Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19.

SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain viral pathology to the nasopharynx. Which cells SARS-CoV-2 primarily targets and how infection influences the respiratory epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy and COVID-19 participants. During COVID-19, we observe expansion of secretory, loss of ciliated, and epithelial cell repopulation via deuterosomal cell expansion. In mild and moderate COVID-19, epithelial cells express anti-viral/interferon-responsive genes, while cells in severe COVID-19 have muted anti-viral responses despite equivalent viral loads. SARS-CoV-2 RNA+ host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1high goblet, and KRT13+ "hillock"-like cells, and we identify genes associated with susceptibility, resistance, or infection response. Our study defines protective and detrimental responses to SARS-CoV-2, the direct viral targets of infection, and suggests that failed nasal epithelial anti-viral immunity may underlie and precede severe COVID-19.

Radiation-induced nasopharyngeal ulcers after re-irradiation with intensity-modulated radiotherapy in locoregional recurrent nasopharyngeal carcinoma patients: a dose-volume-outcome analysis.

OBJECTIVE: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. RESULTS: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ [Formula: see text]D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ [Formula: see text]D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. CONCLUSIONS: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical re­irradiation with IMRT and we propose a EQD2_ [Formula: see text]D80 threshold of 137.035 Gy for the nasopharynx.

Ectopic Olfactory Neuroblastoma Arising in the Nasopharynx.

ABSTRACT: Olfactory neuroblastoma (ONB) is an uncommon malignant tumor typically located in the upper nasal cavity. Olfactory neuroblastoma originating in the nasopharynx is extremely rare and tends to be misdiagnosed. The authors describe a rare case of ONB arising ectopically in the nasopharynx. The patient was a 65-year-old woman with recurrent epistaxis and a feeling of fullness in the right ear. After evaluation, endoscopic surgery was performed. The pathological result proved to be ONB. Postoperative magnetic resonance imaging showed that the tumor was completely resected. The patient proceeded to have 66 Gy of postoperative intensity-modulated radiotherapy and was followed for 36 months without tumor recurrence. Olfactory neuroblastoma originating from the nasopharynx is more rare condition compared with ONB located in other areas in the literature. The symptoms of ONB ectopic to the nasopharynx are similar to those of other nasopharyngeal tumors, which were likely to be misdiagnosed. The treatment principle is the same as that of nonectopic ONB, which is surgery combined with radiotherapy. Surgery can be performed using an endoscopic transnasal approach.

Development and validation of predictive models for skeletal malocclusion classification using airway and cephalometric landmarks.

OBJECTIVE: This study aimed to develop a deep learning model to predict skeletal malocclusions with an acceptable level of accuracy using airway and cephalometric landmark values obtained from analyzing different CBCT images. BACKGROUND: In orthodontics, multitudinous studies have reported the correlation between orthodontic treatment and changes in the anatomy as well as the functioning of the airway. Typically, the values obtained from various measurements of cephalometric landmarks are used to determine skeletal class based on the interpretation an orthodontist experiences, which sometimes may not be accurate. METHODS: Samples of skeletal anatomical data were retrospectively obtained and recorded in Digital Imaging and Communications in Medicine (DICOM) file format. The DICOM files were used to reconstruct 3D models using 3DSlicer (slicer.org) by thresholding airway regions to build up 3D polygon models of airway regions for each sample. The 3D models were measured for different landmarks that included measurements across the nasopharynx, the oropharynx, and the hypopharynx. Male and female subjects were combined as one data set to develop supervised learning models. These measurements were utilized to build 7 artificial intelligence-based supervised learning models. RESULTS: The supervised learning model with the best accuracy was Random Forest, with a value of 0.74. All the other models were lower in terms of their accuracy. The recall scores for Class I, II, and III malocclusions were 0.71, 0.69, and 0.77, respectively, which represented the total number of actual positive cases predicted correctly, making the sensitivity of the model high. CONCLUSION: In this study, it is observed that the Random Forest model was the most accurate model for predicting the skeletal malocclusion based on various airway and cephalometric landmarks.

Retrospective analysis of the upper airway anatomy and Sella turcica morphology across different skeletal malocclusions: a computerized technique.

OBJECTIVE: This study aimed to investigate the normal volumetric space and variations in the measurements of different landmarks in adults with different skeletal relations of the maxilla and the mandible based on CBCT data. The study also analyses these landmarks to locate any correlations. BACKGROUND: Numerous studies in orthodontics have found a relationship between orthodontic treatment and changes in the anatomy and function of the airway. Severe changes in airway morphology can cause breathing difficulties, lower quality of life, and even result in life-threatening conditions such as obstructive sleep apnoea. Consequently, orthodontic diagnosis and treatment planning require a thorough understanding of the airway space and its function. METHODS: The present retrospective study was conducted using CBCT records of 120 adult patients, containing 40 samples of each skeletal class (20 males and 20 females). The boundaries were defined for the 3 major regions: the nasopharynx, the oropharynx, and the hypopharynx. Various measurements were recorded across these regions, as well as selective cephalometric landmarks. The obtained data was used to calculate average and standard deviation, while regression analysis was used to evaluate correlations and t-test was used to test statistical significance of gender differences. RESULTS: The results demonstrate that skeletal Class III individuals exhibit a reduced airway volume in the nasopharynx compared to other groups, whereas skeletal Class II individuals displayed a diminished airway volume in the hypopharynx. A strong correlation was observed for Sella turcica parameters. There were no significant differences in skeletal parameters across genders. Nasopharynx cavity volume demonstrated significant differences between skeletal Class I-Class III as well as between skeletal Class II-Class III. Hypopharynx cavity volume also demonstrated significant differences between skeletal Class I-Class II and between skeletal Class II-Class III. CONCLUSION: The major findings are the presence of a reduced nasopharyngeal volume in skeletal Class III malocclusions while skeletal Class II individuals displayed a diminished hypopharyngeal volume, making these critical areas to consider during the diagnostic and orthodontic treatment planning stages. This study also revealed a consistent correlation between Sella turcica parameters across various facial skeletal profiles, with skeletal Class II patients exhibiting a distinct pattern and skeletal Class I and Class III demonstrating an average relationship.

Endoscopic Features of Chronic Rhinosinusitis in Patients with Gastroesophageal Reflux Disease.

Chronic rhinosinusitis (CRS) is a complex inflammatory condition affecting the nasal and paranasal sinus mucosa. Gastroesophageal reflux disease (GERD) has been implicated as a potential exacerbating factor in CRS, but the specific endoscopic features of nasopharyngeal pathology in this context remain poorly understood. Background and Objectives: Chronic rhinosinusitis is a multifactorial disease with various underlying etiologies, including inflammation, anatomical factors, and environmental triggers. While gastroesophageal reflux disease has been suggested as a potential contributor to chronic rhinosinusitis, the specific endoscopic features indicative of nasopharyngeal pathology in CRS patients with GERD symptoms have not been clearly elucidated. Our aim is to identify specific endoscopic features of nasopharyngeal pathology in patients with CRS associated with GERD symptoms and to propose a method for assessing the influence of gastroesophageal reflux disease on the mucosal layer of the nose and nasopharynx. Materials and Methods: We conducted a cross-sectional observational study involving 521 adult patients presenting with symptoms suggestive of CRS. From this cohort, 95 patients with the highest scores on the Reflux Symptom Index (RSI) and Reflux Symptom Score-12 (RSS-12) questionnaires were selected as the main group. Endoscopic examinations were performed to assess the nasal and nasopharyngeal mucosa. Results: Our study revealed significant alterations in the nasopharyngeal mucosa of patients with CRS associated with GERD symptoms. Increased vascularity of the nasopharyngeal mucosa was observed in 91 patients (95.7%), while hypertrophy was noted in 83 patients (87.4%). Mucus was present in the nasopharynx of 77 patients (81.1%), exhibiting varying characteristics of color and consistency. Asymmetric hypertrophy of the oropharyngeal mucosa was noted in 62 patients (65.3%). Conclusions: We propose a method for assessing the influence of gastroesophageal reflux disease on the mucosal layer of the nose and nasopharynx, which may aid in diagnostic and management decisions. Further research is warranted to explore the potential impact of GERD symptoms on the course and severity of CRS exacerbations.

Endoscopic, endoscopic-assisted and open approaches in the treatment of juvenile angiofibroma: what has been new in the past decade (and 1586 cases)?

PURPOSE: Juvenile angiofibroma (JA) is a benign, but locally invasive tumor of the nasopharynx. Surgical resection of JA is performed through endoscopic (EA), endoscopic-assisted (EAA), or open approaches (OA). The management of these tumors is constantly evolving. We aimed to compare the surgical efficiency and morbidity of EA, EAA, and OA in JA treatment by conducting a systematic review of the literature published over the last 10 years. METHODS: A systematic review of the English literature on surgical cases of JA published between 2012 and 2022 was performed. Eligible articles were analyzed for individual patient data (IPD) and aggregate patient data (APD). The primary predictor variable was the surgical approach. The primary outcome variable was recurrence rate. RESULTS: The search retrieved 75 articles reporting 1586 JA surgical cases; 129 in IPD, and 1457 in APD data sets. Within the IPD data set, recurrence rates were significantly lower in cases completed by EA than that by OA (p < 0.05). There was no significant difference in recurrence rates between the EA and EAA groups (p > 0.05). EAA had a lower recurrence rate than that of OA (p < 0.05). For the APD data set, the recurrence rate following EA was significantly lower than that following OA (p < 0.05). There was no significant difference in recurrence between the EA and EAA groups (p > 0.05), and between the EAA and OA groups (p > 0.05). CONCLUSIONS: EA represents the method of choice for mild and moderately advanced JA. EAA and OA still play important roles in the treatment of advanced-stage JA.

[Clinicopathological features of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma].

Objective: To investigate the clinicopathological features, immunophenotype and gene alterations of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA). Methods: Fifteen case of TL-LGNPPA diagnosed at Zhejiang Cancer Hospital (5 cases) and the First Affiliated Hospital, Zhejiang University School of Medicine (10 cases) from November 2011 to August 2020 were collected. Clinical and pathological examinations, immunohistochemical staining and next-generation sequencing were performed. The clinicopathological and molecular characteristics were summarized, and relevant literature was reviewed. Results: Fifteen patients were identified and included. Their median age was 36 years (range, 20-60 years). The male-female ratio was 1.0∶1.1. The most common symptoms were epistaxis and nasal obstruction. The neoplasms were located on the roof of the nasopharynx or the posterior margin of the nasal septum. The pathological features included complex papillary and glandular structures mainly composed of single or pseudostratified cubic and columnar cells, with mild to moderate cytological atypia. In some cases, spindle cell features, nuclear grooves, ground glass nuclei, squamous metaplasia, or scattered psammoma bodies were identified. In addition, nuclear polar reversal cells, hobnail cells and micropapillary structures were found, but have not been reported in previous literature. Immunohistochemistry showed that the tumor cells were diffusely positive for TTF1, CK7, vimentin and CKpan; focally positive for p40, CK5/6 and p16; and negative for Tg, NapsinA, CK20, CDX2, S-100 and PAX8. The Ki-67 positive rates ranged from 1% to 20% and were≤10% in thirteen cases (13/15). EBER in situ hybridization was negative in all cases. DNA sequencing of 6 specimens was performed and all specimens were found harboring gene mutations (EWSR1, SMAD2, ROS1, JAK3, GRIN2A, ERRCC5, STAT3, and TET2), but no hot spot gene alterations were found. No MSI-H and MMR related gene changes were detected. All tumors showed low tumor mutation burden. All 15 patients underwent endoscopic surgery, and only 1 of them underwent radiotherapy postoperatively. All patients were recurrence free and alive at the end of follow-up periods (range: 23 to 129 months). Conclusions: TL-LGNPPA is a rare indolent tumor of the nasopharynx and exhibits a unique morphology and immunophenotype. Endoscopic resection is an effective treatment for TL-LGNPPA with excellent overall prognosis.

Clinical Characteristics and Prognosis of Small Cell Carcinoma in the Nasopharynx: A Population-Based Study.

BACKGROUND: Nasopharyngeal small cell carcinoma (SmCC) is a rare histological type of nasopharyngeal cancer, and its prognosis remains poor. This study aimed to determine the clinical characteristics and survival prognostic factors of nasopharyngeal SmCC. METHODS: Detailed clinicopathologic and therapeutic characteristics of a patient diagnosed with nasopharyngeal SmCC were determined. Nasopharyngeal SmCC cases reported previously were reviewed and summarized. Furthermore, a retrospective analysis was performed on data from the Surveillance, Epidemiology, and End Results (SEER) Program database. Kaplan-Meier analysis was conducted to compare survival within groups. Univariate and multivariate analyses were performed to investigate prognostic factors. RESULTS: A nasopharyngeal SmCC patient treated with chemoradiotherapy who achieved 46 months long-term survival was reported. In reviewing 16 reported cases with epidemiologic and therapeutic details, we found most of nasopharyngeal SmCC patients were diagnosed with advanced grades and received chemoradiotherapy. In total, 13,993 cases of nasopharyngeal cancer were extracted from the SEER database, from which 57 nasopharyngeal SmCC cases were eventually screened out. The mean age of the patients was 55.70 years, and 64.9% of these cases were either grade III or IV; the median overall survival (OS) was 18 months. Statistically significant differences were observed in the OS values of groups categorized by age (P = .025) or radiotherapy (P = .037). Age (<70 years) and radiotherapy were identified as independent survival and prognostic factors. CONCLUSION: Patients with nasopharyngeal SmCC are usually diagnosed with advanced grades and have poor prognoses; nevertheless, they can benefit from radiotherapy with prolonged overall survival.

NKILA represses nasopharyngeal carcinoma carcinogenesis and metastasis by NF-κB pathway inhibition.

The role of long non-coding RNA (lncRNA) in the progression of Nasopharyngeal carcinoma (NPC) has not been fully elucidated. The study was designed to explore the functional role of NKILA, a newly identified lncRNA, in the progression of NPC. We performed a lncRNA expression profile microarray using four NPC and paired para-cancerous tissues. NKILA was identified as a potential functional lncRNA by this lncRNA expression profile. We used 107 paraffin-embedded NPC tissues with different TNM stages to detect the expression of NKILA and analyzed the survival data by Log-rank test and Cox regression. The role of NKILA and its underlying mechanisms in the progression of NPC were evaluated by a series of experiments in vitro and vivo by silencing or expressing NKILA. Compared with control tissues, NKILA expression was identified to be decreased in NPC tissues. Low NKILA expression was correlated with unfavorable clinicopathological features and predicted poor survival outcome in NPC patients. After adjusting for potential confounders, low expression of NKILA was confirmed to be an independent prognostic factor correlated with poor survival outcomes. Furthermore, we found that NKILA overexpression in high-metastatic-potential NPC cells repressed motile behavior and impaired the metastatic capacity in vitro and in vivo. In contrast, RNAi-mediated NKILA depletion increased the invasive motility of cells with lower metastatic potential. Further experiments demonstrated that NKILA regulated the metastasis of NPC through the NF-κB pathway. Taken together, NKILA plays vital roles in the pathogenesis of NPC. The unique histological characteristics of NPC indicate that local inflammation plays a vital role in carcinogenesis of nasopharyngeal carcinoma.

EBV infection is associated with histone bivalent switch modifications in squamous epithelial cells.

Epstein-Barr virus (EBV) induces histone modifications to regulate signaling pathways involved in EBV-driven tumorigenesis. To date, the regulatory mechanisms involved are poorly understood. In this study, we show that EBV infection of epithelial cells is associated with aberrant histone modification; specifically, aberrant histone bivalent switches by reducing the transcriptional activation histone mark (H3K4me3) and enhancing the suppressive mark (H3K27me3) at the promoter regions of a panel of DNA damage repair members in immortalized nasopharyngeal epithelial (NPE) cells. Sixteen DNA damage repair family members in base excision repair (BER), homologous recombination, nonhomologous end-joining, and mismatch repair (MMR) pathways showed aberrant histone bivalent switches. Among this panel of DNA repair members, MLH1, involved in MMR, was significantly down-regulated in EBV-infected NPE cells through aberrant histone bivalent switches in a promoter hypermethylation-independent manner. Functionally, expression of MLH1 correlated closely with cisplatin sensitivity both in vitro and in vivo. Moreover, seven BER members with aberrant histone bivalent switches in the EBV-positive NPE cell lines were significantly enriched in pathway analysis in a promoter hypermethylation-independent manner. This observation is further validated by their down-regulation in EBV-infected NPE cells. The in vitro comet and apurinic/apyrimidinic site assays further confirmed that EBV-infected NPE cells showed reduced DNA damage repair responsiveness. These findings suggest the importance of EBV-associated aberrant histone bivalent switch in host cells in subsequent suppression of DNA damage repair genes in a methylation-independent manner.

Diagnosis of possible nasopharyngeal malignancy in adults with isolated serous otitis media; a systematic review and proposal of a management algorithm.

PURPOSE: The objective of this study was (1) to systematically review the evidence of routine post-nasal space blind biopsies and/or imaging of adults with isolated serous otitis media (SOM) of unknown cause for detection nasopharyngeal malignancy (NPM), and (2) to design a clinical management algorithm for these patients. METHODS: A systematic search was conducted in the databases PubMed, Embase and Cochrane Library guided by the study question "Should adults with isolated SOM of unknown cause undergo routine biopsies of the post-nasal space and/or diagnostic imaging for detection of NPM?". All retrieved studies were reviewed and quantitatively analyzed. RESULTS: The systematic literature search identified 552 publications accessible for title-abstract screening. This yielded 23 studies for full text assessment, of which 6 were found eligible for inclusion. All six studies dealt with nasopharyngeal blind biopsies, whereas no studies on cross-sectional imaging were identified. The derived summarized results of the included studies showed that 5.5% (31/568) of patients with isolated SOM of unknown cause were diagnosed with NPM. Of these, 6.5% (2/31) had normal nasopharyngeal endoscopy (i.e., malignancy was discovered by blind biopsies). Finally, 0.35% (2/568) of patients with isolated SOM of unknown cause diagnosed with NPM had normal nasopharyngeal endoscopy findings (i.e., nasopharyngeal endoscopy ruled-out malignancy in 99.65% of patients). CONCLUSIONS: We found no evidence supporting routine use of blind biopsies or cross-sectional imaging in adults with isolated serous otitis media of unknown cause. We propose a pragmatic management algorithm for workup of adults with persistent secretory otitis media.

Nasopharyngeal Presentation of a Pharyngeal Cleft Cyst in a Dog.

A 2 yr old castrated male shih tzu was presented for assessment of worsening chronic snoring since first detected at 3 mo of age. An upper respiratory endoscopic examination and a computed tomographic scan showed a well-circumscribed, fluid-filled nasopharyngeal mass located in the median plane on the nasal side of the soft palate. This lesion was removed using a ventral approach to the nasopharynx by blunt-sharp dissection from the submucosal tissues of the soft palate. Histopathology revealed a cystic lesion lined by a single layer of a pseudostratified columnar ciliated epithelium, characteristic of a pharyngeal cyst. Follow-up 5 mo after surgery revealed complete resolution of the clinical signs with no evidence of local recurrence. Pharyngeal cysts are developmental abnormalities of the branchial apparatus. Most derive from the second branchial arch and cause cysts, sinuses, and fistulae to develop in the neck region. In our case, the lesion was located in the nasopharynx, leading to snoring and exercise intolerance. This condition should be included in the differential diagnosis of suspected nasopharyngeal obstruction.

Persistent SARS-CoV-2 RNA Shedding Without Evidence of Infectiousness: A Cohort Study of Individuals With COVID-19.

BACKGROUND: To better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding and infectivity, we estimated SARS-CoV-2 RNA shedding duration, described participant characteristics associated with the first negative rRT-PCR test (resolution), and determined if replication-competent viruses was recoverable ≥10 days after symptom onset. METHODS: We collected serial nasopharyngeal specimens from 109 individuals with rRT-PCR-confirmed COVID-19 in Utah and Wisconsin. We calculated viral RNA shedding resolution probability using the Kaplan-Meier estimator and evaluated characteristics associated with shedding resolution using Cox proportional hazards regression. We attempted viral culture for 35 rRT-PCR-positive nasopharyngeal specimens collected ≥10 days after symptom onset. RESULTS: The likelihood of viral RNA shedding resolution at 10 days after symptom onset was approximately 3%. Time to shedding resolution was shorter among participants aged <18 years (adjusted hazards ratio [aHR], 3.01; 95% confidence interval [CI], 1.6-5.6) and longer among those aged ≥50 years (aHR, 0.50; 95% CI, .3-.9) compared to participants aged 18-49 years. No replication-competent viruses were recovered. CONCLUSIONS: Although most patients were positive for SARS-CoV-2 for ≥10 days after symptom onset, our findings suggest that individuals with mild to moderate COVID-19 are unlikely to be infectious ≥10 days after symptom onset.

Severe Acute Respiratory Syndrome Coronavirus 2 Total and Subgenomic RNA Viral Load in Hospitalized Patients.

BACKGROUND: Previous studies demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected for weeks after infection. The significance of this finding is unclear and, in most patients, does not represent active infection. Detection of subgenomic RNA has been proposed to represent productive infection and may be a useful marker for monitoring infectivity. METHODS: We used quantitative reverse-transcription polymerase chain reaction (RT-qPCR) to quantify total and subgenomic nucleocapsid (sgN) and envelope (sgE) transcripts in 185 SARS-CoV-2-positive nasopharyngeal swab samples collected on hospital admission and to relate to symptom duration. RESULTS: We find that all transcripts decline at the same rate; however, sgE becomes undetectable before other transcripts. The median duration of symptoms to a negative test is 14 days for sgE and 25 days for sgN. There is a linear decline in subgenomic compared to total RNA, suggesting that subgenomic transcript copy number is dependent on copy number of total transcripts. The mean difference between total and sgN is 16-fold and the mean difference between total and sgE is 137-fold. This relationship is constant over duration of symptoms, allowing prediction of subgenomic copy number from total copy number. CONCLUSIONS: Subgenomic RNA may be no more useful in determining infectivity than a copy number threshold determined for total RNA.

Severe Acute Respiratory Syndrome Coronavirus 2 Normalized Viral Loads and Subgenomic RNA Detection as Tools for Improving Clinical Decision Making and Work Reincorporation.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) provides a highly variable cycle threshold (Ct) value that cannot distinguish viral infectivity. Subgenomic ribonucleic acid (sgRNA) has been used to monitor active replication. Given the importance of long RT-PCR positivity and the need for work reincorporation and discontinuing isolation, we studied the functionality of normalized viral loads (NVLs) for patient monitoring and sgRNA for viral infectivity detection. METHODS: The NVLs measured through the Nucleocapsid and RNA-dependent-RNA-polymerase genes and sgRNA RT-PCRs were performed in 2 consecutive swabs from 84 healthcare workers. RESULTS: The NVLs provided similar and accurate quantities of both genes of SARS-CoV-2 at 2 different timepoints of infection, overcoming Ct-value and swab collection variability. Among SARS-CoV-2-positive samples, 51.19% were sgRNA-positive in the 1st RT-PCR and 5.95% in the 2nd RT-PCR. All sgRNA-positive samples had >4 log10 RNA copies/1000 cells, whereas samples with ≤1 log10 NVLs were sgRNA-negative. Although NVLs were positive until 29 days after symptom onset, 84.1% of sgRNA-positive samples were from the first 7 days, which correlated with viral culture viability. Multivariate analyses showed that sgRNA, NVLs, and days of symptoms were significantly associated (P < .001). CONCLUSIONS: The NVLs and sgRNA are 2 rapid accessible techniques that could be easily implemented in routine hospital practice providing a useful proxy for viral infectivity and coronavirus disease 2019 patient follow-up.

Investigation of the feasibility of synthetic MRI in the differential diagnosis of non-keratinising nasopharyngeal carcinoma and benign hyperplasia using different contoured methods for delineation of the region of interest.

AIM: To assess the feasibility and preliminary diagnostic performances of relaxation times derived from synthetic magnetic resonance imaging (syMRI) for differentiating nasopharyngeal carcinoma from nasopharyngeal benign lymphoid hyperplasia, and to assess the influence of tissue segmentation method on relaxation estimates. MATERIALS AND METHODS: Fifty participants with nasopharyngeal carcinoma (NPC) and 40 participants with benign hyperplasia (NPH) who underwent syMRI examination were enrolled prospectively. T1, T2, and proton density (PD) values were obtained from four different regions of interest (ROIs), namely, partial-section, single-section, three-sections, and whole-lesion. The metrics between NPC and NPH or among different ROIs were compared using Student's t-test or one-way ANOVA. The area under curve (AUC) was calculated to assess the performance of metrics obtained from different ROIs to differentiate NPC and NPH. RESULTS: The T1, T2, and PD values for NPH were significantly higher than those for NPC, regardless of the type of ROI used, except for the PD value obtained from the whole-lesion ROI. The T2 values obtained from the single-section ROI showed the highest diagnostic accuracy in distinguishing NPC from NPH, with an AUC of 0.894, sensitivity of 0.900, and specificity of 0.800. Additionally, the T1, T2, and PD values for nasopharyngeal lesions showed no statistical difference among different kinds of ROI, except for the difference in T1 value between partial-section and other methods. CONCLUSION: Quantitative analysis of syMRI has the potential to distinguish NPC from NPH. Moreover, different types of ROI showed limited influence on the relaxation time estimation for nasopharyngeal lesions.

Hypoxia induced factor-1α levels in patients undergoing adenoidectomy.

Among  the most common causes of nasal congestion in childhood is adenoid hypertrophy (AH) which leads to hypoxia. In this study, we studied plasma concentrations of hypoxia induced factor-1α (HIF-1α) in children undergoing adenoidectomy. The study included a total of 86 participants: 39 patients with AH and 47 healthy individuals. Serum HIF-1α levels (ng/mL) were measured by ELISA. HIF-1α concentrations were compared to the adenoid-nasopharyngeal ratio (ANR) of patients with AH, as recorded in the medical records. We found significantly higher concentrations of HIF-1α (0.30 ± 0.47 ng/mL) in patients with AH as compared to healthy controls (0.24 ± 0.07 ng/mL, p = .011). HIF-1α levels were not significantly different regarding gender between patients with AH (p = .77) and in the control group (p = .97). In patients with AH, there was a moderately significant positive correlation between HIF-1α levels and Hb (p = .000), (correlation coefficient r = 0.542). There was a positive correlation between HIF-1α and ANR in patients with AH (p = .005, r = 0.439). This study indicates that AH increases HIF-1α levels. We also observed a moderately significant positive correlation between HIF-1α and ANR in patients with AH. HIF-1α levels are a potential biomarker for hypoxia in patients with AH.

Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease.

BACKGROUND: The World Health Organization estimates that air pollution is responsible for 7 million deaths per annum, with 7% of these attributable to pneumonia. Many of these fatalities have been linked to exposure to high levels of airborne particulates, such as diesel exhaust particles (DEPs). OBJECTIVES: We sought to determine whether exposure to DEPs could promote the progression of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae to invasive pneumococcal disease. METHODS: We used mouse models and in vitro assays to provide a mechanistic understanding of the link between DEP exposure and pneumococcal disease risk, and we confirmed our findings by using induced sputum macrophages isolated from healthy human volunteers. RESULTS: We demonstrate that inhaled exposure to DEPs disrupts asymptomatic nasopharyngeal carriage of S pneumoniae in mice, leading to dissemination to lungs and blood. Pneumococci are transported from the nasopharynx to the lungs following exposure to DEPs, leading to increased proinflammatory cytokine production, reduced phagocytic function of alveolar macrophages, and consequently, increased pneumococcal loads within the lungs and translocation into blood. These findings were confirmed by using DEP-exposed induced sputum macrophages isolated from healthy volunteers, demonstrating that impaired innate immune mechanisms following DEP exposure are also at play in humans. CONCLUSION: Lung inhaled DEPs increase susceptibility to pneumococcal disease by leading to loss of immunological control of pneumococcal colonisation, increased inflammation, tissue damage, and systemic bacterial dissemination.

Performing nasopharyngeal swabs-Guidelines based on an anatomical study.

Nasopharyngeal swabs are performed to collect material for diagnosing diseases affecting the respiratory system, such as Covid-19. Yet, no systematic anatomical study defines concrete prerequisites for successfully targeting the nasopharyngeal mucosa. We therefore aim at simulating nasopharyngeal swabs in human body donors to characterize parameters allowing and supporting to enter the nasopharynx with a swab, while avoiding endangering the cribriform plate. With the aid of metal probes and commercial swabs a total of 314 nasopharyngeal swabs in anatomical head/neck specimens stemming from 157 body donors were simulated. Important anatomical parameters were photo-documented and measured. We provide information on angles and distances between prominent anatomical landmarks and particularly important positions the probe occupies during its advancement through the nares to the upper and lower parts of the nasopharynx and cribriform plate. Based on these data we suggest a simple and safe three-step procedure for conducting nasopharyngeal swabs. In addition, we define easily recognizable signals for its correct performance. Evaluations prove that this procedure in all specimens without deformations of the nasal cavity allows the swab to enter the nasopharynx, whereas a widespread used alternative only succeeds in less than 50%. Our data will be the key for the successful collection of nasopharyngeal material for detecting and characterizing pathogens, such as SARS-CoV-2, which have a high affinity to pharyngeal mucosa. They demonstrate that the danger for damaging the cribriform plate or olfactory mucosa with swabs is unlikely, but potentially higher when performing nasal swabs.