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Supportive care and antiviral treatments in primary herpetic gingivostomatitis: a systematic review.Clinical Oral Investigations Nov 2023Herpes simplex virus 1 (HSV-1) is the main pathogen responsible for herpes infections. In 13-30% of the cases, primary HSV-1 leads to the primary herpetic... (Review)
Review
OBJECTIVES
Herpes simplex virus 1 (HSV-1) is the main pathogen responsible for herpes infections. In 13-30% of the cases, primary HSV-1 leads to the primary herpetic gingivostomatitis (PHGS), often a self-limiting infection; however, it can limit the ability to drink/eat with, sometimes, the need for hospitalization. Multiple therapeutic methods have been proposed. This systematic review aims to collect and critically appraise the available evidence about the clinical management of PHGS.
MATERIALS AND METHODS
Literature search including three databases (PubMed, Scopus, Embase), study design, and data analysis were performed following PRISMA guidelines, according to the PICO tool (PROSPERO n° CRD42023391386). Risk of bias was assessed with RoB 2 and ROBINS-I.
RESULTS
Five studies on a total of 364 patients (average age: 7.6 years) were identified. The treatment regimens were summarized in acyclovir; acyclovir + honey; fluids and analgesic; maalox + diphenhydramine; lidocaine; chlorhexidine (CHX); CHX + ialuronic acid; CHX + Mucosyte®; antimicrobial photodynamic therapy (aPDT); topical antiviral; topical antiviral + aPDT; and others.
CONCLUSIONS
Although PHGS is a disease with a high worldwide prevalence, the lack of consensus about therapeutic management indicates gaps in existing evidence. Most of the proposed treatment consists in symptomatic drugs with empiric regimens which are ineffective for the viral replication. The main limit to realize randomized clinical trial is due to the rapid onset and remission of the disease. In fact, the diagnostic delay, estimated in 72 h, decreases the effectiveness of any antiviral drugs.
CLINICAL RELEVANCE
Out of the five studies included in this systematic review, only one was able to provide some weak evidence that ACV is an effective treatment, improving healing of oral lesions and reducing duration of symptoms.
Topics: Humans; Child; Stomatitis, Herpetic; Delayed Diagnosis; Antiviral Agents; Acyclovir; Lidocaine; Randomized Controlled Trials as Topic
PubMed: 37733027
DOI: 10.1007/s00784-023-05250-5 -
Redox Biology Aug 2023Cholesterol-24-hydroxylase (CH24H or Cyp46a1) is a reticulum-associated membrane protein that plays an irreplaceable role in cholesterol metabolism in the brain and has...
Cholesterol-24-hydroxylase (CH24H or Cyp46a1) is a reticulum-associated membrane protein that plays an irreplaceable role in cholesterol metabolism in the brain and has been well-studied in several neuro-associated diseases in recent years. In the present study, we found that CH24H expression can be induced by several neuroinvasive viruses, including vesicular stomatitis virus (VSV), rabies virus (RABV), Semliki Forest virus (SFV) and murine hepatitis virus (MHV). The CH24H metabolite, 24-hydroxycholesterol (24HC), also shows competence in inhibiting the replication of multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 24HC can increase the cholesterol concentration in multivesicular body (MVB)/late endosome (LE) by disrupting the interaction between OSBP and VAPA, resulting in viral particles being trapped in MVB/LE, ultimately compromising VSV and RABV entry into host cells. These findings provide the first evidence that brain cholesterol oxidation products may play a critical role in viral infection.
Topics: Animals; Mice; Cholesterol; COVID-19; Homeostasis; SARS-CoV-2; Virus Internalization; Cholesterol 24-Hydroxylase
PubMed: 37285742
DOI: 10.1016/j.redox.2023.102769 -
Cureus Sep 2023Denture stomatitis (DS), a common oral condition among denture wearers, is frequently associated with () colonization. This systematic review and meta-analysis aimed to... (Review)
Review
Denture stomatitis (DS), a common oral condition among denture wearers, is frequently associated with () colonization. This systematic review and meta-analysis aimed to provide a comprehensive assessment of DS prevalence and its relationship with in the Indian population. We conducted a thorough search of multiple databases for studies without any limitation to the publication timeframe, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies were assessed for quality and included in the meta-analysis. Data regarding DS prevalence, risk factors, and colonization were extracted and analyzed. A total of four studies comprising 415 participants were included in the review. The overall odds ratio (OR) and risk ratio (RR) for the prevalence of in DS patients were 0.75 (95% CI 0.56 to 0.99) and 0.83 (95% CI 0.70 to 1.00), respectively, indicating a statistically significant association between DS and colonization. Several risk factors, including continuous denture wearing, advanced denture age, poor denture hygiene, and high sugar intake, were identified as contributing to DS development. This systematic review and meta-analysis highlight the substantial burden of DS and its association with colonization in the Indian population. The findings emphasize the need for comprehensive oral care, improved denture hygiene, dietary counseling, and interventions to enhance salivary flow in denture wearers to mitigate the risk of DS. These insights can inform healthcare providers and policymakers to develop targeted strategies for DS prevention and management in India. Furthermore, this study emphasizes the significance of oral health awareness and preventive strategies in groups with a high frequency of denture usage in a larger population.
PubMed: 37842362
DOI: 10.7759/cureus.45182 -
PLoS Pathogens Jul 2023The innate immune system is the first line of the host's defense, and studying the mechanisms of the negative regulation of interferon (IFN) signaling is important for...
The innate immune system is the first line of the host's defense, and studying the mechanisms of the negative regulation of interferon (IFN) signaling is important for maintaining the balance of innate immune responses. Here, we found that the host GTP-binding protein 4 (NOG1) is a negative regulator of innate immune responses. Overexpression of NOG1 inhibited viral RNA- and DNA-mediated signaling pathways, and NOG1 deficiency promoted the antiviral innate immune response, resulting in the ability of NOG1 to promote viral replication. Vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) infection induced a higher level of IFN-β protein in NOG1 deficient mice. Meanwhile, NOG1-deficient mice were more resistant to VSV and HSV-1 infection. NOG1 inhibited type I IFN production by targeting IRF3. NOG1 was also found to interact with phosphorylated IFN regulatory factor 3 (IRF3) to impair its DNA binding activity, thereby downregulating the transcription of IFN-β and downstream IFN-stimulated genes (ISGs). The GTP binding domain of NOG1 is responsible for this process. In conclusion, our study reveals an underlying mechanism of how NOG1 negatively regulates IFN-β by targeting IRF3, which uncovers a novel role of NOG1 in host innate immunity.
Topics: Animals; Mice; Interferon Regulatory Factor-3; Interferon-beta; Gene Expression; Immunity, Innate; Herpes Simplex; Herpesviridae Infections; DNA; Interferon Type I
PubMed: 37410776
DOI: 10.1371/journal.ppat.1011511 -
International Journal of Molecular... Jul 2023In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant... (Review)
Review
In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant effectiveness, they are not free from side effects, such as allergic and dermatological reactions. These reactions can vary in severity and outcome, including potential death. Examples, among others, are type I-IV hypersensitivity reactions of various origins and skin reactions including rashes, itching and redness, but also severe cutaneous syndromes. Due to the therapy used, these may include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis. In some cases, it is necessary to interrupt therapy, which may result in a poorer outcome and shorten the patient's survival. This paper reviews various types of research documents published since 2016. It aims to systematize the latest knowledge and highlight the need for further research into ways to avoid adverse reactions.
Topics: Humans; Skin; Stevens-Johnson Syndrome; Acute Generalized Exanthematous Pustulosis; Drug Hypersensitivity Syndrome; Eosinophilia
PubMed: 37511017
DOI: 10.3390/ijms241411257 -
Oral Oncology Sep 2023Radiation-induced mucositis is the most common, debilitating and painful acute toxicity associated with active treatment in head and neck cancer area, severely affecting... (Review)
Review
Radiation-induced mucositis is the most common, debilitating and painful acute toxicity associated with active treatment in head and neck cancer area, severely affecting more than 65% of patients. Oral microbiota significantly changes during cancer therapy and appears to be involved on its pathophysiology. This review aims to present a comprehensive update of new etiopathogenic factors and treatments that may decrease the incidence of mucositis, mainly modifications of dietary interventions to modify microbiome. Despite advances in recent years, its management is mainly symptomatic opioid-based with variable results on different substances analyzed for its prevention. Immunonutrition seems to play a significant role, particularly the supplementation of compounds such as fatty acids, polyphenols or selected probiotics have shown to promote commensal bacteria diversity and reduced incidence of ulcerative mucositis. Modification of the microbiome is a promising preventive treatment for mucositis although its evidence is still scarce. Large studies are needed to demonstrate the efficacy of interventions on microbiome and its clinical impact on radiation-induced mucositis.
Topics: Humans; Mucositis; Stomatitis; Head and Neck Neoplasms; Radiation Injuries; Microbiota
PubMed: 37399707
DOI: 10.1016/j.oraloncology.2023.106488 -
The Journal of Infectious Diseases Nov 2023The filovirus Bundibugyo virus (BDBV) causes severe disease with a mortality rate of approximately 20%-51%. The only licensed filovirus vaccine in the United States,...
BACKGROUND
The filovirus Bundibugyo virus (BDBV) causes severe disease with a mortality rate of approximately 20%-51%. The only licensed filovirus vaccine in the United States, Ervebo, consists of a recombinant vesicular stomatitis virus (rVSV) vector that expresses Ebola virus (EBOV) glycoprotein (GP). Ervebo was shown to rapidly protect against fatal Ebola disease in clinical trials; however, the vaccine is only indicated against EBOV. Recent outbreaks of other filoviruses underscore the need for additional vaccine candidates, particularly for BDBV infections.
METHODS
To examine whether the rVSV vaccine candidate rVSVΔG/BDBV-GP could provide therapeutic protection against BDBV, we inoculated seven cynomolgus macaques with 1000 plaque-forming units of BDBV, administering rVSVΔG/BDBV-GP vaccine to 6 of them 20-23 minutes after infection.
RESULTS
Five of the treated animals survived infection (83%) compared to an expected natural survival rate of 21% in this macaque model. All treated animals showed an early circulating immune response, while the untreated animal did not. Surviving animals showed evidence of both GP-specific IgM and IgG production, while animals that succumbed did not produce significant IgG.
CONCLUSIONS
This small, proof-of-concept study demonstrated early treatment with rVSVΔG/BDBV-GP provides a survival benefit in this nonhuman primate model of BDBV infection, perhaps through earlier initiation of adaptive immunity.
Topics: Animals; Hemorrhagic Fever, Ebola; Ebolavirus; Vesicular Stomatitis; Antibodies, Viral; Vesiculovirus; Glycoproteins; Viral Vaccines; Macaca fascicularis; Immunoglobulin G; Ebola Vaccines
PubMed: 37290053
DOI: 10.1093/infdis/jiad207 -
Frontiers in Immunology 2023Metastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint...
A phase I oncolytic virus trial with vesicular stomatitis virus expressing human interferon beta and tyrosinase related protein 1 administered intratumorally and intravenously in uveal melanoma: safety, efficacy, and T cell responses.
INTRODUCTION
Metastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint inhibitors (ICIs). Oncolytic viruses (OV) represent a novel approach to immunotherapy for patients with MUM.
METHODS
We developed an OV with a Vesicular Stomatitis Virus (VSV) vector modified to express interferon-beta (IFN-β) and Tyrosinase Related Protein 1 (TYRP1) (VSV-IFNβ-TYRP1), and conducted a Phase 1 clinical trial with a 3 + 3 design in patients with MUM. VSV-IFNβ-TYRP1 was injected into a liver metastasis, then administered on the same day as a single intravenous (IV) infusion. The primary objective was safety. Efficacy was a secondary objective.
RESULTS
12 patients with previously treated MUM were enrolled. Median follow up was 19.1 months. 4 dose levels (DLs) were evaluated. One patient at DL4 experienced dose limiting toxicities (DLTs), including decreased platelet count (grade 3), increased aspartate aminotransferase (AST), and cytokine release syndrome (CRS). 4 patients had stable disease (SD) and 8 patients had progressive disease (PD). Interferon gamma (IFNγ) ELIspot data showed that more patients developed a T cell response to virus encoded TYRP1 at higher DLs, and a subset of patients also had a response to other melanoma antigens, including gp100, suggesting epitope spreading. 3 of the patients who responded to additional melanoma antigens were next treated with ICIs, and 2 of these patients experienced durable responses.
DISCUSSION
Our study found that VSV-IFNβ -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM. Although there were no clear objective radiographic responses to VSV-IFNβ-TYRP1, dose-dependent immunogenicity to TYRP1 and other melanoma antigens was seen.
Topics: Animals; Humans; Interferon-beta; Melanoma-Specific Antigens; Monophenol Monooxygenase; Oncolytic Virotherapy; Oncolytic Viruses; T-Lymphocytes; Vesicular Stomatitis; Vesicular stomatitis Indiana virus
PubMed: 38022659
DOI: 10.3389/fimmu.2023.1279387 -
Cancer Treatment Reviews Apr 2024Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the... (Review)
Review
Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery of cytotoxic agents to tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2 (TROP2), a protein that is broadly expressed in several types of solid tumors. Dato-DXd is being investigated across multiple solid tumor indications. In the ongoing, first-in-human TROPION-PanTumor01 phase I study (ClinicalTrials.gov: NCT03401385), encouraging and durable antitumor activity and a manageable safety profile was demonstrated in patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor2-negative breast cancer (HR+/HER2- BC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC). Improved understanding of the adverse events (AEs) that are associated with Dato-DXd and their optimal management is essential to ensure safe and successful administration. Interstitial lung disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, and ocular surface events have been identified as AEs of special interest (AESIs) for which appropriate prevention, monitoring, and management is essential. This article summarizes the incidence of AESIs among patients with HR+/HER2- BC, TNBC, and NSCLC reported in TROPION-PanTumor01. We report our recommendations for AESI prophylaxis, early detection, and management, using experience gained from treating AESIs that occur with Dato-DXd in clinical trials.
Topics: Humans; Female; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Lung Neoplasms; Antineoplastic Agents; Immunoconjugates; Trastuzumab; Breast Neoplasms; Receptor, ErbB-2; Camptothecin; Clinical Trials, Phase I as Topic
PubMed: 38502995
DOI: 10.1016/j.ctrv.2024.102720