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Journal of Clinical Medicine Jul 2023Xerostomia and hyposalivation are highly prevalent conditions in old age, particularly among multimorbid elders, and are often attributed to the use of multiple... (Review)
Review
Xerostomia and hyposalivation are highly prevalent conditions in old age, particularly among multimorbid elders, and are often attributed to the use of multiple medications. These conditions negatively affect oral functions, such as chewing, swallowing, speech, and taste. Additionally, the lack of lubrication of the oral mucosa frequently leads to super-infections with candida. Denture retention and comfort may also be compromised. The risk of dental caries and erosion of natural teeth increases since saliva, which is essential for repairing initial lesions in tooth structures, is insufficient. The dry sensation in the mouth also impacts the emotional and social well-being of elderly individuals. Patients experiencing xerostomia often avoid certain foods that are uncomfortable or difficult to consume. However, some foods may alleviate the symptoms or even stimulate salivation. This review discusses the limited available evidence on nutritional advice for patients with xerostomia and aims to provide insight into the patient's perspective while offering clinical recommendations. Future studies should focus on investigating the nutritional intake of individuals suffering from xerostomia or hyposalivation in order to ensure oral health comfort, prevent malnutrition, and minimize the impact on their quality of life.
PubMed: 37510706
DOI: 10.3390/jcm12144592 -
Biomedicines May 2024Adiponectin is primarily known for its protective role in metabolic diseases, and it also possesses immunoregulatory properties. Elevated levels of adiponectin have been...
Adiponectin is primarily known for its protective role in metabolic diseases, and it also possesses immunoregulatory properties. Elevated levels of adiponectin have been observed in various inflammatory diseases. However, studies investigating adiponectin levels in the serum of COVID-19 patients have yielded conflicting results. This study aimed to assess serum adiponectin levels in 26 healthy controls, as well as in 64 patients with moderate and 60 patients with severe COVID-19, to determine a potential association between serum adiponectin and the severity of COVID-19. Serum adiponectin levels in severe COVID-19 patients were significantly lower than in those with moderate disease and healthy controls, who exhibited similar serum adiponectin levels. Among patients with moderate disease, positive correlations were observed between serum adiponectin and C-reactive protein levels. Of note, serum adiponectin levels of severe COVID-19 cases were comparable between patients with and without dialysis or vasopressor therapy. Superinfection with bacteria did not exert a notable influence on serum adiponectin levels in patients with severe disease. Patients who were diagnosed with severe COVID-19 and vancomycin-resistant enterococci bacteremia showed a significant reduction in their serum adiponectin levels. An analysis conducted on the entire cohort, including both moderate and severe COVID-19 patients, showed that individuals who did not survive had lower serum adiponectin levels when compared to those who survived. In summary, this study highlights a decrease in serum adiponectin levels in severe COVID-19 cases, indicating the potential utility of adiponectin as an additional biomarker for monitoring disease severity in COVID-19 or critical illnesses in general.
PubMed: 38791005
DOI: 10.3390/biomedicines12051043 -
The Journal of Experimental Medicine Aug 2023Type I interferons are important antiviral cytokines, but prolonged interferon production is detrimental to the host. The TLR3-driven immune response is crucial for...
Type I interferons are important antiviral cytokines, but prolonged interferon production is detrimental to the host. The TLR3-driven immune response is crucial for mammalian antiviral immunity, and its intracellular localization determines induction of type I interferons; however, the mechanism terminating TLR3 signaling remains obscure. Here, we show that the E3 ubiquitin ligase ZNRF1 controls TLR3 sorting into multivesicular bodies/lysosomes to terminate signaling and type I interferon production. Mechanistically, c-Src kinase activated by TLR3 engagement phosphorylates ZNRF1 at tyrosine 103, which mediates K63-linked ubiquitination of TLR3 at lysine 813 and promotes TLR3 lysosomal trafficking and degradation. ZNRF1-deficient mice and cells are resistant to infection by encephalomyocarditis virus and SARS-CoV-2 because of enhanced type I interferon production. However, Znrf1-/- mice have exacerbated lung barrier damage triggered by antiviral immunity, leading to enhanced susceptibility to respiratory bacterial superinfections. Our study highlights the c-Src-ZNRF1 axis as a negative feedback mechanism controlling TLR3 trafficking and the termination of TLR3 signaling.
Topics: Animals; Mice; Antiviral Agents; COVID-19; Interferon Type I; SARS-CoV-2; Toll-Like Receptor 3; Genes, src
PubMed: 37158982
DOI: 10.1084/jem.20220727 -
Infection Ecology & Epidemiology 2023The use of steroids has been proposed as a pharmacological approach to treat the SARS-CoV-2 infection to improve outcomes. However, there are doubts about safety... (Review)
Review
The use of steroids has been proposed as a pharmacological approach to treat the SARS-CoV-2 infection to improve outcomes. However, there are doubts about safety against the development of superinfections and their worse outcomes. To establish the relative frequency of superinfection associated with using steroids in patients with SARS-CoV-2 infection. We conducted a systematic literature review and meta-analysis using PRISMA standards in 5 databases (PubMed/Scopus/Cochrane/EMBASE/Google Scholar). The search was carried out between February 2020 and May 2023. The search terms were 'steroids' or 'superinfection' 'and' followed by 'SARS-CoV-2' or 'COVID-19'. We found 77 studies, but only 10 with 3539 patients were included in the systematic review. All patients developed severe disease. The documented OR for superinfection through the meta-analysis was 1.437 (95% IC 0.869-2.378) with a p-value of 0.158 without showing a risk attributed to steroids and the development of superinfections. In the Funnel-plot analysis, no publication biases were found. No relationship was found between using steroids and superinfection in patients with SARS-CoV-2.
PubMed: 38187166
DOI: 10.1080/20008686.2023.2277000 -
Cureus May 2024Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis mainly involving the ear, nose, and upper and lower airways. Diagnosis is based on clinical...
Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis mainly involving the ear, nose, and upper and lower airways. Diagnosis is based on clinical manifestations, positive antineutrophil cytoplasmic antibodies (ANCA) serology, and histopathological findings. We report a case of inflammatory polyarthralgia with a high titer of rheumatoid factor (RF), which was revealed to be GPA after extensive diagnosis workup. However, the disease was complicated by superinfections, which delayed and limited immunosuppressive treatment. Methotrexate was at last initiated with antibiotic prophylaxis, and there was significant clinical improvement. This case underlines the importance of an adequate diagnosis workup and the difficulties that often arise when other entities are present.
PubMed: 38894781
DOI: 10.7759/cureus.60606 -
Clinical Infectious Diseases : An... Feb 2024Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a frequent superinfection in critically ill patients with COVID-19 and is associated... (Observational Study)
Observational Study
BACKGROUND
Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a frequent superinfection in critically ill patients with COVID-19 and is associated with increased mortality rates. The increasing proportion of severely immunocompromised patients with COVID-19 who require mechanical ventilation warrants research into the incidence and impact of CAPA during the vaccination era.
METHODS
We performed a retrospective, monocentric, observational study. We collected data from adult patients with severe COVID-19 requiring mechanical ventilation who were admitted to the intensive care unit (ICU) of University Hospitals Leuven, a tertiary referral center, between 1 March 2020 and 14 November 2022. Probable or proven CAPA was diagnosed according to the 2020 European Confederation for Medical Mycology/International Society for Human and Animal Mycology (ECMM/ISHAM) criteria.
RESULTS
We included 335 patients. Bronchoalveolar lavage sampling was performed in 300 (90%), and CAPA was diagnosed in 112 (33%). The incidence of CAPA was 62% (50 of 81 patients) in European Organisation for Research and Treatment of Cancer (EORTC)/Mycosis Study Group Education and Research Consortium (MSGERC) host factor-positive patients, compared with 24% (62 of 254) in host factor-negative patients. The incidence of CAPA was significantly higher in the vaccination era, increasing from 24% (57 of 241) in patients admitted to the ICU before October 2021 to 59% (55 of 94) in those admitted since then. Both EORTC/MSGERC host factors and ICU admission in the vaccination era were independently associated with CAPA development. CAPA remained an independent risk factor associated with mortality risk during the vaccination era.
CONCLUSIONS
The presence of EORTC/MSGERC host factors for invasive mold disease is associated with increased CAPA incidence and worse outcome parameters, and it is the main driver for the significantly higher incidence of CAPA in the vaccination era. Our findings warrant investigation of antifungal prophylaxis in critically ill patients with COVID-19.
Topics: Adult; Animals; Humans; COVID-19; Critical Illness; Respiration, Artificial; Retrospective Studies; Pulmonary Aspergillosis; Immunocompromised Host; Invasive Pulmonary Aspergillosis
PubMed: 37691392
DOI: 10.1093/cid/ciad546 -
PLoS Pathogens Oct 2023SARS-CoV-2 causes COVID-19, an infectious disease with symptoms ranging from a mild cold to severe pneumonia, inflammation, and even death. Although strong inflammatory...
SARS-CoV-2 causes COVID-19, an infectious disease with symptoms ranging from a mild cold to severe pneumonia, inflammation, and even death. Although strong inflammatory responses are a major factor in causing morbidity and mortality, superinfections with bacteria during severe COVID-19 often cause pneumonia, bacteremia and sepsis. Aberrant immune responses might underlie increased sensitivity to bacteria during COVID-19 but the mechanisms remain unclear. Here we investigated whether SARS-CoV-2 directly suppresses immune responses to bacteria. We studied the functionality of human dendritic cells (DCs) towards a variety of bacterial triggers after exposure to SARS-CoV-2 Spike (S) protein and SARS-CoV-2 primary isolate (hCoV-19/Italy). Notably, pre-exposure of DCs to either SARS-CoV-2 S protein or a SARS-CoV-2 isolate led to reduced type I interferon (IFN) and cytokine responses in response to Toll-like receptor (TLR)4 agonist lipopolysaccharide (LPS), whereas other TLR agonists were not affected. SARS-CoV-2 S protein interacted with the C-type lectin receptor DC-SIGN and, notably, blocking DC-SIGN with antibodies restored type I IFN and cytokine responses to LPS. Moreover, blocking the kinase Raf-1 by a small molecule inhibitor restored immune responses to LPS. These results suggest that SARS-CoV-2 modulates DC function upon TLR4 triggering via DC-SIGN-induced Raf-1 pathway. These data imply that SARS-CoV-2 actively suppresses DC function via DC-SIGN, which might account for the higher mortality rates observed in patients with COVID-19 and bacterial superinfections.
Topics: Humans; SARS-CoV-2; Toll-Like Receptor 4; Lipopolysaccharides; Superinfection; COVID-19; Lectins, C-Type; Cytokines; Dendritic Cells
PubMed: 37844099
DOI: 10.1371/journal.ppat.1011735 -
Health Science Reports Jan 2024Co-infections occur when two or more different types of pathogens infect the same host at the same time. Initially, it may develop via a primary infection and then later...
BACKGROUND AND AIMS
Co-infections occur when two or more different types of pathogens infect the same host at the same time. Initially, it may develop via a primary infection and then later segue into a superinfection. Although some research suggests that coinfections do not affect the effect of disease outcomes, alternate evidence says otherwise. While the disease outcomes are frequently influenced by the interactions between many viruses, how these viruses interact during coinfections is poorly understood. This article aims to shed light on the interaction between viruses at a cellular and subcellular level, and the clinical implications for the same.
METHODS
The articles were sought by conducting a thorough literature search on Google Scholar, ScienceDirect, PubMed, PubMed Central, Dimensions, and EBSCO Host, using keywords such as coinfections, virus, viral hybrids, and superinfection. The articles pertinent to the concept were then included.
RESULTS
There is a growing body of evidence that suggests the formation of hybrid viral particles (HVPs) which conjugate at the cellular and subcellular level. While the formation of HVPs is bizarre, it may potentially have a profound effect on the clinical manifestations.
CONCLUSION
While there has been evidence of the formation of HVPs between a couple of viruses, researchers fear the existence of several other combinations, including zoonotic viruses. While this could be detrimental to the human race both at an individual-as well as a community-level, an in-depth understanding of the same may help in better management of the clinical manifestations of the disease.
PubMed: 38186927
DOI: 10.1002/hsr2.1780 -
Global Pediatric Health 2023Meningocele is a rare congenital malformation of the central nervous system resulting from a herniation of the meninges containing cerebrospinal fluid through a bony...
Meningocele is a rare congenital malformation of the central nervous system resulting from a herniation of the meninges containing cerebrospinal fluid through a bony defect in the skull. It is part of neural tube closure anomalies. The overall incidence of meningocele is 0.8 to 3 per 10 000 live births; it varies based on geographical location and race, with a predominance of occipital localization. Among diagnostic methods, computed tomography (CT) and magnetic resonance imaging (MRI) remain crucial examinations. Prenatal diagnosis of this malformation primarily relies on ultrasound and screening through maternal serum alpha-fetoprotein (AFP) levels. They typically manifest very early at birth with a highly suggestive radioclinical presentation. Surgical treatment usually allows for a definitive cure. Superinfection and rupture of the meningocele are exceptional, resulting from delayed diagnosis and management. In several developed countries, prevention through genetic counseling and the intake of folic acid during the periconceptional period, along with accurate prenatal diagnosis and the legalization of therapeutic abortion, has led to a decrease in the prevalence of meningoceles. In less developed countries, where there is a delay in diagnosis in exceptional cases, superinfection and rupture may occur. We present the case of an 8-month-old infant with a complicated occipital meningocele with superinfection and rupture.
PubMed: 37846398
DOI: 10.1177/2333794X231204498 -
Frontiers in Immunology 2023The co-infection of hepatitis B (HBV) patients with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis and thus drastically worsens the course of...
BACKGROUND AND AIMS
The co-infection of hepatitis B (HBV) patients with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis and thus drastically worsens the course of the disease. Therapy options for HBV/HDV patients are still limited. Here, we investigated the potential of natural killer (NK) cells that are crucial drivers of the innate immune response against viruses to target HDV-infected hepatocytes.
METHODS
We established co-culture models using HDV-infected hepatoma cell lines and human peripheral blood NK cells. We determined NK cell activation by flow cytometry, transcriptome analysis, bead-based cytokine immunoassays, and NK cell-mediated effects on T cells by flow cytometry. We validated the mechanisms using CRISPR/Cas9-mediated gene deletions. Moreover, we assessed the frequencies and phenotype of NK cells in peripheral blood of HBV and HDV superinfected patients.
RESULTS
Upon co-culture with HDV-infected hepatic cell lines, NK cells upregulated activation markers, interferon-stimulated genes (ISGs) including the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), produced interferon (IFN)-γ and eliminated HDV-infected cells via the TRAIL-TRAIL-R2 axis. We identified IFN-β released by HDV-infected cells as an important enhancer of NK cell activity. In line with our data, we observed activation of peripheral blood NK cells from HBV/HDV co-infected, but not HBV mono-infected patients.
CONCLUSION
Our data demonstrate NK cell activation in HDV infection and their potential to eliminate HDV-infected hepatoma cells via the TRAIL/TRAIL-R2 axis which implies a high relevance of NK cells for the design of novel anti-viral therapies.
Topics: Humans; Carcinoma, Hepatocellular; Ligands; Hepatitis D; Interferons; Hepatitis Delta Virus; Killer Cells, Natural; Tumor Necrosis Factors; Apoptosis; Liver Neoplasms
PubMed: 38143742
DOI: 10.3389/fimmu.2023.1287367