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Wellcome Open Research 2023(StrepA) causes a significant burden of disease globally from superficial infections to invasive disease. It is responsible for over 500,000 deaths each year,...
BACKGROUND
(StrepA) causes a significant burden of disease globally from superficial infections to invasive disease. It is responsible for over 500,000 deaths each year, predominantly in low- and middle-income countries (LMIC). Superficial StrepA infections of the skin and pharynx can lead to rheumatic heart disease, the largest cause of StrepA-related deaths in LMIC. StrepA can also asymptomatically colonise normal skin and the pharynx (carriage), potentially increasing infection risk. (SDSE) carriage is also common in LMIC and may interact with StrepA. This study aims to investigate StrepA and SDSE carriage and infection epidemiology, transmission dynamics and naturally acquired immunity within households in The Gambia.
METHODS
A longitudinal household observational cohort study will be conducted over one year. 45 households will be recruited from the urban area of Sukuta, The Gambia, resulting in approximately 450 participants. Households will be visited monthly, and available participants will undergo oropharyngeal and normal skin swabbing. Incident cases of pharyngitis and pyoderma will be captured via active case reporting, with swabs taken from disease sites. Swabs will be cultured for the presence of group A, C and G beta-haemolytic streptococci. Isolates will undergo whole genome sequencing. At each visit, clinical, socio-demographic and social mixing data will be collected. Blood serum will be collected at baseline and final visit. Oral fluid and dried blood spot samples will be collected at each visit. Mucosal and serum anti-StrepA antibody responses will be measured.
OUTCOME
This study will report StrepA and SDSE clinical epidemiology, risk factors, transmission dynamics, and serological responses to carriage and infection. Detailed social mixing behaviour will be combined with phylogenetic relatedness to model the extent of transmission occurring withing and between households. The study will provide data to help meet global strategic StrepA research goals.
PubMed: 37954923
DOI: 10.12688/wellcomeopenres.18716.2 -
Journal of Stomatology, Oral and... Jun 2024Despite a satisfactory primary repair, velopharyngeal insufficiency (VPI) may be a sequel of soft palate clefts, resulting in hypernasality and phonation disorders. In...
Despite a satisfactory primary repair, velopharyngeal insufficiency (VPI) may be a sequel of soft palate clefts, resulting in hypernasality and phonation disorders. In order to increase the function of the pharyngeal flap during a secondary pharyngoplasty, we have developed a strip pharyngoplasty technique involving the middle constrictor muscle of the pharynx. This article describes the successive steps of the intervention and discuss its indications, advantages and limitations. Strip pharyngoplasty as a secondary functional surgery for persistent VPI after primary cleft palate repair is an attractive surgical procedure, particularly adapted to cases with defective muscle contraction by providing a muscle contingent in addition to the mucosal flap.
Topics: Velopharyngeal Insufficiency; Humans; Cleft Palate; Pharynx; Surgical Flaps; Plastic Surgery Procedures; Pharyngeal Muscles; Palate, Soft; Reoperation
PubMed: 37951499
DOI: 10.1016/j.jormas.2023.101684 -
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 -
Briefings in Functional Genomics Nov 2023Our understanding of RNA biology has evolved with recent advances in research from it being a non-functional product to molecules of the genome with specific regulatory...
Our understanding of RNA biology has evolved with recent advances in research from it being a non-functional product to molecules of the genome with specific regulatory functions. Competitive endogenous RNA (ceRNA), which has gained prominence over time as an essential part of post-transcriptional regulatory mechanism, is one such example. The ceRNA biology hypothesis states that coding RNA and non-coding RNA co-regulate each other using microRNA (miRNA) response elements. The ceRNA components include long non-coding RNAs, pseudogene and circular RNAs that exert their effect by interacting with miRNA and regulate the expression level of its target genes. Emerging evidence has revealed that the dysregulation of the ceRNA network is attributed to the pathogenesis of various cancers, including the head and neck squamous cell carcinoma (HNSCC). This is the most prevalent cancer developed from the mucosal epithelium in the lip, oral cavity, larynx and pharynx. Although many efforts have been made to comprehend the cause and subsequent treatment of HNSCC, the morbidity and mortality rate remains high. Hence, there is an urgent need to understand the holistic progression of HNSCC, mediated by ceRNA, that can have immense relevance in identifying novel biomarkers with a defined therapeutic intervention. In this review, we have made an effort to highlight the ceRNA biology hypothesis with a focus on its involvement in the progression of HNSCC. For the identification of such ceRNAs, we have additionally highlighted a number of databases and tools.
PubMed: 37941447
DOI: 10.1093/bfgp/elad049 -
Head & Neck Feb 2024We evaluated clinical and dosimetric outcomes of radiotherapy using two anterior oblique portals (AOP), to reduce the dose to the bilateral internal carotid arteries...
BACKGROUND
We evaluated clinical and dosimetric outcomes of radiotherapy using two anterior oblique portals (AOP), to reduce the dose to the bilateral internal carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) during early-stage glottic cancer (ESGC) treatment.
METHODS
We identified patients with ESGC who underwent definitive radiotherapy between June 2014 and May 2020.
RESULTS
Among the 66 patients, 32 (48%) underwent radiotherapy using AOP, and the remaining underwent typical radiotherapy using parallel opposed lateral portals (POLP). The median follow-up duration was 53 months. No significant differences were observed in the 5-year local failure (0%/9.4%), progression-free survival (90.6%/90.8%), and overall survival (90.6%/91.0%) rates between the two groups. The grade ≥2 acute mucositis incidence rate was significantly lower in the AOP group (44%/85%). Radiotherapy using AOP maintained an adequate dose coverage to the target while markedly reducing the CAs and PCM doses.
CONCLUSION
Radiotherapy with AOP resulted in favorable clinical and dosimetric outcomes.
Topics: Humans; Carotid Artery, Internal; Laryngeal Neoplasms; Radiotherapy, Intensity-Modulated; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Muscles; Radiotherapy Dosage
PubMed: 37933710
DOI: 10.1002/hed.27568 -
Science Advances Nov 2023The constant exposure of the fish branchial cavity to aquatic pathogens causes local mucosal immune responses to be extremely important for their survival. Here, we used...
The constant exposure of the fish branchial cavity to aquatic pathogens causes local mucosal immune responses to be extremely important for their survival. Here, we used a marker for T lymphocytes/natural killer (NK) cells (ZAP70) and advanced imaging techniques to investigate the lymphoid architecture of the zebrafish branchial cavity. We identified a sub-pharyngeal lymphoid organ, which we tentatively named "Nemausean lymphoid organ" (NELO). NELO is enriched in T/NK cells, plasma/B cells, and antigen-presenting cells embedded in a network of reticulated epithelial cells. The presence of activated T cells and lymphocyte proliferation, but not V(D)J recombination or hematopoiesis, suggests that NELO is a secondary lymphoid organ. In response to infection, NELO displays structural changes including the formation of T/NK cell clusters. NELO and gill lymphoid tissues form a cohesive unit within a large mucosal lymphoid network. Collectively, we reveal an unreported mucosal lymphoid organ reminiscent of mammalian tonsils that evolved in multiple teleost fish families.
Topics: Humans; Animals; Palatine Tonsil; Zebrafish; Lymphoid Tissue; Pharynx; T-Lymphocytes; Mammals
PubMed: 37910624
DOI: 10.1126/sciadv.adj0101 -
Digestive Endoscopy : Official Journal... Nov 2023The aging population, including patients with superficial esophageal cancer, encounters critical dysphagia- and postoperative pneumonia-related issues. Although...
OBJECTIVES
The aging population, including patients with superficial esophageal cancer, encounters critical dysphagia- and postoperative pneumonia-related issues. Although endoscopic submucosal dissection (ESD) provides advantages over other modalities, older patients are at higher risk of postoperative pneumonia. Furthermore, the etiologies of pneumonia are complex and include patient- (such as sarcopenia) and treatment- (including ESD) related factors. Therefore, this study evaluated swallowing function in patients with superficial esophageal cancer and identified post-ESD pneumonia-associated factors.
METHODS
Comprehensive swallowing function and sarcopenia were evaluated in patients pre-ESD and 2 months post-ESD using high-resolution manometry and several swallowing studies by multiple experts. The effects of mucosal resection and sarcopenia on swallowing function changes post-ESD, the relationship between preoperative swallowing function and sarcopenia, and the factors influencing postoperative pneumonia were investigated.
RESULTS
Twenty patients were included in the study. Patients with preoperative sarcopenia had significantly lower pharyngeal/upper esophageal sphincter and tongue pressures than those without sarcopenia. However, ESD did not worsen pharyngeal or upper esophageal pressure. Post-ESD pneumonia incidence tended to be higher in patients with sarcopenia than in those without sarcopenia. The lower upper esophageal sphincter-integrated relaxation pressure (UES-IRP) was a significant factor in pneumonia development. Furthermore, the receiver operating characteristic curve for UES-IRP in pneumonia yielded an area under the curve of 0.82.
CONCLUSIONS
Sarcopenia is associated with preoperative dysphagia, which increases post-ESD pneumonia risk. Therefore, postoperative pneumonia incidence is expected to increase with an aging population, making preoperative sarcopenia and swallowing function evaluation crucial.
PubMed: 37908188
DOI: 10.1111/den.14715 -
Klinicka Onkologie : Casopis Ceske a... 2023The term metastatic carcinoma to cervical lymph nodes from an unknown primary includes a small group of tumors that present themselves with metastases to the cervical...
The term metastatic carcinoma to cervical lymph nodes from an unknown primary includes a small group of tumors that present themselves with metastases to the cervical nodes, and in which diagnostic methods do not reveal the primary source of these metastases. Histologically, in most cases, these are metastases of squamous cell carcinoma. Carcinomas of unknown primary metastatic to cervical nodes account for < 5% of carcinomas of unknown primary and < 5% of head and neck cancers. The optimal treatment has not yet been defined. In the absence of distant metastases, the intention of treatment is curative. Patients are treated mostly with combined approaches including surgery, radiotherapy, or concomitant chemoradiotherapy. Radiotherapy is part of the treatment algorithm in most of the referenced works and includes irradiation of the mucosal sites of the pharyngeal axis as a potential localization of the primary tumor and unilateral or, more often, bilateral irradiation of the neck. Due to the higher risk of late toxicities observed, individualization of irradiated volumes based on the extent of the disease or other clinical parameters is a rational way to reduce these risks. Purpose: The presented work discusses the treatment options for patients with metastatic carcinoma to cervical lymph nodes from an unknown primary. Furthermore, the work reports on the high effectiveness of curative radiotherapy in this group of tumors.
Topics: Humans; Neoplasms, Unknown Primary; Neck; Lymph Nodes; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Retrospective Studies
PubMed: 37877528
DOI: 10.48095/ccko2023364 -
Radiotherapy and Oncology : Journal of... Dec 2023Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment...
PURPOSE
Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment paradigms have been refined and continue to evolve in the modern era.
METHODS AND MATERIALS
This study was designed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A literature search of peer-reviewed publications was undertaken to identify works pertaining to the use of radiation for squamous cell carcinoma of unknown primary origin presenting as cervical lymph node metastases. Articles published from January 2002 to January 2023 with full text available on PubMed and restricted to the English language and human subjects were included. The full bibliographies of identified articles were reviewed and irrelevant studies were removed.
RESULTS
While such breakthroughs as intensity-modulated radiotherapy, positron emission tomography, biomarker testing with immune-histochemistry, and minimally invasive surgical techniques such as transoral robotic surgery have fundamentally changed the approach to this disease in recent decades, controversies still exist with respect to the manner in which radiation is delivered. Although the incidence of head and neck unknown primary cancer is relatively low, questions regarding the necessity of comprehensive radiation using the age-old standard method of targeting the bilateral necks and entire pharyngeal axis to encompass all putative sites of mucosal disease persist.
CONCLUSIONS
Prospective evidence is lacking, and the available studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in work-up, treatment, inclusion criteria, and follow-up. Regardless, advances in science and technology have ushered in more precise approaches with a high degree of customization, particularly given the increased proportion of patients presenting with human papillomavirus-related disease.
Topics: Humans; Head and Neck Neoplasms; Human Papillomavirus Viruses; Meta-Analysis as Topic; Neoplasms, Unknown Primary; Papillomavirus Infections; Systematic Reviews as Topic
PubMed: 37844736
DOI: 10.1016/j.radonc.2023.109952 -
International Journal of Clinical... Jan 2024The optimal chemotherapy regimen in concurrent chemoradiotherapy (CCRT) for cisplatin-ineligible head and neck squamous cell carcinoma (HNSCC) has not been established....
Multicenter prospective phase II trial of concurrent chemoradiotherapy with weekly low-dose carboplatin for cisplatin-ineligible patients with advanced head and neck squamous cell carcinoma.
BACKGROUND
The optimal chemotherapy regimen in concurrent chemoradiotherapy (CCRT) for cisplatin-ineligible head and neck squamous cell carcinoma (HNSCC) has not been established. We aimed to evaluate the feasibility, efficacy, and safety of CCRT with weekly low-dose carboplatin for the treatment of advanced HNSCC in patients who are cisplatin-ineligible.
METHODS
This prospective phase II study enrolled adult patients (age ≥ 20 years) with HNSCC receiving whole-neck irradiation including bilateral levels II-IV and who were aged (≥ 75-year-old patients with 40 mL/min estimated glomerular filtration rate [eGFR] or better) or had renal dysfunction (< 75-year-old patients with 30-60 mL/min eGFR). Carboplatin was administered weekly (area under the plasma concentration-time curve = 2.0) for up to seven cycles during concurrent radiotherapy (70 Gy/35 Fr). The primary endpoint was the completion rate of CCRT. Secondary endpoints included overall response rate and incidence of adverse events.
RESULTS
Among the 30 patients enrolled, 28 were men. The median age was 73.5 years. Seventeen patients were < 75 years whereas 13 were ≥ 75 years old. The completion rate of CCRT was 90%. The overall response rate was 90%. Grade 3 adverse events that occurred in 10% or more patients were oral/pharyngeal mucositis (47%), leukocytopenia (20%), and neutropenia (10%). Grade 4 adverse events occurred in one patient (elevation of alanine aminotransferase level). No treatment-related deaths occurred.
CONCLUSION
CCRT with weekly low-dose carboplatin is a promising treatment option, with favorable feasibility, efficacy, and acceptable toxicity, for patients who are cisplatin-ineligible with advanced HNSCC.
CLINICAL TRIAL REGISTRATION NUMBER
jRCTs031190028.
Topics: Adult; Male; Humans; Aged; Female; Cisplatin; Squamous Cell Carcinoma of Head and Neck; Carboplatin; Prospective Studies; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37843751
DOI: 10.1007/s10147-023-02423-w