Αρχειοθήκη ιστολογίου

Κυριακή 13 Ιουνίου 2021

Expression of cathepsins B and D by cancer stem cells in head and neck metastatic malignant melanoma

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We have previously demonstrated cancer stem cell (CSC) subpopulations in head and neck metastatic malignant melanoma (HNmMM), and the expression of components of the renin–angiotensin system (RAS) by these CSCs. Cathepsins B, D and G are involved in carcinogenesis and constitute bypass loops of the RAS . This study investigated the expression and localization of cathepsins B, D and G, in relation to these CSCs. Immunohistochemical staining demonstrated expression of cathepsins B, D and G in HNmMM sections from all 20 patients. Western blotting confirmed the presence of cathepsins B and D proteins in all six HNmMM tissue samples and four HNmMM-derived primary cell lines. RT-qPCR showed transcript expression of cathepsins B, D and G in all six HNmMM tissue samples, and cathepsins B and D but not cathepsin G in all four HNmMM-derived primary cell lines. Enzymatic activity assays demonstrated cathepsins B and D were active in all six HNmMM tissue samples. Immunofluorescence staining performed on two of the HNmMM tissue samples demonstrated expression of cathepsins B and D by the CSCs, and cathepsin G by cells within the peritumoral. Our novel findings suggest the possibility of targeting these CSCs by modulation of paracrine RAS signaling. Received 14 January 2021 Accepted 2 May 2021 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to Swee T. Tan, MBBS, FRACS, PhD, Gillies McIndoe Research Institute, PO Box 7184, Newtown, Wellington 6242, New Zealand, Tel: +64 (0) 4 2820366; e-mail: swee.tan@gmri.org.nz Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Nasal Mucociliary Clearance in Prolonged Tracheostomy Patients: A Prospective Case–Control Study

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Abstract

Prolonged tracheostomy bypasses the upper airways leading to absence or reduction of nasal airflow. This altered nasal physiology not only impairs olfaction but also may cause mucociliary dysfunction and consequent nasal crusting and rhinosinusitis.To objectively evaluate the extent of nasal mucociliary impairment in patients with prolonged duration of tracheostomy.This is a prospective case–control study done in a tertiary care center wherein the nasal mucocilary function was assessed by saccharin test in patients who were tracheostomized for a period of more than 4 weeks and the saccharin transit time (time taken to appreciate the sweet taste after endoscopic insertion of saccharin pellet on anterior end of inferior turbinate) was compared by the same test in age and sex matched healthy individuals. The saccharin transit time in the two groups was statistically analyzed using student t-test. Mean saccharin transit time in 30 patients with prolonged trach eostomy was 934.97 s with a standard deviation of 75.95 s whereas in 30 controls, the meantime was 447.4 s with a standard deviation of 63.22 s, which was statistically significant (p < 0.001). Conclusion Prolonged duration of tracheostomy leads to impaired nasal mucociliary clearance, which in turn could cause chronic rhinosinusitis.

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Impact of Adjuvant Medical Therapies on Surgical Outcomes in Idiopathic Subglottic Stenosis

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Objectives/Hypothesis

Adjuvant medications including proton pump inhibitors (PPI), antibiotics (trimethoprim/sulfamethoxazole [TMP-SMX]), and inhaled corticosteroids (ICS) may be prescribed for patients with idiopathic subglottic stenosis (iSGS). We describe medication use with endoscopic dilation (ED) or endoscopic resection with medical treatment (ERMT) and evaluate impact on outcomes.

Study Design

International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS.

Methods

Post hoc secondary analysis of prospectively collected North American Airway Collaborative data on outcomes linked with adjuvant medication utilization. Primary outcome was time to recurrent operation, evaluated using Kaplan–Meier curves and Cox regression analysis. Secondary outcomes of change in peak expiratory flow (PEF) and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score over 12 months were compared.

Results

Sixty-one of 129 patients undergoing ED received PPI (47%), and 10/143 patients undergoing ED received ICS (7%). TMP-SMX was used by 87/115 patients (76%) undergoing EMRT. PPI use in the ED group did not affect time to recurrence (hazard ratio [HR] = 1.00, 95% confidence interval [CI]: 0.53–1.88; P = .99) or 12-month change in PEF (L/min) (median [interquartile range], 12.0 [10.7–12.2] vs. 8.7 [−5.1 to 24.9]; P = .59), but was associated with 12-month change in CCQ (−0.05 [−0.97 to 0.75] vs. −0.50 [−1.60 to 0.20]; P = .04). ICS did not affect outcome measures. TMP-SMX use in ERMT did not affect time to recurrence (HR = 0.842, 95% CI: 0.2345–3.023; P = .79), PEF at 12 months (75 [68–89] vs. 81 [68–89]; P = .92), or 12-month change in CCQ (0.20 [−1.05 to 0.47] vs. −0.30 [−1.00 to 0.10]; P = .45).

Conclusion

There is no standard practice for prescribing adjuvant medications. These data do not support that adjuvant medications prolong time to recurrence or increase PEF. Patients with iSGS and gastroesophageal reflux disease may experience some symptom benefit with PPI.

Level of evidence

Level 3 Laryngoscope, 2021

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Predictors of Respiratory Dysfunction at Diagnosis of Robin Sequence

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Objectives/Hypothesis

Robin sequence (RS) consists of associated micrognathia, glossoptosis, and respiratory dysfunction, with or without cleft palate. Studies on how different patient characteristics impact the severity of respiratory dysfunction are scarce and contradictory; this study investigates how different features affect respiratory obstruction severity at diagnosis of RS in controlled analysis.

Study Design

Retrospective cohort study that enrolled 71 RS patients under 90 days old who received care in our institution from 2009 to 2020.

Methods

The primary outcome, respiratory dysfunction, was categorized into four severity groups and analyzed using a multinomial logistic regression model that considered age, sex, mandible length, cleft palate, syndromic diagnosis, other airway anomalies, and degree of glossoptosis.

Results

Mandible length, syndromic diagnosis, and Yellon grade 3 glossoptosis were related to poorer respiratory outcomes (need for respiratory support). In univariate analysis, for each additional 1 mm of mandible length at diagnosis, a mean reduction of 28% in the risk of needing respiratory support was observed (OR = 0.72; 0.58–0.89); syndromic diagnosis and grade 3 glossoptosis also raised the risk (OR = 6.50; 1.59–26.51 and OR = 12.75; 1.03–157.14, respectively). In multivariate analysis, only mandible length significantly maintained its effects (OR = 0.73; 0.56–0.96), a 27% reduction.

Conclusions

Mandible length was an independent predictor for more severe respiratory dysfunction in RS patients, with larger mandibles showing protective effects. Syndromic diagnosis and Yellon grade 3 glossoptosis are also likely to be associated with poorer respiratory outcomes, although this was not demonstrated in multivariate analysis.

Level of Evidence

4 Laryngoscope, 2021

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Reliability of the ‘M-Line’ in the Prediction of the Facial Nerve Position in Patients with Parotid Neoplasms

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Abstract

Preoperative radiological assessment of parotid tumours represents a crucial step in the planning of a parotidectomy in order to avoid post-operative facial nerve paralysis. The purpose of this study is to determine the reliability of the novel 'M-line' in predicting the facial nerve position and compare it to various radiological methods in the same context. 66 patients whom had underwent parotidectomy for parotid tumours from January 2012 to February 2021 were analyzed. Parotid tumour location were identified using the retromandibular vein, facial nerve line, Conn's arc, Utrecht line and the 'M'-line were compared to the intraoperative location of parotid tumours.The 'M'-line is a novel hypothetical line (drawn between the lateral surface of the mandible to the lateral border of the mastoid process) used to identify the location of the facial nerve radiologically. The 'M-Line' and other methods of radiological assessments were associated with statistical significance in predicting if the parotid tumours were superficial or deep to the facial nerve (p-value < 0.05).The 'M-line' had demonstrated a sensitivity of 73.6% and 92.3% specificity.It had also yielded the highest accuracy (77.3%) in the prediction of the parotid tumour location in relation to the facial nerve. While the radiological lines represented by the Retromandibular vein,facial nerve line,Utrecht line and Conn's arc were statistically significant in predicting the location of the parotid tumour in relation to the facial nerve, the M-line was the most accurate and sensitive predictor in our study.The M-Line is a potentially useful tool to predict the location of the facial nerve in relation to a parotid tumour.

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Πέμπτη 10 Ιουνίου 2021

Low-grade (polymorphous) adenocarcinoma of the middle ear mimicking a jugulotympanic paraganglioma

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Via hno

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HNO. 2021 Jun 7. doi: 10.1007/s00106-021-01028-x. Online ahead of print.

ABSTRACT

A 64-year-old female patient presented with otalgia and hearing loss in the right ear. On otoscopy, the right tympanic membrane was highly vascularized and bulged into the anteroinferior quadrant. High-resolution computed tomography revealed an osteolytic lesion with occupation of the hypotympanum extending into the petrous apex and right parapharyngeal space as well as infiltration of the wall of the right internal carotid artery. MRI strengthened the suspicion of a jugulotympanic paraganglioma. The biopsy material obtained through exploratory tympanotomy was assessed as a low-grade polymorphic adenocarcinoma. The tumor was treated with definitive chemoradiotherapy. Posttherapeutic imaging after 4 months did not show any evidence of tumor progression.

PMID:34097084 | DOI:10.1007/s00106-021-01028-x

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Received dose variability after administration of I-131 for treatment of hyperthyroidism in cats

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J Vet Intern Med. 2021 Jun 6. doi: 10.1111/jvim.16185. Online ahead of print.

ABSTRACT

BACKGROUND: Injectable radioactive iodine (I-131) frequently is used to treat hyperthyroidism in cats. In human medicine, residual activity after injection of radionuclides has been reported, and the actual quantity administered is recorded after administration.

OBJECTIVE: Our aim was to evaluate actual administered dose variability after administration of preprepared I-131 single unit dose s for the treatment of hyperthyroidism in cats.

ANIMALS: Twenty-seven cats with hyperthyroidism treated with I-131 between April 2017 and March 2019.

METHODS: Retrospective observational study of cats treated with preprepared single unit I-131 doses. For each dose, the measured activity before administration and residual activity were recorded. The measured dose and the actual dose administered were compared to the prescribed dose.

RESULTS: Measured activity before administration ranged from 88.4% to 103.3% of the prescribed dose. Mean residual activity was 5.2 ± 3.0 MBq (ranging from 1.5% to 15% of the prescribed dose). The actual dose administered (measured activity - residual activity) ranged from 79.1% to 100.2% of the prescribed dose. Seventeen of 28 (60.7%) of the actual administered doses differed between 10% and 20% of the prescribed dose. One administered dose had a >20% difference compared to the prescribed dose (79.10% of the prescribed dose).

CONCLUSION AND CLINICAL IMPORTANCE: Our study identified variability in the residual and actual administered activity of I-131 as compared to the prescribed dose, which should be taken into consideration when treating cats with (predrawn) I-131.

PMID:34096090 | DOI:10.1111/jvim.16185

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Effects of Superomedial Partial Arytenoidectomy on Incomplete Posterior Glottal Closure Caused by Arytenoid Positional Asymmetry in Excised Human Larynges

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To analyze the effects that arytenoid positional asymmetry has on posterior glottic closure and to determine whether superomedial partial arytenoidectomy (SPA) can provide a benefit in cases of such asymmetry.
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Assessment of Subjective and Objective Voice Analysis According to Types of Sulcus Vocalis

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Sulcus vocalis (SV) subtypes are difficult to diagnose. Non-invasive techniques are sometimes not feasible in the diagnosis. The study aims to demonstrate the effectiveness and applicability of objective and subjective voice analysis combined with videolaryngostroboscopic examination (VLS) in the diagnosis of SV types.
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C-C motif chemokine ligand 14 inhibited colon cancer cell proliferation and invasion through suppressing M2 polarization of tumor-associated macrophages

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Histol Histopathol. 2021 Jun 7:18348. doi: 10.14670/HH-18-348. Online ahead of print.

ABSTRACT

BACKGROUND: Colon cancer is one of the most common cancers with a high incidence and high mortality. Chemokines play a crucial role in the development of cancer.

METHODS: Here, qRT-PCR was performed to detect gene expression. Western blot and immunohistochemistry were implemented to examine the expression of C-C motif chemokine ligand 14 (CCL14) in colon tumors. Besides, the expression of CD68 and CD206 in tumors was measured by immunohistochemistry. The percentages of M1- and M2-polarized macrophages were detected by flow cytometry. Furthermore, CCK-8 assay was performed to detect cell proliferation, and Transwell assay for cell invasion.

RESULTS: CCL14 was decreased in both colon tumors and colon cancer cells, and many tumor-associated macrophages (TAMs) infiltrated into the tumor. An increase CCL14 inhibited colon cancer cell p roliferation. Importantly, CCL14 promoted THP-1 to M1 polarization induced by LPS and IFN-γ, and inhibited THP-1 to M2 polarization induced by IL-4 and IL-13. Besides, CCL14 enhanced the inhibition of M1-polarized macrophages to colon cancer cell proliferation and invasion, but reversed the promotion of M2-polarized macrophages to cell proliferation and invasion.

CONCLUSION: Our data demonstrated that CCL14 inhibited the proliferation and invasion of colon cancer cells through suppressing the formation of M2-like TAMs.

PMID:34096611 | DOI:10.14670/HH-18-348

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Changes in metabolic syndrome status and risk of laryngeal cancer: A nationwide cohort study

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by Hyun-Bum Kim, Geun-Jeon Kim, Kyung-do Han, Young-Hoon Joo

Background

Whether dynamic changes of metabolic syndrome (MetS) affects the subsequent laryngeal cancer occurrence remains unknown.

Objective

This study investigated the effects of changes of MetS on the incidence of laryngeal cancer due to a lack of knowledge regarding the development of MetS in Korean population.

Methods

A total of 6,757,048 individuals who received national health checkup in 2009 and follow-up health examination in 2011 were analyzed and followed up until 2018. MetS status included the following categories: MetS-chronic (n = 941,609), MetS-developed (n = 614,229), MetS-recovery (n = 455,835), and MetS-free (n = 4,745,375).

Results

With a median follow-up duration of 6.403 years, 1,350 subjects were newly diagnosed with laryngeal cancer. Compared to participants without MetS, adjusted hazard ratios (HR) (95% confidence interval) for those with MetS were 1.320 (1.17–1.489) for laryngeal cancer. The HR of laryngeal cancer was found to be inc reased with increasing number of MetS components. The MetS-developed group had a significantly higher risk of laryngeal cancer than the MetS-free group (HR: 1.296; 95% CI: 1.093–1.537). The MetS-recovery group within two years also had an increased risk of laryngeal cancer compared with the MetS-free group (HR: 1.220; 95% CI: 1.008–1.476). Among MetS components, abdominal obesity had the highest risk of laryngeal cancer (HR: 1.374; 95% CI: 1.123–1.681).

Conclusion

Changes in MetS status were associated with the risk of laryngeal cancer. Results of this study have implications for etiological investigations and prevention strategies.

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