Home High-Flow Therapy in Patients with Chronic Respiratory Diseases: Physiological Rationale and Clinical Results.

High-flow therapy (HFT) is the administration of gas flows above 15 L/min. It is a non-invasive respiratory support that delivers heated (up to 38 °C), humidified (100% Relative Humidity, RH; 44 mg H2O/L Absolute Humidity, AH), oxygen-enriched air when necessary, through a nasal cannula or a tracheostomy interface. Over the last few years, the use of HFT in critically ill hypoxemic adults has increased. Although the clinical benefit of home high-flow therapy (HHFT) remains unclear, some research findings would support the use of HHFT in chronic respiratory diseases. The aim of this review is to describe the HFT physiological principles and summarize the published clinical findings. Finally, we will discuss the differences between hospital and home implementation, as well as the various devices available for HHFT application.

Simulation workflows to predict the circular dichroism and circularly polarized luminescence of chiral materials.

Chiral materials are attracting considerable interest in various fields in view of their unique properties and optical activity. Indeed, the peculiar features of chiral materials to absorb and emit circularly polarized light enable their use in an extensive range of applications. Motivated by the interest in boosting the development of chiral materials characterized by enhanced chiroptical properties such as circular dichroism (CD) and circular polarized luminescence (CPL), we herein illustrate in this tutorial how theoretical simulations can be used for the predictions and interpretations of chiroptical data and for the identification of chiral geometries. We are focusing on computational frameworks that can be used to investigate the theoretical aspects of chiral materials' photophysical and conformational characteristics. We will then illustrate ab initio methods based on density functional theory (DFT) and its time-dependent extension (TD-DFT) to simulate CD and CPL signals, and we will exemplify a variety of enhanced sampling techniques useful for an adequate sampling of the configurational space for chiral systems.

Keratin/Polylactic acid/graphene oxide composite nanofibers for drug delivery.

In this work keratin/poly(lactic acid) (PLA) 50/50 wt blend nanofibers with different loadings of graphene-oxide (GO) were prepared by electrospinning and tested as delivery systems of Rhodamine Blue (RhB), selected as a model of a drug. The effect of GO on the electrospinnability and drug release mechanism and kinetics was investigated. Rheological measurements carried out on the blend solutions revealed unsatisfactory compatibility between keratin and PLA under quiet condition. Accordingly, poor interfacial adhesion between the two phases was observed by SEM analysis of a film prepared by solution casting. On the contrary, keratin chains seem to rearrange under the flux conditions of the electrospinning process thus promoting better interfacial interactions between the two polymers, thereby enhancing their miscibility, which resulted in homogeneous and defect-free nanofibers. The loading of GO into the keratin/PLA solution contributes to increase its viscosity, its shear thinning behavior, and its conductivity. Accordingly, thinner and more homogeneous nanofibers resulted from solutions with a relatively high conductivity coupled with a pronounced shear thinning behavior. FTIR and DSC analyses have underlined, that while the PLA/GO interfacial interactions significantly compete with the PLA/keratin ones, there are no significant effects of GO on the structural organization of keratin in blend with the PLA. However, GO offers several advantages from the application point of view by slightly improving the mechanical properties of the electrospun mats and by slowing down the release of the model drug through the reduction of the matrix swelling.

Effects of non-invasive respiratory supports on inspiratory effort in moderate-severe COVID-19 patients. A randomized physiological study.

RATIONALE AND OBJECTIVE: Various forms of Non-invasive respiratory support (NRS) have been used during COVID-19, to treat Hypoxemic Acute Respiratory Failure (HARF), but it has been suggested that the occurrence of strenuous inspiratory efforts may cause Self Induced Lung Injury(P-SILI). The aim of this investigation was to record esophageal pressure, when starting NRS application, so as to better understand the potential risk of the patients in terms of P-SILI and ventilator induced lung injury (VILI). METHODS AND MEASUREMENTS: 21 patients with early de-novo respiratory failure due to COVID-19, underwent three 30 min trials applied in random order: high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and non-invasive ventilation (NIV). After each trial, standard oxygen therapy was reinstituted using a Venturi mask (VM). 15 patients accepted a nasogastric tube placement. Esophageal Pressure (ΔPes) and dynamic transpulmonary driving pressure (ΔPLDyn), together with the breathing pattern using a bioelectrical impedance monitor were recorded. Arterial blood gases were collected in all patients. MAIN RESULTS: No statistically significant differences in breathing pattern and PaCO2 were found. PaO2/FiO2 ratio improved significantly during NIV and CPAP vs VM. NIV was the only NRS to reduce significantly ΔPes vs. VM (-10,2 ±5 cmH20 vs -3,9 ±3,4). No differences were found in ΔPLDyn between NRS (10,2±5; 9,9±3,8; 7,6±4,3; 8,8±3,6 during VM, HFNC, CPAP and NIV respectively). Minute ventilation (Ve) was directly dependent on the patient's inspiratory effort, irrespective of the NRS applied. 14% of patients were intubated, none of them showing a reduction in ΔPes during NRS. CONCLUSIONS: In the early phase of HARF due to COVID-19, the inspiratory effort may not be markedly elevated and the application of NIV and CPAP ameliorates oxygenation vs VM. NIV was superior in reducing ΔPes, maintaining ΔPLDyn within a range of potential safety.

Corrigendum: Case Report: Hodgkin Lymphoma and Refractory Systemic Lupus Erythematosus Unveil Activated Phosphoinositide 3-Kinase-δ Syndrome 2 in an Adult Patient.

[This corrects the article DOI: 10.3389/fped.2021.702546.].

Case Report: Hodgkin Lymphoma and Refractory Systemic Lupus Erythematosus Unveil Activated Phosphoinositide 3-Kinase-δ Syndrome 2 in an Adult Patient.

Introduction: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is a rare primary immune regulatory disorder caused by heterozygous gain of function mutation in the PIK3R1 gene encoding PI3Kδ regulatory p85α subunit and resulting in PI3Kδ hyperactivation. Clinical features range from recurrent infections to manifestations of immune dysregulation like autoimmunity, inflammation, systemic lymphoproliferation, and increased risk of cancer. We describe a new dominant PIK3R1 mutation causing APDS2 presenting with lymphoma and systemic refractory autoimmunity. Case Presentation: A 30-year-old woman was referred to the Immunology Unit of our hospital for uncontrolled systemic lupus erythematosus, including chilblains lesions, systemic lymphoproliferation and IgA deficiency. At 19 years of age, she was diagnosed with Hodgkin's lymphoma. Subsequently, she presented systemic lupus erythematosus onset, with episodes of severe exacerbation, including autoimmune hemolytic anemia and pleuro-pericarditis. Initial clinical response to conventional treatments was reported. Immunological investigations performed during our first observation showed severe lymphopenia, IgA deficiency, elevated IgM with reduced IgG2 levels, and low vaccination antibody titers. Quantitative real-time polymerase chain reaction (PCR) assay for Cytomegalovirus and Epstein-Barr virus showed low viral loads for both viruses in serum. An increase of serum inflammatory markers highlighted persistent systemic hyperinflammation. The next-generation sequencing (NGS)-based gene panel tests for primary immunodeficiency showed a heterozygous A>G substitution in the splice acceptor site at c.1300-2 position of PIK3R1, leading to exon-skipping. Conclusion: This case emphasizes the importance of suspecting primary immune regulatory disorders in young adults, predominantly showing a severe, aggressive, and refractory to treatment immune dysregulation phenotype, even in the absence of major infectious diseases at the onset. Different treatments can be promptly started, and a delayed diagnosis can highly impact the outcome. Targeted therapy against PI3Kδ pathway defect effectively improves drug-resistant autoimmunity, lymphoproliferation, and risk of progression to malignancy; eligible patients could benefit from its use even as a bridge therapy to transplantation, currently the only definitive curative treatment. Therefore, identifying genetic mutation and prompt targeted treatment are essential to control disease manifestations, prevent long-term sequelae, and enable curative HSCT in APDS2 patients.

Optically activated and interrogated plasmonic hydrogels for applications in wound healing.

We disclose the use of hybrid materials featuring Au/Ag core/shell nanorods in porous chitosan/polyvinyl alcohol scaffolds for applications in tissue engineering and wound healing. The combination of Au and Ag in a single construct provides synergistic opportunities for optical activation of functions as near infrared laser tissue bonding, and remote interrogation to return parameters of prognostic relevance in wound healing monitoring. In particular, the bimetallic component ensures optical tunability, enhanced shelf life and photothermal stability, serves as a reservoir of germicidal silver cations, and changes in near-infrared and visible color according to the environmental level of oxidative stress. At the same time, the polymeric blend is ideal to bind connective tissue upon photothermal activation, and to support fabrication processes that provide high porosity, such as electrospinning, thus putting all the premises for cellular repopulation and antimicrobial protection.

Respiratory treatment in a patient with nemaline myopathy.

Respiratory involvement of nemaline myopathy is evident on the diaphragm and intercostal muscles function. The present case study aimed to describe the characteristics of the respiratory physiotherapeutic treatment in a patient with nemaline myopathy. Here, we describe a case of a 43-yearold woman with nemaline myopathy undergoing pulmonary rehabilitation during short hospital admission for an acute exacerbation. At the time of hospitalisation, the patient was already under oxygen therapy (1 L/min) and noninvasive home ventilation using bi-level positive airway pressure with a nasal interface. Supplementary therapeutic exercises were implemented in addition to daily nasal noninvasive ventilation. At discharge, ultrasound examination revealed increased diaphragm trophism if compared with data obtained at hospital admission.

Chest ultrasonography in health surveillance of asbestos-related lung diseases.

OBJECTIVES: Exposure to asbestos fibers can lead to different lung diseases, such as pleural thickening and effusion, asbestosis, mesothelioma, and lung cancer. These diseases are expected to peak in the next few years. The aim of the study was to validate ultrasonography (US) as a diagnostic tool in the management of lung diseases in subjects with a history of occupational exposure to asbestos. METHODS: Fifty-nine retired male workers previously exposed to asbestos were enrolled in the study. Chest US was performed in all the subjects. The US operator was blinded to earlier performed computed tomography (CT) scan reports and images. The sonographic pathological findings were pleural thickening (with or without calcifications), peripheral lung consolidation, and focal sonographic interstitial syndrome and diffuse pneumogenic sonographic interstitial syndrome (pulmonary asbestosis). Significant US findings were recorded, stored, and subsequently compared with CT scans. RESULTS: With some patients falling into more than one category, on CT scan, pleural thickening was reported in 33 cases (56%, 26 with calcifications), focal interstitial peripheral alterations in 23 (39%), asbestosis in 6 (10%), and peripheral lung consolidation in 13 cases (22%). Comparing each pathological condition to CT scan reports, US findings had high levels of sensitivity, specificity, positive, and negative predictive values. US did not prove effective for the detection of central lung nodules or diaphragmatic pleural thickenings. Chest US was considered to be the best technique to detect minimal pleural effusions (six subjects, 10%). CONCLUSIONS: Chest US might be considered an additional tool to follow up subjects occupationally exposed to asbestos who have already undergone CT scan examination and whose pathology is detectable by US as well.