la différenciation des nodules bénins et malins. Le volume d'un nodule pulmonaire et le temps de doublement déterminent la suite de la prise en charge de ce nodule. Ces deux paramètres sont inclus dans la plupart des recommandations actuelles. Les logiciels de détection assistés par ordinateur (CAD) ne sont pas utilisés en routine clinique actuellement. Des avancées dans ce domaine sont attendues en utilisant l'intelligence artificielle, notamment dans le cadre de la prise de décision multidisciplinaire.

Iatrogenic bleeding during flexible bronchoscopy: risk factors, prophylactic measures and management.

Significant iatrogenic bleeding during flexible bronchoscopy is fortunately rare and usually self-limiting. Life-threatening bleeding, however, can occur, especially after conventional or cryoprobe-assisted transbronchial biopsy. The aim of this review is to provide the practising pulmonologist with a concise overview of the incidence, severity and risk factors for bleeding, to provide sensible advice on prophylactic measures and to suggest a plan of action in the case of significant bleeding. Bronchoscopy units should have a standardised approach and plan of action in the case of life-threatening haemorrhage. Wedging the bronchoscope in the bleeding segment, turning the patient in an anti-Trendelenburg position and onto the side in order for the bleeding lung to be in the dependent position, installing vasoconstrictors and using a tamponade balloon early are the recommended first-line strategies. Involving a resuscitation team should be considered early in the case of massive bleeding, desaturation and haemodynamic instability.

Radial Ultrasound-Assisted Transbronchial Biopsy: A New Diagnostic Approach for Non-Resolving Pulmonary Infiltrates in Neutropenic Hemato-Oncological Patients.

The role of radial-endobronchial ultrasound (R-EBUS) assisted transbronchial biopsy (TBB) for the diagnosis of peripheral pulmonary lesions is well established. However, no study has addressed its safety and value in hemato-oncological patients presenting with non-resolving infiltrates during persistent febrile neutropenia. To assess safety and feasibility of R-EBUS assisted TBB in severe thrombocytopenic and neutropenic patients. Over a period of 18 months, eight patients were assessed with R-EBUS assisted TBB after adequate platelet transfusion. This technique allowed precise localisation and sampling of the pulmonary lesions in seven of eight patients. In the seven patients, R-EBUS assisted TBB enabled treatment optimization. Invasive fungal infection was diagnosed in four patients, idiopathic acute fibrinous and organising pneumonia in three patients, and a granulomatous inflammation of undetermined origin in one patient. Importantly, no complications, such as bleeding, were observed. R-EBUS assisted TBB is a promising and safe procedure for the evaluation of nonresolving pulmonary infiltrates in febrile neutropenic hemato-oncological patients.

Modeling the Structure of Complex Aluminosilicate Glasses: The Effect of Zinc Addition.

An empirical potential structure refinement of neutron and X-ray diffraction data combined with extended absorption fine structure evidence has been applied to the investigation of two distinct sets of complex aluminosilicate glasses containing different quantities of zinc. Data come from (i) neutron and X-ray total scattering experiments, which have been performed at the ISIS neutron spallation source (SANDALS beamline) and at the European Synchrotron Radiation Facility (ID11 beamline), and (ii) EXAFS experiments which have been performed at the European Synchrotron Radiation Facility (BM23 beamline). By careful examination of the modeled ensemble of atoms, a wide range of structural information has been extracted: coordination numbers, bond distances, cluster sizes, type of oxygen sharing, and the preference of large cations to adopt a charge-compensating role. The first series of glasses, which is characterized by a fixed network modifier element content (i.e., Na), shows how the introduction of Zn at the expense of Si and Al network forming elements does not significantly alter the polymerization degree, as a result of its dominant 4-fold coordination. In the case of the second series, which is characterized by fixed network forming element content (i.e., Si and Al), it is shown how the replacement of a network modifier element (i.e., Ca) with the introduction of Zn does not change the propensity of Zn to be mainly 4-fold coordinated by promoting the network. Where appropriate the experimental results have been compared with classical theoretical approaches such as stoichiometric models based on Zachariasen's rules and computational routines.

Gold(I)-catalyzed enantioselective [3+2] and [3+3] cycloaddition reactions of propargyl acetals/ketals.

An asymmetric gold(I)-catalyzed [3+2] cycloaddition of propargyl acetals/ketals and aldehydes is reported, which proceeds via stepwise migration-fragmentation of acetals/ketals and cycloaddition of the in situ generated gold-carbenoid intermediate. Various functionalized 2, 5-dihydrofurans were obtained in good yields and high enantioselectivities. Furthermore, an example of the first gold(I) catalyzed [3+3] cycloaddition of secondary propargyl ketals and nitrones is presented.

Asymmetric hydrogenation of maleic acid diesters and anhydrides.

Asymmetric hydrogenation of maleic and fumaric acid derivatives with iridium catalysts based on N,P ligands provides an efficient route to chiral enantioenriched succinates. A new catalyst derived from a 2,6-difluorophenyl-substituted pyridine-phosphinite ligand was developed and enables the conversion of a wide range of 2-alkyl and 2-arylmaleic acid diesters into the corresponding succinates in high enantiomeric purity. Mixtures of cis/trans substrates can be hydrogenated in an enantioconvergent fashion with high enantioselectivity, and further enhances the scope of this transformation. The products are valuable chiral building blocks with a structural motif found in many bioactive compounds, such as metalloproteinase inhibitors.

Iridium-catalyzed asymmetric hydrogenation of 3,3-disubstituted allylic alcohols in ethereal solvents.

Ir-phosphinomethyl-oxazoline complexes have been identified as efficient, highly enantioselective catalysts for the asymmetric hydrogenation of 3,3-disubstituted allylic alcohols and related homoallylic alcohols. In contrast to other N,P ligand complexes, which require weakly coordinating solvents, such as dichloromethane, these catalysts perform well in more ecofriendly THF or 2-MeTHF. Their synthetic potential was demonstrated with the formal total synthesis of four bisabolane sesquiterpenes.

Chiral N-heterocyclic carbene/pyridine ligands for the iridium-catalyzed asymmetric hydrogenation of olefins.

Swapping N,P for C,N: Iridium complexes of bidentate pyridine-based C,N ligands with an N-heterocylic carbene (NHC) unit proved to be efficient and highly enantioselective hydrogenation catalysts. As a result of the lower acidity of iridium hydride intermediates produced from NHC-based complexes, these catalysts are much better suited than analogous N,P-ligand complexes for the hydrogenation of acid-sensitive substrates.

The yield of different pleural fluid volumes for Mycobacterium tuberculosis culture.

We prospectively compared the culture yields of two pleural fluid volumes (5 and 100 ml) inoculated in liquid culture medium in 77 patients of whom 58 (75.3%) were diagnosed with pleural tuberculosis. The overall fluid culture yield was high (60.3% of cases with pleural tuberculosis). The larger volume had a faster time to positivity (329 vs 376 h, p=0.055) but its yield was not significantly higher (53.5% vs 50%; p=0.75). HIV-positive patients were more likely to have positive cultures (78.9% vs 51.5%; p=0.002).

Speed of ascent during stair climbing identifies operable lung resection candidates.

BACKGROUND: Preoperative evaluation of lung resection candidates with impaired pulmonary reserves includes measurement of aerobic capacity. Stair climbing is an attractive low-cost alternative to treadmill exercise testing but it lacks standardisation. OBJECTIVES: To directly compare stair climbing and treadmill exercise testing with respect to an established cut-off value for lung resection. METHODS: We subjected 56 lung resection candidates to both symptom-limited treadmill exercise testing and stair climbing to a maximum of 20 m. Both exercise tests were monitored with the same portable spiroergometer. Subjects were on average 46.6 years old, 61% were male and 54% had FEV(1)/FVC < 70%. Mean FEV(1) and DLCO(c) were 51.6 and 57.1%, respectively. RESULTS: Mean altitude reached, exercise time, speed of ascent and peak VO(2) were 16.9 m, 74 s, 14.7 m/min and 22.4 ml/min/kg, respectively, in 54 subjects completing stair climbing. Thirty-one subjects (58%) reached 20 m without stopping. Treadmill tests were completed by 51 subjects and lasted longer (432 s; p < 0.001), but VO(2max) was not different compared to stair climbing (22.7 ml/min/kg; p = 0.673). Speed of ascent was significantly correlated to both stair climbing peak VO(2) (r = 0.63) and treadmill VO(2max) (r = 0.67). All 19 subjects (34%) who reached 20 m in 80 s or less (≥15 m/min) had a VO(2max) of ≥20 ml/min/kg. CONCLUSIONS: We found a clinically useful correlation between speed of ascent during stair climbing and VO(2max) during treadmill exercise testing. Climbing to 20 m with an average speed of ascent of ≥15 m/min accurately identified subjects qualifying for pneumonectomy according to established criteria.

Midregional proatrial natriuretic peptide predicts survival in exacerbations of COPD.

BACKGROUND: Recently, the use of systemic biomarkers to monitor and assess the clinical evolution of respiratory disease has gained interest. We investigated whether midregional proatrial natriuretic peptide (MR-proANP) predicts survival in patients with COPD when they are admitted to the hospital for exacerbation. METHODS: One hundred sixty-seven patients (mean age 70 years old, 75 men) admitted to the hospital for exacerbation were followed up for 2 years. MR-proANP was measured on admission, after 14 days, and at 6 months. The predictive value of clinical, functional, and laboratory parameters on admission were assessed by Cox regression analyses. The time to death was analyzed by Kaplan-Meier survival curves. RESULTS: MR-proANP level was significantly higher on admission for exacerbation, compared with recovery and stable state (P = .004 for the comparison among all time points). MR-proANP correlated with the Charlson condition and age-related score (P < .0001), left ventricular ejection fraction (P < .0001), C-reactive protein (P = .037), and FEV(1)% predicted (P = .004). MR-proANP levels were similar in patients requiring ICU treatment and in those treated in the medical ward (P = .086). Thirty-seven patients (22%) died within 2 years. MR-proANP levels were higher in nonsurvivors compared with survivors (median [interquartile range] 185 pmol/L [110-286] vs 92 pmol/L [56-158], P < .001). Mortality was higher across MR-proANP quartiles (log rank P < .0001). Charlson condition and age-related score (P = .001), Paco(2) (P < .0001), and MR-proANP (P = .001) predicted mortality in the univariate Cox-regression model. Both MR-proANP and Paco(2) were independent predictors of mortality in the multivariate Cox regression model. CONCLUSIONS: MR-proANP at exacerbation is associated with 2-year long-term survival in patients with exacerbation of COPD.

Comparison of combined oximetry and cutaneous capnography using a digital sensor with arterial blood gas analysis.

BACKGROUND: Cutaneous carbon dioxide tension (PcCO(2)) is a promising non-invasive surrogate measure of arterial partial pressure of carbon dioxide (PaCO(2)). OBJECTIVES: To compare values of PcCO(2) and oxygen saturation (SpO(2)) with arterial blood gas (ABG) analysis. METHODS: SpO(2) and PcCO(2) were measured with a v-Sign-sensor (Sentec AG, Therwil, Switzerland) and the values compared with simultaneously obtained SaO(2) and PaCO(2) obtained from ABG analysis (ABL 725, Radiometer, Copenhagen, Denmark) in 275 adult patients referred to the lung function laboratory. RESULTS: Median of the PcCO(2) was 4.7 kPa (interquartile range [IQR] 0.9 kPa). Median of the SpO(2) was 97% (IQR 3%). Bland-Altman analysis for comparison of PcCO(2) with PaCO(2) showed a bias of -0.1 kPa with a precision of +/- 0.9 kPa with 3.7% outlying values. Bland-Altman analysis for the comparison of SpO(2) and SaO(2) showed a bias of 20.1 % with a precision of +/- 3.5%. There were no complications. CONCLUSION: There is a good agreement between combined cutaneous capnography and oximetry values with ABG analysis. Due to the excellent safety profile and the short time to get a continuous measurement, this technique should be examined in settings where it can complement repeated ABG analysis when ventilatory disturbances are suspected or non-invasive monitoring of ventilation is needed.