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Advances in Experimental Medicine and... 2024As for other mammals, the digestive system of dogs (facultative carnivores) and cats (obligate carnivores) includes the mouth, teeth, tongue, pharynx, esophagus,...
As for other mammals, the digestive system of dogs (facultative carnivores) and cats (obligate carnivores) includes the mouth, teeth, tongue, pharynx, esophagus, stomach, small intestine, large intestine, and accessory digestive organs (salivary glands, pancreas, liver, and gallbladder). These carnivores have a relatively shorter digestive tract but longer canine teeth, a tighter digitation of molars, and a greater stomach volume than omnivorous mammals such as humans and pigs. Both dogs and cats have no detectable or a very low activity of salivary α-amylase but dogs, unlike cats, possess a relatively high activity of pancreatic α-amylase. Thus, cats select low-starch foods but dogs can consume high-starch diets. In contrast to many mammals, the vitamin B (cobalamin)-binding intrinsic factor for the digestion and absorption of vitamin B is produced in: (a) dogs primarily by pancreatic ductal cells and to a lesser extent the gastric mucosa; and (b) cats exclusively by the pancreatic tissue. Amino acids (glutamate, glutamine, and aspartate) are the main metabolic fuels in enterocytes of the foregut. The primary function of the small intestine is to digest and absorb dietary nutrients, and its secondary function is to regulate the entry of dietary nutrients into the blood circulation, separate the external from the internal milieu, and perform immune surveillance. The major function of the large intestine is to ferment undigested food (particularly fiber and protein) and to absorb water, short-chain fatty acids (serving as major metabolic fuels for epithelial cells of the large intestine), as well as vitamins. The fermentation products, water, sloughed cells, digestive secretions, and microbes form feces and then pass into the rectum for excretion via the anal canal. The microflora influences colonic absorption and cell metabolism, as well as feces quality. The digestive tract is essential for the health, survival, growth, and development of dogs and cats.
Topics: Humans; Cats; Dogs; Animals; Swine; Cat Diseases; Dog Diseases; Mouth; Vitamins; Mammals; Starch; Water
PubMed: 38625523
DOI: 10.1007/978-3-031-54192-6_2 -
BMC Cancer Apr 2024Head and neck squamous cell carcinoma (HNSCC) represents a common and heterogeneous malignancy of the oral cavity, pharynx and larynx. Surgery and radio(chemo)therapy...
Partial recovery of peripheral blood monocyte subsets in head and neck squamous cell carcinoma patients upon radio(chemo)therapy is associated with decreased plasma CXCL11.
BACKGROUND
Head and neck squamous cell carcinoma (HNSCC) represents a common and heterogeneous malignancy of the oral cavity, pharynx and larynx. Surgery and radio(chemo)therapy are the standard treatment options and also have great influence on the composition of the tumor microenvironment and immune cell functions. However, the impact of radio(chemo)therapy on the distribution and characteristics of circulating monocyte subsets in HNSCC are not fully understood.
METHODS
Expression patterns of adhesion molecules and chemokine receptors CD11a (integrin-α L; LFA-1), CD11b (integrin-α M; Mac-1), CD11c (integrin-α X), CX3CR1 (CX3CL1 receptor) and checkpoint molecule PD-L1 (programmed cell death ligand-1) were investigated upon radio(chemo)therapeutic treatment using flow cytometry. Furthermore, comprehensive analysis of plasma cytokines was performed before and after treatment using ELISA measurements.
RESULTS
Our data reveal a partial recovery of circulating monocytes in HNSCC patients upon radio(chemo)therapeutic treatment, with differential effects of the individual therapy regimen. PD-L1 expression on non-classical monocytes significantly correlates with the individual plasma levels of chemokine CXCL11 (C-X-C motif chemokine 11).
CONCLUSIONS
Further comprehensive investigations on larger patient cohorts are required to elucidate the meaningfulness of peripheral blood monocyte subsets and chemokine CXCL11 as potential bioliquid indicators in HNSCC with regard to therapy response and the individual immunological situation.
Topics: Humans; Monocytes; B7-H1 Antigen; Squamous Cell Carcinoma of Head and Neck; Chemokine CXCL11; Head and Neck Neoplasms; Tumor Microenvironment
PubMed: 38609887
DOI: 10.1186/s12885-024-12177-x -
Cells Mar 2024Nasopharyngeal carcinoma (NPC) is a type of cancer that originates from the mucosal lining of the nasopharynx and can invade and spread. Although contemporary...
Nasopharyngeal carcinoma (NPC) is a type of cancer that originates from the mucosal lining of the nasopharynx and can invade and spread. Although contemporary chemoradiotherapy effectively manages the disease locally, there are still challenges with locoregional recurrence and distant failure. Therefore, it is crucial to have a deeper understanding of the molecular basis of NPC cell movement in order to develop a more effective treatment and to improve patient survival rates. Cancer cell line models are invaluable in studying health and disease and it is not surprising that they play a critical role in NPC research. Consequently, scientists have established around 80 immortalized human NPC lines that are commonly used as in vitro models. However, over the years, it has been observed that many cell lines are misidentified or contaminated by other cells. This cross-contamination leads to the creation of false cell lines that no longer match the original donor. In this commentary, we discuss the impact of misidentified NPC cell lines on the scientific literature. We found 1159 articles from 2000 to 2023 that used NPC cell lines contaminated with HeLa cells. Alarmingly, the number of publications and citations using these contaminated cell lines continued to increase, even after information about the contamination was officially published. These articles were most commonly published in the fields of oncology, pharmacology, and experimental medicine research. These findings highlight the importance of science policy and support the need for journals to require authentication testing before publication.
Topics: Humans; Nasopharyngeal Carcinoma; HeLa Cells; Nasopharyngeal Neoplasms; Cell Line, Tumor; Neoplasm Recurrence, Local; Nasopharynx
PubMed: 38606998
DOI: 10.3390/cells13070559 -
Journal of Sleep Research Apr 2024Obstructive sleep apnea (OSA) is common in sickle cell disease (SCD) despite the absence of overweight, suggesting a specific pathophysiology. We previously showed that...
Obstructive sleep apnea (OSA) is common in sickle cell disease (SCD) despite the absence of overweight, suggesting a specific pathophysiology. We previously showed that otherwise healthy children with increased pharyngeal compliance, a main endotype of OSA, exhibited decreased sympathetic modulation. Our objective was to assess whether modifications of heart rate variability (HRV) and compliance are associated in SCD. Cases (children with SCD, African or Caribbean ethnicity) and controls (otherwise healthy children, same ethnicity), aged 4-18 years, were selected from our database of children referred for OSA and matched for sex, age, and obstructive apnea-hypopnoea index (OAHI) score. The children underwent polysomnography and acoustic pharyngometry (to compute compliance). HRV analyses were performed from 5 min ECG recordings in wakeful, NREM, and REM sleep states and from the whole night. Twenty-one pairs were analysed (median age 10.5 years, 24 girls). Children with SCD had lower BMI z-scores and more tonsil hypertrophy than control children. Children with SCD and OSA (OAHI ≥2/hour) were characterised by lower compliance than children with SCD without OSA. An inverse relationship between compliance and SD2 (HRV from whole night, inversely related to sympathetic modulation) was evidenced (negative relationship in SCD: R = -0.63, p = 0.002 vs. positive relationship in controls R = 0.59, p = 0.006). In conclusion, while the decrease in sympathetic modulation in control children may contribute to increasing pharyngeal compliance, its decrease seems protective in children with sickle cell disease, which underlines the specificity of OSAS pathophysiology in SCD that could be due to sickle cell disease related smooth muscle dystonia.
PubMed: 38590226
DOI: 10.1111/jsr.14209 -
European Archives of... Jul 2024Adenoidectomy is one of the most commonly performed surgeries in pediatric otolaryngological practice. This prospective study compared three different adenoidectomy... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVES
Adenoidectomy is one of the most commonly performed surgeries in pediatric otolaryngological practice. This prospective study compared three different adenoidectomy techniques' intra-operative and postoperative outcomes in pediatric patients. The techniques evaluated were classical (blind curettage), coblation, and a combined approach.
MATERIALS AND METHODS
Ninety pediatric patients undergoing adenoidectomy were enrolled in the study. The patients were divided into three groups based on the technique used: Group A, classical adenoidectomy (blind curettage); Group B, coblation adenoidectomy and Group C, combined (blind curettage + coblation) adenoidectomy. The intra-operative time, degree of bleeding, and complications during and after the operations were recorded.
RESULTS
Group A had a significantly shorter operative time than the other groups. However, there was no significant difference in the mean operative time between Groups B and C. The mean amount of intra-operative bleeding differed significantly among the groups. Group B had significantly less bleeding than Group A or Group C. The amount of bleeding also differed significantly between Groups A and C. The postoperative pain scores did not differ significantly among the groups. While complications were infrequent in all groups, Group C did not exhibit a higher complication rate than Groups A and B. The absence of residual or recurrent adenoid tissue in any of the groups during long-term follow-up examinations highlights the effectiveness of all three adenoidectomy techniques in preventing adenoid regrowth.
CONCLUSIONS
The combined approach, which was one of the techniques studied, demonstrated an intermediate profile in terms of operative time and intra-operative bleeding compared to the classical and coblation techniques. These findings suggest that this combined approach may be a feasible option for adenoidectomy in pediatric patients, considering its similar low incidence of postoperative complications.
Topics: Humans; Adenoidectomy; Prospective Studies; Female; Male; Child; Child, Preschool; Single-Blind Method; Operative Time; Treatment Outcome; Postoperative Complications; Blood Loss, Surgical; Curettage; Adenoids
PubMed: 38581574
DOI: 10.1007/s00405-024-08617-w -
International Journal of Radiation... Apr 2024Recurrent head and neck cancer presents a therapeutic challenge because of cumulative toxicity from initial radiation therapy, limiting reirradiation options. Boron...
Clinical Results and Prognostic Factors in Boron Neutron Capture Therapy for Recurrent Squamous Cell Carcinoma of the Head and Neck Under the Japan National Health Insurance System: A Retrospective Study of the Initial 47 Patients.
PURPOSE
Recurrent head and neck cancer presents a therapeutic challenge because of cumulative toxicity from initial radiation therapy, limiting reirradiation options. Boron neutron capture therapy (BNCT) offers a promising alternative, selectively delivering a radical dose to tumors while sparing adjacent normal tissue. This study investigates the initial clinical outcomes and prognostic factors associated with BNCT for recurrent squamous cell carcinoma of the head and neck.
METHODS AND MATERIALS
This retrospective analysis investigated the initial 47 patients treated with BNCT between May 2020 and February 2021 in Japan. All patients had received radiation therapy with a median dose of 70 Gy (range, 44-176) before BNCT. Median tumor size was 11 cm (range, 1-117 cm), with 23% of tumors larger than 30 cm, and 87% of patients had prior systemic therapy. The most common prescribed dose to the pharyngeal mucosa was 15 Gy-Eq (36%), followed by 18 Gy-Eq (34%). The minimum dose given to tumor was 27.4 Gy-Eq (range, 13.3-45.2). In 23 patients, F-fluoro-borono-phenylalanine positron emission tomography was performed within 1 week before BNCT, and the tumor-to-blood B ratio was 3.5 (range, 2.0-8.7).
RESULTS
Efficacy analysis revealed a 51% complete response rate and a 74% overall response rate. Disease-free survival rates at 1 and 2 years were 34.6% and 26.6%, respectively. Overall survival rates at 1 and 2 years were 86.1% and 66.5%, respectively. Multivariate analysis revealed that, among the patient characteristics, whether the lesion was mucosal had a significant effect on achieving complete response.
CONCLUSIONS
This study provided valuable insights into the early integration of BNCT into routine clinical practice, highlighting its efficacy and safety. Technical improvements are needed to ensure precise dose administration. Ongoing prospective studies, such as the phase II REBIVAL study, will further elucidate the role of BNCT in recurrent head and neck cancer.
PubMed: 38580084
DOI: 10.1016/j.ijrobp.2024.03.041 -
The American Journal of Tropical... Jun 2024A 2-year-old boy presented to Kapsowar Mission Hospital in Kenya with a history of general tiredness associated with mild, unilateral epistaxis and one episode of...
A 2-year-old boy presented to Kapsowar Mission Hospital in Kenya with a history of general tiredness associated with mild, unilateral epistaxis and one episode of hematemesis. On admission, he had a hemoglobin value of 3.5 g/dL, with a white cell count of 20.6 × 109/L. The child was examined by the physician on call, with no source of bleeding found. Later that day, after a local physician noted that the presentation could be due to an unrecognized leech infestation, a deep examination of the oropharynx was performed with a laryngoscope and revealed a leech attached deep in the oropharynx. The anesthetist visualized the leech with a laryngoscope and removed it with Magill forceps. After the procedure and blood transfusion, the child's hemoglobin level improved to 10.4 g/dL, and on the following day, the child was much improved in energy and was playing outside. He was discharged home on iron supplements and made a full recovery.
Topics: Male; Humans; Animals; Child, Preschool; Leeches; Oropharynx; Anemia; Blood Transfusion
PubMed: 38574555
DOI: 10.4269/ajtmh.23-0677 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Apr 2024To explore the selection, efficacy and application of indications for parapharyngeal space tumor resection assisted by plasma and HD endoscopic system through oral...
To explore the selection, efficacy and application of indications for parapharyngeal space tumor resection assisted by plasma and HD endoscopic system through oral approach. The clinical data of 23 patients with parapharyngeal space tumor resection assisted by plasma and HD endoscopic system were retrospectively analyzed in Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hospital of Bengbu Medical University from January 2013 to June 2023. All cases were examined by high-resolution CT and MRI before operation, and some cases were examined by CTA or DSA. During the operation, the high definition nasal endoscopic recording system was assisted, and low temperature plasma knife was used in some cases. The follow-up time was from 3 to 115 months, and the median follow-up time was 45 months. There were no deaths in this group. All patients had complete tumor resection. The maximum tumor diameter was as follows: (5.20±1.00) cm, the operation time was(128.70±46.67) min, and the average blood loss was(80.87±32.74) mL. One case of vascular smooth muscle tumor had more bleeding during the operation and was assisted by tracheotomy after operation. One case of nourishing vascular bleeding after operation of giant Schwannoma was investigated and hemostasis + external carotid artery ligation. Bleeding in the remaining cases was below 120 mL. Postoperative pathologies were all benign tumors, including 11 pleomorphic adenoma, 4 schwannoma, 2 base cell adenoma, 1 epidermoid cyst, 1 lymphatic cyst with infection, 1 angiomyoma, 1 solitary fibroma, 1 salivary gland cyst, and 1 tendon giant cell tumor. All patients were followed up. One patient originating from vagal schwannoma had 2-month vocal cord paralysis and 1 recurrence(recurrence of the skull base of schwannoma). Oral approach assisted by plasma and high-definition endoscopic system is suitable for partial selective resection of benign tumors in parapharyngeal space, which has the advantages of less trauma and rapid recovery. When the tumor is blood-rich, suspected to be malignant, the top of the tumor is deep into the cranial base nerve canal,located outside the internal carotid artery, and larger than 6.0 cm considering pleomorphic adenoma, it is recommended to conduct an external open or auxiliary cervical small incision approach.
Topics: Humans; Adenoma, Pleomorphic; Endoscopy; Neurilemmoma; Parapharyngeal Space; Pharyngeal Neoplasms; Retrospective Studies
PubMed: 38563172
DOI: 10.13201/j.issn.2096-7993.2024.04.007 -
The Lancet. Oncology May 2024Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of... (Randomized Controlled Trial)
Randomized Controlled Trial
Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial.
BACKGROUND
Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of pembrolizumab to concurrent chemoradiotherapy for locally advanced HNSCC.
METHODS
In the randomised, double-blind, phase 3 KEYNOTE-412 trial, participants with newly diagnosed, high-risk, unresected locally advanced HNSCC from 130 medical centres globally were randomly assigned (1:1) to pembrolizumab (200 mg) plus chemoradiotherapy or placebo plus chemoradiotherapy. Randomisation was done using an interactive response technology system and was stratified by investigator's choice of radiotherapy regimen, tumour site and p16 status, and disease stage, with participants randomly assigned in blocks of four per stratum. Participants, investigators, and sponsor personnel were masked to treatment assignments. Local pharmacists were aware of assignments to support treatment preparation. Pembrolizumab and placebo were administered intravenously once every 3 weeks for up to 17 doses (one before chemoradiotherapy, two during chemoradiotherapy, 14 as maintenance therapy). Chemoradiotherapy included cisplatin (100 mg/m) administered intravenously once every 3 weeks for two or three doses and accelerated or standard fractionation radiotherapy (70 Gy delivered in 35 fractions). The primary endpoint was event-free survival analysed in all randomly assigned participants. Safety was analysed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03040999, and is active but not recruiting.
FINDINGS
Between April 19, 2017, and May 2, 2019, 804 participants were randomly assigned to the pembrolizumab group (n=402) or the placebo group (n=402). 660 (82%) of 804 participants were male, 144 (18%) were female, and 622 (77%) were White. Median study follow-up was 47·7 months (IQR 42·1-52·3). Median event-free survival was not reached (95% CI 44·7 months-not reached) in the pembrolizumab group and 46·6 months (27·5-not reached) in the placebo group (hazard ratio 0·83 [95% CI 0·68-1·03]; log-rank p=0·043 [significance threshold, p≤0·024]). 367 (92%) of 398 participants treated in the pembrolizumab group and 352 (88%) of 398 participants treated in the placebo group had grade 3 or worse adverse events. The most common grade 3 or worse adverse events were decreased neutrophil count (108 [27%] of 398 participants in the pembrolizumab group vs 100 [25%] of 398 participants in the placebo group), stomatitis (80 [20%] vs 69 [17%]), anaemia (80 [20%] vs 61 [15%]), dysphagia (76 [19%] vs 62 [16%]), and decreased lymphocyte count (76 [19%] vs 81 [20%]). Serious adverse events occurred in 245 (62%) participants in the pembrolizumab group versus 197 (49%) participants in the placebo group, most commonly pneumonia (43 [11%] vs 25 [6%]), acute kidney injury (33 [8%] vs 30 [8%]), and febrile neutropenia (24 [6%] vs seven [2%]). Treatment-related adverse events led to death in four (1%) participants in the pembrolizumab group (one participant each from aspiration pneumonia, end-stage renal disease, pneumonia, and sclerosing cholangitis) and six (2%) participants in the placebo group (three participants from pharyngeal haemorrhage and one participant each from mouth haemorrhage, post-procedural haemorrhage, and sepsis).
INTERPRETATION
Pembrolizumab plus chemoradiotherapy did not significantly improve event-free survival compared with chemoradiotherapy alone in a molecularly unselected, locally advanced HNSCC population. No new safety signals were seen. Locally advanced HNSCC remains a challenging disease that requires better treatment approaches.
FUNDING
Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.
Topics: Humans; Antibodies, Monoclonal, Humanized; Double-Blind Method; Chemoradiotherapy; Male; Squamous Cell Carcinoma of Head and Neck; Female; Middle Aged; Aged; Head and Neck Neoplasms; Antineoplastic Agents, Immunological; Progression-Free Survival; Adult
PubMed: 38561010
DOI: 10.1016/S1470-2045(24)00100-1 -
Science Advances Mar 2024The pharyngeal endoderm, an innovation of deuterostome ancestors, contributes to pharyngeal development by influencing the patterning and differentiation of pharyngeal...
The pharyngeal endoderm, an innovation of deuterostome ancestors, contributes to pharyngeal development by influencing the patterning and differentiation of pharyngeal structures in vertebrates; however, the evolutionary origin of the pharyngeal organs in vertebrates is largely unknown. The endostyle, a distinct pharyngeal organ exclusively present in basal chordates, represents a good model for understanding pharyngeal organ origins. Using Stereo-seq and single-cell RNA sequencing, we constructed aspatially resolved single-cell atlas for the endostyle of the ascidian . We determined the cell composition of the hemolymphoid region, which illuminates a mixed ancestral structure for the blood and lymphoid system. In addition, we discovered a cluster of hair cell-like cells in zone 3, which has transcriptomic similarity with the hair cells of the vertebrate acoustico-lateralis system. These findings reshape our understanding of the pharynx of the basal chordate and provide insights into the evolutionary origin of multiplexed pharyngeal organs.
Topics: Animals; Urochordata; Pharynx; Vertebrates; Biological Evolution; Cell Differentiation
PubMed: 38552007
DOI: 10.1126/sciadv.adi9035