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Journal of Medical Genetics Jul 2021Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants...
BACKGROUND
Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility.
METHODS
We performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues.
RESULTS
A large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare variants, a common variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within (LOD=4.09). Carriage of the missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel variants were identified in 12 families and individuals with OM. A role for in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased expression in human cholesteatoma.
CONCLUSION
variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.
Topics: Adult; Animals; Bacteria; Child; Disease Susceptibility; Ear, External; Ear, Middle; Exome; Female; Genetic Predisposition to Disease; Humans; Male; Mice; Microbiota; Mouth; Nasopharynx; Otitis Media; Pedigree; Sequence Analysis, DNA; Sequence Analysis, RNA; Serine Peptidase Inhibitor Kazal-Type 5
PubMed: 32709676
DOI: 10.1136/jmedgenet-2020-106844 -
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 -
Acta Medica Okayama Apr 2019The efficacy and safety of endoscopic submucosal dissection (ESD) for superficial cancer of the pharynx are still unclear. To identify clinicopathological features of...
The efficacy and safety of endoscopic submucosal dissection (ESD) for superficial cancer of the pharynx are still unclear. To identify clinicopathological features of superficial pharyngeal cancer, and the efficacy and safety of ESD, we retrospectively assessed 70 pharyngeal cancers in 59 patients who underwent ESD. Of these patients, 61.0% and 50.8% had a history of esophageal cancer and head and neck cancer, respectively. The median tumor size was 15 mm, and 75.7% of the lesions were located at the piriform sinus. The en bloc resection rate was 94.9%. Treatment-related adverse events occurred in 8 cases, but there was no treatment-related death. The lateral margin was positive for neoplasm in 3 lesions (4.3%) and inconclusive in 27 lesions (38.6%), but no local recurrence was observed. Cervical lymph node metastasis was observed in 6 patients, and was successfully treated by cervical lymph node dissection. The three-year overall survival rate was 91.5% (95%CI: 76.6-97.3%) and the cause-specific survival rate was 97.6% (95%CI: 84.9-99.7%). In conclusion, ESD for superficial pharyngeal cancer was safe and effective. "Resect and watch" is probably a feasible and rational strategy for treatment of patients with superficial pharyngeal cancer.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Endoscopic Mucosal Resection; Female; Humans; Male; Margins of Excision; Middle Aged; Pharyngeal Neoplasms; Retrospective Studies; Survival Rate
PubMed: 31015745
DOI: 10.18926/AMO/56646 -
American Journal of Otolaryngology 2020Surgeons resuming elective procedures during the COVID-19 pandemic should consider strategies to mitigate risk of exposure. For otolaryngologists performing surgery on... (Review)
Review
PURPOSE
Surgeons resuming elective procedures during the COVID-19 pandemic should consider strategies to mitigate risk of exposure. For otolaryngologists performing surgery on children, unique vulnerability to SARS-CoV-2 results from a regular interface with the upper respiratory tract mucosa. A growing interest in perioperative application of povidone‑iodine (PVP-I) to the nasopharynx and oropharynx has emerged. The purpose of this review is to provide an evidence-based assessment of PVP-I in pediatric oral, nasal and pharyngeal surgery.
METHODS
A contemporary literature review with algorithmic approach to the potential use of PVP-I in pediatric mucosal surgery.
RESULTS
Several formulations of PVP-I have shown rapid in vitro virucidal activity against SARS-CoV-2. Antisepsis using 1.0% PVP-I mouthwash and 0.45% PVP-I throat spray can occur after 30 seconds of contact time. To date, in vivo effectiveness of PVP-I against SARS-CoV-2 has yet to be established and possible risks of its direct use on upper aerodigestive mucosa of children must be weighed.
CONCLUSION
Further research is required prior to strongly recommending PVP-I use in preparation for nasal, oral or pharyngeal surgery in children.
Topics: Anti-Infective Agents, Local; Betacoronavirus; COVID-19; Child; Coronavirus Infections; Humans; Infectious Disease Transmission, Patient-to-Professional; Nasopharynx; Oropharynx; Otorhinolaryngologic Surgical Procedures; Pandemics; Pneumonia, Viral; Povidone-Iodine; SARS-CoV-2
PubMed: 32979667
DOI: 10.1016/j.amjoto.2020.102737 -
Surgical Endoscopy May 2023Advances in endoscopic imaging technology have led to an increase in detection of superficial pharyngeal squamous carcinoma. Endoscopic submucosal dissection (ESD) has...
BACKGROUND
Advances in endoscopic imaging technology have led to an increase in detection of superficial pharyngeal squamous carcinoma. Endoscopic submucosal dissection (ESD) has been reported to be effective for the treatment of these lesions, however there is still insufficient evidence on the long-term results of pharyngeal ESD.
METHODS
This is a single-center retrospective study of all cases of superficial pharyngeal cancer that underwent ESD as primary treatment between January 2010 and May 2022. A total of 83 lesions in 63 patients were analyzed.
RESULTS
The en bloc resection rate was 100%, and R0 resection rate was 59.0%, with an adverse event rate of 6.0%. During a mean observation period of 1134 days, there were 0 cases of disease-specific metastasis or death. However, the 5-year cumulative incidence of metachronous head and neck cancer after resection was 27.1% and the 5-year overall survival and 10-year overall survival after pharyngeal ESD were 87.0% and 69.6%, respectively. Of the 34 cases with non-R0 resection, local recurrence occurred in 8.8%. Location of lesion (p = 0.011), disparity between demarcation of the lesion with NBI and iodine staining (p = 0.026), and non-effective laryngeal elevation (p = 0.080) were risk factors for non-R0 resection.
CONCLUSION
Pharyngeal ESD is effective and safe. Further studies are needed to improve and standardize indications and strategies for pharyngeal ESD.
Topics: Humans; Retrospective Studies; Endoscopic Mucosal Resection; Prognosis; Endoscopy; Treatment Outcome; Pharyngeal Neoplasms; Risk Factors; Neoplasm Recurrence, Local
PubMed: 36624214
DOI: 10.1007/s00464-022-09820-8 -
Journal of Applied Physiology... Mar 2015Mechanical processes underlying pharyngeal closure have not been examined. We hypothesized that the pharyngeal mucosal surface would fold during closure, and lowering...
Mechanical processes underlying pharyngeal closure have not been examined. We hypothesized that the pharyngeal mucosal surface would fold during closure, and lowering the upper airway lining liquid surface tension would unfold areas of mucosal apposition, i.e., folds. We compared baseline pharyngeal fold numbers and response to reduction in upper airway liquid surface tension in healthy and obstructive sleep apnea (OSA) subjects. Awake, gated magnetic resonance pharyngeal airway images of 10 healthy and 11 OSA subjects were acquired before and after exogenous surfactant administration (beractant). Upper airway liquid surface tension was measured at the beginning and end of image acquisition and averaged. Velopharyngeal and oropharyngeal images were segmented and analyzed separately for average cross-sectional area, circumference, and fold number. Compared with healthy subjects, at baseline, velopharynx for OSA subjects had a smaller cross-sectional area (98.3 ± 32.5 mm(2) healthy, 52.3 ± 23.6 mm(2) OSA) and circumference (46.5 ± 8.1 mm healthy, 30.8 ± 6.1 mm OSA; both P < 0.05, unpaired t-test), and fewer folds (4.9 ± 1.6 healthy, 3.1 ± 1.8 OSA, P < 0.03). There were no differences in oropharynx for cross-sectional area, circumference, or folds. Reduction in upper airway liquid surface tension from 61.3 ± 1.2 to 55.3 ± 1.5 mN/m (P < 0.0001) did not change cross-sectional area or circumference for velopharynx or oropharynx in either group; however, in OSA subjects, oropharyngeal folds fell from 6.8 ± 3.1 to 4.7 ± 1.2 (n = 8, P < 0.05), and velopharyngeal folds from 3.3 ± 1.9 to 2.3 ± 1.2 (P = 0.08), and were unchanged in healthy subjects. Subjects with OSA have fewer velopharyngeal wall folds, which decrease further when surface tension falls. We speculate that reduced pharyngeal wall folds contribute to an increase in pharyngeal collapsibility.
Topics: Adult; Female; Humans; Male; Middle Aged; Oropharynx; Pulmonary Surfactants; Respiratory Mucosa; Respiratory System; Sleep Apnea, Obstructive; Surface Tension; Wakefulness
PubMed: 25635002
DOI: 10.1152/japplphysiol.00691.2014 -
BMC Microbiology Sep 2022The palatine tonsils are part of the mucosal immune system and stimulate immune responses through M cell uptake sampling of antigens and bacteria in the tonsillar...
BACKGROUND
The palatine tonsils are part of the mucosal immune system and stimulate immune responses through M cell uptake sampling of antigens and bacteria in the tonsillar crypts. Little is known about the development of the tonsillar microbiota and the factors determining the establishment and proliferation of disease-associated bacteria such as Streptococcus suis. In this study, we assessed tonsillar microbiota development in piglets during the first 5 weeks of life and identified the relative importance of maternal and environmental farm parameters influencing the tonsillar microbiota at different ages. Additionally, we studied the effect sow vaccination with a bacterin against S. suis on microbiota development and S. suis colonisation in their offspring.
RESULTS
Amplicon sequencing of the 16S rRNA gene V3-V4 region revealed that a diverse tonsillar microbiota is established shortly after birth, which then gradually changes during the first 5 weeks of life without a large impact of weaning on composition or diversity. We found a strong litter effect, with siblings sharing a more similar microbiota compared to non-sibling piglets. Co-housing in rooms, within which litters were housed in separate pens, also had a large impact on microbiota composition. Sow parity and prepartum S. suis bacterin vaccination of sows had weaker but significant associations with microbiota composition, impacting on the abundance of Streptococcus species before and after weaning. Sex and birthweight had limited impact on the tonsillar microbiota, and none of the measured factors had consistent associations with microbiota diversity.
CONCLUSIONS
The piglet tonsillar microbiota is established shortly after birth. While microbiota development is associated with both environmental and maternal parameters, weaning has limited impact on microbiota composition. Intramuscular vaccination of sows pre-partum had a significant effect on the tonsillar microbiota composition of their piglets. These findings provide new insights into the mechanisms shaping the tonsillar microbiota.
Topics: Animals; Animals, Newborn; Bacteria; Bacterial Vaccines; Female; Lactation; Microbiota; Palatine Tonsil; Pregnancy; RNA, Ribosomal, 16S; Swine; Weaning
PubMed: 36163011
DOI: 10.1186/s12866-022-02625-8 -
The Cochrane Database of Systematic... Sep 2018Placing a small volume of colostrum directly onto the buccal mucosa of preterm infants during the early neonatal period may provide immunological and growth factors that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Placing a small volume of colostrum directly onto the buccal mucosa of preterm infants during the early neonatal period may provide immunological and growth factors that stimulate the immune system and enhance intestinal growth. These benefits could potentially reduce the risk of infection and necrotising enterocolitis (NEC) and improve survival and long-term outcome.
OBJECTIVES
To determine if early (within the first 48 hours of life) oropharyngeal administration of mother's own fresh or frozen/thawed colostrum can reduce rates of NEC, late-onset invasive infection, and/or mortality in preterm infants compared with controls. To assess trials for evidence of safety and harm (e.g. aspiration pneumonia). To compare effects of early oropharyngeal colostrum (OPC) versus no OPC, placebo, late OPC, and nasogastric colostrum.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE via PubMed (1966 to August 2017), Embase (1980 to August 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to August 2017). We also searched clinical trials registries for ongoing and recently completed trials (clinicaltrials.gov; the World Health Organization International Trials Registry (www.whoint/ictrp/search/en/), and the ISRCTN Registry), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We performed the last search in August 2017. We contacted trial investigators regarding unpublished studies and data.
SELECTION CRITERIA
We searched for published and unpublished randomised controlled trials comparing early administration of oropharyngeal colostrum (OPC) versus sham administration of water, oral formula, or donor breast milk, or versus no intervention. We also searched for studies comparing early OPC versus early nasogastric or nasojejunal administration of colostrum. We considered only trials that included preterm infants at < 37 weeks' gestation. We did not limit the review to any particular region or language.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened retrieved articles for inclusion and independently conducted data extraction, data analysis, and assessments of 'Risk of bias' and quality of evidence. We graded evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We contacted study authors for additional information or clarification when necessary.
MAIN RESULTS
We included six studies that compared early oropharyngeal colostrum versus water, saline, placebo, or donor, or versus no intervention, enrolling 335 preterm infants with gestational ages ranging from 25 to 32 weeks' gestation and birth weights of 410 to 2500 grams. Researchers found no significant differences between OPC and control for primary outcomes - incidence of NEC (typical risk ratio (RR) 1.42, 95% confidence interval (CI) 0.50 to 4.02; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence), incidence of late-onset infection (typical RR 0.86, 95% CI 0.56 to 1.33; six studies, 335 infants; P = 0.50; I² = 0%; very low-quality evidence), and death before hospital discharge (typical RR 0.76, 95% CI 0.34 to 1.71; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence). Similarly, meta-analysis showed no difference in length of hospital stay between OPC and control groups (mean difference (MD) 0.81, 95% CI -5.87 to 7.5; four studies, 293 infants; P = 0.65; I² = 49%). Days to full enteral feeds were reduced in the OPC group with MD of -2.58 days (95% CI -4.01 to -1.14; six studies, 335 infants; P = 0.0004; I² = 28%; very low-quality evidence).The effect of OPC was uncertain because of small sample sizes and imprecision in study results (very low-quality evidence).No adverse effects were associated with OPC; however, data on adverse effects were insufficient, and no numerical data were available from the included studies.Overall the quality of included studies was low to very low across all outcomes. We downgraded GRADE outcomes because of concerns about allocation concealment and blinding, reporting bias, small sample sizes with few events, and wide confidence intervals.
AUTHORS' CONCLUSIONS
Large, well-designed trials would be required to evaluate more precisely and reliably the effects of oropharyngeal colostrum on important outcomes for preterm infants.
Topics: Administration, Oral; Colostrum; Enterocolitis, Necrotizing; Hospital Mortality; Humans; Immunity, Mucosal; Infant, Newborn; Infant, Premature; Length of Stay; Mouth Mucosa; Oropharynx; Randomized Controlled Trials as Topic; Sepsis
PubMed: 30191961
DOI: 10.1002/14651858.CD011921.pub2 -
Viruses May 2023The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors.
BACKGROUND
The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors.
MATERIAL AND METHODS
This cross-sectional prospective study consecutively enrolled PLHIV attending our specialist outpatient units. At visit, HIV-related clinical and analytical variables were gathered, and oropharyngeal mucosa exudates were taken to detect HPV and other STIs by polymerase chain reaction. Samples were also taken from the anal canal of all participants and from the genital mucosa of the women for HPV detection/genotyping and cytological study.
RESULTS
The 300 participants had a mean age of 45.1 years; 78.7% were MSM and 21.3% women; 25.3% had a history of AIDS; 99.7% were taking ART; and 27.3% had received an HPV vaccine. HPV infection prevalence in the oropharynx was 13%, with genotype 16 being the most frequent (2.3%), and none had dysplasia. Simultaneous infection with (HR: 4.02 (95% CI: 1.06-15.24)) and a history of anal HSIL or SCCA (HR: 21.52 (95% CI: 1.59-291.6)) were risk factors for oropharyngeal HPV infection, whereas ART duration (8.8 vs. 7.4 years) was a protective factor (HR: 0.989 (95% CI: 0.98-0.99)).
CONCLUSIONS
The prevalence of HPV infection and dysplasia was low in the oropharyngeal mucosae. A higher exposure to ART was protective against oral HPV infection.
Topics: Male; Humans; Female; Middle Aged; Anal Canal; Papillomavirus Infections; HIV Infections; Homosexuality, Male; Cross-Sectional Studies; Prospective Studies; Papillomaviridae; Risk Factors; Mucous Membrane; Genotype; Hyperplasia; Oropharynx; Genitalia; Prevalence
PubMed: 37243256
DOI: 10.3390/v15051170