Biofilms in Chronic Rhinosinusitis: A Review

Background Bacterial biofilms consist of a complex, organized community of bacteria that anchor to both biotic and abiotic surfaces. They are composed of layers of embedded, live bacteria within extruded exopolymeric matrix. This configuration allows for evasion of host defenses and decreased susceptibility to antibiotic therapy while maintaining the ability to deliberately release planktonic bacteria, resulting in recurrent acute infections. Thus, bacterial biofilms were hypothesized to contribute to the progression and persistence of chronic rhinosinusitis. Methods This review summarizes several of the seminal papers supporting this hypothesis. Results Multiple reports using various imaging modalities have demonstrated the presence of biofilms in sinonasal mucosa of patients with chronic rhinosinusitis. More recently, several studies have correlated the presence of biofilms with poor clinical outcomes in the disease process. Early therapeutic interventions have generated mixed results. Conclusions Bacterial biofilms appear to contribute to the progression of chronic rhinosinusitis in a subset of patients, although substantial effort toward therapeutic intervention is still necessary.

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Demonstration of Biofilm in Human Bacterial Chronic Rhinosinusitis

American Journal of Rhinology ◽

10.1177/194589240501900506 ◽

2005 ◽

Vol 19 (5) ◽

pp. 452-457 ◽

Cited By ~ 110

Author(s):

Berrylin J. Ferguson ◽

Donna B. Stolz

Keyword(s):

Chronic Rhinosinusitis ◽

Culture Media ◽

Cellular Membrane ◽

Anaerobic Growth ◽

Bacterial Biofilms ◽

Topical Steroids ◽

Fungal Sinusitis ◽

Allergic Fungal Sinusitis ◽

Planktonic Bacteria ◽

Transmission Electron

Background Bacterial biofilms may explain why some patients with bacterial chronic rhinosinusitis (CRS) improve while on antibiotics but relapse after completion of the antibiotic. In the human host, biofilms exist as a community of bacteria surrounded by a glycocalyx that is adherent to a foreign body or a mucosal surface with impaired host defense. Biofilms generate planktonic, nonadherent bacterial forms that may metastasize infection and generate systemic illness. These planktonic bacteria are susceptible to antibiotics, unlike the adherent biofilm. Methods We reviewed four cases of CRS using transmission electron microscopy (TEM) to assay for typical colony architecture of biofilms. Bacterial communities surrounded by a glycocalyx of inert cellular membrane materials consistent with a biofilm were shown in two patients. Results In the two patients without biofilm, a nonbacterial etiology was discovered (allergic fungal sinusitis) in one and in the other there was scant anaerobic growth on culture and the Gram stain was negative. Culture of the material from the biofilm grew Pseudomonas aeruginosa in both patients. Pseudomonas from the biofilm showed a glycocalyx, not present in Pseudomonas cultured for 72 hours on culture media. Both patients’ symptoms with bacterial biofilms were refractory to culture-directed antibiotics, topical steroids, and nasal lavages. Surgery resulted in cure or significant improvement. Conclusion Biofilms are refractory to antibiotics and often only cured by mechanical debridement. We believe this is the first TEM documentation of bacterial biofilms in CRS in humans.

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Activity of Natural Polyether Ionophores: Monensin and Salinomycin against Clinical Staphylococcus epidermidis Strains

Polish Journal of Microbiology ◽

10.5604/01.3001.0009.2122 ◽

2015 ◽

Vol 64 (3) ◽

pp. 273-278 ◽

Cited By ~ 3

Author(s):

Joanna Stefańska ◽

Karolina Stępień ◽

Adam Huczyński ◽

Stefan Tyski

Keyword(s):

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Bacterial Biofilm ◽

Bacterial Biofilms ◽

Coagulase Negative Staphylococcus ◽

Bacterial Strains ◽

Natural Substances ◽

Planktonic Bacteria ◽

Abiotic Surfaces ◽

Extracellular Slime

Staphylococcus epidermidis, a coagulase-negative Staphylococcus, is the most important pathogen responsible for chronic nosocomial infections. These bacteria produce extracellular slime and form biofilms on various biotic and abiotic surfaces. Bacterial biofilms are very resistant to standard antimicrobial therapy and difficult to eradicate, so it is important to search for new more effective anti-biofilm agents, for example in the group of natural substances. The aim of the study was to examine the activity of two ionophores-salinomycin and monensin against clinical S. epidermidis strains, using MIC/MBC method and biofilm formation inhibition assay. Bacterial strains were tested also for slime production using Congo Red Agar. Both tested ionophore antibiotics showed the highest activity against planktonic bacteria of clinical as well as standard S. epidermidis strains and effectively inhibited the formation of bacterial biofilm.

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Assessment of Biomarker Heterogeneity in Sinus Versus Inferior Turbinate Tissue in Patients Without Chronic Rhinosinusitis

American Journal of Rhinology and Allergy ◽

10.1177/19458924211012808 ◽

2021 ◽

pp. 194589242110128

Author(s):

Taylor R. Carle ◽

Tara J. Wu ◽

Vivian Wung ◽

Jeffrey D. Suh ◽

Marilene B. Wang ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Sphenoid Sinus ◽

Inferior Turbinate ◽

Optimal Choice ◽

Control Specimen ◽

Luminex Assay ◽

Healthy Control ◽

History Of ◽

Sinonasal Mucosa ◽

Sinus Mucosa

Background Currently, no consensus exists on the appropriate control specimen site to utilize in studies evaluating for biomarkers in chronic rhinosinusitis (CRS). Studies thus far have utilized tissue from various anatomic sites despite regional heterogeneity. Objective We set out to quantify the differences in biomarker levels present in inferior turbinate versus sphenoid sinus mucosa in paired healthy control patients. We hypothesize that statistically significant differences in cytokine/chemokine expression exist between these two distinct sites. Methods A 38-plex commercially available cytokine/chemokine Luminex Assay was performed on 54 specimens encompassing paired inferior turbinate and sphenoid sinus mucosa samples from 27 patients undergoing endoscopic anterior skull base surgery. Patients with a history of CRS were excluded. Paired sample t-tests and Fisher’s exact tests were performed. Results Twenty-seven patients were included in the study, including 10 male and 17 female patients with an average age of 48 years. The following 8 biomarkers had statistically significant concentration differences between inferior turbinate mucosa and sphenoid mucosa sites: Flt-3L, Fractalkine, IL-12p40, IL-1Ra, IP-10, MCP-1, MIP-1β, and VEGF, with all P-values <0.01. Conclusion No consensus exists regarding the optimal choice of control specimen for CRS research. We present statistically significant quantitative differences in biomarker levels between paired inferior turbinate and sphenoid mucosa samples. This confirms the presence of heterogeneity between different subsites of sinonasal mucosa and highlights the need for standardization in future CRS research.

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Measuring Disease Modification in Alzheimer's Disease

CNS Spectrums ◽

10.1017/s109285290002589x ◽

2007 ◽

Vol 12 (S1) ◽

pp. 11-14

Author(s):

Jeffrey L. Cummings

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immunoglobulin A ◽

Disease Process ◽

Underlying Disease ◽

Therapeutic Interventions ◽

Disease Modification ◽

Amyloid Disease ◽

Therapeutic Modalities ◽

Disease Modifying

AbstractWe appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ42 secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β -amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.

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NeuroTec Sitem-Insel Bern: Closing the Last Mile in Neurology

Clinical and Translational Neuroscience ◽

10.3390/ctn5020013 ◽

2021 ◽

Vol 5 (2) ◽

pp. 13

Author(s):

Kaspar A. Schindler ◽

Tobias Nef ◽

Maxime O. Baud ◽

Athina Tzovara ◽

Gürkan Yilmaz ◽

...

Keyword(s):

Diagnostic Tests ◽

Current Model ◽

Disease Process ◽

Therapeutic Interventions ◽

Sleep Studies ◽

Last Mile ◽

Specialized Equipment ◽

The One ◽

Treatment Procedures ◽

Digital Biomarkers

Neurology is focused on a model where patients receive their care through repeated visits to clinics and doctor’s offices. Diagnostic tests often require expensive and specialized equipment that are only available in clinics. However, this current model has significant drawbacks. First, diagnostic tests, such as daytime EEG and sleep studies, occur under artificial conditions in the clinic, which may mask or wrongly emphasize clinically important features. Second, early detection and high-quality management of chronic neurological disorders require repeat measurements to accurately capture the dynamics of the disease process, which is impractical to execute in the clinic for economical and logistical reasons. Third, clinic visits remain inaccessible to many patients due to geographical and economical circumstances. Fourth, global disruptions to daily life, such as the one caused by COVID-19, can seriously harm patients if access to in-person clinical visits for diagnostic and treatment purposes is throttled. Thus, translating diagnostic and treatment procedures to patients’ homes will convey multiple substantial benefits and has the potential to substantially improve clinical outcomes while reducing cost. NeuroTec was founded to accelerate the re-imagining of neurology and to promote the convergence of technological, scientific, medical and societal processes. The goal is to identify and validate new digital biomarkers that can close the last mile in neurology by enabling the translation of personalized diagnostics and therapeutic interventions from the clinic to the patient’s home.

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Mucus composition abnormalities in sinonasal mucosa of chronic rhinosinusitis with and without nasal polyps

Inflammation ◽

10.1007/s10753-021-01471-6 ◽

2021 ◽

Author(s):

Yanyi Tu ◽

Jing Liu ◽

Tao Li ◽

Xiangmin Zhou ◽

Kai Sen Tan ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Sinonasal Mucosa

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Persistently activated, proliferative memory autoreactive B cells promote inflammation in rheumatoid arthritis

Science Translational Medicine ◽

10.1126/scitranslmed.aaz5327 ◽

2020 ◽

Vol 12 (570) ◽

pp. eaaz5327

Author(s):

Hendy Kristyanto ◽

Nienke J. Blomberg ◽

Linda M. Slot ◽

Ellen I. H. van der Voort ◽

Priscilla F. Kerkman ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

Autoimmune Disease ◽

Clinical Remission ◽

Immune Cell ◽

Disease Process ◽

Therapeutic Interventions ◽

Autoreactive B Cells ◽

Autoimmune Pathology ◽

Activated State

Autoreactive B cells mediate autoimmune pathology, but exactly how remains unknown. A hallmark of rheumatoid arthritis (RA), a common autoimmune disease, is the presence of disease-specific anticitrullinated protein antibodies (ACPAs). Here, we showed that ACPA-positive B cells in patients with RA strongly expressed T cell–stimulating ligands, produced abundant proinflammatory cytokines, and were proliferative while escaping inhibitory signals. This activated state was found at different degrees in different stages of disease: highest in patients with recent-onset RA, moderate in patients with established RA, and far less pronounced in ACPA-positive individuals “at risk” for developing disease. The activated autoreactive B cell response persisted in patients who achieved clinical remission with conventional treatment. ACPA-positive B cells in blood and synovial fluid secreted increased amounts of the chemoattractant interleukin-8, which attracted neutrophils, the most abundant immune cell in arthritic joints. Tetanus toxoid–specific B cells from the same patients exhibited properties of memory B cells without the activation and proliferation phenotype, but these cells transiently acquired a similar proliferative phenotype upon booster vaccination. Together, these data indicated that continuous antigenic triggering of autoreactive B cells occurs in human autoimmune disease and support the emerging concept of immunological activity that persists under treatment even in clinical remission, which may revise our current concept of treatment targets for future therapeutic interventions. In addition, our data pointed to a pathogenic role of ACPA-positive B cells in the inflammatory disease process underlying RA and favor approaches that aim at their antigen-specific inactivation or depletion.

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Raman Spectroscopy for Inverted Papilloma: A Proof-of-Concept Study

Otolaryngology ◽

10.1177/0194599818776640 ◽

2018 ◽

Vol 159 (3) ◽

pp. 587-589 ◽

Cited By ~ 1

Author(s):

Marco A. Mascarella ◽

Abdulaziz Alrasheed ◽

Naif Fnais ◽

Ophelie Gourgas ◽

Ghulam Jalani ◽

...

Keyword(s):

Principal Component Analysis ◽

Raman Spectroscopy ◽

Chronic Rhinosinusitis ◽

Principal Component ◽

Inverted Papilloma ◽

Proof Of Concept ◽

Linear Discriminant ◽

Acceptable Accuracy ◽

Sinonasal Mucosa ◽

Inverted Papillomas

Inverted papillomas are tumors of the sinonasal tract with a propensity to recur. Raman spectroscopy can potentially identify inverted papillomas from other tissue based on biochemical signatures. A pilot study comparing Raman spectroscopy to histopathology for 3 types of sinonasal tissue was performed. Spectral data of biopsies from patients with normal sinonasal mucosa, chronic rhinosinusitis, and inverted papillomas are compared to histopathology using principal component analysis and linear discriminant analysis after data preprocessing. A total of 18 normal, 15 chronic rhinosinusitis, and 18 inverted papilloma specimens were evaluated. The model distinguished normal sinonasal mucosa, chronic rhinosinusitis, and inverted papilloma tissue with an overall accuracy of 90.2% (95% confidence interval, 0.86-0.94). In conclusion, Raman spectroscopy can distinguish inverted papilloma, normal sinonasal mucosa, and chronically rhinosinusitis tissue with acceptable accuracy.

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