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Science (New York, N.Y.) Aug 2020Viral infections of the lower respiratory tract are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune...
Viral infections of the lower respiratory tract are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune responses and do not depend on viral burden. In this study, we assessed how type III interferons (IFN-λ) contribute to the pathogenesis induced by RNA viruses. We report that IFN-λ is present in the lower, but not upper, airways of patients with coronavirus disease 2019 (COVID-19). In mice, we demonstrate that IFN-λ produced by lung dendritic cells in response to a synthetic viral RNA induces barrier damage, causing susceptibility to lethal bacterial superinfections. These findings provide a strong rationale for rethinking the pathophysiological role of IFN-λ and its possible use in clinical practice against endemic viruses, such as influenza virus as well as the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Topics: Animals; Betacoronavirus; Bronchoalveolar Lavage Fluid; COVID-19; Cell Proliferation; Coronavirus Infections; Cytokines; Dendritic Cells; Humans; Interferon Type I; Interferons; Lung; Mice; Mice, Inbred C57BL; Nasopharynx; Pandemics; Pneumonia, Viral; Poly I-C; Respiratory Mucosa; SARS-CoV-2; Signal Transduction; Staphylococcal Infections; Superinfection; Toll-Like Receptor 3; Interferon Lambda
PubMed: 32527925
DOI: 10.1126/science.abc3545 -
EBioMedicine Dec 2023Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in...
BACKGROUND
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.pneumoniae carriage in children with recurrent respiratory infections and identified associated factors.
METHODS
We tested M.pneumoniae carriage by qPCR in children with recurrent infections and their healthy family members in a cross-sectional study. Serum and mucosal total and M.pneumoniae-specific antibody levels were measured by ELISA and nasopharyngeal microbiota composition was characterized by 16S-rRNA sequencing.
FINDINGS
Prevalence of M.pneumoniae carriage was higher in children with recurrent infections (68%) than their family members without infections (47% in siblings and 27% in parents). M.pneumoniae carriage among family members appeared to be associated with transmission within the household, likely originating from the affected child. In logistic regression corrected for age and multiple comparisons, IgA (OR 0.16 [0.06-0.37]) and total IgG deficiency (OR 0.15 [0.02-0.74]) were less prevalent in M.pneumoniae carriers (n = 78) compared to non-carriers (n = 36). In multivariable analysis, the nasopharyngeal microbiota of M.pneumoniae carriers had lower alpha diversity (OR 0.27 [0.09-0.67]) and a higher abundance of Haemophilus influenzae (OR 45.01 [2.74-1608.11]) compared to non-carriers.
INTERPRETATION
M.pneumoniae carriage is highly prevalent in children with recurrent infections and carriers have a less diverse microbiota with an overrepresentation of disease-associated microbiota members compared to non-carriers. Given the high prevalence of M.pneumoniae carriage and the strong association with H. influenzae, we recommend appropriate antibiotic coverage of M.pneumoniae and H. influenzae in case of suspected pneumonia in children with recurrent respiratory tract infections or their family members.
FUNDING
Wilhelmina Children's Hospital Research Fund, 'Christine Bader Stichting Irene KinderZiekenhuis', Sophia Scientific Research Foundation, ESPID Fellowship funded by Seqirus, Hypatia Fellowship funded by Radboudumc and The Netherlands Organisation for Health Research and Development (ZonMW VENI grant to LM Verhagen).
Topics: Child; Humans; Infant; Streptococcus pneumoniae; Mycoplasma pneumoniae; Pneumococcal Infections; Cross-Sectional Studies; Reinfection; Respiratory Tract Infections; Nasopharynx; Pneumonia; Haemophilus influenzae; Carrier State; Microbiota
PubMed: 37950996
DOI: 10.1016/j.ebiom.2023.104868 -
Journal of Applied Physiology... Jan 2017Recent studies show that nasal high flow (NHF) therapy can support ventilation in patients with acute or chronic respiratory disorders. Clearance of dead space has been... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Recent studies show that nasal high flow (NHF) therapy can support ventilation in patients with acute or chronic respiratory disorders. Clearance of dead space has been suggested as being the key mechanism of respiratory support with NHF therapy. The hypothesis of this study was that NHF in a dose-dependent manner can clear dead space of the upper airways from expired air and decrease rebreathing. The randomized crossover study involved 10 volunteers using scintigraphy with Krypton (Kr) gas during a breath-holding maneuver with closed mouth and in 3 nasally breathing tracheotomized patients by volumetric capnography and oximetry through sampling CO and O in the trachea and measuring the inspired volume with inductance plethysmography following NHF rates of 15, 30, and 45 l/min. The scintigraphy revealed a decrease in Kr gas clearance half-time with an increase of NHF in the nasal cavities [Pearson's correlation coefficient cc = -0.55, P < 0.01], the pharynx (cc = -0.41, P < 0.01), and the trachea (cc = -0.51, P < 0.01). Clearance rates in nasal cavities derived from time constants and MRI-measured volumes were 40.6 ± 12.3 (SD), 52.5 ± 17.7, and 72.9 ± 21.3 ml/s during NHF (15, 30, and 45 l/min, respectively). Measurement of inspired gases in the trachea showed an NHF-dependent decrease of inspired CO that correlated with an increase of inspired O (cc = -0.77, P < 0.05). NHF clears the upper airways of expired air, which reduces dead space by a decrease of rebreathing making ventilation more efficient. The dead space clearance is flow and time dependent, and it may extend below the soft palate.
NEW & NOTEWORTHY
Clearance of expired air in upper airways by nasal high flow (NHF) can be extended below the soft palate and de facto causes a reduction of dead space. Using scintigraphy, the authors found a relationship between NHF, time, and clearance. Direct measurement of CO and O in the trachea confirmed a reduction of rebreathing, providing the actual data on inspired gases, and this can be used for the assessment of other forms of respiratory support.
Topics: Carbon Dioxide; Cross-Over Studies; Female; Humans; Male; Middle Aged; Nasal Cavity; Nasal Mucosa; Nose; Oxygen; Pulmonary Ventilation; Respiration; Respiratory Dead Space; Tidal Volume; Trachea
PubMed: 27856714
DOI: 10.1152/japplphysiol.00584.2016 -
Annals of Palliative Medicine Sep 2023Pharyngocutaneous fistula is a serious complication after head and neck reconstruction and concurrent chemoradiotherapy, yet no consensus or practical protocols... (Review)
Review
Pharyngocutaneous fistula is a serious complication after head and neck reconstruction and concurrent chemoradiotherapy, yet no consensus or practical protocols regarding the surgical timing and specific procedures could be found in the current literature. The authors aimed to review their clinical experience in surgical management and develop an algorithmic approach accordingly. A retrospective review of all hypopharyngeal cancer patients who developed pharyngocutaneous fistula during 2017 to 2021 at E-Da Hospital was conducted. Seventeen patients developed pharyngocutaneous fistula in all 321 pharyngeal cancer admissions during this period. Three patients received interventions at acute stage (≤2 weeks), with two direct repairs Three patients received interventions at acute stage (≤2 weeks), with two direct repairs and one regional flap coverage then negative pressure wound therapy. Nine received interventions at subacute stages (2 weeks to 3 months), with 4 resolved after debridement and direct repair yet another 4 underwent regional flap reconstruction and 1 free flap reconstruction. Five chronic fistula (>3 months) received secondary reconstructions utilizing a double-layered repair of local turn-over flaps for the internal mucosal opening and another flap harvest (four regional flaps and one free flap) to cover the outer skin defect. All patients after the palliative surgery achieved complete remission of fistula at follow follow-up. Different conservative and surgical approaches should be adopted according to the acute, subacute, and chronic stages of pharyngocutaneous fistula after palliative head and neck reconstructions.
Topics: Humans; Cutaneous Fistula; Head and Neck Neoplasms; Pharyngeal Diseases; Plastic Surgery Procedures; Postoperative Complications; Retrospective Studies; Surgical Flaps
PubMed: 37691332
DOI: 10.21037/apm-22-1475 -
International Archives of... Jul 2019Suspension laryngoscopy (SL) is a commonly performed procedure among otolaryngologists. Several studies have shown that adverse effects occur regularly with SL....
Suspension laryngoscopy (SL) is a commonly performed procedure among otolaryngologists. Several studies have shown that adverse effects occur regularly with SL. To evaluate the postoperative complications of SL, and to determine if protecting the dentition and the oral mucosa and limiting suspension times decrease the overall incidence of oral cavity and pharyngeal complications of SL. All of the cases of SL performed by 1 surgeon from November 2008 through September 2014 were retrospectively reviewed. A consistent technique for dental and mucosal protection was utilized, and suspension times were strictly limited to 30 consecutive minutes. The incidence of postoperative complications was calculated and analyzed with respect to gender, smoking status, dentition, laryngoscope type, and suspension system. A total of 213 consecutive SL cases were reviewed, including 174 patients (94 male, 80 female). The overall postoperative complication rate was of 3.8%. Four patients experienced tongue-related complications, two experienced oral mucosal alterations, one had a dental injury, and one experienced a minor facial burn. The complication incidence was greater with the Zeitels system (12.5%) compared with the Lewy suspension system (3.3%), although it was not significant ( = 0.4). Likewise, the association of complications with other patient factors was not statistically significant. Only 8 out of 213 cases in the present series experienced complications, which is significantly less than the complication rates observed in other reports. Consistent and conscientious protection of the dentition and of the oral mucosa and limiting suspension times to 30 minutes are factors unique to our series that appear to reduce complications in endolaryngeal surgery.
PubMed: 31360250
DOI: 10.1055/s-0039-1684036 -
Microbiology (Reading, England) Jul 2015The genus Neisseria contains the important pathogens Neisseria meningitidis and Neisseria gonorrhoeae. These Gram-negative coccoid bacteria are generally thought to be... (Review)
Review
The genus Neisseria contains the important pathogens Neisseria meningitidis and Neisseria gonorrhoeae. These Gram-negative coccoid bacteria are generally thought to be restricted to humans and inhabit mucosal surfaces in the upper respiratory and genito-urinary tracts. While the meningococcus and gonococcus have been widely studied, far less attention has been paid to other Neisseria species. Here we review current knowledge of the distribution of commensal Neisseria in humans and other hosts. Analysis of the microbiome has revealed that Neisseria is an abundant member of the oropharyngeal flora, and we review its potential impact on health and disease. Neisseria also exhibit remarkable diversity, exhibiting both coccoid and rod-shaped morphologies, as well as environmental strains which are capable of degrading complex organic molecules.
Topics: Animals; Carrier State; Environmental Microbiology; Gram-Negative Bacterial Infections; Host-Pathogen Interactions; Humans; Neisseria; Oropharynx; Symbiosis
PubMed: 25814039
DOI: 10.1099/mic.0.000086 -
Journal of Cancer Research and... Apr 2023This study aimed to estimate the fitting parameters of sigmoidal dose-response (SDR) curve of radiation-induced acute oral and pharyngeal mucositis in head-and-neck (H...
PURPOSE/OBJECTIVE(S)
This study aimed to estimate the fitting parameters of sigmoidal dose-response (SDR) curve of radiation-induced acute oral and pharyngeal mucositis in head-and-neck (H and N) cancer patients treated with Intensity Modulated Radiation Therapy (IMRT) for the calculation of normal tissue complication probability (NTCP).
MATERIALS AND METHODS
Thirty H-and-N cancer patients were enrolled to model the SDR curve for oral and pharyngeal mucositis. The patients were evaluated weekly for acute radiation-induced (ARI) oral and pharyngeal mucositis toxicity, and their scoring was performed as per the common terminology criteria adverse events version 5.0. The radiobiological parameters, namely n, m, TD50, and γ50 were calculated from the fitted SDR curve obtained from the clinical data of H-and-N cancer patients.
RESULTS
ARI toxicity for oral and pharyngeal mucosa in carcinoma of H-and-N cancer patients was calculated for the endpoint oral mucositis and pharyngeal mucositis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade 1 and Grade 2 oral mucositis were found to be [0.10, 0.32, 12.35 ± 3.90 (confidence interval [CI] 95%) and 1.26] and [0.06, 0.33, 20.70 ± 6.95 (CI 95%) and 1.19] respectively. Similarly for pharyngeal mucositis, n, m, TD50, and γ50 parameters for Grade 1 and Grade 2 were found to be [0.07, 0.34, 15.93 ± 5.48 (CI. 95%) and 1.16 ] and [0.04, 0.25, 39.02 ± 9.98(CI. 95%) and 1.56] respectively.
CONCLUSION
This study presents the fitting parameters for NTCP calculation of Grade 1 and Grade 2 ARI toxicity for the endpoint of oral and pharyngeal mucositis. The provided nomograms of volume versus complication and dose versus complication for different grades of oral mucositis and pharyngeal mucositis help radiation oncologists to decide the limiting dose to reduce the acute toxicities.
Topics: Humans; Mucositis; Stomatitis; Head and Neck Neoplasms; Radiotherapy, Intensity-Modulated; Radiation Injuries; Mouth Mucosa; Carcinoma, Squamous Cell
PubMed: 37147947
DOI: 10.4103/jcrt.jcrt_504_21 -
Molecules (Basel, Switzerland) Feb 2016This review paper summarizes the antibacterial effects of phytochemicals of various medicinal plants against pathogenic and cariogenic streptococcal species. The... (Review)
Review
This review paper summarizes the antibacterial effects of phytochemicals of various medicinal plants against pathogenic and cariogenic streptococcal species. The information suggests that these phytochemicals have potential as alternatives to the classical antibiotics currently used for the treatment of streptococcal infections. The phytochemicals demonstrate direct bactericidal or bacteriostatic effects, such as: (i) prevention of bacterial adherence to mucosal surfaces of the pharynx, skin, and teeth surface; (ii) inhibition of glycolytic enzymes and pH drop; (iii) reduction of biofilm and plaque formation; and (iv) cell surface hydrophobicity. Collectively, findings from numerous studies suggest that phytochemicals could be used as drugs for elimination of infections with minimal side effects.
Topics: Bacterial Adhesion; Bacterial Proteins; Biofilms; Dental Caries; Gene Expression Regulation, Bacterial; Humans; Hydrophobic and Hydrophilic Interactions; Pharynx; Phytochemicals; Skin; Streptococcus
PubMed: 26901172
DOI: 10.3390/molecules21020215 -
Clinical Oncology (Royal College of... Apr 2022To determine if multi-isocentric volumetric modulated arc radiotherapy for craniospinal irradiation (CSI-VMAT) can be implemented safely and accurately using robust...
AIMS
To determine if multi-isocentric volumetric modulated arc radiotherapy for craniospinal irradiation (CSI-VMAT) can be implemented safely and accurately using robust optimisation in a commercially available treatment planning system. Our initial clinical experience is reported for the first 20 patients treated with the technique.
MATERIALS AND METHODS
Patients received between 23.4 and 39.6 Gy (mode 23.4 Gy) in 13-22 fractions with CSI-VMAT. The heart mean dose was 4.2-10.3 Gy (median 5.3 Gy) for patients prescribed up to 24 Gy and 6.5-16.3 Gy (median 10.1 Gy) for patients receiving 35 Gy or more. The lung mean dose was 5.5-7.6 Gy (median 6.8 Gy) for patients prescribed up to 24 Gy and 6.9-11.1 Gy (median 10.0 Gy) for patients receiving 35 Gy or more. The robustness of the planning target volume D and D to systematic errors in the isocentre superoinferior position of up to 5 mm was evaluated. These remained acceptable but were correlated to the length of the available beam overlap through the neck.
RESULTS
As of January 2021, one patient was deceased after 508 days and one patient was lost to follow-up after completing treatment. The median follow-up was 399 days (range 175-756 days) and progression-free survival was 131 days (34-490 days). Acute toxicities at Common Terminology Criteria for Adverse Events v5.0 grade 3+ included lowered white blood cell count (16/20), decreased platelet count (8/20), nausea (5/20), vomiting (2/20), pharyngeal mucositis (1/20) and oral mucositis (1/20). Three patients developed grade 4 neutropenia or decreased white blood cell count.
CONCLUSIONS
CSI-VMAT can be implemented safely and accurately using robust optimisation functions in a commercially available treatment planning system.
Topics: Craniospinal Irradiation; Heart; Humans; Organs at Risk; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 35063327
DOI: 10.1016/j.clon.2022.01.004 -
Frontiers in Immunology 2023HIV-infected patients are at higher risk of developing oral mucosal infection and Epstein-Barr virus (EBV)-associated B cell malignancies. However, the potential role of...
HIV-infected patients are at higher risk of developing oral mucosal infection and Epstein-Barr virus (EBV)-associated B cell malignancies. However, the potential role of oral immunity in the pathogenesis of oral lesions is unknown. Tonsils are oral-pharyngeal mucosal-associated lymphoid tissues that play an important role in oral mucosal immunity. In this study, we investigated the changes of innate and adaptive immune cells in macaque tonsils during chronic SIV infection. We found significantly higher frequencies of classical monocytes, CD3+CD56+ (NKT-like) cells, CD3CD4CD8 (DP), and CD161 CD4 T cells in tonsils from chronic infected compared to naïve animals. On the contrary, intermediate monocytes and CD3CD4CD8 (DN) cells were lower in chronic SIV-infected macaques. We further confirmed a recently described small B-cell subset, NKB cells, were higher during chronic infection. Furthermore, both adaptive and innate cells showed significantly higher TNF-α and cytotoxic marker CD107a, while IL-22 production was significantly reduced in innate and adaptive immune cells in chronic SIV-infected animals. A dramatic reduction of IFN-γ production by innate immune cells might indicate enhanced susceptibility to EBV infection and potential transformation of B cells in the tonsils. In summary, our observation shows that the SIV-associated immune responses are distinct in the tonsils compared to other mucosal tissues. Our data extends our understanding of the oral innate immune system during SIV infection and could aid future studies in evaluating the role of tonsillar immune cells during HIV-associated oral mucosal infections.
Topics: Animals; Persistent Infection; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Mouth Mucosa; Palatine Tonsil
PubMed: 37671159
DOI: 10.3389/fimmu.2023.1201677