A retrospective review of implementation of an inhaled epoprostenol protocol in the emergency department.

INTRODUCTION: Inhaled epoprostenol is a selective pulmonary vasodilator that has shown a potentially broad number of applications in the management of critically ill patients. To date, the vast majority of the literature with regard to efficacy, indications for use, and adverse effects of inhaled epoprostenol is focused on use of this agent in critical care settings, with relatively little literature describing use of inhaled epoprostenol in the Emergency Department. This retrospective review sought to examine instances in which inhaled epoprostenol was administered in the Emergency Department of a tertiary-care, Level I trauma center following implementation of a clinical pathway for administration of this medication for cases of refractory hypoxemia, RV dysfunction, and refractory hypoxemia. Primary outcomes were monitoring for adverse effects (i.e. hypotension), trend in FiO2 requirement over time, and clinical indication for initiation of inhaled epoprostenol. METHODS: An automated review was performed to query cases in which inhaled epoprostenol had been initiated in the Emergency Department following adoption of the inhaled epoprostenol clinical pathway. Cases were excluded if the medication was initiated in the prehospital setting, ordered but not administered, or administered for a period of <1 h. Vital signs and co-administration of vasopressors were followed before and following epoprostenol administration to assess for change over time. Clinical indication of epoprostenol administration was assessed via manual chart review. RESULTS: Inhaled epoprostenol was administered in 20 instances, with 15 cases ultimately meeting inclusion criteria. There were no cases of clinically significant hypotension (MAP <65) in any of the cases in which inhaled epoprostenol was administered in the Emergency Department, and mean vasopressor requirement did not increase over time. A majority of patients saw a reduction in FiO2 requirement following administration of inhaled epoprostenol. The most common indication for initiation of inhaled epoprostenol based on manual chart review was pulmonary embolism. DISCUSSION: In this review of cases in which inhaled epoprostenol was administered following adoption of a clinical pathway for medication administration, there were no cases of hypotension or other adverse effects that appear to be attributable to medication administration. Pulmonary embolism and refractory hypoxemia were the most common noted indications for administration of inhaled epoprostenol. Further research is warranted regarding development of clinical protocols for administration of inhaled pulmonary vasodilators in the Emergency Department setting.

TIN-a combinatorial compound collection of synthetically feasible multicomponent synthesis products.

The synthetic feasibility of any compound library used for virtual screening is critical to the drug discovery process. TIN, a recursive acronym for 'TIN Is Not commercial', is a virtual combinatorial database enumeration of diversity-orientated multicomponent syntheses (MCR). Using a 'one-pot' synthetic technique, 12 unique small molecule scaffolds were developed, predominantly styrylisoxazoles and bis-acetylenic ketones, with extensive derivatization potential. Importantly, the scaffolds were accessible in a single operation from commercially available sources containing R-groups which were then linked combinatorially. This resulted in a combinatorial database of over 28 million product structures, each of which is synthetically feasible. These structures can be accessed through a free Web-based 2D structure search engine or downloaded in SMILES, MOL2, and SDF formats. Subsets include a 10% diversity subset, a drug-like subset, and a lead-like subset that are also freely available for download and virtual screening ( http://mmg.rcsi.ie:8080/tin ).

How manual therapy provided a gateway to a biopsychosocial management approach in an adult with chronic post-surgical low back pain: a case report.

BACKGROUND: The management of patients with chronic post-surgical low back pain can be very challenging to surgeons, physiotherapists, and patients alike. Subsequent surgery is often associated with post-operative complications and even lower levels of success than the initial spinal surgery. Physiotherapy is often recommended as the first-line management, however, debate exists amongst physiotherapists regarding the optimal treatment strategy. A key focus of this debate has been the use of manual therapy in chronic pain populations, leading clinicians to reevaluate its use. CASE DESCRIPTION: A 44-year-old female presented to physiotherapy with a 13-year history of persistent pain, having had a spinal fusion 12 years prior, following a skiing accident. Her primary complaints were pain and decreased self-efficacy. The patient was treated with a 12-week multimodal approach consisting of manual therapy, exercise rehabilitation, and pain neuroscience education. OUTCOMES: The patient had a significant reduction in the Numerical Pain Rating Scale (NPRS), the Oswestry Disability Index (ODI) and the Fear Avoidance Belief Questionnaire Physical Activity Subscale (FABQ-PA) scores following the intervention. She returned to running and cycling, reporting that pain was something she would 'work with instead of against'. DISCUSSION: This case study suggests that manual therapy can enhance an individualized biopsychosocial approach in the physiotherapy management of a patient with chronic post-surgical low back pain. Further research is needed to evaluate optimal intervention dosages and effective strategies in the management of patients with chronic low back pain following spinal surgery.

Digital Imaging and Communications in Medicine Whole Slide Imaging Connectathon at Digital Pathology Association Pathology Visions 2017.

As digital pathology systems for clinical diagnostic work applications become mainstream, interoperability between these systems from different vendors becomes critical. For the first time, multiple digital pathology vendors have publicly revealed the use of the digital imaging and communications in medicine (DICOM) standard file format and network protocol to communicate between separate whole slide acquisition, storage, and viewing components. Note the use of DICOM for clinical diagnostic applications is still to be validated in the United States. The successful demonstration shows that the DICOM standard is fundamentally sound, though many lessons were learned. These lessons will be incorporated as incremental improvements in the standard, provide more detailed profiles to constrain variation for specific use cases, and offer educational material for implementers. Future Connectathon events will expand the scope to include more devices and vendors, as well as more ambitious use cases including laboratory information system integration and annotation for image analysis, as well as more geographic diversity. Users should request DICOM features in all purchases and contracts. It is anticipated that the growth of DICOM-compliant manufacturers will likely also ease DICOM for pathology becoming a recognized standard and as such the regulatory pathway for digital pathology products.

Prevalence of and attitudes about concussion in Irish schools' rugby union players.

BACKGROUND: Youth rugby players represent 45.2% (N = 69,472) of the Irish rugby union playing population. The risk and consequences of concussion injury are of particular concern in these young athletes, but limited epidemiological data exists. This study investigated annual and lifetime prevalence of concussion in an Irish schoolboy rugby union cohort. METHODS: An anonymous cross-sectional survey of youth rugby players was conducted. Diagnosed concussion was defined as an incident where diagnosis was confirmed by a health professional or coach. Demographics, prevalence, and attitudes to concussion were collated. Data were analyzed with descriptive statistics, chi-square test, t-tests, Mann-Whitney tests, and logistic regression. RESULTS: Overall, 304 youth (aged 12-18 years) responded. Lifetime prevalence of diagnosed concussion was 19.4%, with annual (2010) prevalence 6.6%. Approximately 25.4% of players with diagnosed concussions returned to play without medical advice. Internal motivation (11.8%) was the predominant factor in feeling pressure to play while concussed. A desire for further concussion education was expressed by 89.5% of participants. CONCLUSIONS: Reform is required to prevent and manage concussion injuries among youth players in the rugby union, including mandatory education specific to concussion and implementation of return-to-play protocols. These findings have relevance for governing bodies, coaches, clinicians, schools, parents, and rugby union players.

RNASET2--an autoantigen in anaplastic large cell lymphoma identified by protein array analysis.

Characterising tumour-associated antigens (TAAs) not only represents an important approach to the identification of new diagnostic/prognostic markers, but can also provide information on disease processes and additional potential therapeutic targets. Preliminary screening of a protein macroarray, containing more than 12,000 different proteins, with sera from anaplastic lymphoma kinase (ALK)-negative and ALK-positive anaplastic large cell lymphoma (ALCL) patients identified ribonuclease and tumour suppressor protein Ribonuclease T2 (RNASET2), phosphatase lipid phosphate phosphatase-related protein type 3 (LPPR3) and apoptotic adaptor molecule Fas-associating protein (FADD) as ALK-negative ALCL-associated TAAs. Further validation of these observations was confirmed using the ALCL sera in reverse ELISAs. The circulating anti-RNASET2 autoantibodies present in ALCL patients' sera also recognised eukaryotically expressed RNASET2 protein. RNASET2 expression was then investigated in normal tissues and in lymphomas to explore its clinical potential. RNASET2 protein and mRNA levels showed highest expression in the spleen, leucocytes and pancreas. RNASET2 protein expression was not restricted to ALK-negative ALCL (81%), being expressed in ALK-positive ALCL (65%) as well as in a number of other lymphomas. The immunological recognition of RNASET2, its expression in ALCL and other lymphomas together with its known tumourigenic properties suggest that further studies on this autoantigen are warranted.

Protein macroarray profiling of serum autoantibodies in pseudoexfoliation glaucoma.

PURPOSE: Complex repertoires of IgG autoantibodies have been detected against ocular antigens in patients with glaucoma. The goal was to identify and characterize the IgG autoantibody repertoires in sera of patients with pseudoexfoliation glaucoma (PXFG) with protein macroarrays. METHODS: Serum samples of 21 patients with PXFG and 19 age- and sex-matched control subjects were profiled on high-density colony protein macroarrays expressing His-tagged recombinant human proteins derived from a human fetal brain cDNA library. Statistically prevalent expression clones in the PXFG group were sequenced. mRNA expression of identified antigens was examined in the rat ganglion cell line RGC-5 and in human brain and optic nerve cDNA. The IgG immunoreactivity of the sera of 20 control and 26 PXFG patients to purified C6orf129 was analyzed in a reverse enzyme-linked immunosorbent assay. RESULTS: An increased prevalence was detected among the PXFG patients of serum antibodies to seven proteins: C6orf129; stathmin-like 4; transmembrane protein 9 domain family, member B; fibroblast growth factor receptor 3; cleft lip and palate transmembrane protein 1; EH-domain-containing protein 1; and eukaryotic translation elongation factor 2. All antigens were expressed in the RGC-5 cells and in cDNA from human brain and optic nerve, with the exception of stathmin-like 4, which was not expressed in the RGC-5 cells. The patients with PXFG had increased anti-C6orf129 IgG immunoreactivity compared with that in the control subjects (P < 0.05). CONCLUSIONS: Screening high-density protein arrays identifies unique antibody profiles that may discriminate between patients with and without PXFG. Characterization of the autoantibody repertoire may provide new insights into the pathophysiology of PXFG.

Genomes2Drugs: identifies target proteins and lead drugs from proteome data.

BACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i) homologous to previously crystallized proteins or (ii) targets of known drugs, but are (iii) not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under 'change-of-application' patents.