Differences in Mortality Among Patients With Asthma and COPD Hospitalized With COVID-19.

BACKGROUND: It remains unclear whether patients with asthma and/or chronic obstructive pulmonary disease (COPD) are at increased risk for severe coronavirus disease 2019 (COVID-19). OBJECTIVE: Compare in-hospital COVID-19 outcomes among patients with asthma, COPD, and no airway disease. METHODS: A retrospective cohort study was conducted on 8,395 patients admitted with COVID-19 between March 2020 and April 2021. Airway disease diagnoses were defined using International Classification of Diseases, 10th Revision codes. Mortality and sequential organ failure assessment (SOFA) scores were compared among groups. Logistic regression analysis was used to identify and adjust for confounding clinical features associated with mortality. RESULTS: The median SOFA score in patients without airway disease was 0.32 and mortality was 11%. In comparison, asthma patients had lower SOFA scores (median 0.15; P < .01) and decreased mortality, even after adjusting for age, diabetes, and other confounders (odds ratio 0.65; P = .01). Patients with COPD had higher SOFA scores (median 0.86; P < .01) and increased adjusted odds of mortality (odds ratio 1.40; P < .01). Blood eosinophil count of 200 cells/µL or greater, a marker of type 2 inflammation, was associated with lower mortality across all groups. Importantly, patients with asthma showed improved outcomes even after adjusting for eosinophilia, indicating that noneosinophilic asthma was associated with protection as well. CONCLUSIONS: COVID-19 severity was increased in patients with COPD and decreased in those with asthma, eosinophilia, and noneosinophilic asthma, independent of clinical confounders. These findings suggest that COVID-19 severity may be influenced by intrinsic immunological factors in patients with airway diseases, such as type 2 inflammation.

Pigmented villonodular synovitis: dedicated PET imaging findings.

Pigmented villonodular synovitis (PVNS) is an uncommon entity, which has the potential to cause severe pain. The gold standard for evaluation is MRI, and previous PET findings associated with PVNS have only been documented in the setting of concurrent malignancy. In the setting of recurrent disease, PET is being used to evaluate prebiological and postbiological treatment responses. Recurrent PVNS demonstrates greater hypermetabolic activity than previously documented, supporting the case as a potential mimic of malignant/metastatic disease. Post-treatment evaluations demonstrate decreased metabolic activity, which suggests response to treatment. This behaviour further supports the contention that there is a neoplastic origin to PVNS.

Practical implementation issues and challenges for biobanks in the return of individual research results.

Whether or not to give research results back to individuals whose specimens are used for biomedical research is a subject of considerable controversy. Much of the debate has been focused around the ethical and legal concerns with some consideration of broader social issues such as whether or not people will be affected by such information for employment or health care. Much less attention has been paid to biobanks that collect the specimens used to generate the research findings and the issues and operational requirements for implementing return of individual research results. In this article, we give the biobanks' perspective and highlight that given the diversity among the types of biobanks, it may be difficult to design and implement a blanket policy in this complex area. We discuss the variability in the types of biobanks and some important issues that should be considered in determining whether or not research results should be provided to individuals whose specimens are used in biomedical research. We also discuss challenges that should be considered in implementing any approaches to the return of research results.

Mathematical representation of fluorescence intensity of probes in aqueous binary solvent mixtures.

Fluorescence intensities of propranolol and atenolol in binary solvent mixtures at various temperatures are measured and mathematical models are proposed to represent the fluorescence intensity data. The results showed that the proposed models are able to correlate/predict the data with reasonable error. The fluorescence intensity of pyridoxal HCl in binary solvents at 25 °C is also determined and represented by the proposed model as an additional test probe.

Evaluation of a nanoemulsion-based formulation for respiratory delivery of budesonide by nebulizers.

The aim of this work was to evaluate the in vitro performance of a nebulized nanoemulsion formulation which had been optimised previously. To do so, a transparent nanoemulsion preparation containing 1.5 mg/ml of budesonide was prepared and diluted to achieve concentrations of 250 and 500 µg/ml budesonide. The in vitro characteristics of the diluted nanoemulsions were then compared with the commercially available suspension of budesonide (Pulmicort Respules®) when nebulized using a jet and a vibrating mesh nebulizer. A smaller MMAD with improved aerosol output was observed in the nanoemulsion preparations compared with the corresponding suspension formulations indicating an improved in vitro performance for the nanoemulsion-based preparations.

Factors affecting the stability of nanoemulsions--use of artificial neural networks.

PURPOSE: The aim of this study was to identify the dominant factors affecting the stability of nanoemulsions, using artificial neural networks (ANNs). METHODS: A nanoemulsion preparation of budesonide containing polysorbate 80, ethanol, medium chain triglycerides and saline solution was designed, and the particle size of samples with various compositions, prepared using different rates and amounts of applied ultrasonic energy, was measured 30 min and 30 days after preparation. Using ANNs, data were modelled and assessed. The derived predictive model was validated statistically and then used to determine the effect of different formulation and processing input variables on particle size growth of the nanoemulsion preparation as an indicator of the preparation stability. RESULTS: The results indicated that the data can be satisfactorily modelled using ANNs, while showing a high degree of complexity between the dominant factors affecting the stability of the preparation. CONCLUSION: The total amount of applied energy and concentration of ethanol were found to be the dominant factors controlling the particle size growth.

Evaluation of supercritical fluid engineered budesonide powder for respiratory delivery using nebulisers.

OBJECTIVES: Currently, suspensions prepared from micronised drug substances are the only delivery system marketed for nebulisation of steroids, and reported inconsistent or low bioavailability arising from their use provides a rationale for researching alternative formulations. Supercritical fluid processing of drug substances to obtain respirable-sized particles has been used over the last decade to formulate dry powder inhalers. We aimed thus to process budesonide powder to improve its deposition characteristics. METHODS: In an attempt to overcome the limitations of nebuliser suspensions when prepared from micronised drug particles, budesonide powder was processed using a supercritical fluid based process and suspended using Tween 80 as a surfactant to provide an aqueous nebuliser formulation. The in-vitro characteristics of the emitted dose on nebulisation for the prepared suspension were then compared to a commercially available suspension formulation of budesonide using a jet and a vibrating mesh nebuliser. KEY FINDINGS: The results showed a significant improvement of the in-vitro deposition properties of the suspension containing supercritical fluid engineered budesonide particles. CONCLUSIONS: The results indicated the benefit of such materials compared with traditionally micronised drug powders.

Comparison between monolithic and particle-packed platinum C18 columns in HPLC determination of acidic and basic test mixtures.

Herein we report the results of a comparative study on the performance of Monolithic RP-18e and Platinum C(18) 3 mum columns for isocratic separation of acidic and basic test compounds. The inter- and intraday precision of different practical parameters including number of theoretical plates (N), capacity factor (K'), tailing factor (T(0.05)), and resolution (R(s)) were determined for both columns. Two different production batches were used for each column and batch to batch reproducibility of both columns was evaluated. The column backpressure drop over flow rate range 0.5-2 mL/min at the monolithic columns was two- to three-times lower than that on the platinum column without loss of the column efficiency. The plate heights were used to estimate the columns efficiency using Van Deemter plots. Both types of columns were able to separate the tested compounds well with sufficient resolution and peak symmetry but they differ in the analysis time and column backpressure, significantly. Monolithic column was more convenient as it enables the analytical run under low backpressure at shorter time with sufficient separation efficiency.

Development and validation of a rapid and efficient method for simultaneous determination of methylxanthines and their metabolites in urine using monolithic HPLC columns.

A new rapid, sensitive and validated HPLC method has been developed for the determination of methylxanthines and their metabolites in asthmatic patients. The method was initiated by using spiked urine samples on a silica monolithic column as a novel packing material. The mobile phase consisted of 10 mM potassium dihydrogen phosphate buffer/methanol (87.5:12.5 v/v), at a flow rate 1 mL/min. Detection was set at 274 nm. The LOQ for all the compounds ranged from 14 to 41 ng/mL. Excellent linearity was achieved over the studied range of concentration with correlation coefficients 0.9991-0.9998 (n = 6). The developed method was validated by precision and accuracy with RSD <2.55%. On extraction of the drugs and metabolites from the urine samples high recoveries were achieved ranging from 82.06 to 98.34% w/w on RP18 cartridges and methanol/chloroform (20:80 v/v) as the extraction solvent. This method has advantages over other methods using conventional C18 packings.

Determination of factors controlling the particle size in nanoemulsions using Artificial Neural Networks.

The purpose of this study was to use Artificial Neural Networks (ANNs) in identifying factors, in addition to surfactant and internal phase content, that influence the particle size of nanoemulsions. The phase diagram and rheometric characteristics of a nanoemulsion system containing polysorbate 80, ethanol, medium chain triglycerides and normal saline loaded with budesonide were investigated. The particle size of samples of various compositions prepared using different rates and amounts of applied energy was measured. Data, divided into training, test and validation sets, were modelled by ANNs. The developed model was assessed and found to be of high quality. The model was then used to explore the effect of composition and processing factors on particle size of the nanoemulsion preparation. The study demonstrates the potential of ANNs in identifying critical parameters controlling preparation for this system, with the total amount of applied energy during preparation found to be the dominant factor in controlling the final particle size.

Tissue banking in a regulated environment--does this help the patient? Part 1--Legislation, regulation and ethics in the UK.

The difficulties with 'retained organs' in the UK have resulted in a new legislation relating to human organs, tissues, and bodies - the Human Tissue Act 2004 and the Human Tissue Act Scotland 2006 are now in place. The new laws apply to a wide range of activities including transplantation, education, clinical audit, the practice of autopsies, anatomical examination and others, including the use of human tissues in research. Pathobiology research that uses human tissues is now undertaken in a regulated environment in the UK. The details of these regulations are described and the consequences discussed. In the second part of the paper the patient's views and expectations in this new setting are forwarded.

Protocol for the use of polymerase chain reaction in the detection of intraocular large B-cell lymphoma in ocular samples.

To determine the usefulness of polymerase chain reaction (PCR) analyses in the diagnosis of lymphoid infiltrate cells in ocular samples, PCR was performed using oligonucleotide primers specific for immunoglobulin heavy chain rearrangement at framework 2, framework 3, and t(14;18) translocation of the bcl-2 gene. These were used to successfully generate amplicons of 220 to 230 bp, 110 to 120 bp, and 175 to 200 bp, respectively. After PCR amplification, primers directed against the t(14;18) detected 10 pg of B-cell lymphoma DNA. PCR against Fr2 and Fr3 IgH rearrangement detected 10 fg and 10 pg in the seminested PCR, respectively. Conventional pathological methods were highly accurate at establishing the correct final diagnosis in formalin-fixed, paraffin-embedded samples but were much less sensitive and predictive in cytological specimens of intraocular fluid. A combination of the three PCR reactions was an equally successful diagnostic approach on paraffin-embedded samples, whereas single PCR reactions did not significantly improve diagnosis over histopathological diagnostic techniques. Thus, a combination of PCR reactions is useful in the detection of B-cell monoclonality, aids the differentiation between lymphomatous and inflammatory infiltrates, and is more powerful as a diagnostic method than single PCR or conventional cytopathology for lymphoid infiltrates in ocular fluid aspirates.

Isolation and characterization of murine Cds (CDP-diacylglycerol synthase) 1 and 2.

Phototransduction in Drosophila is a phosphoinositide-mediated signalling pathway. Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a central role in this process, and its levels are tightly regulated. A photoreceptor-specific form of the enzyme CDP-diacylglycerol synthase (CDS), which catalyzes the formation of CDP-diacylglycerol from phosphatidic acid, is a key regulator of the amount of PIP2 available for signalling. cds mutants develop light-induced retinal degeneration. We report here the isolation and characterization of two murine genes encoding this enzyme, Cds1 and Cds2. The genes encode proteins that are 73% identical and 92% similar but exhibit very different expression patterns. Cds1 shows a very restricted expression pattern but is expressed in the inner segments of the photoreceptors whilst Cds2 shows a ubiquitous pattern of expression. Using fluorescent in situ hybridization we have mapped Cds1 and Cds2 to chromosomes 5E3 and 2G1 respectively. These are regions of synteny with the corresponding human gene localization (4q21 and 20p13). Transient transfection experiments with epitope tagged proteins have also demonstrated that both are associated with the endoplasmic reticulum.

Expression analysis of SIX3 and SIX6 in human tissues reveals differences in expression and a novel correlation between the expression of SIX3 and the genes encoding isocitrate dehyhrogenase and cadherin 18.

SIX3 and SIX6 are transcription factors expressed during early stages of eye development. Limited expression data for SIX3 and SIX6 are available in the literature but, to date, there are no reports of the relative levels of expression of these genes throughout the human body and in adult tissues in particular. In this paper, we report extensive real-time quantitative PCR analyses of SIX3 and SIX6 expression in many different tissues of the adult human body, including ocular tissues, and a comparison of expression data with that of many other genes to identify similarity in expression. Using this powerful technique, we have detected a novel statistical correlation between the spatial distribution and the quantitative expression of SIX3 and 5 other transcripts including IDH1, the gene encoding the NADP(+)-dependent enzyme isocitrate dehydrogenase, and cadherin 18, type 2 (CDH14). Our data demonstrate that this novel technique can be used to generate hypotheses by comparison of gene expression profiles to identify possible interactions between genes or gene products.

Fourth meeting of the European Network of Research Tissue Banks - future strategy to increase collaborations in the supply of human tissue for biomedical research.

This report records the Fourth meeting of the European Network of Research Tissue Bank (Brussels, 18th March 2004) which was attended by Mel Read MEP. The existing membership of this informal group represents European Human Research Tissue Bankers, biomedical researchers seeking access to human tissue and allied groups including animal welfare representatives. This Fourth meeting provided a forum to update members on individual activity in this area. A particular focus of this meeting was to consider the status of this group and future affiliations to increase the profile and activity of this Network. This meeting addressed differences in legislative and ethical requirements governing the use of human tissue in biomedical research in the different countries represented. Future activity of the ENRTB, planned at this meeting, will target harmonisation of current differences which are currently barriers to increased access to human tissue for biomedical research. Through the harmonisation of procurement, processing and distribution of human tissue specimens the ENRTB will provide a mechanism to benefit human health through increased use of human tissue in pharmacotoxicological studies and the associated replacement of animal tests.