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Current Gastroenterology Reports Jul 2023While guidelines exist for the evaluation and management of esophageal dysphagia in the general population, dysphagia disproportionately affects the elderly. In this... (Review)
Review
PURPOSE OF REVIEW
While guidelines exist for the evaluation and management of esophageal dysphagia in the general population, dysphagia disproportionately affects the elderly. In this article, we reviewed the literature on evaluating esophageal dysphagia in elderly patients and proposed a diagnostic algorithm based on this evidence.
RECENT FINDINGS
In older patients, dysphagia is often well compensated for by altered eating habits and physiologic changes, underreported by patients, and missed by healthcare providers. Once identified, dysphagia should be differentiated into oropharyngeal and esophageal dysphagia to guide diagnostic workup. For esophageal dysphagia, this review proposes starting with endoscopy with biopsies, given its relative safety even in older patients and potential for interventional therapy. If endoscopy shows a structural or mechanical cause, then further cross-sectional imaging should be considered to assess for extrinsic compression, and same session endoscopic dilation should be considered for strictures. If biopsies and endoscopy are normal, then esophageal dysmotility is more likely, and high-resolution manometry and additional workup should be performed following the updated Chicago Classification. Even after diagnosis of the root cause, complications including malnutrition and aspiration pneumonia should also be assessed and monitored, as they both result from and can further contribute to dysphagia. The successful evaluation of esophageal dysphagia in elderly patients requires a thorough, standardized approach to collecting a history, selection of appropriate diagnostic workup, and assessment of risk of potential complications, including malnutrition and aspiration.
Topics: Humans; Aged; Deglutition Disorders; Esophageal Motility Disorders; Endoscopy, Gastrointestinal; Manometry; Malnutrition; Esophageal Achalasia
PubMed: 37312002
DOI: 10.1007/s11894-023-00876-7 -
EBioMedicine Dec 2023Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer with a high incidence in Southern China and Southeast Asia. Patients with remote metastasis and...
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer with a high incidence in Southern China and Southeast Asia. Patients with remote metastasis and recurrent NPC have poor prognosis. Thus, a better understanding of NPC pathogenesis may identify novel therapies to address the unmet clinical needs.
METHODS
H3K27ac ChIP-seq and HiChIP was applied to understand the enhancer landscapes and the chromosome interactions. Whole genome sequencing was conducted to analyze the relationship between genomic variations and epigenetic dysregulation. CRISPRi and JQ1 treatment were used to evaluate the transcriptional regulation of SOX2 SEs. Colony formation assay, survival analysis and in vivo subcutaneous patient-derived xenograft assays were applied to explore the function and clinical relevance of SOX2 in NPC.
FINDINGS
We globally mapped the enhancer landscapes and generated NPC enhancer connectomes, linking NPC specific enhancers and SEs. We found five overlapped genes, including SOX2, among super-enhancer regulated genes, survival related genes and NPC essential genes. The mRNA expression of SOX2 was repressed when applying CRISPRi targeting different SOX2 SEs or JQ1 treatment. Next, we identified a genetic variation (Chr3:181422197, G > A) in SOX2 SE which is correlated with higher expression of SOX2 and poor survival. In addition, SOX2 was highly expressed in NPC and is correlated with short survival in patients with NPC. Knock-down of SOX2 suppressed tumor growth in vitro and in vivo.
INTERPRETATION
Our study demonstrated the super-enhancer landscape with chromosome interactions and identified super-enhancer driven SOX2 promotes tumorigenesis, suggesting that SOX2 is a potential therapeutic target for patients with NPC.
FUNDING
A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
Topics: Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Survival Analysis; Chromatin; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Cell Proliferation; SOXB1 Transcription Factors
PubMed: 37967508
DOI: 10.1016/j.ebiom.2023.104870 -
Cell Death & Disease Jul 2023Nasopharyngeal carcinoma (NPC) is a common malignant epithelial tumor of the head and neck that often exhibits local recurrence and distant metastasis. The molecular...
Nasopharyngeal carcinoma (NPC) is a common malignant epithelial tumor of the head and neck that often exhibits local recurrence and distant metastasis. The molecular mechanisms are understudied, and effective therapeutic targets are still lacking. In our study, we found that the transcription factor ZIC2 was highly expressed in NPC. Although ZIC family members play important roles in neural development and carcinogenesis, the specific mechanism and clinical significance of ZIC2 in the tumorigenesis and immune regulation of NPC remain elusive. Here, we first reported that high expression of ZIC2 triggered the secretion of MCSF in NPC cells, induced M2 polarization of tumor-associated macrophages (TAMs), and affected the secretion of TAM-related cytokines. Mechanistically, ChIP-seq and RNA-seq analyses identified JUNB as a downstream target of ZIC2. Furthermore, ZIC2 was significantly enriched in the promoter site of JUNB and activated JUNB promoter activity, as shown by ChIP-qPCR and luciferase assays. In addition, JUNB and MCSF participated in ZIC2-induced M2 TAMs polarization. Thus, blocking JUNB and MCSF could reverse ZIC2-mediated M2 TAMs polarization. Moreover, Kaplan-Meier survival analyses indicated that high expression of ZIC2, JUNB, and CD163 was positively associated with a poor prognosis in NPC. Overexpression of ZIC2 induced tumor growth in vivo, with the increase of JUNB, MCSF secretion, and CD163. In summary, our study implies that ZIC2 induces M2 TAM polarization, at least in part through regulation of JUNB/MCSF and that ZIC2, JUNB, and CD163 can be utilized as prognostic markers for NPC and as therapeutic targets for cancer immunotherapy.
Topics: Humans; Nasopharyngeal Carcinoma; Carcinogenesis; Carcinoma; Nasopharyngeal Neoplasms; Macrophages; Nuclear Proteins; Transcription Factors
PubMed: 37479694
DOI: 10.1038/s41419-023-05983-x -
Auris, Nasus, Larynx Aug 2023The COVID-19 omicron variant has a low affinity for the lower respiratory tract. However, upper respiratory tract symptoms, such as nasal discharge and sore throat,...
OBJECTIVES
The COVID-19 omicron variant has a low affinity for the lower respiratory tract. However, upper respiratory tract symptoms, such as nasal discharge and sore throat, characterize the infection with this variant. Therefore, in laryngeal stenosis, disease severity assessment through blood oxygen saturation has not been useful.
METHODS
We report the case of "omicron laryngitis" in a 59-year-old male who visited the ear, nose, and throat (ENT) clinic with complaints of a sore throat and difficulty in swallowing saliva that persisted for a day.
RESULTS
Laryngoscopy revealed severe swelling of the transglottic region and exudates on the larynx. He was then diagnosed with COVID-19 and subjected to emergency tracheostomy for airway management. Until the emergence of the omicron variant, COVID-19 showed mainly lower airway and mild upper airway inflammatory features. However, upper airway stenosis should be suspected in cases presenting with "muffled speech," "dysphagia," "severe pain on swallowing," and "inspiratory dyspnea or stridor."
CONCLUSION
Therefore, laryngeal and pharyngeal evaluation using a flexible laryngoscope under appropriate infection control measures is necessary, considering the possibility of progression to fatal laryngeal stenosis, as noted in this case.
Topics: Male; Humans; Middle Aged; Laryngitis; Laryngostenosis; COVID-19; SARS-CoV-2; Pharyngitis
PubMed: 36114072
DOI: 10.1016/j.anl.2022.08.007 -
Cellular and Molecular Life Sciences :... Aug 2023Radiotherapy resistance is a major obstacle to nasopharyngeal carcinoma (NPC) therapy and contributes to tumour recurrence and metastasis. Lipid metabolism is a key...
Radiotherapy resistance is a major obstacle to nasopharyngeal carcinoma (NPC) therapy and contributes to tumour recurrence and metastasis. Lipid metabolism is a key regulatory mechanism in cancer biology; however, its role in NPC radiotherapy resistance remains unclear. In this study, we identified hypoxia-inducible lipid droplet-associated protein (HILPDA) as a newly discovered regulator of radioresistance that induces not only lipid droplet (LD) formation but also intracellular lipid remodelling, notably changing mitochondrial cardiolipin (CL) levels. Additionally, we found that the upregulation of CL promotes mitophagy in response to irradiation exposure. Mechanistically, HILPDA inhibits PINK1-mediated CLS1 ubiquitination and degradation. The combination of a mitophagy inhibitor and irradiation significantly increases the radiosensitivity of NPC cells. Human cancer-derived data confirmed that the HILPDA-CLS1 pathway promotes NPC radioresistance. Collectively, these findings suggest that HILPDA plays a critical role in promoting NPC radioresistance and might be targeted to overcome radiotherapeutic resistance in NPC patients in the clinic.
Topics: Humans; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Lipidomics; Mitophagy; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Proteins
PubMed: 37552373
DOI: 10.1007/s00018-023-04891-9 -
Critical Reviews in Oncology/hematology Oct 2023We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with anti-angiogenesis or anti-EGFR treatment in recurrent/metastatic nasopharyngeal... (Review)
Review
We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with anti-angiogenesis or anti-EGFR treatment in recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) patients who progressed to previous anti-PD1 therapy. Enrolled patients were divided into a combination group and a chemotherapy only group. A total of 145 patients were enrolled. The median progress-free survival (mPFS) was 7.9 months and 4.4 months, respectively for the two groups. The combination group exhibited significantly longer PFS (HR=0.363, p < 0.001), and better disease control ratio (DCR, p = 0.022) compared with the chemotherapy group. Among the combination group, longer PFS was found in those patients who received different PD1 inhibitor from prior therapy, reached object response rate (ORR) from prior anti-PD1 therapy, and EBV DNA ≤ 1500 copy/ml before therapy, comparing to the corresponding other patients. R/M NPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with anti-angiogenesis or anti-EGFR agents.
Topics: Humans; Nasopharyngeal Carcinoma; Immunotherapy; Immune Checkpoint Inhibitors; Nasopharyngeal Neoplasms
PubMed: 37633346
DOI: 10.1016/j.critrevonc.2023.104113 -
Nutrients Aug 2023Most patients with stroke suffer from complications and these include dysphagia. Dysphagia can cause malnutrition, and malnutrition affects prognosis and recovery....
Most patients with stroke suffer from complications and these include dysphagia. Dysphagia can cause malnutrition, and malnutrition affects prognosis and recovery. However, there is a lack of accurate studies on the nutritional status of stroke patients with dysphagia and its associated factors in different phases of stroke. This study retrospectively investigated 620 stroke patients who underwent a videofluoroscopic swallowing study (VFSS) due to dysphagia, from March 2018 to February 2021. The study aimed to evaluate the nutritional state and associated factors of malnutrition in acute and subacute stroke patients with dysphagia. Serum albumin and percentage of current weight to ideal weight were used to determine nutritional status. Malnutrition was observed in 58.9 and 78.9% of acute and subacute stroke patients. Exact logistic regression analysis revealed that old age and high penetration-aspiration scale score were significantly associated factors for malnutrition in patients with acute stroke. Old age, stroke history, bilateral hemiplegia, high modified Rankin score, low Korean Mini-Mental State Examination, pneumonia, and high functional dysphagia score were significantly associated factors for malnutrition in patients with subacute stroke. Patients with these associated factors in each phase of stroke require active nutritional assessment and care to decrease the risk of malnutrition.
Topics: Humans; Deglutition Disorders; Retrospective Studies; Malnutrition; Nutritional Status; Stroke
PubMed: 37686771
DOI: 10.3390/nu15173739 -
Health and Quality of Life Outcomes Jan 2024Nutrition care can positively affect multiple aspects of patient's health; outcomes are commonly evaluated on the basis of their impact on a patient's (i)... (Review)
Review
BACKGROUND
Nutrition care can positively affect multiple aspects of patient's health; outcomes are commonly evaluated on the basis of their impact on a patient's (i) illness-specific conditions and (ii) health-related quality of life (HRQoL). Our systematic review examined how HRQoL was measured in studies of nutritional interventions. To help future researchers select appropriate Quality of Life Questionnaires (QoLQ), we identified commonly-used instruments and their uses across populations in different regions, of different ages, and with different diseases.
METHODS
We searched EMCare, EMBASE, and Medline databases for studies that had HRQoL and nutrition intervention terms in the title, the abstract, or the MeSH term classifications "quality of life" and any of "nutrition therapy", "diet therapy", or "dietary supplements" and identified 1,113 studies for possible inclusion.We then reviewed titles, abstracts, and full texts to identify studies for final inclusion.
RESULTS
Our review of titles, abstracts, and full texts resulted in the inclusion of 116 relevant studies in our final analysis. Our review identified 14 general and 25 disease-specific QoLQ. The most-used general QoLQ were the Short-Form 36-Item Health Survey (SF-36) in 27 studies and EuroQol 5-Dimension, (EQ-5D) in 26 studies. The European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC-QLQ), a cancer-specific QoLQ, was the most frequently used disease-specific QoLQ (28 studies). Disease-specific QoLQ were also identified for nutrition-related diseases such as diabetes, obesity, and dysphagia. Sixteen studies used multiple QoLQ, of which eight studies included both general and disease-specific measures of HRQoL. The most studied diseases were cancer (36 studies) and malnutrition (24 studies). There were few studies focused on specific age-group populations, with only 38 studies (33%) focused on adults 65 years and older and only 4 studies focused on pediatric patients. Regional variation in QoLQ use was observed, with EQ-5D used more frequently in Europe and SF-36 more commonly used in North America.
CONCLUSIONS
Use of QoLQ to measure HRQoL is well established in the literature; both general and disease-specific instruments are now available for use. We advise further studies to examine potential benefits of using both general and disease-specific QoLQ to better understand the impact of nutritional interventions on HRQoL.
Topics: Humans; Deglutition Disorders; Europe; Malnutrition; Quality of Life
PubMed: 38267976
DOI: 10.1186/s12955-024-02229-y -
Medical Sciences (Basel, Switzerland) Oct 2023Malnutrition in esophageal and pharyngeal cancer patients constitutes a common and serious concern, which significantly reduces patients' prognoses. Cancers of the... (Review)
Review
May Nutritional Status Positively Affect Disease Progression and Prognosis in Patients with Esophageal and Pharyngeal Cancers? A Scoping Review of the Current Clinical Studies.
BACKGROUND
Malnutrition in esophageal and pharyngeal cancer patients constitutes a common and serious concern, which significantly reduces patients' prognoses. Cancers of the esophagus and the pharynx can considerably impair feeding in patients, resulting in severe undernutrition. This is a scoping review that intends to critically analyze the most well-designed clinical studies investigating the potential beneficial impact of diverse nutritional assessment tools on the prognosis of patients with esophageal and pharyngeal cancers.
METHODS
The most accurate and remarkable scientific databases were comprehensively explored utilizing relative keywords to detect clinical studies that investigate whether nutritional status may affect disease prognosis.
RESULTS
Several assessment tools have evaluated and highlighted the potential beneficial impact of nutritional status on disease progression and patients' prognosis in both esophageal and pharyngeal cancers. Regarding esophageal cancer, CONUT, PNI, PG-SGA, and NRS-2002 are more commonly used, while albumin is also frequently evaluated. Regarding pharyngeal cancers, fewer studies are currently available. PNI has been evaluated, and its significance as a factor for shorter survival' times has been highlighted. The Comprehensive Nutritional Index has also been evaluated with positive results, as well as NRS 2002, GPS, and body-weight status. However, there is currently a lack of studies with an adequate number of women with cancer. An international literature gap was identified concerning follow-up studies with adequate methodology.
CONCLUSIONS
Nutritional status may significantly affect disease progression and patients' survival, highlighting the significance of a great nutritional status in individuals with esophageal and pharyngeal cancers. Further large-scale and well-designed prospective surveys should be performed to verify the potential beneficial effects of adequate nourishment in people suffering from cancer of the esophagus and pharynx.
Topics: Humans; Female; Nutritional Status; Prospective Studies; Prognosis; Disease Progression; Esophageal Neoplasms; Pharyngeal Neoplasms
PubMed: 37873749
DOI: 10.3390/medsci11040064 -
BMC Neuroscience Oct 2023Increasingly, non-pharmacological interventions are being identified and applied to post-stroke dysphagia. Nevertheless, there is insufficient evidence to assess which... (Meta-Analysis)
Meta-Analysis Review
Increasingly, non-pharmacological interventions are being identified and applied to post-stroke dysphagia. Nevertheless, there is insufficient evidence to assess which type of interventions are more effective. In this study, the randomized controlled trials of non-pharmacological interventions on post-stroke dysphagia were retrieved from the relevant databases. Including 96 studies and 12 non-drug treatments. Then, and the network meta-analysis is carried out by statistical software. The results show: In the aspects of videofluoroscopic swallowing study (VFSS), Standardized Swallowing Assessment (SSA), swallowing-quality of life (SWAL-QOL), Water swallow test (WST); Acupuncture + electrotherapy + rehabilitation training, acupuncture + rehabilitation training + massage, electrotherapy + rehabilitation training, acupuncture + electrotherapy + rehabilitation training, electrotherapy, acupuncture + rehabilitation training + acupoints sticking application have significant effects in post-stroke dysphagia. Compared with other interventions, they have more advantages in improving the above indicators. A substantial number of high-quality randomized clinical trials are still necessary in the prospective to validate the therapeutic effectiveness of non-pharmacological interventions in post-stroke dysphagia and the results of this Bayesian network meta-analysis.
Topics: Humans; Deglutition Disorders; Quality of Life; Prospective Studies; Bayes Theorem; Network Meta-Analysis; Treatment Outcome; Stroke; Acupuncture Therapy; Randomized Controlled Trials as Topic
PubMed: 37845642
DOI: 10.1186/s12868-023-00825-0