87 research outputs found

    Graft-versus-host reaction and the mucosal immune response

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    Nurses' and surgeons' views and experiences of surgical wounds healing by secondary intention : a qualitative study

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    AIMS AND OBJECTIVES: To explore surgeons' and nurses' perspectives of managing surgical wounds healing by secondary intention. BACKGROUND: Every year, more than 10 million surgical operations are performed in the NHS in the UK. Most surgical wounds heal by primary intention, where the edges of the wound are brought together with staples, sutures, adhesive glue or clips. Sometimes wounds are deliberately left open to heal, from the base up, known as 'healing by secondary intention'. These wounds are often slow to heal, prone to infection, and complex to manage. DESIGN: A qualitative, descriptive approach, using semi-structured interviews. METHODS: Interviews with five (general, vascular and plastic) surgeons and 7 nurses (3 tissue viability nurses, 2 district and 1 community nurse, and 1 hospital nurse) working in hospital and community care settings in two locations in the north of England. Data analysis followed the recommended sequential steps of 'Framework' approach. Consolidated criteria for reporting qualitative research guided the study report. RESULTS: Participants reported that the main types of wounds healing by secondary intention that they manage are extensive abdominal cavity wounds; open wounds relating to treatment for pilonidal sinus; large open wounds on the feet of patients with diabetes; and axilla and groin wounds, associated with removal of lymph nodes for cancer. Infection and prolonged time to healing were the main challenges. Negative pressure wound therapy was the most favoured treatment option. CONCLUSIONS: Negative pressure wound therapy was advocated by professionals despite a lack of research evidence indicating clinical or cost-effectiveness. Our findings underscore the need for rigorous evaluation of negative pressure wound therapy, and other wound care treatments, through studies that include economic evaluation. RELEVANCE FOR CLINICAL PRACTICE: Clinical decision making in wound care could be optimised through further robust studies to inform practitioners about the cost-effectiveness of available treatments

    Is proflavine exposure associated with disease progression in women with cervical dysplasia? A brief report

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    Proflavine is an acridine dye used with high-resolution microendoscopy for in vivo diagnostic evaluation of cervical epithelial cells. However, there are concerns that even short-term exposure of cervical tissue to dilute proflavine may increase cervical cancer risk. We performed a retrospective analysis of women referred for colposcopy to Barretos Cancer Hospital comparing the risk of cervical disease progression in those whose cervical tissue was (n = 232) or was not exposed (n = 160) to proflavine. Patients in both groups underwent treatment and follow-up based on histopathologic results and per the local standards of care. Progression of disease was evaluated by comparing histopathology from the initial visit to the worst subsequent histopathology result from all follow-up visits. Mean duration of follow-up was 18.7 and 20.1 months for the proflavine-exposed and controls groups, respectively. There were no significant differences in disease progression from normal/CIN1 to CIN2/3 or from any initial diagnosis to invasive cancer between the proflavine exposed and control groups overall. Risks of cervical dysplasia progression observed in this study are in agreement with those of the natural history of cervical cancer. Our results suggest that cervical exposure to dilute proflavine does not increase the risk of cervical precancer and cancer.Research reported in this publication was supportedby the NCI of the NIH under Award Numbers UH2CA189910, UH3CA189910 and CA016672. The content is solely the responsibilityof the authors and does not necessarily represent the official views of the NIH.info:eu-repo/semantics/publishedVersio

    Generation and analysis of recombinant Bunyamwera orthobunyaviruses expressing V5 epitope-tagged L proteins

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    The L protein of Bunyamwera virus (BUNV; family Bunyaviridae) is an RNA-dependent RNA polymerase, 2238 aa in length, that catalyses transcription and replication of the negative-sense, tripartite RNA genome. To learn more about the molecular interactions of the L protein and to monitor its intracellular distribution we inserted a 14 aa V5 epitope derived from parainfluenza virus type 5, against which high-affinity antibodies are available, into different regions of the protein. Insertion of the epitope at positions 1935 or 2046 resulted in recombinant L proteins that retained functionality in a minireplicon assay. Two viable recombinant viruses, rBUNL4V5 and rBUNL5V5, expressing the tagged L protein were rescued by reverse genetics, and characterized with respect to their plaque size, growth kinetics and protein synthesis profile. The recombinant viruses behaved similarly to wild-type (wt) BUNV in BHK-21 cells, but formed smaller plaques and grew to lower titres in Vero E6 cells compared with wt BUNV. Immunofluorescent staining of infected cells showed the L protein to have a punctate to reticular distribution in the cytoplasm, and cell fractionation studies indicated that the L protein was present in both soluble and microsomal fractions. Co-immunoprecipitation and confocal microscopic assays confirmed an interaction between BUNV L and N proteins. The recombinant viruses expressing tagged L protein will be highly valuable reagents for the detailed dissection of the role of the BUNV L protein in virus replication

    Sensitivity to BST-2 restriction correlates with Orthobunyavirus host range

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    Orthobunyaviruses include several recently emerging viruses of significant medical and veterinary importance. There is currently very limited understanding on what determines the host species range of these pathogens. In this study we discovered that BST-2/tetherin restricts orthobunyavirus replication in a host-specific manner. We show that viruses with human tropism (Oropouche virus and La Crosse virus) are restricted by sheep BST-2 but not by the human orthologue, while viruses with ruminant tropism (Schmallenberg virus and others) are restricted by human BST-2 but not by the sheep orthologue. We also show that BST-2 blocks orthobunyaviruses replication by reducing the amount of envelope glycoprotein into viral particles egressing from infected cells. This is the first study identifying a restriction factor that correlates with species susceptibility to orthobunyavirus infection. This work provides insight to help us dissect the adaptive changes that bunyaviruses require to cross the species barrier and emerge into new species

    Surgical wounds healing by secondary intention: characterising and quantifying the problem, identifying effective treatments, and assessing the feasibility of conducting a randomised controlled trial of negative pressure wound therapy versus usual care

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    Background: Most surgical incisions heal by primary intention (i.e. wound edges are apposed with sutures, clips or glue); however some heal by secondary intention (i.e. the wound is left open and heals by formation of granulation tissue). There is, however, a lack of evidence regarding the epidemiology, management, and impact on patients’ quality of life of these surgical wounds healing by secondary intention (SWHSI), resulting in uncertainty regarding effective treatments and difficulty in planning care and research. Objectives: To derive a better understanding of the nature, extent, costs, impact and outcomes of SWHSI, effective treatments and the value and nature of further research. Design: Cross-sectional survey; inception cohort; cost-effectiveness and value of implementation analyses; qualitative interviews; and a pilot, feasibility randomised controlled trial (RCT). Setting: Acute and community care settings in Leeds and Hull, Yorkshire, UK. Participants: Adults with (or for qualitative interviews, patients or practitioners with previous experience of) a SWHSI. Inclusion criteria varied between the individual Workstreams. Interventions: The pilot, feasibility RCT compared negative pressure wound therapy (NPWT) – a device applying a controlled vacuum to a wound via a dressing - with Usual Care (no NPWT). Results: Survey data estimated that treated SWHSI have a point prevalence of 4.1 per 10,000 population (95% CI: 3.5 to 4.7). SWHSI most frequently occurred following colorectal surgery (n=80, 42.8% - Cross-sectional survey, n=136, 39.7% - Inception cohort), and were often planned before surgery (n=89, 47.6% - Survey, n=236, 60.1% - Cohort). Wound care was frequently delivered in community settings (n=109, 58.3%) and most patients (n=184, 98.4%) received active wound treatment. Cohort data identified hydrofibre dressings (n=259, 65.9%) as the most common treatment, although 29.3% (n=115) participants used NPWT at some time during the study. SWHSI healing occurred in 81.4% (n=320) of participants at a median of 86 days (95% CI: 75 to 103). Baseline wound area (p=<0.01), surgical wound contamination (determined during surgery) (p=0.04) and wound infection at any time (p=<0.01) (i.e. at baseline or post-operatively) were found to be predictors of prolonged healing. Econometric models, using observational, cohort study data, identified that with little uncertainty, that NPWT treatment is more costly and less effective than standard dressing treatment for the healing of open surgical wounds: Model A (ordinary least squares with imputation): Effectiveness: 73 days longer than those who did not receive NPWT (95% Credible Interval (CrI): 33.8 to 112.8); Cost Effectiveness (Associated incremental quality adjusted life years): -0.012 (SE 0.005) (Observables); -0.008 (SE 0.011) (Unobservables) , Model B (Two Stage Model – Logistic and linear regression): Effectiveness: 46 days longer the those who did not receive NPWT (95% CrI: 19.6 to 72.5); Cost Effectiveness (Associated incremental quality adjusted life years): -0.007 (Observables) and -0.027 (Unobservables) (SE 0.017). Patient interviews (n=20) identified initial reactions to SWHSI of shock and disbelief. Impaired quality of life characterised the long healing process, with particular impact on daily living for patients with families or in paid employment. Patients were willing to try any treatment promising wound healing. Health professionals (n=12) had variable knowledge of SWHSI treatments, and frequently favoured NPWT despite the lack of robust evidence, The pilot, feasibility RCT screened 248 patients for eligibility and subsequently recruited and randomised 40 participants to receive NPWT or Usual Care (no NPWT). Data indicated that it was feasible to complete a full RCT to provide definitive evidence for the effectiveness of NPWT as a treatment for SWHSI. Key elements and recommendations for a larger RCT were identified. Limitations: This research programme was conducted in a single geographical area (Yorkshire and the Humber, UK) and local guidelines and practices may have affected treatment availability and so may not represent UK wide treatment choices. A wide range of wound types were included, however, some wound types may be underrepresented meaning this research may not represent the overall SWHSI population. The lack of RCT data on the relative effects of NPWT in SWHSI resulted in much of the economic modelling being based on observational data. Observational data, even with adjustment, does not negate the potential for unresolved confounding to affect the results. This may reduce confidence in the conclusions drawn and may lead to calls for definitive evidence from an RCT. Conclusions: This research has provided new information regarding the nature, extent, costs, impacts and outcomes of SWHSI, treatment effectiveness and the value and nature of future research; addressing previous uncertainties regarding the problem of SWHSI. Aspects of our research indicate that NPWT is more costly and less effective than standard dressing for the healing of open surgical wounds. However, because this conclusion is based solely on observational data it may be affected by unresolved confounding. Should a future RCT be considered necessary, its design should reflect careful consideration of the findings of this programme of research

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