-
Molecular Therapy Oncolytics Dec 2023Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection...
Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we describe the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic vesicular stomatitis virus (VSV), VSV-IFNβ-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNβ-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a "tail" of long-term survivors (∼35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNA-seq analysis showed that all the long-term responders had increased expression of a T cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNβ-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.
PubMed: 37965295
DOI: 10.1016/j.omto.2023.100736 -
Journal of Dentistry Oct 2023Denture stomatitis is prevalent in older people and poses serious health risks. Ready-to-use (RTU) neutral-pH Electrolysed Oxidizing Water (EOW) is an effective...
OBJECTIVES
Denture stomatitis is prevalent in older people and poses serious health risks. Ready-to-use (RTU) neutral-pH Electrolysed Oxidizing Water (EOW) is an effective environmental disinfectant used in residential care settings and geriatric wards. However, the influence of storage on stability and effectiveness for denture disinfection has not been established. This research investigated the storage-related stability and antimicrobial activity of RTU EOW, and its efficacy against Candida albicans biofilms formed on denture resin.
METHODS
The pH, oxidation/reduction potential (mV), available chlorine content (mg/L) and [HOCl] (mM) of RTU EOW (Envirolyte, New Zealand) solutions (n = 22) were measured from bottle opening to 28 days following storage at 4 °C, room temperature (RT) or 37 °C. Staphylococcus aureus and C. albicans cells were incubated in 80% EOW for contact times (CTs) up to 15 min and colony-forming units (cfu) determined. Minimum inhibitory concentrations (MIC EOW-HOCl) after CTs up to five minutes were determined for S. aureus and C. albicans reference strains and clinical isolates. C. albicans-denture resin disc biofilms were assessed after a five-minute CT with undiluted EOW by XTT-metabolic activity assay.
RESULTS
[HOCl] remained stable when RTU EOW was stored at 4 °C or RT for five months after manufacture. One-minute CT resulted in log cfu reductions of >6 for S. aureus and >5 for C. albicans. Mean MIC for five-minute CT was 37 µM (S. aureus) and 54 µM (C. albicans). Undiluted EOW reduced C. albicans biofilm metabolic activity by 86%.
CONCLUSIONS
RTU neutral-pH EOW is stable over five-months storage and is an effective denture disinfectant.
CLINICAL SIGNIFICANCE
The efficacy of the RTU neutral EOW against C. albicans isolates and biofilms formed on denture resin surfaces supports its use as a denture disinfectant and can inform future research to assess its potential for preventing denture-related oral Candida infections in the older population, especially in resource-limited communities.
Topics: Humans; Aged; Water; Staphylococcus aureus; Candida albicans; Disinfectants; Biofilms; Hydrogen-Ion Concentration; Denture Bases
PubMed: 37567495
DOI: 10.1016/j.jdent.2023.104656 -
Current Drug Safety 2024Paracetamol (Acetaminophen) is a very common OTC drug that is found in more than 200 OTC products sold as pain, cough and cold remedies. Paracetamol is commonly used as... (Review)
Review
INTRODUCTION
Paracetamol (Acetaminophen) is a very common OTC drug that is found in more than 200 OTC products sold as pain, cough and cold remedies. Paracetamol is commonly used as an antipyretic to reduce fever and as an alternative to Non-steroidal anti-inflammatory drugs (NSAIDs) that are contraindicated in certain patients to relieve mild-moderate pain.
OBJECTIVE
This review article focuses on SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes associated with the use of paracetamol or paracetamol-containing products.
METHODS
To find published articles relevant to paracetamol-associated SJS, TEN, AGEP, and DRESS, we searched the online databases Medline/Pubmed/PMC, Google Scholar, Science Direct, Ebsco, Scopus, Web of Science, Embase, and reference lists using keywords like Stevens-Johnson Syndrome, Acetaminophen, Paracetamol, Toxic epidermal necrolysis, Acute generalized exanthematous pustulosis, Drug reaction with eosinophilia and systemic symptoms.
RESULTS
The paracetamol-associated SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes have been identified by a number of publications.
CONCLUSION
When evaluating drug-induced hypersensitivity skin reactions, healthcare professionals, including prescribers, pharmacists, and others, should be aware of this rare risk. Patients who exhibit signs and symptoms of paracetamol-associated hypersensitivity should be referred to physicians by pharmacists for further treatment. At the first sign of a skin rash or other hypersensitivity reaction while taking paracetamol, patients should be told to stop taking it and see a doctor right away.
Topics: Humans; Stevens-Johnson Syndrome; Drug Hypersensitivity Syndrome; Acute Generalized Exanthematous Pustulosis; Acetaminophen; Pain
PubMed: 37151075
DOI: 10.2174/1574886318666230505144014 -
Clinical Microbiology and Infection :... Dec 2023To report 5-year persistence and avidity of antibodies produced by the live-attenuated recombinant vesicular stomatitis virus (rVSV) expressing the Zaire Ebolavirus...
OBJECTIVES
To report 5-year persistence and avidity of antibodies produced by the live-attenuated recombinant vesicular stomatitis virus (rVSV) expressing the Zaire Ebolavirus (ZEBOV) glycoprotein (GP), known as rVSV-ZEBOV (Ervebo®).
METHODS
Healthy adults vaccinated with 300,000 or 10-50 million plaque-forming units of rVSV-ZEBOV in the WHO-coordinated trials of 2014-2015 were followed for up to 4 (Lambaréné, Gabon) and 5 (Geneva, Switzerland) years. We report seropositivity rates, geometric mean titres (GMTs), and population distribution of ZEBOV-GP ELISA IgG antibodies, neutralizing antibodies (pseudovirus and live-virus neutralization) and antibody avidity; the primary outcome was ZEBOV-GP ELISA IgG GMTs at 4 or 5 years compared with 1 year (Y1) after immunization.
RESULTS
Among the 168 eligible vaccinees (Geneva: 97 and Lambaréné: 71) enrolled 1 year post-immunization, 146 (87%) remained enrolled at 4 years (Geneva: n = 88, Lambaréné: n = 58), and 84 (87%, Geneva) at 5 years post-vaccination. ZEBOV-GP ELISA IgG GMTs plateaued, with no declining trend from 1 year through the last time point assessed (1147.8 [95% CI 874.3-1507.0] at Y1 versus 1548.1 [95% CI 1136.6-2108.5] at Y5 in Geneva volunteers receiving ≥10 million plaque-forming units of rVSV-ZEBOV), their avidity matching that of ZEBOV convalescents. Live-virus neutralizing antibodies were detected for shorter periods and in fewer vaccinees (53/95 [56%] at Y1 versus 35/84 [42%] at Y5 in Geneva volunteers, all dose levels).
DISCUSSION
Titres at Y1 emerged as a correlate of antibody persistence at Y5. The findings of persistent ZEBOV-GP ELISA IgG titres yet shorter-lasting, lower titres of live-virus neutralizing antibodies suggest the contribution of antibody-mediated protective mechanisms other than neutralization. Long-term clinical efficacy of rVSV-ZEBOV, however, requires further study.
Topics: Adult; Animals; Humans; Hemorrhagic Fever, Ebola; Ebolavirus; Antibody Formation; Democratic Republic of the Congo; Ebola Vaccines; Vesicular Stomatitis; Antibodies, Viral; Vaccination; Antibodies, Neutralizing; Immunoglobulin G; Antibodies, Blocking
PubMed: 37661067
DOI: 10.1016/j.cmi.2023.08.026 -
European Journal of Dermatology : EJD Aug 2023
Topics: Humans; Tramadol; Stevens-Johnson Syndrome; Erythema Multiforme
PubMed: 37823501
DOI: 10.1684/ejd.2023.4520 -
Pediatric Dermatology 2023Mucocutaneous eruptions are associated with numerous infectious processes and can present as erythema multiforme (EM), reactive infectious mucocutaneous eruption (RIME),... (Review)
Review
Mucocutaneous eruptions are associated with numerous infectious processes and can present as erythema multiforme (EM), reactive infectious mucocutaneous eruption (RIME), Stevens Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN). Limited reports have detailed the association of these eruptions with SARS-CoV-2 infection. We present a series of eight cases of severe mucocutaneous blistering eruptions associated with SARS-CoV-2 infection. A retrospective case series was performed at six tertiary medical centers from March 1, 2020 to August 1, 2022. Inclusion criteria were met with a clinical diagnosis of EM, RIME, SJS, or TEN and a positive SARS-CoV-2 test (rapid antigen or polymerase chain reaction) less than 4 weeks prior to onset of dermatologic manifestation. Data was collected at time of each patient encounter. Eight patients met criteria with six pediatric patients (<18 years of age) having a median age of 15 years and two adult patients (>18 years of age) having a median age of 36 years. Patients were found to have a clinical diagnosis of RIME in 85.7% of cases. Oral mucosal involvement was the most common clinical finding (100%), followed by ocular (50.0%), urogenital (50.0%), and skin (37.5%) involvement. Evaluation did not reveal any additional infectious triggers in four patients. Evidence of possible concurrent or previous infectious triggers were identified in four patients. This case series highlights the development of severe mucocutaneous eruptions in association with COVID-19 infection, as well as the potential contributing role of concurrent or prior infections.
Topics: Adult; Humans; Child; Adolescent; Retrospective Studies; COVID-19; SARS-CoV-2; Stevens-Johnson Syndrome; Erythema Multiforme; Exanthema
PubMed: 37526023
DOI: 10.1111/pde.15407 -
PloS One 2023To assess S-1 and 5-fluorouracil (5-FU)-related adverse events in patients with advanced gastric cancer and provide focused health care approaches to improve patient... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess S-1 and 5-fluorouracil (5-FU)-related adverse events in patients with advanced gastric cancer and provide focused health care approaches to improve patient compliance and quality of survival.
METHODS
The PubMed, Web of Science, Medline, Cochrane Library, EMbase, SinoMed, Wan Fang Data, CNKI, and VIP databases were searched, and relevant literature was screened from the database construction date through March 31, 2023. Review Manager 5.4.1 and Stata 12.0 were used to analyze the data and GRADEpro was used to assess the quality of the literature. Relative risk ratio (RR) and a 95% confidence interval (CI) were employed as markers to compare adverse events due to S-1 vs 5-FU.
RESULTS
Eight randomized controlled trials (RCT) were included, which contained 3,455 patients. The S-1 group had 1,804 patients, and the 5-FU group had 1,651 patients. There were 17 recorded adverse events in total. Stomatitis, hypokalemia, mucosal inflammation, and hypophosphatemia were more common in the 5-FU group than in the S-1 group (P < 0.001). No significant difference was observed between S-1 and 5-FU for other adverse events.
CONCLUSIONS
Although both S-1 and 5-FU cause a variety of side effects, 5-FU resulted in a higher incidence of stomatitis, hypokalemia, mucosal inflammation, and hypophosphatemia than S-1. Medical professionals should closely monitor the occurrence of adverse drug events and provide timely, rational guidance and nursing care to improve patient compliance and quality of life.
Topics: Humans; Fluorouracil; Stomach Neoplasms; Hypokalemia; Hypophosphatemia; Stomatitis; Inflammation
PubMed: 37566608
DOI: 10.1371/journal.pone.0290003 -
Indian Journal of Otolaryngology and... Sep 2023Recurrent aphthous stomatitis (RAS) is characterized by painful, oral mucosal ulcers with wide range of prevalence ranging from 2 to 78%. Etiology of RAS is idiopathic...
Recurrent aphthous stomatitis (RAS) is characterized by painful, oral mucosal ulcers with wide range of prevalence ranging from 2 to 78%. Etiology of RAS is idiopathic and multifactorial. There are numerous gaps in assessment and management of RAS and the absence of guidelines or a consensus document makes the treatment further difficult. The aim of this document is to provide an Indian expert consensus for management of RAS. Experts from different specialties such as Otorhinolaryngology, Oral Medicine/Dentistry and Internal Medicine from India were invited for face to face and online meetings. After a deliberate discussion of current literature, evidence and clinical practice during advisory meetings, experts developed a consensus for management of RAS. We identify that the prevalence of RAS may lie between 2 and 5%. In defining RAS, we advocate three or more recurrences of aphthous ulcers per year as criterion for RAS. Investigation should include basic hematological (complete blood count) and nutritional (serum vitamin B12, and iron studies) parameters. Primary aim of treatment is to reduce the pain, accelerate ulcer healing, reduce the recurrences and improve the quality of life. In treating RAS, initial choice of medications is determined by pain intensity, number and size of ulcers and previous number of recurrences. Topical and systemic agents can be used in combination for effective relief. In conclusion, this consensus will help physicians and may harmonize effective diagnosis and treatment of RAS.
PubMed: 37636607
DOI: 10.1007/s12070-023-03708-2 -
The Journal of Prosthetic Dentistry Aug 2023Dental hygiene for institutionalized patients and recurring Candida-associated denture stomatitis remain problematic because of a patient's limited dexterity or... (Review)
Review
STATEMENT OF PROBLEM
Dental hygiene for institutionalized patients and recurring Candida-associated denture stomatitis remain problematic because of a patient's limited dexterity or inability to eliminate Candida from denture surfaces. Although there has been extensive research into antimicrobial modification of denture base resins with inorganic materials, scoping reviews of the literature to identify knowledge gaps or efficacy of inorganic antimicrobial materials in denture base resins are lacking.
PURPOSE
The purpose of this scoping review was to provide a synopsis of the efficacy of the major classes of inorganic antimicrobial materials currently incorporated into denture base resins.
MATERIAL AND METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews was applied. Four electronic databases, including Embase, PubMed, Web of Science, and Google Scholar, were accessed for articles in the English language, up to February 2019, without restrictions on the date of publication.
RESULTS
From the 53 articles selected, 25 distinguishable inorganic materials were found and divided into 3 subgroups. Forty-three articles evaluated nanomaterials, where mostly silver ion nanoparticles and/or titanium dioxide nanoparticles were incorporated into denture base resins. Fourteen articles examined antimicrobial drugs and medications, including azole group medications, amphotericin-B, Bactekiller, chlorhexidine, Novaron, and Zeomic. Two articles classified as others explored hydroxyapatite- and fiber-incorporated denture base resins.
CONCLUSIONS
Although nanotechnology and antimicrobial medications or drugs have been successfully used to reduce Candida-associated denture stomatitis, long-term solutions are still lacking, and their disadvantages continue to outweigh their advantages.
Topics: Humans; Stomatitis, Denture; Denture Bases; Anti-Infective Agents; Candida; Nanoparticles; Materials Testing
PubMed: 34756425
DOI: 10.1016/j.prosdent.2021.09.004 -
Animals : An Open Access Journal From... Nov 2023Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host...
Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis ( = 12), healthy cats ( = 9), and cats with tooth resorption or periodontitis ( = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method. Collectively, our work furthers our understanding of the dysbiosis and composition of bacteria in the oral microbiome in FCGS, with hopes of contributing to the prevention, diagnosis, and treatment of this challenging condition in felines.
PubMed: 38003162
DOI: 10.3390/ani13223544