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EBioMedicine Oct 2023Dysbiosis of the oral mycobiome has been linked to some diseases, including cancers. However, the role of oral fungal communities in nasopharyngeal carcinoma (NPC)...
BACKGROUND
Dysbiosis of the oral mycobiome has been linked to some diseases, including cancers. However, the role of oral fungal communities in nasopharyngeal carcinoma (NPC) carcinogenesis has not previously been investigated.
METHODS
We characterized the oral salivary fungal mycobiome in 476 untreated incident NPC patients and 537 population-based controls using fungal internal transcribed spacer (ITS)-2 sequencing. The relationship between oral fungal mycobiome and the risk of NPC was assessed through bioinformatic and biostatistical analyses.
FINDINGS
We found that lower fungal alpha diversity was associated with an increased odds of NPC [lower vs. higher: observed features (adjusted odds ratio [OR] = 5.81, 95% confidence interval [CI] = 3.60-9.38); Simpson diversity (1.53, 1.03-2.29); Shannon diversity (2.03, 1.35-3.04)]. We also observed a significant difference in global fungal community patterns between cases and controls based on Bray-Curtis dissimilarity (P < 0.001). Carriage of oral fungal species, specifically, Saccharomyces cerevisiae, Candida tropicalis, Lodderomyces elongisporus, Candida albicans, and Fusarium poae, was associated with significantly higher odds of NPC, with ORs ranging from 1.56 to 4.66. Individuals with both low fungal and low bacterial alpha diversity had a profoundly elevated risk of NPC.
INTERPRETATION
Our results suggest that dysbiosis in the oral mycobiome, characterized by a loss of fungal community diversity and overgrowth of several fungal organisms, is associated with a substantially increased risk of NPC.
FUNDING
This work was funded by the US National Institutes of Health, the Swedish Research Council, the High-level Talents Research Start-up Project of Fujian Medical University, and the China Scholarship Council.
Topics: Humans; Nasopharyngeal Carcinoma; Dysbiosis; Case-Control Studies; Mycobiome; Saccharomyces cerevisiae; Nasopharyngeal Neoplasms
PubMed: 37776725
DOI: 10.1016/j.ebiom.2023.104813 -
Der Nervenarzt Apr 2024The number of tracheotomized patients with dysphagia and their need for treatment are continuously increasing in clinical and community settings. The revised version of... (Review)
Review
The number of tracheotomized patients with dysphagia and their need for treatment are continuously increasing in clinical and community settings. The revised version of the directive on home care and community-based intensive care of the Federal Joint Committee (G-BA) requires that tracheotomized patients are regularly evaluated with the aim of identifying and promoting the therapeutic potential after hospital discharge. Dysphagia treatment plays a crucial role as without improvement of severe dysphagia there is practically no possibility for decannulation. Tracheotomized patients with dysphagia are treated by speech and language therapists (SLT); however, the contents of tracheostomy management (TM) are not obligatory in the speech and language therapeutic training curricula, so that there is a need for further education and treatment standards must be secured. Therefore, the German Interdisciplinary Society for Dysphagia (DGD) in cooperation with the participating German medical and therapeutic societies developed a postgraduate curriculum for TM. This should serve as the basis for contents in TM and qualification of therapists within the framework of the delegation of medical services. The goals of the TM curriculum are the definition of theoretical and practical contents of TM, the qualification to perform TM according to current standards of care and quality assurance. The curriculum defines two qualification levels (user and trainer), entry requirements, curricular contents, examination and qualification criteria as well as transitional regulations for SLTs already experienced in TM.
Topics: Humans; Deglutition Disorders; Tracheostomy; Curriculum; Language Therapy; Home Care Services; Speech Therapy
PubMed: 38277047
DOI: 10.1007/s00115-023-01598-x -
Cancer Biology & Therapy Dec 2024N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in...
N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in the regulation of tumor microenvironment (TME) cell infiltration in several tumors. Nevertheless, the potential role and mechanism of m6A modification in nasopharyngeal carcinoma (NPC) remains unknown. mRNA expression data and clinical information from GSE102349, and GSE53819 datasets obtained from Gene Expression Omnibus (GEO) was used for differential gene expression and subsequent analysis. Consensus clustering was used to identify m6A-related molecular patterns of 88 NPC samples based on prognostic m6A regulators using Univariate Cox analysis. The TME cell-infiltrating characteristics of each m6A-related subclass were explored using single-sample gene set enrichment (ssGSEA) algorithm and CIBERSORT algotithm. DEGs between two m6A-related subclasses were screened using edgeR package. The prognostic signature and predicated nomogram were constructed based on the m6A-related DEGs. The cell infiltration and expression of prognostic signature in NPC was determined using immunohistochemistry (IHC) analysis. Chi-square test was used to analysis the significance of difference of the categorical variables. And survival analysis was performed using Kaplan-Meier plots and log-rank tests. The NPC samples were divided into two m6A-related subclasses. The TME cell-infiltrating characteristics analyses indicated that cluster 1 is characterized by immune-related and metabolism pathways activation, better response to anit-PD1 and anti-CTLA4 treatment and chemotherapy. And cluster 2 is characterized by stromal activation, low expression of HLA family and immune checkpoints, and a worse response to anti-PD1 and anti-CTLA4 treatment and chemotherapy. Furthermore, we identified 1558 DEGs between two m6A-related subclasses and constructed prognostic signatures to predicate the progression-free survival (PFS) for NPC patients. Compared to non-tumor samples, REEP2, TMSB15A, DSEL, and ID4 were upregulated in NPC samples. High expression of REEP2 and TMSB15A showed poor survival in NPC patients. The interaction between REEP2, TMSB15A, DSEL, ID4, and m6A regulators was detected. Our finding indicated that m6A modification plays an important role in the regulation of TME heterogeneity and complexity.
Topics: Humans; Epigenesis, Genetic; Nasopharyngeal Carcinoma; Tumor Microenvironment; Nasopharyngeal Neoplasms; Adenine
PubMed: 38532632
DOI: 10.1080/15384047.2024.2333590 -
International Immunopharmacology Dec 2023The treatment of nasopharyngeal carcinoma (NPC) is currently based on concurrent chemoradiotherapy. The prognosis of early NPC is better, while the prognosis of advanced... (Review)
Review
BACKGROUND
The treatment of nasopharyngeal carcinoma (NPC) is currently based on concurrent chemoradiotherapy. The prognosis of early NPC is better, while the prognosis of advanced NPC is poor. Immunotherapy is becoming increasingly commonly employed in clinical practice as a new strategy for treating malignant tumors. It has shown promising results in the treatment of certain malignant tumors, making it a current clinical research hotspot.
METHODS
This review summarizes the current immunotherapy on NPC, highlighting the application of immunotherapy and radiotherapy in the treatment of NPC.
RESULTS
X-rays can either increase or suppress anti-tumor immune responses through various pathways and mechanisms. Immune checkpoint inhibitors can usually enhance X-ray-induced anti-tumor immune responses. Detecting the immune checkpoint markers and tumor mutation markers, and the functional status of effector cells in patients can aid in the development of individualized treatment that improves the treatment efficacy with reducing drug resistance and adverse reactions. The development of a multivalent vaccine for NPC will help improve the efficacy of the vaccine. Combining techniques that increase the tumor antigens release, such as radiotherapy and oncolytic virus vaccines, may enhance the ability of the immune response.
CONCLUSIONS
To shed further light on the application of immunotherapy in NPC, large pooled studies must accumulate sufficient cases with detailed exposure data.
Topics: Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Immunotherapy; Chemoradiotherapy; Biomarkers, Tumor
PubMed: 37871379
DOI: 10.1016/j.intimp.2023.111094 -
Folia Medica Cracoviensia Oct 2023Our umbrella review aimed to summarize and revisit the evidence from all of the meta-analyses and systematic reviews regarding the treatments of oropharyngeal squamous... (Review)
Review
INTRODUCTION
Our umbrella review aimed to summarize and revisit the evidence from all of the meta-analyses and systematic reviews regarding the treatments of oropharyngeal squamous cell carcinoma (OPSCC).
MATERIALS AND METHODS
Major medical databases such as PubMed, Scopus, Embase, Web of Science, Google Scholar, Cochrane Library, BIOSIS, and EBSCO were searched. The overall search process was conducted in 3 stages.
RESULTS
Finally, a total of 28 studies met the inclusion criteria and were included in this study. Out of those 28 meta-analyses, a total of 315 primary studies were screened in order to extract the data and perform the statistical analysis. In total, data from 22,619 patients was analyzed.
CONCLUSION
The main objective of the present umbrella review was to summarize and analyze all of the evidence-based data provided by numerous meta-analyses and systematic reviews regarding the treatment of OPSCC. Our study delivers the most up-to-date and evidence-based results regarding the different therapeutic modalities of this malignancy in one concise review, making it the ultimate tool for physicians treating OPSCC.
Topics: Humans; Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 38310532
DOI: 10.24425/fmc.2023.147217 -
Journal of Pediatric Hematology/oncology Apr 2024Nasopharyngeal carcinoma (NPC) is a rare and locally aggressive form of childhood cancer. Treatment of pediatric NPC includes chemotherapy and radiotherapy. Most studies... (Review)
Review
Nasopharyngeal carcinoma (NPC) is a rare and locally aggressive form of childhood cancer. Treatment of pediatric NPC includes chemotherapy and radiotherapy. Most studies on the treatment of pediatric NPC are single-arm studies. With current treatment protocols survival rates for patients with nonmetastatic disease exceed 80%, although most children will have long-term treatment-related late effects. Efforts to reduce early and late toxicities include reduced radiotherapy doses in children with good responses to induction chemotherapy. Further studies are needed to evaluate the role of immunotherapy in both the primary setting and in children with progressive or relapsed disease. This review summarizes current clinical approaches to the treatment of pediatric NPC.
Topics: Child; Humans; Nasopharyngeal Carcinoma; Carcinoma; Nasopharyngeal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy
PubMed: 38447121
DOI: 10.1097/MPH.0000000000002848 -
BMC Medicine Nov 2023Treatment options beyond the first-line setting for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are limited. The role of the multitarget tyrosine kinase...
BACKGROUND
Treatment options beyond the first-line setting for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are limited. The role of the multitarget tyrosine kinase inhibitor anlotinib in RM-NPC is unclear.
METHODS
In this prospective, single-arm, phase 2 trial, patients with histologically confirmed RM-NPC and failure of at least two lines of prior systemic treatments were eligible. Anlotinib was given at 12 mg once daily on days 1-14 every 3 weeks until disease progression or intolerable toxicities. The primary end point was disease control rate, defined as the percentage of patients achieving complete response, partial response, or stable disease by RECIST criteria.
RESULTS
From April 2019 to March 2021, 39 patients were enrolled and received a median of 4 cycles (range, 0.5-20) of anlotinib treatment. Partial response and stable disease were observed in 8 and 20 patients, respectively. The disease control rate was 71.8%, and objective response rate was 20.5%. With a median follow-up of 17.2 months, the median progression-free survival was 5.7 months. The 12-month overall survival was 58.3%, and the median overall survival was not reached. The most frequent grade 3/4 treatment-related adverse events were hand-foot syndrome (23.7%), oral mucositis (21.0%), hypertension (7.9%), and triglyceride elevation (7.9%). Hemorrhage, all grade 1 or 2, occurred in 34.2% of the patients.
CONCLUSIONS
Anlotinib monotherapy exhibited promising anti-tumor activities and disease control for heavily pretreated RM-NPC patients with a tolerable toxicity profile.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT03906058.
Topics: Humans; Nasopharyngeal Carcinoma; Prospective Studies; Neoplasm Recurrence, Local; Nasopharyngeal Neoplasms
PubMed: 37936166
DOI: 10.1186/s12916-023-03140-x -
BMC Medicine Nov 2023Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC)...
Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.
BACKGROUND
Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC.
METHODS
This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes.
RESULTS
The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity.
CONCLUSIONS
We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.
Topics: Humans; Nasopharyngeal Carcinoma; Retrospective Studies; Neoplasm Recurrence, Local; Prognosis; Nasopharyngeal Neoplasms; Magnetic Resonance Imaging
PubMed: 38012705
DOI: 10.1186/s12916-023-03164-3 -
Dysphagia Oct 2023Dysphagia occurs temporarily or permanently following esophageal replacement in at least half of the cases. Swallowing disorder, in addition to severe decline in the...
Dysphagia occurs temporarily or permanently following esophageal replacement in at least half of the cases. Swallowing disorder, in addition to severe decline in the quality of life, can lead to a deterioration of the general condition, which may lead to death if left untreated. For this reason, their early detection and treatment are a matter of importance. Between 1993 and 2012, 540 esophageal resections were performed due to malignant tumors at the Department of Surgery, Medical Center of the University of Pécs. Stomach was used for replacement in 445 cases, colon in 38 cases, and jejunum in 57 cases. The anastomosis with a stomach replacement was located to the neck in 275 cases and to the thorax in 170 cases. The colon was pulled up to the neck in each case. There were 29 cases of free jejunal replacements located to the neck and 28 cases with a Roux loop reconstruction located to the thorax. Based on the literature data and own experience, the following were found to be the causes of dysphagia in the order of frequency: anastomotic stenosis, conduit obstruction, peptic and ischemic stricture, foreign body, local recurrence, functional causes, new malignant tumor in the esophageal remnant, and malignant tumor in the organ used for replacement. Causes may overlap each other, and their treatment may be conservative or surgical. The causes of many dysphagic complications might be prevented by improving the anastomosis technique, by better preservation the blood supply of the substitute organ, by consistently applying a functional approach, and by regular follow-up.
Topics: Humans; Deglutition Disorders; Quality of Life; Postoperative Complications; Stomach; Esophageal Stenosis
PubMed: 36719515
DOI: 10.1007/s00455-023-10557-2 -
Epilepsy & Behavior : E&B Sep 2023Our study aimed to describe the prevalence and characteristics of gastrointestinal and eating problems in Dravet syndrome (DS) and other SCN1A-related seizure disorders...
OBJECTIVE
Our study aimed to describe the prevalence and characteristics of gastrointestinal and eating problems in Dravet syndrome (DS) and other SCN1A-related seizure disorders and to determine the association between the occurrence of gastrointestinal and eating problems and core features of DS.
METHODS
Gastrointestinal and eating problems were assessed with a questionnaire in a Dutch cohort of participants with an SCN1A-related seizure disorder. Associations between the number of gastrointestinal and eating problems and core features of DS, seizure severity, level of intellectual disability, impaired mobility, behavioral problems, and use of anti-seizure medication, were explored by multivariate ordinal regression analyses. Symptoms were divided into the categories dysphagia-related, behavioral, and gastrointestinal, and were assessed separately.
RESULTS
One hundred sixty-nine participants with an SCN1A-related seizure disorder, of whom 118 (69.8%) with DS and 51 (30.2%) with Generalized Epilepsy with Febrile Seizures Plus / Febrile Seizures (GEFS+/FS), the non-DS phenotype, were evaluated. Gastrointestinal and eating problems were highly prevalent in DS participants, 50.8% had more than three symptoms compared to 3.9% of non-DS participants. Of participants with DS, 17.8% were fully or partly fed by a gastric tube. Within the three different symptom categories, the most prevalent dysphagia-related symptom was drooling (60.7%), distraction during mealtimes (61.4%) the most prevalent behavioral symptom, and constipation and loss of appetite (both 50.4%) the most prevalent gastrointestinal symptoms. DS participants who use a wheelchair (odds ratio (OR) 4.9 95%CI (1.9-12.8) compared to walking without aid), who use ≥3 anti-seizure medications (ASM) (OR 5.9 95%CI (1.9-18.2) compared to <3 ASM) and who have behavioral problems (OR 3.0 95%CI (1.1-8.1) compared to no behavioral problems) had more gastrointestinal and eating problems.
CONCLUSION
Gastrointestinal and eating problems are frequently reported symptoms in DS. Distinguishing between symptom categories will lead to tailored management of patients at risk, will improve early detection, and enable a timely referral to a dietitian, behavioral expert, and/or speech therapist, ultimately aiming to improve the quality of life of both patients and caregivers.
Topics: Humans; NAV1.1 Voltage-Gated Sodium Channel; Quality of Life; Deglutition Disorders; Mutation; Epilepsy; Epilepsies, Myoclonic
PubMed: 37523795
DOI: 10.1016/j.yebeh.2023.109361