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Nutrients May 2024(1) Background: Pediatric dysphagia presents significant nutritional challenges, often impacting growth and development due to reduced oral intake, increased nutritional...
(1) Background: Pediatric dysphagia presents significant nutritional challenges, often impacting growth and development due to reduced oral intake, increased nutritional needs, and gastrointestinal complications; (2) Methods: This prospective quasi-experimental study assessed 117 children under 14 years old (20 patients were under 1 year old, 80 were aged 1-7 years, and 17 were older than 7 years), diagnosed with swallowing disorders, to analyze their caloric, macro-, and micronutrient intake and identify potential deficiencies. The severity of dysphagia was established using functional oral intake scales, and dietary records were reviewed over a 3-day period; (3) Results: The study revealed that 39.8% of participants did not meet their total energy expenditure (TEE), highlighting a high prevalence of malnutrition among these children. Furthermore, patients using feeding devices exhibited a significantly lower caloric intake, and over half required significantly modified food textures. After individualized speech therapy and nutritional rehabilitation, participants showed significant improvements in caloric intake, with their energy coverage increasing from 958% to 1198% of the daily requirement. Rehabilitation also improved tolerance to a broader range of food textures; (4) Conclusions: This research underscores the importance of multidisciplinary, individualized nutritional strategies to address the specific challenges of pediatric dysphagia, emphasizing the role of enteral nutrition and therapeutic interventions in improving the quality of life and nutritional outcomes of these children. Further studies are recommended to assess the long-term impact of such strategies.
Topics: Humans; Deglutition Disorders; Child; Child, Preschool; Male; Female; Prospective Studies; Infant; Nutritional Status; Energy Intake; Adolescent; Malnutrition; Enteral Nutrition; Energy Metabolism; Quality of Life
PubMed: 38892523
DOI: 10.3390/nu16111590 -
International Journal of Molecular... May 2024Hypopharyngeal squamous cell carcinoma (HSCC) is a kind of malignant tumor with a poor prognosis and low quality of life in the otolaryngology department. It has been...
Hypopharyngeal squamous cell carcinoma (HSCC) is a kind of malignant tumor with a poor prognosis and low quality of life in the otolaryngology department. It has been found that microRNA (miRNA) plays an important role in the occurrence and development of various tumors. This study found that the expression level of miRNA-107 (miR-107) in HSCC was significantly reduced. Subsequently, we screened out the downstream direct target gene Neuronal Vesicle Trafficking Associated 1 (NSG1) related to miR-107 through bioinformatics analysis and found that the expression of NSG1 was increased in HSCC tissues. Following the overexpression of miR-107 in HSCC cells, it was observed that miR-107 directly suppressed NSG1 expression, leading to increased apoptosis, decreased proliferation, and reduced invasion capabilities of HSCC cells. Subsequent experiments involving the overexpression and knockdown of NSG1 in HSCC cells demonstrated that elevated NSG1 levels enhanced cell proliferation, migration, and invasion, while the opposite effect was observed upon NSG1 knockdown. Further investigations revealed that changes in NSG1 levels in the HSCC cells were accompanied by alterations in ERK signaling pathway proteins, suggesting a potential regulatory role of NSG1 in HSCC cell proliferation, migration, and invasion through the ERK pathway. These findings highlight the significance of miR-107 and NSG1 in hypopharyngeal cancer metastasis, offering promising targets for therapeutic interventions and prognostic evaluations for HSCC.
Topics: Humans; MicroRNAs; Hypopharyngeal Neoplasms; Cell Proliferation; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; MAP Kinase Signaling System; Cell Movement; Carcinoma, Squamous Cell; Apoptosis; Disease Progression; Vesicular Transport Proteins; Squamous Cell Carcinoma of Head and Neck; Male; Neoplasm Invasiveness
PubMed: 38892156
DOI: 10.3390/ijms25115961 -
BMC Cancer Jun 2024Nasopharyngeal adenoid cystic carcinoma (NACC) is a relatively rare salivary gland tumor that is generally associated with poor outcomes. High-dose radiotherapy is a key...
BACKGROUND
Nasopharyngeal adenoid cystic carcinoma (NACC) is a relatively rare salivary gland tumor that is generally associated with poor outcomes. High-dose radiotherapy is a key treatment for patients with NACC. This study reported the long-term efficacy and safety of particle beam radiation therapy (PBRT) for NACC.
METHODS AND MATERIALS
Twenty-six patients with nonmetastatic NACC who received definitive PBRT alone were included in this retrospective study. The majority of patients (92.3%) had locally advanced disease. Twenty-five (96.15%) patients received intensity-modulated proton radiotherapy (IMPT) followed by a carbon ion radiotherapy (CIRT) boost, and one patient received CIRT alone. Overall survival (OS), local control (LC), regional control (RC), and distant metastasis control (DMC) rates were calculated via the Kaplan-Meier method.
RESULTS
The median follow-up time was 46.95 months for the entire cohort. Seven patients experienced local recurrence, and one patient experience neck lymph node recurrence. The 3- and 4-year OS, LC, RC, and DMC rates were 100% and 91.7%, 92.3% and 84.6%, 95.8% and 87.8%, and 90.2% and 71.3%, respectively. A total of 91.3% of the patients achieved complete remission of gross tumors at 1 year after PBRT. Severe acute toxicity was observed in only two patients. A grade 4 decrease in visual acuity was observed in one patient with orbital apex invasion. No late grade 3 or 5 toxicity was observed.
CONCLUSION
Definitive PBRT provided a satisfactory 4-year OS for patients with locally advanced NACC. The toxicity was acceptable and mild. Further follow-up is necessary to confirm the efficacy and safety of definitive PBRT for patients with NACC.
Topics: Humans; Carcinoma, Adenoid Cystic; Male; Female; Middle Aged; Nasopharyngeal Neoplasms; Adult; Retrospective Studies; Treatment Outcome; Aged; Proton Therapy; Radiotherapy, Intensity-Modulated; Young Adult; Follow-Up Studies; Nasopharyngeal Carcinoma; Neoplasm Recurrence, Local; Heavy Ion Radiotherapy
PubMed: 38890585
DOI: 10.1186/s12885-024-12471-8 -
Cell Death & Disease Jun 2024Mitochondria play a crucial role in the progression of nasopharyngeal carcinoma (NPC). YME1L, a member of the AAA ATPase family, is a key regulator of mitochondrial...
Mitochondria play a crucial role in the progression of nasopharyngeal carcinoma (NPC). YME1L, a member of the AAA ATPase family, is a key regulator of mitochondrial function and has been implicated in various cellular processes and diseases. This study investigates the expression and functional significance of YME1L in NPC. YME1L exhibits significant upregulation in NPC tissues from patients and across various primary human NPC cells, while its expression remains relatively low in adjacent normal tissues and primary nasal epithelial cells. Employing genetic silencing through the shRNA strategy or knockout (KO) via the CRISPR-sgRNA method, we demonstrated that YME1L depletion disrupted mitochondrial function, leading to mitochondrial depolarization, reactive oxygen species (ROS) generation, lipid peroxidation, and ATP reduction within primary NPC cells. Additionally, YME1L silencing or KO substantially impeded cell viability, proliferation, cell cycle progression, and migratory capabilities, concomitant with an augmentation of Caspase-apoptosis activation in primary NPC cells. Conversely, ectopic YME1L expression conferred pro-tumorigenic attributes, enhancing ATP production and bolstering NPC cell proliferation and migration. Moreover, our findings illuminate the pivotal role of YME1L in Akt-mTOR activation within NPC cells, with Akt-S6K phosphorylation exhibiting a significant decline upon YME1L depletion but enhancement upon YME1L overexpression. In YME1L-silenced primary NPC cells, the introduction of a constitutively-active Akt1 mutant (caAkt1, at S473D) restored Akt-S6K phosphorylation, effectively ameliorating the inhibitory effects imposed by YME1L shRNA. In vivo studies revealed that intratumoral administration of YME1L-shRNA-expressing adeno-associated virus (AAV) curtailed subcutaneous NPC xenograft growth in nude mice. Furthermore, YME1L downregulation, concurrent with mitochondrial dysfunction and ATP reduction, oxidative injury, Akt-mTOR inactivation, and apoptosis induction were evident within YME1L-silenced NPC xenograft tissues. Collectively, these findings shed light on the notable pro-tumorigenic role by overexpressed YME1L in NPC, with a plausible mechanism involving the promotion of Akt-mTOR activation.
Topics: Humans; Nasopharyngeal Carcinoma; Animals; Nasopharyngeal Neoplasms; Cell Proliferation; Cell Line, Tumor; Mice; Mitochondria; Apoptosis; Mice, Nude; Reactive Oxygen Species; Proto-Oncogene Proteins c-akt; Cell Movement; Gene Expression Regulation, Neoplastic; TOR Serine-Threonine Kinases; Male; Adenosine Triphosphatases; Female; Signal Transduction
PubMed: 38890304
DOI: 10.1038/s41419-024-06811-6 -
Signal Transduction and Targeted Therapy Jun 2024Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related...
Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3-36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9-7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.
Topics: Humans; Male; Middle Aged; Female; Nasopharyngeal Carcinoma; Adult; Aged; Neoplasm Metastasis; Programmed Cell Death 1 Receptor; Antibodies, Monoclonal, Humanized; Nasopharyngeal Neoplasms; Immune Checkpoint Inhibitors
PubMed: 38890298
DOI: 10.1038/s41392-024-01865-6 -
BMJ Case Reports Jun 2024Actinomycosis is a rare endogenous infection characterised by indolent progression, contiguous spreading, abscess formation and draining sinuses. Here, we present a case...
Actinomycosis is a rare endogenous infection characterised by indolent progression, contiguous spreading, abscess formation and draining sinuses. Here, we present a case of causing a mediastinal abscess that is unique in its acuity and location. Our patient presented with worsening dysphagia, and CT of her chest revealed a new mass in the posterior mediastinum displacing the oesophagus. Oesophagram revealed mild motility disorder, but no masses or ulcers within the oesophagus. Oesophagogastroduodenoscopy with endoscopic ultrasound revealed extrinsic compression of the oesophagus. Fine-needle aspiration of the mass yielded purulent fluid, which was cultured. A single colony of was isolated. Initially, medical treatment was favoured, but as she developed worsening dysphagia, the abscess was drained. She continued on long-term antibiotic therapy after drainage and had complete resolution of the abscess at 1 year.
Topics: Humans; Female; Actinomycosis; Deglutition Disorders; Mediastinal Diseases; Immunocompromised Host; Diagnosis, Differential; Abscess; Anti-Bacterial Agents; Tomography, X-Ray Computed; Drainage; Middle Aged; Mediastinum
PubMed: 38890117
DOI: 10.1136/bcr-2023-258996 -
Journal of Otolaryngology - Head & Neck... 2024Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life...
A Descriptive Study of Quality of Life Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.
BACKGROUND
Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life (QOL). Transoral robotic surgery (TORS) has an established role in the management of early OPSCC but adjuvant treatment is often indicated postoperatively due to the high incidence of nodal metastasis associated with advanced human papillomavirus (HPV)-related OPSCC. To overcome the need for adjuvant radiation therapy (RT), neoadjuvant chemotherapy followed by TORS and neck dissection (ND) is proposed. This study aimed to assess if QOL in HPV-associated OPSCC receiving neoadjuvant chemotherapy followed by TORS and ND returns to baseline within 12 months of completing treatment.
METHODS
A 12 month longitudinal study was carried out at McGill University Health Centre in Montreal, Canada, among a convenience sample of patients with American Joint Committee on Cancer Seventh Edition stage III and IVa HPV-related OPSCC who were treated with neoadjuvant chemotherapy followed by TORS and ND. QOL data were obtained pretreatment and at 1, 3, 6, and 12 months following treatment completion using the European Organisation for Research and Treatment of Cancer Core and Head and Neck extension modules. Paired tests and mixed models for repeated measures analysis were used to assess changes in QOL from baseline to 12 months postoperatively and over time, respectively.
RESULTS
Nineteen of 23 patients (median age 58 years) who received the study treatment fulfilled the eligibility criteria. OPSCC subsites were palatine tonsil (n = 12) and base of tongue (n = 7). All 19 patients were treated per protocol and none required adjuvant RT as per pathology review and protocol requirements at a postoperative multidisciplinary team tumor board discussion. No significant differences were found when comparing 12 month QOL follow-up scores to pretreatment scores in measures that would likely be affected by RT [eg, swallowing ( = .7), social eating ( = .8), xerostomia ( = .9)].
CONCLUSION
In HPV-related OPSCC, neoadjuvant chemotherapy followed by TORS and ND as definitive treatment is associated with excellent QOL outcomes. Postoperative QOL scores returned to baseline by 3 months and were maintained for all measures, indicating a return to normal function.
Topics: Humans; Quality of Life; Robotic Surgical Procedures; Male; Middle Aged; Female; Oropharyngeal Neoplasms; Neoadjuvant Therapy; Papillomavirus Infections; Aged; Carcinoma, Squamous Cell; Longitudinal Studies; Neck Dissection; Chemotherapy, Adjuvant; Adult; Human Papillomavirus Viruses
PubMed: 38888957
DOI: 10.1177/19160216241248670 -
Journal of Cellular and Molecular... Jun 2024In patients with nasopharyngeal carcinoma (NPC), the alteration of immune responses in peripheral blood remains unclear. In this study, we established an immune cell...
In patients with nasopharyngeal carcinoma (NPC), the alteration of immune responses in peripheral blood remains unclear. In this study, we established an immune cell profile for patients with NPC and used flow cytometry and machine learning (ML) to identify the characteristics of this profile. After isolation of circulating leukocytes, the proportions of 104 immune cell subsets were compared between NPC group and the healthy control group (HC). Data obtained from the immune cell profile were subjected to ML training to differentiate between the immune cell profiles of the NPC and HC groups. We observed that subjects in the NPC group presented higher proportions of T cells, memory B cells, short-lived plasma cells, IgG-positive B cells, regulatory T cells, MHC II T cells, CTLA4 T cells and PD-1 T cells than subjects in the HC group, indicating weaker and compromised cellular and humoral immune responses. ML revealed that monocytes, PD-1 CD4 T cells, memory B cells, CTLA4 CD4 T cells and PD-1 CD8 T cells were strongly contributed to the difference in immune cell profiles between the NPC and HC groups. This alteration can be fundamental in developing novel immunotherapies for NPC.
Topics: Humans; Nasopharyngeal Carcinoma; Machine Learning; Flow Cytometry; Male; Female; Middle Aged; Nasopharyngeal Neoplasms; Adult; Programmed Cell Death 1 Receptor; CD8-Positive T-Lymphocytes; Case-Control Studies; Aged
PubMed: 38888489
DOI: 10.1111/jcmm.18404 -
Infection and Immunity Jun 2024The major gram-positive pathogen group A (GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics...
The major gram-positive pathogen group A (GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics have been ascribed to the emergence of clones producing increased amounts of key virulence factors such as streptolysin O (SLO). Herein, we sought to identify mechanisms underlying our recently identified temporal clonal emergence among GAS, given that emergent strains did not produce augmented levels of virulence factors relative to historic isolates. By creating and analyzing isoallelic strains, we determined that a conserved mutation in a previously undescribed gene encoding a putative carbonic anhydrase was responsible for the defective growth observed in the emergent strains. We also identified that the emergent strains survived better inside macrophages and killed macrophages at lower rates than the historic strains. the creation of isogenic mutant strains, we linked the emergent strain "survival" phenotype to the downregulation of the SLO encoding gene and upregulation of the operon which encodes proteins involved in defense against extracellular oxidative stress. Our findings are in accord with recent surveillance studies which found a high ratio of mucosal (i.e., pharyngeal) relative to invasive infections among GAS. Since ever-increasing virulence is unlikely to be evolutionarily advantageous for a microbial pathogen, our data further understanding of the well-described oscillating patterns of virulent GAS infections by demonstrating mechanisms by which emergent strains adapt a "survival" strategy to outcompete previously circulating isolates.
PubMed: 38888310
DOI: 10.1128/iai.00152-24 -
Microsurgery Jul 2024Total pharyngolaryngectomy is sometimes combined with total glossectomy for advanced hypopharyngeal or cervical esophageal cancers involving the tongue base. The optimal...
BACKGROUND
Total pharyngolaryngectomy is sometimes combined with total glossectomy for advanced hypopharyngeal or cervical esophageal cancers involving the tongue base. The optimal reconstruction method for total pharyngolaryngectomy with total glossectomy has not been established due to a considerable diameter mismatch between the floor of mouth and the esophageal stump. This report describes two reconstruction methods using free jejunal transfer.
METHODS
Five consecutive patients who underwent total pharyngolaryngectomy with total glossectomy were included, with a mean age of 67.0 (range 55-75) years. Primary tumors included tongue, hypopharyngeal, cervical esophagus, and laryngeal cancers. The mean defect size was 17.0 (16-19) × 6.8 (6-7) cm. Surgical techniques involved either a simple incision or a two-segment method to address the size mismatch between the jejunum and the floor of mouth. In the simple incision method, a longitudinal cut was made to the antimesenteric or paramesenteric border of a jejunum wall to expand the orifice. In the two-segment method, a jejunal graft was separated into two segments to reconstruct the floor of mouth and the cervical esophagus, and these segments were connected with a longitudinal incision to the cervical esophageal segment to form a funnel-shaped conduit.
RESULTS
Of the five patients, three underwent the simple incision method and two the two-segment method. Postoperative pharyngoesophagography showed a smooth passage for all patients. Postoperative courses were uneventful except for one flap loss due to arterial thrombosis. Four patients achieved oral feeding, while one became gastric-tube dependent. At a mean follow-up of 22.1 (4-39) months, one patient required tube feeding, two tolerated full liquid, and two consumed a soft diet.
CONCLUSIONS
Both the simple incision and two-segment methods achieved satisfactory swallowing function. The choice between these reconstruction methods may depend on the extent of resection of the posterior pharyngeal wall.
Topics: Humans; Middle Aged; Jejunum; Laryngectomy; Pharyngectomy; Male; Aged; Glossectomy; Plastic Surgery Procedures; Female; Free Tissue Flaps; Tongue Neoplasms; Hypopharyngeal Neoplasms; Treatment Outcome; Laryngeal Neoplasms
PubMed: 38887961
DOI: 10.1002/micr.31204