Bronchial Rheoplasty for Chronic Bronchitis: Results from a Canadian Feasibility Study with RheOx®.

Purpose: Chronic bronchitis (CB), a chronic obstructive pulmonary disease (COPD) phenotype defined by persistent mucus hypersecretion and cough, is associated with poor quality of life, exacerbations, and lung function impairment. Bronchial Rheoplasty (BR) delivers non-thermal pulsed electric fields to airway epithelium and submucosa. Preliminary studies demonstrated reduced airway goblet cell hyperplasia and symptom improvement in response to BR. This study aimed to further assess the safety and clinical feasibility of BR in the setting of CB. Patients and Methods: This 3-center, single-arm study evaluated the safety and feasibility of BR in Canadian patients. The major inclusion criteria were the sum of CAT first 2 questions (cough and mucus) ≥ 7 out of 10 and FEV1 ≥ 30% predicted. Right-sided airways were treated first; left, 1 month later. Serious adverse events (SAEs) were tabulated through 12 months. Outcomes were evaluated using the SGRQ and CAT. Results: Ten patients with CB were enrolled and followed for 12 months. The BR procedure was successful in all patients (mean age 69 ± 5.8 years, post-BD FEV1 77.1 ± 28.3, SGRQ 56.2 ± 8.8, CAT 25.4 ± 4.7). Only one SAE, a COPD exacerbation 13 days following the BR procedure, was considered device related. No additional SAEs occurred through 12 months, and 90% of the patients were CAT responders (≥ 2-point improvement) at 3 and 6 months. Similar results were observed in SGRQ. Conclusion: BR was safe and well-tolerated. Meaningful symptom improvement was observed through 12 months, suggesting BR may be a viable treatment option for patients with CB.

Acute isometric and dynamic exercise do not alter cerebral sympathetic nerve activity in healthy humans.

The impact of physiological stressors on cerebral sympathetic nervous activity (SNA) remains controversial. We hypothesized that cerebral noradrenaline (NA) spillover, an index of cerebral SNA, would not change during both submaximal isometric handgrip (HG) exercise followed by a post-exercise circulatory occlusion (PECO), and supine dynamic cycling exercise. Twelve healthy participants (5 females) underwent simultaneous blood sampling from the right radial artery and right internal jugular vein. Right internal jugular vein blood flow was measured using Duplex ultrasound, and tritiated NA was infused through the participants' right superficial forearm vein. Heart rate was recorded via electrocardiogram and blood pressure was monitored using the right radial artery. Total NA spillover increased during HG (P = 0.049), PECO (P = 0.006), and moderate cycling exercise (P = 0.03) compared to rest. Cerebral NA spillover remained unchanged during isometric HG exercise (P = 0.36), PECO after the isometric HG exercise (P = 0.45), and during moderate cycling exercise (P = 0.94) compared to rest. These results indicate that transient increases in blood pressure during acute exercise involving both small and large muscle mass do not engage cerebral SNA in healthy humans. Our findings suggest that cerebral SNA may be non-obligatory for exercise-related cerebrovascular adjustments.

Molecular analysis of endobronchial ultrasound needle aspirates in patients with non-small cell lung cancer: Results from the SCOPE database.

OBJECTIVE: Molecular subtyping of non-small cell lung cancer (NSCLC) is critical in the diagnostic evaluation of patients with advanced disease. This study aimed to examine whether samples from endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of intrathoracic lymph nodes and/or lung lesions are adequate for molecular analysis across various institutions. METHODS: We retrospectively reviewed all cases of linear EBUS-TBNA with a final bronchoscopic diagnosis of NSCLC entered in the Stather Canadian Outcomes registry for chest ProcEdures database. The primary outcome was specimen inadequacy rate for each molecular target, as defined by the local laboratory or pathologist. RESULTS: A total of 866 EBUS-TBNA procedures for NSCLC were identified. Specimen inadequacy rates were 3.8% for EGFR, 2.5% for ALK-1 and 3.5% for PD-L1. Largest target size was not different between adequate and inadequate specimens, and rapid onsite evaluation did not increase specimen adequacy rates. One centre using next-generation sequencing for EGFR had lower adequacy rates than 2 others using matrix-assisted laser desorption/ionization time-of-flight mass spectrophotometry. CONCLUSION: EBUS-TBNA specimens have a very low-specimen inadequacy rate for molecular subtyping of non-small cell lung cancer.

An International Survey of Practices in the Investigation and Endoscopic Treatment of Peripheral Pulmonary Lesions amongst Interventional Bronchoscopists.

INTRODUCTION: The investigation of peripheral pulmonary lesions (PPLs) can be challenging. Several bronchoscopic modalities have been developed to reach and biopsy PPL but the level of adoption of these techniques by interventional pulmonologists (IPs) is unknown. This international survey was conducted to describe current practices in PPL investigation among IP. METHODS: This survey was sent to all members of the World Association for Bronchology and Interventional Pulmonology, Canadian Thoracic Society Procedures Assembly, AABIP, and the Groupe d'Endoscopie Thoracique et Interventionnel Francophone. The survey was composed of 48 questions and three clinical cases to establish a portrait of modalities used to investigate and treat PPL by IP around the world. RESULTS: Three hundred and twelve IP responded to the survey. Most of them practice in Europe (n = 122), North America (n = 97), and Asia (n = 49). Half of responders perform more than 100 endoscopic procedures for PPL annually. General anesthesia and conscious sedation are used in similar proportions (53% and 47%, respectively). Rapid on site evaluation (ROSE) is used when sampling PPL by 42%. Radial EBUS (69%), fluoroscopy (55%), and electromagnetic navigation (27%) are the most widely used techniques. Most IP combine techniques (89%). Robotic bronchoscopy (15%) and cone-beam CT (8%) are almost exclusively used in the USA where, respectively, 60% and 37% of respondents reported using these modalities. Ten percent of IP currently had access to endoscopic treatment modalities for PPL. However, half of the remaining IP plan to acquire an endoscopic treatment modality in the next 2 years. CONCLUSION: Available techniques and practices worldwide vary significantly regarding PPL investigation and treatment.

Improving the 3D Printability of Sugar Glass to Engineer Sacrificial Vascular Templates.

A prominent obstacle in scaling up tissue engineering technologies for human applications is engineering an adequate supply of oxygen and nutrients throughout artificial tissues. Sugar glass has emerged as a promising 3D-printable, sacrificial material that can be used to embed perfusable networks within cell-laden matrices to improve mass transfer. To characterize and optimize a previously published sugar ink, we investigated the effects of sucrose, glucose, and dextran concentration on the glass transition temperature (Tg), printability, and stability of 3D-printed sugar glass constructs. We identified a sucrose ink formulation with a significantly higher Tg (40.0 ± 0.9°C) than the original formulation (sucrose-glucose blend, Tg = 26.2 ± 0.4°C), which demonstrated a pronounced improvement in printability, resistance to bending, and final print stability, all without changing dissolution kinetics and decomposition temperature. This formulation allowed printing of 10-cm-long horizontal cantilever filaments, which can enable the printing of complex vascular segments along the x-, y-, and z-axes without the need for supporting structures. Vascular templates with a single inlet and outlet branching into nine channels were 3D printed using the improved formulation and subsequently used to generate perfusable alginate constructs. The printed lattice showed high fidelity with respect to the input geometry, although with some channel deformation after alginate casting and gelation-likely due to alginate swelling. Compared with avascular controls, no significant acute cytotoxicity was noted when casting pancreatic beta cell-laden alginate constructs around improved ink filaments, whereas a significant decrease in cell viability was observed with the original ink. The improved formulation lends more flexibility to sugar glass 3D printing by facilitating the fabrication of larger, more complex, and more stable sacrificial networks. Rigorous characterization and optimization methods for improving sacrificial inks may facilitate the fabrication of functional cellular constructs for tissue engineering, cellular biology, and other biomedical applications.

Tumor Shape-Specific Brachytherapy Implants by 3D-Printing, Precision Radioactivity Painting, and Biomedical Imaging.

In brachytherapy (BT), or internal radiation therapy, cancer is treated by radioactive implants. For instance, episcleral plaques (EPs) for the treatment of uveal melanoma, are designed according to generic population approximations. However, more personalized implants can enhance treatment precision through better adjustment of dose profiles to the contours of cancerous tissues. An original approach integrating biomedical imaging, 3D printing, radioactivity painting, and biomedical imaging, is developed as a workflow for the development of tumor shape-specific BT implants. First, computer-aided design plans of EP are prepared according to guidelines prescribed by the Collaborative Ocular Melanoma Study protocol. Polyetheretherketone (PEEK), a high-performance polymer suitable for permanent implants, is used to 3D-print plaques and the geometrical accuracy of the printed design is evaluated by imaging. The possibility to modulate the dose distribution in a tridimensional manner is demonstrated by painting the inner surfaces of the EPs with radioactive 103Pd, followed by dose profile measurements. The possibility to modulate dose distributions generated by these 3D-printed plaques through radioactivity painting is therefore confirmed. Ex vivo surgical tests on human eyeballs are performed as an assessment of manipulation ease. Overall, this work provides a solution for the fabrication of tumor-specific radioactive implants requiring higher dose precision.

Design of experiment and machine learning inform on the 3D printing of hydrogels for biomedical applications.

In the biomedical field, 3D printing has the potential to deliver on some of the promises of personalized therapy, notably by enabling point-of-care fabrication of medical devices, dosage forms and bioimplants. To achieve this full potential, a better understanding of the 3D printing processes is necessary, and non-destructive characterization methods must be developed. This study proposes methodologies to optimize the 3D printing parameters for soft material extrusion. We hypothesize that combining image processing with design of experiment (DoE) analyses and machine learning could help obtaining useful information from a quality-by-design perspective. Herein, we investigated the impact of three critical process parameters (printing speed, printing pressure and infill percentage) on three critical quality attributes (gel weight, total surface area and heterogeneity) monitored with a non-destructive methodology. DoE and machine learning were combined to obtain information on the process. This work paves the way for a rational approach to optimize 3D printing parameters in the biomedical field.

Gold-Enhanced Brachytherapy by a Nanoparticle-Releasing Hydrogel and 3D-Printed Subcutaneous Radioactive Implant Approach.

Brachytherapy (BT) is a widely used clinical procedure for localized cervical cancer treatment. In addition, gold nanoparticles (AuNPs) have been demonstrated as powerful radiosensitizers in BT procedures. Prior to irradiation by a BT device, their delivery to tumors can enhance the radiation effect by generating low-energy photons and electrons, leading to reactive oxygen species (ROS) production, lethal to cells. No efficient delivery system has been proposed until now for AuNP topical delivery to localized cervical cancer in the context of BT. This article reports an original approach developed to accelerate the preclinical studies of AuNP-enhanced BT procedures. First, an AuNP-containing hydrogel (Pluronic F127, alginate) is developed and tested in mice for degradation, AuNP release, and biocompatibility. Then, custom-made 3D-printed radioactive BT inserts covered with a AuNP-containing hydrogel cushion are designed and administered by surgery in mice (HeLa xenografts), which allows for measuring AuNP penetration in tumors (≈100 µm), co-registered with the presence of ROS produced through the interactions of radiation and AuNPs. Biocompatible AuNPs-releasing hydrogels could be used in the treatment of cervical cancer prior to BT, with impact on  the total amount of radiation needed per BT treatment, which will result in benefits to the preservation of healthy tissues surrounding cancer.

A Nanoparticle Ink Allowing the High Precision Visualization of Tissue Engineered Scaffolds by MRI.

Hydrogels are widely used as cell scaffolds in several biomedical applications. Once implanted in vivo, cell scaffolds must often be visualized, and monitored overtime. However, cell scaffolds appear poorly contrasted in most biomedical imaging modalities such as magnetic resonance imaging (MRI). MRI is the imaging technique of choice for high-resolution visualization of low-density, water-rich tissues. Attempts to enhance hydrogel contrast in MRI are performed with "negative" contrast agents that produce several image artifacts impeding the delineation of the implant's contours. In this study, a magnetic ink based on ultra-small iron oxide nanoparticles (USPIONs; <5 nm diameter cores) is developed and integrated into biocompatible alginate hydrogel used in cell scaffolding applications. Relaxometric properties of the magnetic hydrogel are measured, as well as biocompatibility and MR-visibility (T1 -weighted mode; in vitro and in vivo). A 2-week MR follow-up study is performed in the mouse model, demonstrating no image artifacts, and the retention of "positive" contrast overtime, which allows very precise delineation of tissue grafts with MRI. Finally, a 3D-contouring procedure developed to facilitate graft delineation and geometrical conformity assessment is applied on an inverted template alginate pore network. This proof-of-concept establishes the possibility to reveal precisely engineered hydrogel structures using this USPIONs ink high-visibility approach.

Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy: A Prospective Multi-Centre Agreement Clinical Trial (CAN-ICE).

Rationale: Transbronchial cryobiopsy (TBCB) for the diagnosis of interstitial lung disease (ILD) has shown promising results, but prospective studies with matched surgical lung biopsy (SLB) have yielded conflicting results. Objectives: We aimed to assess within- and between-center diagnostic agreement between TBCB and SLB at both the histopathologic and multidisciplinary discussion (MDD) levels in patients with diffuse ILD. Methods: In a multicenter prospective study, we performed matched TBCB and SLB in patients referred for SLB. After a blinded review by three pulmonary pathologists, all cases were reviewed by three independent ILD teams in an MDD. MDD was performed first with TBCB, then with SLB in a second session. Within-center and between-center diagnostic agreement was evaluated using percentages and correlation coefficients. Measurements and Main Results: Twenty patients were recruited and underwent contemporaneous TBCB and SLB. Within-center diagnostic agreement between TBCB-MDD and SLB-MDD was reached in 37 of the 60 (61.7%) paired observations, resulting in a Cohen's κ value of 0.46 (95% confidence interval [CI], 0.29-0.63). Diagnostic agreement increased among high-confidence or definitive diagnoses on TBCB-MDD (21 of 29 [72.4%]), but not significantly, and was more likely among cases with SLB-MDD diagnoses of idiopathic pulmonary fibrosis than fibrotic hypersensitivity pneumonitis (13 of 16 [81.2%] vs. 16 of 31 [51.6%]; P = 0.047). Between-center agreement for cases was markedly higher for SLB-MDD (κ = 0.71 [95% CI, 0.52-0.89]) than TBCB-MDD (κ = 0.29 [95% CI, 0.09-0.49]). Conclusions: This study demonstrated moderate TBCB-MDD and SLB-MDD diagnostic agreement for ILD, while between-center agreement was fair for TBCB-MDD and substantial for SLB-MDD. Clinical trial registered with www.clinicaltrials.gov (NCT02235779).

Retrospective Assessment of Complementary Liquid Biopsy on Tissue Single-Gene Testing for Tumor Genotyping in Advanced NSCLC.

Biomarker testing is key for non-small cell lung cancer (NSCLC) management and plasma based next-generation sequencing (NGS) is increasingly characterized as a non-invasive alternative. This study aimed to evaluate the value of complementary circulating tumor DNA (ctDNA) NGS on tissue single-gene testing (SGT). Ninety-one advanced stage NSCLC patients with tumor genotyping by tissue SGT (3 genes) followed by ctDNA (38 genes amplicon panel) were included. ctDNA was positive in 47% (n = 43) and identified a targetable biomarker in 19 patients (21%). The likelihood of positivity on ctDNA was higher if patients had extra-thoracic disease (59%) or were not under active treatment (59%). When compared to SGT, ctDNA provided additional information in 41% but missed a known alteration in 8%. Therapeutic change for targeted therapy based on ctDNA occurred in five patients (5%), while seven patients with missed alterations on ctDNA had EGFR mutations or ALK fusions. The median turnaround time of ctDNA was 10 days (range 6-25), shorter (p = 0.002) than the cumulative delays for the tissue testing trajectory until biomarker availability (13 d; range 7-1737). Overall, the results from this study recapitulate the potential and limitations of ctDNA when used complementarily to tissue testing with limited biomarker coverage.

High sensitivity detection of nanoparticles permeation through polymer membranes: A physico-chemical and nuclear imaging measurement approach.

Diffusion cells are devices made of donor and acceptor compartments (DC and AC), separated by a membrane. They are widely used in pharmaceutical, cosmetic, toxicology, and protective equipment tests (e.g., gloves) to measure the kinetics of permeants (molecules and nanoparticles) across biological membranes as the skin. However, rarely is the concentration of permeants in the AC measured in continuous or in real-time, and this limitation leads to significant discrepancies in the calculations of kinetic parameters that define the permeation mechanisms. In this study, a diffusion cell compatible with positron emission tomography was used to measure the permeation kinetics of nanoparticles across glove membranes. The technology allows for the measurement of nanoparticle concentration in real-time in the two compartments (DC and AC) and at a detection sensitivity several orders of magnitude higher compared with conventional spectroscopies, thus allowing a much more precise extraction of kinetic parameters. Ultra-small (<10 nm) gold nanoparticles were used as a model nanoparticle contaminant. They were radiolabeled, and their diffusion kinetics was measured in continuous through latex and nitrile polymer membranes. Permeation profiles were recorded at sub-nanomolar sensitivity and in real-time, thus allowing the high precision extraction of kinetic permeation parameters. The technology, methodology, and data extraction process developed in this work could be applied to measure in real-time the kinetics of diffusion of a whole range of potentially toxic molecules and nanoparticles across polymer membranes, including glove membranes.

An unusual isolated anterior mediastinal lesion.

Malignant pleural mesothelioma (MPM) is an infrequent tumour of poor prognosis with a strong association with asbestos exposure. Pleural effusion or thickening is the most common radiological finding. Thoracoscopic biopsy is the diagnostic modality of choice. In our report, we present the case of a career welder who consulted with vocal cord palsy and an atypical anterior mediastinal lesion. An EBUS-TBNA-guided biopsy and a thorough cytological assessment led to an unexpected diagnosis of epithelioid MPM. A localized anterior mediastinal lesion is an extremely infrequent presentation of MPM that deserves clinical recognition.

Safety of Bronchoscopy after Acute Coronary Syndrome.

BACKGROUND: Bronchoscopy is a safe procedure which is frequently performed for the investigation of respiratory diseases. Current guidelines recommend to delay bronchoscopy for 4-6 weeks after acute coronary syndrome (ACS), as this period is theoretically considered at risk for new onset of ACS. We therefore aimed to evaluate the safety and the tolerance of bronchoscopy in patients with ACS (≤30 days) and to compare outcomes with matched controls. METHODS: All consecutive patients who had a bronchoscopy performed in the first 30 days after an ACS in the bronchoscopy suite were included. A group of patients with ACS who did not undergo bronchoscopy (controls) were also included and matched for age, sex, type of ACS, and severity of ACS (GRACE score). RESULTS: Of the 13,646 patients who underwent bronchoscopy between 2010 and 2019, 2,181 had an history of ACS and among those, 87 patients had an ACS (19 with STEMI, 52 with NSTEMI, and 16 unstable angina). Mean interval between ACS and bronchoscopy was of 10.1 ± 8.9 days. Systolic blood pressure and heart rate significantly increased and oxygen saturation significantly decreased during bronchoscopy. The most frequent adverse event was desaturation which occurred in 26% of patients. Reinfarction rate (1.1% vs. 2.3% p = 1.00) and all-cause 30-day mortality (2.3% vs. 4.6%; p = 0.68) were similar in patients who underwent bronchoscopy and in matched controls (n = 87). CONCLUSION: Our study reinforces the safety of bronchoscopy after ACS. When clinically indicated with potential benefits outweighing risks, ACS should not contraindicate bronchoscopy.

Endobronchial Ultrasound Transbronchial Needle Aspiration With a 19-Gauge Needle vs 21- and 22-Gauge Needles for Mediastinal Lymphadenopathy.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used to evaluate mediastinal lymphadenopathy. Studies focusing on malignant lymphadenopathy have compared 21- and 22-gauge (21G and 22G, respectively) needles and have not identified an advantage of one needle size over the other in terms of diagnostic yield. RESEARCH QUESTION: Does the 19-gauge (19G) EBUS needle offer greater diagnostic yield and sensitivity vs the 21G and 22G EBUS needles for a diagnosis of sarcoidosis, lymphoma, or mediastinal lymphadenopathy not yet diagnosed? STUDY DESIGN AND METHODS: This study retrospectively examined records of 730 patients from the Stather Canadian Outcomes Registry for Chest Procedures (SCOPE) database who underwent EBUS-TBNA for a diagnosis of suspected sarcoidosis, lymphoma, or mediastinal lymphadenopathy not yet diagnosed. A propensity score analysis of two groups was performed. One group comprised patients undergoing EBUS-TBNA with a 19G needle, the other with a 21G or 22G needle. Cases for analysis were selected with a 1:2 ratio of 19G vs 21/22G using logistic regression and random matching with all eligible 19G cases included. RESULTS: There were 137 patients (312 targets) in the 19G group and 274 patients (631 targets) in the 21/22G group in the propensity score analysis. The diagnostic yield was 107 of 137 (78.1%) in the 19G group vs 194 of 274 (70.8%) in the 21/22G group (difference, 7.3%; 95% CI, -1.9 to 15.6; P = .116). The sensitivity of EBUS-TBNA for sarcoidosis was 80 of 83 (96.4%) in the 19G group vs 150 of 156 (96.2%) in the 21/22G group (difference, 0.24%; 95% CI, -6.6 to 85.1; P = .93). In patients with a final diagnosis of lymphoma, EBUS was diagnostic in 10 of 13 (76.9%) in the 19G group vs 12 of 12 (100%) in the 21/22G group (difference, 23.1%; 95% CI, -5.4 to 50.3; P = .08). INTERPRETATION: The study did not identify an advantage of the 19G EBUS needle over the 21/22G EBUS needles for diagnostic yield nor sensitivity for sarcoidosis or lymphoma.

Dilation versus laser resection in subglottic stenosis: protocol for a prospective international multicentre randomised controlled trial (AERATE trial).

INTRODUCTION: Subglottic stenosis (SGS) is a rare condition that results from progressive narrowing of the upper airways. Outcomes and treatment options depend on the benign or complex nature of the stenosis. Treatment options for SGS include surgery and endoscopic techniques. The main endoscopic techniques used are dilation and laser resection. Observational and retrospective studies suggest that endoscopic laser resection may be more effective than dilation. We, therefore, aimed to compare the effectiveness of dilation and laser resection in preventing recurrence of SGS. METHODS AND ANALYSIS: AERATE (dilAtion vs laser Endoscopic Resection in subglottic trAcheal sTEnosis) is a multicentre, investigator-initiated, randomised controlled trial, comparing endoscopic dilation to endoscopic laser resection for simple benign SGS (less than 1 cm long without underlying cartilaginous damage) referred for endoscopic treatment (first treatment or recurrence). The study will be conducted in three centres in France and one in Canada with other centres from France and Canada expected to join. The primary outcome is the recurrence rate of stenosis at 2 years. Recurrence is defined as having a new onset of symptoms along with a stenosis of more than 40% (confirmed by bronchoscopy) requiring a new procedure. A sample size of 100 patients is calculated for the primary endpoint assuming a 10% recurrence rate in the laser resection group and 33% in the dilation group with a statistical significance level of 5%, a power of 80%. ETHICS AND DISSEMINATION: This study is approved by local and national ethics committees as required. Results will be published, and trial data will be made available. TRIAL REGISTRATION NUMBER: NCT04719845.

A Three-Dimensional Printable Hydrogel Formulation for the Local Delivery of Therapeutic Nanoparticles to Cervical Cancer.

Cervical cancer is the fourth most common malignancy among women. Compared to other types of cancer, therapeutic agents can be administrated locally at the mucosal vaginal membrane. Thermosensitive gels have been developed over the years for contraception or for the treatment of bacterial, fungal, and sexually transmitted infections. These formulations often carry therapeutic nanoparticles and are now being considered in the arsenal of tools for oncology. They can also be three-dimensionally (3D) printed for a better geometrical adjustment to the anatomy of the patient, thus enhancing the local delivery treatment. In this study, a localized delivery system composed of a Pluronic F127-alginate hydrogel with efficient nanoparticle (NP) release properties was prepared for intravaginal application procedures. The kinetics of hydrogel degradation and its NP releasing properties were demonstrated with ultrasmall gold nanoparticles (∼80% of encapsulated AuNPs released in 48 h). The mucoadhesive properties of the hydrogel formulation were assayed by the periodic acid/Schiff reagent staining, which revealed that 19% of mucins were adsorbed on the gel's surface. The hydrogel formulation was tested for cytocompatibility in three cell lines (HeLa, CRL 2616, and BT-474; no sign of cytotoxicity revealed). The release of AuNPs from the hydrogel and their accumulation in vaginal membranes were quantitatively measured in vitro/ex vivo with positron emission tomography, a highly sensitive modality allowing real-time imaging of nanoparticle diffusion (lag time to start of permeation of 3.3 h, 47% of AuNPs accumulated in the mucosa after 42 h). Finally, the potential of the AuNP-containing Pluronic F127-alginate hydrogel for 3D printing was demonstrated, and the geometrical precision of the 3D printed systems was measured by magnetic resonance imaging (<0.5 mm precision; deviation from the design values <2.5%). In summary, this study demonstrates the potential of Pluronic F127-alginate formulations for the topical administration of NP-releasing gels applied to vaginal wall therapy. This technology could open new possibilities for photothermal and radiosensitizing oncology applications.

Outcomes Following Surgical Lung Biopsy for Interstitial Lung Diseases: A Monocenter Experience.

BACKGROUND: Surgical lung biopsy (SLB) is considered in the investigation of interstitial lung diseases (ILDs) when a complete clinical evaluation and a multidisciplinary discussion (MDD) do not allow the clinician to make a confident diagnosis. Owing to the risk of the procedure, an appropriate assessment of the risk/benefit ratio prior to the intervention is recommended. We aimed to assess the postoperative outcomes and diagnostic yield of SLB for the investigation of ILD in a tertiary care institution. METHODS: We conducted a retrospective cohort study of consecutive subjects who underwent a SLB for the investigation of ILD in our center from 2009 to 2020. The postoperative mortality and complications rates as well as the diagnostic yield of the procedure were assessed. RESULTS: Of the 1,805 patients newly investigated for ILD in our center from 2009 to 2020, 71 (3.93%) underwent a SLB. At days 30 and 90, the mortality rates were 0 and 2.8%, whereas 4.3 and 7.6% patients experienced an acute ILD exacerbation, respectively. In addition, 4 (5.8%) patients experienced infectious complications and 5 (7.0%) presented prolonged air leaks (all within 30 days). A definite pathological diagnosis was made in 47 (66.2%) patients. Following postoperative MDD, a confident diagnosis was made in 61 patients (85.9%) and resulted in a change of therapy in 49 (69.0%) patients. CONCLUSION: SLB for the diagnosis of unclassifiable ILDs is associated with low mortality but significant morbidity. However, it results in a confident diagnosis and a change in therapy in the majority of patients.

Improving the radiopacity of Fe-Mn biodegradable metals by magnetron-sputtered W-Fe-Mn-C coatings: Application for thinner stents.

In this exploratory work, micrometric radiopaque W-Fe-Mn-C coatings were produced by magnetron sputtering plasma deposition, for the first time, with the aim to make very thin Fe-Mn stents trackable by fluoroscopy. The power of Fe-13Mn-1.2C target was kept constant at 400 W while that of W target varied from 100 to 400 W producing three different coatings referred to as P100, P200, P400. The effect of the increased W power on coatings thickness, roughness, structure, corrosion behavior and radiopacity was investigated. The coatings showed a power-dependent thickness and W concentration, different roughness values while a similar and uniform columnar structure. An amorphous phase was detected for both P100 and P200 coatings while γ-Fe, bcc-W and W3C phases found for P400. Moreover, P200 and P400 showed a significantly higher corrosion rate (CR) compared to P100. The presence of W, W3C as well as the Fe amount variation determined two different micro-galvanic corrosion mechanisms significantly changing the CR of coatings, 0.26 ± 0.02, 59.68 ± 1.21 and 59.06 ± 1.16 µm/year for P100, P200 and P400, respectively. Sample P200 with its most uniform morphology, lowest roughness (RMS = 3.9 ± 0.4 nm) and good radiopacity (∼6%) appeared the most suitable radiopaque biodegradable coating investigated in this study.