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European Journal of Neurology Aug 2023Post-stroke dysphagia affects outcome. In acute stroke patients, the aim was to evaluate clinical, cognitive and neuroimaging features associated with dysphagia and...
BACKGROUND AND PURPOSE
Post-stroke dysphagia affects outcome. In acute stroke patients, the aim was to evaluate clinical, cognitive and neuroimaging features associated with dysphagia and develop a predictive score for dysphagia.
METHODS
Ischaemic stroke patients underwent clinical, cognitive and pre-morbid function evaluations. Dysphagia was retrospectively scored on admission and discharge with the Functional Oral Intake Scale.
RESULTS
In all, 228 patients (mean age 75.8 years; 52% males) were included. On admission, 126 (55%) were dysphagic (Functional Oral Intake Scale ≤6). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05), pre-event modified Rankin scale (mRS) score (OR 1.41, 95% CI 1.09-1.84), National Institutes of Health Stroke Scale (NIHSS) score (OR 1.79, 95% CI 1.49-2.14), frontal operculum lesion (OR 8.53, 95% CI 3.82-19.06) and Oxfordshire total anterior circulation infarct (TACI) (OR 1.47, 95% CI 1.05-2.04) were independently associated with dysphagia at admission. Education (OR 0.91, 95% CI 0.85-0.98) had a protective role. At discharge, 82 patients (36%) were dysphagic. Pre-event mRS (OR 1.28, 95% CI 1.04-1.56), admission NIHSS (OR 1.88, 95% CI 1.56-2.26), frontal operculum involvement (OR 15.53, 95% CI 7.44-32.43) and Oxfordshire classification TACI (OR 3.82, 95% CI 1.95-7.50) were independently associated with dysphagia at discharge. Education (OR 0.89, 95% CI 0.83-0.96) and thrombolysis (OR 0.77, 95% CI 0.23-0.95) had a protective role. The 6-point "NOTTEM" (NIHSS, opercular lesion, TACI, thrombolysis, education, mRS) score predicted dysphagia at discharge with good accuracy. Cognitive scores had no role in dysphagia risk.
CONCLUSIONS
Dysphagia predictors were defined and a score was developed to evaluate dysphagia risk during stroke unit stay. In this setting, cognitive impairment is not a predictor of dysphagia. Early dysphagia assessment may help in planning future rehabilitative and nutrition strategies.
Topics: Male; Humans; Aged; Female; Stroke; Brain Ischemia; Deglutition Disorders; Retrospective Studies; Ischemic Stroke; Treatment Outcome
PubMed: 37159487
DOI: 10.1111/ene.15846 -
Annals of Medicine Dec 2023To investigate the treatment of intractable epistaxis after radiotherapy for nasopharyngeal carcinoma (NPC). This review focuses on the anatomy and pathophysiology,... (Review)
Review
To investigate the treatment of intractable epistaxis after radiotherapy for nasopharyngeal carcinoma (NPC). This review focuses on the anatomy and pathophysiology, mechanism, and clinical treatments of epistaxis after NPC radiotherapy. For treating NPC, radiation therapy is the primary therapeutic modality. However, radiotherapy can lead to varied degrees of harm to the neighboring tissues and is correlated with numerous complications. Among these complications, epistaxis is a common occurrence after NPC radiotherapy, owing to damage to the surrounding tissues caused by radiotherapy. Unfortunately, epistaxis, particularly carotid blowout, can have a dangerous course and a high mortality rate. Accurate understanding of epistaxis following radiotherapy, prompt bleeding cessation, and reduction of bleeding volume are key considerations. Nasal tamponade is a crucial rescue treatment, while tracheotomy is an active and effective method. Intravascular balloon embolization is a reliable and effective treatment method for ICA hemorrhage, and vascular embolization is the primary approach for treating external carotid artery maxillary bleeding. Implantation of a covered stent can achieve hemostasis without altering hemodynamics. A comprehensive approach utilizing these methods can improve the success rate of treating nosebleeds following NPC radiotherapy.HighlightsThe mortality rate for carotid blowout following radiotherapy for NPC is high.Radiation therapy and tumor condition are correlated with epistaxis in NPC.Treatment methods for NPC-related epistaxis include posterior nostril tamponade, endoscopic hemostasis, DSA, selective vascular embolization, and stent implantation.The use of a covered stent for NPC-related carotid blowout achieves hemostasis without altering blood perfusion.Effective and timely application of various hemostasis methods is key to improving the success rate of rescue, considering the characteristics of NPC-related epistaxis.
Topics: Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Epistaxis; Carotid Arteries; Embolization, Therapeutic
PubMed: 37074291
DOI: 10.1080/07853890.2023.2200257 -
Frontiers in Immunology 2023Refractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of...
BACKGROUND
Refractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease.
PATIENTS AND METHODS
Between 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 10 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters.
RESULTS
All patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (<3 disease sites), and plasma EBV-DNA <1000 copies/mL had a better outcome.
CONCLUSIONS
Autologous EBV-specific CTLs transplanted following conventional first-line CT demonstrated promising efficacy with several patients obtaining long-lasting disease control. The rationale provided by this study, with the crucial role likely played by the timing of CTL administration when trying to induce synergy with conventional treatment needs to be confirmed in a prospective controlled trial.
Topics: Humans; Nasopharyngeal Carcinoma; Herpesvirus 4, Human; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Carcinoma; Cell- and Tissue-Based Therapy
PubMed: 37497213
DOI: 10.3389/fimmu.2023.1208475 -
Journal of Neuroengineering and... Dec 2023Strokes may cause some swallowing difficulty or associated dysphagia in 25-80% of patients. This phenomenon has been linked to increased morbidity and mortality.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Strokes may cause some swallowing difficulty or associated dysphagia in 25-80% of patients. This phenomenon has been linked to increased morbidity and mortality. Therefore, the aim of this study was to evaluate the efficacy of transcranial direct current stimulation in patients with dysphagia in post-stroke patients.
METHODS
A systematic search in PubMed, Scopus, Web of Science and MEDLINE was conducted. The articles must have to evaluate an intervention that included transcranial direct current stimulation; the sample had to consist exclusively of patients with post-stroke dysphagia; and the experimental design consisted of randomized controlled trial. Difference in mean differences and their 95% confidence interval were calculated as the between-group difference in means divided by the pooled standard deviation. The I statistic was used to determine the degree of heterogeneity.
RESULTS
Of the 9 investigations analyzed, all applied transcranial direct current stimulation in combination with conventional dysphagia therapy to the experimental group. All the studies analyzed identified improvements in swallowing function and meta-analysis confirmed their strong effect on reducing the risk of penetration and aspiration (Hedges's g = 0.55). The results showed that participants who received transcranial direct current stimulation significantly improved swallowing function.
CONCLUSIONS
Transcranial direct current stimulation has positive effects in the treatment of poststroke dysphagia by improving swallowing function, oral and pharyngeal phase times and the risk of penetration and aspiration. Furthermore, its combination with conventional dysphagia therapy, balloon dilatation with catheter or training of the swallowing muscles ensures improvement of swallowing function. PROSPERO registration ID CRD42022314949.
Topics: Humans; Deglutition Disorders; Transcranial Direct Current Stimulation; Stroke; Deglutition; Stroke Rehabilitation; Treatment Outcome
PubMed: 38082316
DOI: 10.1186/s12984-023-01290-w -
American Journal of Human Genetics Jul 2023Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain...
Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR = 0.74, 95% CI = 0.68-0.81, p = 3.08 × 10) and 17q12 (rs226241; OR = 1.42, 95% CI = 1.26-1.60, p = 1.62 × 10). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.
Topics: Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Follow-Up Studies; Genetic Predisposition to Disease; Genetic Association Studies; Polymorphism, Single Nucleotide; Homeodomain Proteins
PubMed: 37352861
DOI: 10.1016/j.ajhg.2023.06.003 -
International Journal of Environmental... Nov 2023While abundant evidence exists linking alcohol, tobacco, and HPV infection to a carcinogenic impact on the oropharynx, the contribution of inhalational workplace hazards... (Review)
Review
While abundant evidence exists linking alcohol, tobacco, and HPV infection to a carcinogenic impact on the oropharynx, the contribution of inhalational workplace hazards remains ill-defined. We aim to determine whether the literature reveals occupational environments at a higher-than-average risk of developing oropharyngeal cancer (OPC) and summarize the available data. To identify studies assessing the relationship between occupational exposure and risk of OPC, a search of the literature through the PubMed-NCBI database was carried out and, ultimately, 15 original articles meeting eligibility criteria were selected. Only original articles in English focusing on the association between occupational exposure and risk or death of specifically OPC were included. The available data are supportive of a potentially increased risk of OPC in waiters, cooks and stewards, artistic workers, poultry and meat workers, mechanics, and World Trade Center responders exposed to dust. However, the available literature on occupation-related OPC is limited. To identify occupational categories at risk, large cohorts with long follow-ups are needed. Identification of causal associations with occupation-related factors would require dose-response analyses adequately adjusted for confounders.
Topics: Humans; Oropharyngeal Neoplasms; Causality; Occupational Exposure; Occupations; Carcinogens; Papillomavirus Infections
PubMed: 37947576
DOI: 10.3390/ijerph20217020 -
Current Opinion in Immunology Aug 2023Epstein-Barr virus (EBV) contributes to oncogenesis and immune evasion in nasopharyngeal carcinoma (NPC). At present, an aggregated, higher-level view on the impact of... (Review)
Review
Epstein-Barr virus (EBV) contributes to oncogenesis and immune evasion in nasopharyngeal carcinoma (NPC). At present, an aggregated, higher-level view on the impact of EBV genes toward the immune microenvironment of NPC is lacking. To this end, we have interrogated tumor-derived RNA sequences of 106 treatment-naive NPC patients for 98 EBV transcripts, and captured the presence of 10 different immune cell populations as well as 23 different modes of T-cell evasion. We discovered 3 clusters of EBV genes that each associate with distinct immunophenotypes of NPC. Cluster 1 associated with gene sets related to immune cell recruitment, such as those encoding for chemoattractants and their receptors. Cluster 2 associated with antigen processing and presentation, such as interferon-related genes, whereas cluster 3 associated with presence of M1-like macrophages, absence of CD4+ T cells, and oncogenic pathways, such as the nuclear factor kappa light-chain enhancer of activated B-cell pathway. We discuss these 3 EBV clusters regarding their potential for stratification for T-cell immunity in NPC together with the next steps needed to validate such therapeutic value.
Topics: Humans; Nasopharyngeal Carcinoma; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Carcinoma; Nasopharyngeal Neoplasms; Transcriptome; Tumor Microenvironment
PubMed: 37235920
DOI: 10.1016/j.coi.2023.102335 -
Cancer Cell Mar 2024The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed...
The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.
Topics: Humans; Nasopharyngeal Carcinoma; Neoplasm Staging; Herpesvirus 4, Human; Prognosis; Nasopharyngeal Neoplasms; Epstein-Barr Virus Infections; Carcinoma; Retrospective Studies
PubMed: 38242125
DOI: 10.1016/j.ccell.2023.12.020 -
Chinese Clinical Oncology Aug 2023Nasopharyngeal carcinoma (NPC) with de novo distant metastasis (M1) is classified as stage IVB in the 8th edition of the staging system jointly adopted by the American... (Review)
Review
BACKGROUND AND OBJECTIVE
Nasopharyngeal carcinoma (NPC) with de novo distant metastasis (M1) is classified as stage IVB in the 8th edition of the staging system jointly adopted by the American Joint Committee on Cancer and the International Union against Cancer Control. Patients with M1 disease generally have a relatively short life expectancy. This review discusses the personalized and intensified treatment strategies for de novo metastatic NPC.
METHODS
A literature search was conducted on PubMed to identify peer-reviewed publications on subdivisions of M1 disease and treatment of de novo metastatic NPC. Clinicaltrials.gov and Chinese Clinical Trial Register were searched to identify ongoing clinical trials evaluating systemic or local therapy of previously untreated metastatic NPC.
KEY CONTENT AND FINDINGS
M1 encompasses a diverse group of diseases. Several important factors, including tumor burden, EBV-DNA levels, location of involvement, the number of metastasis, and treatment strategies, influence the prognosis of NPC patients. Researchers have attempted to define M1 subcategorization to reflect the underlying risk profile and tailor personalized treatment. Recent advancements have brought new hope for this otherwise incurable condition. In the era of immunotherapy, checkpoint inhibitors have become the first-line systemic treatment for metastatic NPC in JUPITER-02, CAPTAIN-1st, and RATIONALE-309. Additionally, the value of radical locoregional radiation therapy and ablative treatment to distant metastatic sites should not be overlooked in patients with de novo metastatic diseases. Locoregional radiation with concurrent chemotherapy, maintenance chemotherapy, and radical local treatment to metastatic sites are emerging as potential treatment options.
CONCLUSIONS
Given the diversity of metastatic NPC, a multimodality approach incorporating chemotherapy, immunotherapy, locoregional radiation and ablative treatment to metastatic sites has been shown to improve overall control. Further research is needed to determine the efficacy and optimal duration of maintenance therapy.
Topics: Humans; Immunotherapy; Multimodal Imaging; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis
PubMed: 37699604
DOI: 10.21037/cco-23-32 -
Genes Jan 2024This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian...
This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian randomization (MR) based on drug targets. Instrumental variables within ±100 kb of the gene locus, impacting low-density lipoprotein cholesterol (LDL-C), were utilized for MR analysis. Coronary heart disease (CHD) served as a positive control to validate the causal relationship between PCSK9 inhibitors and various cancers. We employed reverse MR to address the reverse causation concerns. Data from positive controls and tumors were sourced from OpenGWAS. MR analysis suggested a negative causal relationship between PCSK9 inhibitors and both breast and lung cancers (95% 0.81~0.99, = 2.25 × 10; 95% 0.65~0.94, = 2.55 × 10). In contrast, a positive causal link was observed with gastric, hepatic, and oral pharyngeal cancers and cervical intraepithelial neoplasia (95% 1.14~1.75, = 1.88 × 10; 95% 1.46~2.53, = 1.16 × 10; 95% 4.49~6.33, = 3.36 × 10; 95% 4.56~7.12, = 6.91 × 10), without heterogeneity or pleiotropy ( > 0.05). Sensitivity analyses confirmed these findings. The results of MR of drug targets suggested no causal relationship between PCSK9 inhibitors and bladder cancer, thyroid cancer, pancreatic cancer, colorectal cancer, malignant neoplasms of the kidney (except for renal pelvis tumors), malignant neoplasms of the brain, and malignant neoplasms of the esophagus ( > 0.05). Reverse MR helped mitigate reverse causation effects. The study indicates a divergent causal relationship of PCSK9 inhibitors with certain cancers. While negatively associated with breast and lung cancers, a positive causal association was observed with gastric, hepatic, oral cavity, and pharyngeal cancers and cervical carcinoma in situ. No causal links were found with bladder, thyroid, pancreatic, colorectal, certain kidney, brain, and esophageal cancers.
Topics: Female; Humans; Proprotein Convertase 9; PCSK9 Inhibitors; Subtilisin; Mendelian Randomization Analysis; Proprotein Convertases; Breast Neoplasms; Lung Neoplasms; Pharyngeal Neoplasms; Carcinoma in Situ
PubMed: 38275613
DOI: 10.3390/genes15010132