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Objective:Apart from its role as an inhibitory neurotransmitter, γ-aminobutyric acid is also thought to regulate various stages of cell proliferation and differentiation in the brain and periphery. The present study aimed to assess the levels of γ-aminobutyric acid and its biochemical precursor glutamic acid (glutamate) in benign parotid tumours and in unstimulated parotid saliva.Method:Unstimulated parotid saliva was collected bilaterally, using the swab method, in 20 patients with unilateral pleomorphic adenoma or Warthin's tumour. Samples of tumour and adjacent salivary tissue were collected during tumour resection.Results:Concentrations of γ-aminobutyric acid and glutamate, but not aspartate, were significantly higher in the tumour tissue than in the non-tumour tissue. There was no significant difference in salivary concentrations of γ-aminobutyric acid, glutamate or aspartate, comparing the involved and non-involved side.Conclusion:The present results provide preliminary evidence that γ-aminobutyric acid may be involved in the growth of benign parotid tumours. [ABSTRACT FROM PUBLISHER]

1. Abstract Background Rhabdomyosarcoma is a solid tumor, resulting from dysregulation of the skeletal myogenesis program. For rhabdomyosarcomas (RMS) with a predilection for the head and neck, genitourinary tract, extremities, trunk, retroperitoneum, the larynx is still an unusual site. Till now only several cases of this laryngeal tumor have been described in world literature in the adult population. The entire spectrum of genetic factors underlying RMS development and progression is unclear until today. Multiple signaling pathways seem to be involved in ERMS development and progression. Case presentation In this paper we report an interesting RMS case in which the disease was located within the glottic region. We report an embryonal rhabdomyosarcoma of the larynx in 33 year-old man. After unsuccessful chemotherapy hemilaryngectomy was performed. In follow up CT no signs of recurrence were found. Recently patient is recurrence free for 62 months. Conclusions Considering the histological diagnosis and the highly aggressive nature of the lesion for optimal diagnosis positron electron tomography (PET) and computerized tomography (CT) of the neck and thorax should be performed. At this time surgical treatment with adjuvant radiotherapy seems to be the treatment of choice for this disease. Rhabdomyosarcoma of the larynx has a better prognosis than elsewhere in the body, probably because of its earlier recognition and accessibility to radical surgery.

Abstract Vulvar squamous cell carcinoma (VSCC) is a rare female genital neoplasm. Although numerous molecular changes have been reported in VSCC, biomarkers of clinical relevance are still lacking. On the other hand, there is emerging evidence on the use of mtDNA as a diagnostic tool in oncology. In order to investigate mtDNA status in VSCC patients, haplogroup distribution analysis and D-loop sequencing were performed. The results were compared with available data for the general Polish population, cancer free-centenarians as well as patients with endometrial and head and neck cancer. The obtained data were also compared with the current status of mitochondrial databases. Significant differences in haplogroup distribution between VSCC cohort, general Polish population and cancer-free centenarians cohort were found. Moreover, a correlation between the VSCC patients haplogroup and HPV status was observed. Finally, a specific pattern of mtDNA polymorphisms was found in VSCC. Our results suggest that the mitochondrial genetic background may influence the risk of VSCC occurrence as well as susceptibility to HPV infection.

Abstract Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources of data for systematic review, meta-analysis, or finally for establishment of clinically applicable markers. In this review technical and conceptual errors commonly occurring in the literature are summarized. In the first place we discuss, why many of the published papers cannot be used as a valid and clinically useful sources of evidence in the biomedical and healthcare contexts. The reasons for introduction of noise in data and in consequence - bias for the interpretation of the role of mitochondrial DNA in the complex process of tumorigenesis are listed. In the second part of the text practical aspects of mtDNA research and requirements necessary to fulfill in order to use mtDNA analysis in clinics are shown. Stringent methodological criteria of a case-controlled experiment in molecular medicine are indicated. In the third part we suggest, what lessons can be learned for the future and propose guidelines for mtDNA analysis in oncology. Finally we conclude that, although several conceptual and methodological difficulties hinder the research on mitochondrial patho-physiology in cancer cells, this area of molecular medicine should be considered of high importance for future clinical practice.

Background: Heart rate is an essential diagnostic parameter indicating a patient's condition. The assessment of heart rate is also a crucial parameter in the diagnostics of various sleep disorders, including sleep apnoea, as well as sleep/wake pattern analysis. It is usually measured using an electrocardiograph (ECG)-a device monitoring the electrical activity of the heart using several electrodes attached to a patient's upper body-or photoplethysmography (PPG)., Methods: The following paper investigates an alternative method for heart rate detection and monitoring that operates on tracheal audio recordings. Datasets for this research were obtained from six participants along with ECG Holter (for validation), as well as from fifty participants undergoing a full night polysomnography testing, during which both heart rate measurements and audio recordings were acquired., Results: The presented method implements a digital filtering and peak detection algorithm applied to audio recordings obtained with a wireless sensor using a contact microphone attached in the suprasternal notch. The system was validated using ECG Holter data, achieving over 92% accuracy. Furthermore, the proposed algorithm was evaluated against whole-night polysomnography-derived HR using Bland-Altman's plots and Pearson's Correlation Coefficient, reaching the average of 0.82 (0.93 maximum) with 0 BPM error tolerance and 0.89 (0.97 maximum) at ±3 BPM., Conclusions: The results prove that the proposed system serves the purpose of a precise heart rate monitoring tool that can conveniently assess HR during sleep as a part of a home-based sleep disorder diagnostics process.

Objectives: Contributions of TGFβ to cancer progression are well documented. However, plasma TGFβ levels often do not correlate with clinicopathological data. We examine the role of TGFβ carried in exosomes isolated from murine and human plasma as a contributor to disease progression in head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: The 4-nitroquinoline-1-oxide (4-NQO) mouse model was used to study changes in TGFβ expression levels during oral carcinogenesis. In human HNSCC, TGFβ and Smad3 protein expression levels and TGFB1 gene expression were determined. Soluble TGFβ levels were evaluated by ELISA and TGFβ bioassays. Exosomes were isolated from plasma using size exclusion chromatography, and TGFβ content was quantified using bioassays and bioprinted microarrays., Results: During 4-NQO carcinogenesis, TGFβ levels in tumour tissues and in serum increased as the tumour progressed. The TGFβ content of circulating exosomes also increased. In HNSCC patients, TGFβ, Smad3 and TGFB1 were overexpressed in tumour tissues and correlated with increased soluble TGFβ levels. Neither TGFβ expression in tumours nor levels of soluble TGFβ correlated with clinicopathological data or survival. Only exosome-associated TGFβ reflected tumour progression and correlated with tumour size., Conclusions: Circulating TGFβ + exosomes in the plasma of patients with HNSCC emerge as potential non-invasive biomarkers of disease progression in HNSCC., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Salivary gland tumours (SGTs) are a heterogeneous group of benign tumours of various origins and pathologies, showing a number of DNA modifications. Previously, in malignant head and neck cancer (HNSCC), we found overexpression of ALKBH proteins, the homologs of Escherichia coli AlkB 2-oxoglutarate and Fe(II) dependent dioxygenase. Moreover, we proved the connection of some of these dioxygenases with cancer development. Here, we studied the expression of five of these ALKBH dioxygenases: 1, 3, 4, 5, and FTO in benign SGTs. Using Western blot analysis, we found overexpression of three proteins: ALKBH1, 4, and FTO in SGT as compared to the surrounding, unaffected tissue. ALKBH4 was overexpressed in 76% of patient samples, whereas ALKBH1 and FTO in 65% of the samples. These results differ from those obtained in HNSCC, where FTO overexpression has been observed in 90% of patient samples. We also investigated the relationships between ALKBHs' expression levels in normal and SGT tissues and identified two correlated pairs: ALKBH1-ALKBH3 and ALKBH1-ALKBH5. Additionally, in tumour tissue ALKBHs: ALKBH1, ALKBH3, ALKBH4, and ALKBH5 levels were correlated with each other. Together, these findings show that the ALKBH proteins exhibit pro cancerogenic action in SGT, even though the levels ALKBHs are generally lower in benign SGT than in malignant HNSCC. We suggest that the overexpression of the ALKBHs, especially FTO, may be used as a cancer marker and for its grading.

Purpose: Polysomnography (PSG) is considered the best objective study to diagnose and quantify sleep disorders. However, PSG involves multiple electrodes and is usually performed in a sleep laboratory that in itself may change the physiology of sleep. One of the parameters that can change during PSG is the sleep position, leading to more supine sleep. The aim of this study was to quantify the amount of supine sleep during PSG and compare it to consecutive nights of a home sleep apnea test (HSAT) in the same patients., Methods: This prospective study evaluated 22 consecutive patients undergoing PSG followed by HSAT. Sleep position was analyzed during PSG and subsequently on 2 to 6 nights (mean 3.7 nights) at home, and the amount of supine sleep was recorded during each night., Results: Of 22 patients, there were 12 men (55%). The median age was 60.0 years for women and 45.5 years for men. Median proportion of supine sleep during PSG and HSAT was 61% and 26% (p < 0.001), respectively. Four "phenotypes" were identified according to their sleep position during PSG and HSAT, with 5 patients sleeping mainly supine during all nights, 7 patients sleeping mainly non-supine during all nights, 3 patients sleeping in different positions during each night, and 7 patients sleeping supine during PSG but non-supine at home, during HSAT., Conclusions: There is a higher proportion of supine sleep during PSG compared to home sleep. We identified a subgroup of patients who slept mainly supine during PSG and mainly non-supine during HSAT. PSG may overestimate OSA severity in a specific phenotype of patients., (© 2022. The Author(s).)

INTRODUCTION Tumors of the salivary glands account for approximately 3 to 4% of all head and neck neoplasms. It is estimated that 10-15% of them are malignant. The most common benign tumor is pleomorphic adenoma, while the most common malignant tumors are adenoid cystic carcinoma and mucoepidermoid carcinoma. Neoplasms of the salivary glands are extremely histologically diverse, which results from the complex embryogenesis of the salivary glands. The identified risk factors for tumors of the salivary glands are: ultraviolet radiation, ionizing radiation, viral infections, nicotine and alcohol. MATERIAL AND METHOD The aim of the study was an epidemiological analysis of patients with salivary gland neoplasms, the distribution and histopathological characteristics of individual neoplasms treated at the Department of Otorhinolaryngology of the Medical University of Warsaw in 2010-2020. The diagnoses were analyzed according to the latest WHO 2017 histological classification of salivary gland tumors. In addition, the material was supplemented with data on the 5-year survival rates of patients with malignant neoplasms obtained from the Registry of Marital Status. RESULTS AND DISCUSSION The material contained 407 neoplasms of the salivary glands over a 11-year period, of which malignant neoplasms accounted for 17.4%. The malignant tumors were dominated by: adenoid cystic carcinoma (28,2%), mucoepidermoid carcinoma (12,7%), and acinic cell carcinoma (9,9%). Lymphomas (15,5%) were also a large group. The benign neoplasms were dominated by pleomorphic adenoma (54.1%) and Warthin&apos;s tumor (36%). Tumors of the salivary gland the most often affected the parotid gland (92%). CONCLUSIONS The obtained data are consistent with the general epidemiological data described in the current literature.

(1) Background: The aim of the present study was to assess the cancer stem cell (CSC) markers CD24, CD44, CD133, and ALDH1A1 in rhabdomyosarcoma (RMS) in children and to define their prognostic role in this group of patients. (2) Methods: The study material was archival tissue specimens collected from 49 patients under 18 years of age and who had been diagnosed with RMS. Immunohistochemistry (IHC) was used to evaluate the expression of the selected CSC markers in the tumor tissue. Expression was evaluated using a semiquantitative IRS scale based on the one developed by Remmele and Stenger and was correlated with the clinical and pathomorphological parameters of prognostic importance in RMS. (3) Results: Expression of the selected CSC markers CD24, CD44, CD133, and ALDH1A1 was demonstrated in 83.7%, 55.1%, 81.6%, and 100% of the RMS patients, respectively. The expression of all of the assessed CSC markers was statistically significantly higher in the study group versus the control group. No significant correlation was found between the expression of the selected CSC markers and clinical and pathological prognostic factors that were analyzed. The expression of the CSC markers did not have a significant influence on RMS survival rates. (4) Conclusions: The results of the conducted study confirm the expression of selected CSC markers in rhabdomyosarcoma tissue in children. The study did not support the prognostic relevance of the expression of any of the assessed CSC markers. However, further studies are needed to fully understand the relevance of the selected CSC markers in RMS carcinogenesis.

It is well documented that body position significantly affects breathing indices during sleep in patients with obstructive sleep apnea. They usually worsen while changing from a non-supine to a supine position. Therefore, body position should be an accurately measured and credible parameter in all types of sleep studies. The aim of this study was to specify the accuracy of a neck-based monitoring device (Clebre, Olsztyn, Poland) mounted at the suprasternal notch, in determining a supine and non-supine sleeping position, as well as specific body positions during sleep, in comparison to polysomnography (PSG). A sleep study (PSG along with a neck-based audio-motion sensor) was performed on 89 consecutive patients. The accuracy in determining supine and non-supine positions was 96.9%±3.9% and 97.0%±3.6%, respectively. For lateral positions, the accuracy was 98.6%±2% and 97.4%±4.5% for the right and left side, respectively. The prone position was detected with an accuracy of 97.3%±5.6%. The study showed a high accuracy in detecting supine, as well as other gross positions, during sleep based on a sensor attached to the suprasternal notch, compared to the PSG study. We feel that the suprasternal notch is a promising area for placing wireless sleep study devices.

Melanotic Neuroectodermal Tumor of Infancy (MNTI) is a very rare pediatric neoplasm of neural crest origin. In most cases, it develops in infants as a localized tumor of the maxilla, and surgery is usually curative. In less than 10% of patients with inoperable, metastatic or persistently recurring MNTI, chemotherapy (CHT) may be considered; however, its role is still unclear. The aim of our study was to assess the efficacy of CHT in children with large, inoperable, metastatic and/or recurrent MNTI. Four such infants, treated with CHT in Polish and German centers of pediatric oncology, were presented. Additionally, a systematic literature search of the PubMed/MEDLINE, Scopus and Web of Science databases was performed, yielding 38 similar cases within the last 42 years. Neoadjuvant CHT, based mainly on the protocols for neuroblastoma, was often effective, allowing for complete delayed surgery in most cases. However, the role of adjuvant CHT in preventing recurrences after incomplete resection of MNTI remains unclear. Disseminated inoperable MNTI was almost universally associated with poor response to CHT and unfavorable outcome. Further investigations to elaborate standards of management in patients with inoperable, metastatic or persistently recurring MNTIs are necessary to improve outcomes.

A chronic inflammatory process characteristic of obstructive sleep apnea promotes vascular endothelial dysfunction and atherogenesis. This process can lead to destabilization and rupture of cardiovascular plaques, which clinically manifests as an acute coronary syndrome or stroke. The aim of this study was to investigate the inflammatory pathway leading to plaque destabilization in non-to-mild and moderate-to-severe groups of OSA patients. This prospective study involved enrollment of patients scheduled for endarterectomy. A sleep study was performed prior to surgery. Immunohistochemistry was performed on atherosclerotic plaques from carotid arteries obtained during standard open endarterectomy to determine levels of CD40, CD40L receptors, MCP-1, and MMP-9. The 46 patients included 14 controls, 13 with mild, 11 with moderate, and 8 with severe OSA. Increased expression of CD40, CD40L receptors, MCP-1, and MMP-9 were found to be proportionate with OSA severity. However, significant differences among groups were observed only for MCP-1 ( p = 0.014). Increased expression of inflammatory markers (CD40, CD40L, MCP-1, MMP-9) is associated with increasing OSA severity. This suggests the CD40-CD4-L inflammatory pathway may contribute to plaque instability and rupture in OSA patients.

Purpose: Little is known regarding the influence of in-laboratory polysomnography (PSG) equipment on sleep position, especially on the prevalence of supine positioning, which in many cases may lead to a more severe sleep apnea diagnosis. The aim of this study was to assess the percentage of supine sleep during an in-laboratory PSG compared to that seen during a home sleep apnea test (HSAT)., Methods: This was a retrospective cohort study comparing in-laboratory PSG and HSAT using a peripheral arterial tone (PAT) technology device., Results: Of 445 PSG and 416 HSAT studies analyzed, there was no significant difference in the proportion of supine sleep time between PSG (44%) and HSAT (45%, p = 0.53). Analysis of the differences in sleep position (supine versus non-supine), analyzed by sex, BMI (≥ 30 kg/m2 versus < 30 kg/m2), and age (≥ 60 years versus < 60 years), was significant only for women, who had more supine sleep during HSAT at 61 ± 24% than during PSG at 45 ± 26% (p < 0.001)., Conclusion: Overall there was no difference in the percentage of supine sleep when comparing in-laboratory PSG to HSAT. However, women had more supine sleep with HSAT than with PSG.

(1) Background: The study proposed to analyze microvessel density (MVD) in rhabdomyosarcoma (RMS) based on the expression of angiogenesis markers and define its prognostic role in this group of patients. (2) Methods: The study included forty-nine pediatric patients diagnosed with RMS. Tumor tissue expression of CD31, CD34, and CD105 was analyzed. MVD was calculated and correlated with clinical RMS prognostic parameters. (3) Results: CD31, CD34, and CD105 are expressed in all RMS cases. MVD/CD105 was significantly higher in the RMS group than in the control group. The mean and median values of MVD/CD105 in RMS were lower than MVD/CD31 and MVD/CD34. MVD/CD105 was significantly higher in patients with alveolar RMS and those with metastatic disease. Patients with higher levels of MVD/CD105 had a higher risk of death (HR = 1.009). (4) Conclusion: CD105 is a relevant angiogenesis marker in pediatric RMS, and MVD/CD105 is an independent risk factor of short overall survival in children with RMS.

Background: There is growing evidence that obstructive sleep apnea (OSA) promotes vascular endothelial dysfunction and atherogenesis. Pathways that mediate this pathology may include Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) which play a significant role in proinflammatory processes. The aim of this study was to measure the expression of the above-mentioned receptors in relation to OSA severity in carotid plaques obtained during open endarterectomy., Methods: This prospective study included patients with a sleep study prior to surgery and a plaque specimen obtained during standard open endarterectomy. Immunohistochemistry of TLR2, TLR4, TLR7, TLR9, RAGE, HMGB1, and NF-κB was performed on atherosclerotic plaques from carotid arteries of patients with and without OSA., Results: There were 46 patients (22 women, mean age 73.2 ± 1.3 years): 14 control patients, 13 with mild, 11 with moderate, and 8 with severe OSA. The expression of all TLRs and RAGE increased proportionately with increasing OSA severity. The largest differences between patients with severe OSA and no OSA were found for TLR2 (2.88 ± 0.35 vs. 1.27 ± 0.47, p < 0.001), TLR4 (2.88 ± 0.35 vs. 1.64 ± 0.5, p < 0.001), TLR9 (2.38 ± 0.52 vs. 1.45 ± 0.52, p < 0.01), and RAGE (2.5 ± 0.53 vs. 1.82 ± 0.6, p < 0.05)., Conclusion: TLR2, TLR4, TLR9, and RAGE expression was significantly increased in carotid plaques of patients with moderate-to-severe OSA when compared with control patients with no OSA and those with mild OSA. TLR and RAGE-mediated pathways may play a significant role in OSA-dependent atherogenesis.

Competing Interests: None declared.

The nine identified human homologues of E. coli AlkB 2-oxoglutarate (2OG) and Fe(II)-dependent dioxygenase, ALKBH1-8 and FTO, display different substrate specificities and diverse biological functions. Here we discovered the combined overexpression of members of the ALKBH family in head and neck squamous cell carcinomas (HNSCC). We found direct correlation of ALKBH3 and FTO expression with primary HNSCC tumor size. We observed unidentified thus far cytoplasmic localization of ALKBH2 and 5 in HNSCC, suggesting abnormal role(s) of ALKBH proteins in cancer. Further, high expression of ALKBHs was observed not only in HNSCC, but also in several cancerous cell lines and silencing ALKBH expression in HeLa cancer cells resulted in dramatically decreased survival. Considering the discovered impact of high expression of ALKBH proteins on HNSCC development, we screened for ALKBH blockers among newly synthetized anthraquinone derivatives and demonstrated their potential to support standard anticancer therapy.

Purpose: This is a feasibility study of functional identification of the abductor and adductor recurrent laryngeal nerve branches, which could be used in the donor's larynx for functional laryngeal transplantation., Methods: The study was performed on swine (n = 3) and human (n = 4) models of a donor larynx. The recurrent laryngeal nerve and its branches were found. Using stimulator, abductor and adductor branches were identified, and glottis closing and opening were captured with an endoscope., Results: The result was positive if two ENT specialists noticed at least one adduction and one abduction movement in the same subject. It was obtained in three out of three swine and three out of four humans., Conclusions: This study shows a way of reinnervation of a transplanted larynx which might result in a functional organ. It describes the first step of the procedure: functional identification of the abductor and adductor branches of the recurrent laryngeal nerve in the donor before the larynx is excised for transplantation.

Receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) are the key factors indicating a danger to the organism. They recognize the microbial origin pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). The primary response induced by PAMPs or DAMPs is inflammation. Excessive stimulation of the innate immune system occurs in arterial wall with the participation of effector cells. Persistent adaptive responses can also cause tissue damage and disease. However, inflammation mediated by the molecules innate responses is an important way in which the adaptive immune system protects us from infection. The specific detection of PAMPs and DAMPs by host receptors drives a cascade of signaling that converges at nuclear factor- κ B (NF- κ B) and interferon regulatory factors (IRFs) and induces the secretion of proinflammatory cytokines, type I interferon (IFN), and chemokines, which promote direct killing of the pathogen. Therefore, signaling of these receptors' pathways also appear to present new avenue for the modulation of inflammatory responses and to serve as potential novel therapeutic targets for antiatherosclerotic therapy.

Introduction The association between obstructive sleep apnea and atherosclerosis is confirmed for long time, but the pathomechanism is still not known. The aim of this study was to investigate the prevalence of OSA in patients scheduled for endarterectomy and the influence of this procedure on the sleep study parameters and sleepiness. Materials and methods 46 patients scheduled for open carotid endarterectomy were enrolled in the study. Sleep study and Epworth Sleepiness Scale (ESS) was performed preoperatively. In 11 out of 46 patients, sleep study was performed both before and after the surgery. Results The mean age of the group was 69,9 years (± 8,6), 21 patients (45,7%) were female. For 46 patients mean pAHI, ODI, pRDI and %snoring were 16,2 (± SD=15,2), 10,4 (± SD=12,2) and 18,9 (± SD=14,9), respectively. Normal pAHI was noticed in 14 patients (30%), while mild (pAHI 5-15), moderate (pAHI 15-30) and severe (pAHI&gt;30) OSA was observed in 13 (38%), 11 (24%) and 8 (18%) subjects, respectively. The mean ESS score for 27 out of 46 patients was 6,3 (± SD=5,6). The postoperative results of sleep study in 11 patients showed no significant change. Conclusions This study revealed the prevalence of moderate to severe OSA in 42% of patients scheduled for endarterectomy, while no excessive daytime sleepiness was observed in this group. The results of the study show that patients with carotid atherosclerosis should undergo sleep diagnosis in order to rule out obstructive sleep apnea.

Objectives: The aim of the study was to investigate the prevalence of upper respiratory tract infections (URI) - as indicated by rhinosinusitis (RS), ear infections (EI), and antibiotic consumption - in a general pediatric population and evaluate the relationship between these conditions and habitual snoring and mouth breathing during sleep., Methods: A population-based cross-sectional study was performed in three medium-sized Polish cities from 2011 to 2015., Results: 4837/6963 questionnaires (69.5%) were completed, returned and analyzed. Mean age of studied group was 7.07 ± 0.72 and 7.14 ± 0.73 in girls and boys, respectively. Habitual mouth breathing during sleep (MB) was reported in 907 (18.7%) children and habitual snoring (HS) in 290 (6.0%). 230/290 (79.3%) of children with HS were also MB. Both HS and MB were more prevalent in boys than in girls (p = 0.027 and p < 0.0001, respectively) and neither was associated with BMI (p = 0.11 and p = 0.07, respectively). Habitual snoring and habitual mouth breathing were highly associated with more frequent bouts of rhinosinusitis, ear infections, and antibiotic use (p < 0.0001 for each parameter)., Conclusions: Higher rates of rhinosinusitis, ear infections, and antibiotic consumption were similarly associated with HS and MB. MB is over three times more prevalent in the pediatric population relative to HS, therefore it might be considered as a risk factor for URI and may be included in history of URI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: In the general population, nasal obstruction is a common complaint. However, an objective evaluation of nasal obstruction is difficult. Nose examination, computed tomography (CT), acoustic rhinometry, and anterior rhinomanometry do not accurately reflect the discomfort reported by patients with nasal obstruction. In patients with nasal obstruction, this study evaluated nasal breathing with a unique device for continuous nasal-oral spirometry - a nasal-oral flow analyzer (NOFA); moreover, quality of life was compared between patients with normal nasal breathing on NOFA and of those with impaired nasal breathing on NOFA., Methods: Of 181 adult patients admitted to an ENT department due to nasal obstruction that were enrolled in the study, 97 (53.6%) completed all per-protocol assessments, including the SF-36 questionnaire and 3-hour, continuous nasal-oral spirometry with NOFA. Based on the presence of normal nasal breathing defined as ≥95% of nasal flow, the 97 patients were divided into those with normal nasal breathing (n=31) and impaired nasal breathing (n=66)., Results: Patients with normal nasal breathing differed from those with impaired nasal breathing with respect to all SF-36 subscales (physical functioning, p=0.004; role-physical, p=0.009; bodily pain, p&lt;0.001; general health, p=0.007; vitality, p=0.002; social functioning, p=0.008; mental health, p=0.009; physical component summary, p&lt;0.001; mental component summary, p=0.02), except for the role-emotional subscale (p=0.1)., Conclusions: Among patients with symptoms of nasal obstruction, compared to patients with normal nasal breathing, those with impaired nasal breathing had significantly lower quality of life in the physical and mental domains. Further research needs to determine whether NOFA can be used to diagnose nasal obstruction.

Objective: Sleep-disordered breathing is both a clinical and a social problem. This implies the need for convenient solutions to simplify screening and diagnosis. The aim of the study was to investigate the sensitivity and specificity of a novel wireless system in detecting breathing and snoring episodes during sleep., Methods: A wireless acoustic sensor was elaborated and implemented. Segmentation (based on spectral thresholding and heuristics) and classification of all breathing episodes during recording were implemented through a mobile application. The system was evaluated on 1520 manually labeled episodes registered from 40 real-world, whole-night recordings of 16 generally healthy subjects., Results: The differentiation between normal breathing and snoring had 88.8% accuracy. As the system is intended for screening, high specificity of 95% is reported., Conclusion: The system is a compromise between nonmedical phone applications and medical sleep studies. The presented approach enables the study to be repetitive, personal, and inexpensive. It has additional value in the form of well-recorded data which are reliable and comparable., Significance: The system opens unexplored possibilities in sleep monitoring and study enabling a multinight recording strategy involving the collection and analysis of abundant data from thousands of people.

Renal cell carcinoma (RCC) comprises 2‑3% of all malignant tumors in adults. Many studies have established the key roles of smoking, hypertension and other components of metabolic syndrome in the occurrence of RCC. Diabetes mellitus (DM), one of the main consequences of metabolic syndrome, appears much more often in patients with RCC. The prognosis for patients suffering from both diabetes and RCC is worse than for those with kidney cancer only. Diabetes is linked to higher rate of recurrence and a greater number of distant metastases. These factors contribute to a reduction in overall survival (OS) and cause‑specific survival (CSS). Diabetes can also occur as a paraneoplastic syndrome. Tyrosine kinase inhibitors (TKIs), which are agents used in the therapy of metastatic RCC, may have unexpected effects when administered to patients with diabetes. Studies and case reports have shown that they influence blood glucose levels (BGLs) in diabetic patients, sometimes causing dangerous episodes of hypoglycemia. Hyperinsulinemia and hyperglycemia can be considered independent carcinogenic factors, as they increase the amount of pro‑inflammatory cytokines, reactive oxygen species and lipid peroxidation. TKIs have yet to be re‑evaluated as to their safety of use in patients with diabetes.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric population. In 35% of cases, RMS develops in the head and neck (H&N) region, and only combined therapy is recognized as a curative treatment. However, recent advances in skull base and reconstructive surgery, along with microsurgery and endoscopic surgery, have strengthened the role of surgery as an important part of RMS treatment. In the present study, 36 pediatric RMS cases (24 males and 12 females) were analyzed after surgical treatment. The average age at diagnosis was 7 years. In total, 67% of tumors were localized in the parameningeal region. Alveolar RMS was the most common histopathological type. A total of 16 patients were treated due to disease recurrence or a previous non-radical surgical procedure, while 19 cases had inductive chemotherapy and/or radiotherapy preceding surgical treatment due to locally advanced disease. In 1 case, only diagnostic biopsy was performed. It is recommended that the management of H&N RMS is interdisciplinary from the beginning. Extensive surgical dissection in the H&N region for RMS may result in severe cosmetic defects and functional impairment; thus, these risks should be considered during treatment planning, and the surgical approach should be based on the individual characteristics of each patient.

Background: As somatostatin receptors (SSTRs) may be overexpressed in rapidly growing vessels, the aim of this study was the analysis of in vivo and in vitro SSTR2A expression in juvenile angiofibroma (JA)., Material & Methods: A group of six male adolescents with a diagnosis of primary, recurrent/residual JA was enrolled in the study. All patients underwent (68)Ga-DOTATATE PET/computed tomography (CT) followed by immunohistochemical staining for SSTR expression., Results: (68)Ga-DOTATATE PET/CT showed accumulation in areas matching the pathologic tissue in the nasopharynx of all patients studied with SUVmax of 5.1 ± 0.9 (ranging from 3.6 to 6.4). In all cases, the immunohistochemical examination showed a presence of SSTR2A with a high staining index., Conclusion: In vitro SSTR2A cytoplasm expression was found to be high in all tumor specimens. However, the uptake of (68)Ga-DOTATATE was weak in the PET/CT studies. We postulate that the intracellular localization of the SSTR2A in JA may cause this discrepancy.

Pancreatic cancer is one of the most lethal types of malignant solid tumor and is typically associated with a poor prognosis. The majority of patients are diagnosed with advanced-stage disease, therefore, the median survival period is <6 months. Recently, a number of basic research projects and clinical trials were undertaken with the aim of improving treatment outcomes in pancreatic cancer; however, only one agent, erlotinib, passed the clinical trials. Erlotinib is an inhibitor of epidermal growth factor receptor, which when overexpressed in cancer, promotes angiogenesis, cell proliferation and inhibits apoptosis. The US Food and Drug Administration and European Medicines Agency approved erlotinib in combination with gemcitabine for the first-line treatment of advanced pancreatic cancer. To the best of our knowledge, the current study is the first to report a case of pancreatic cancer treated with this regimen alone to achieve a complete response (CR). A 40-year-old male with a medical history of chronic pancreatitis and hypertension was diagnosed with medically inoperable adenocarcinoma of the pancreas. Following palliative surgery, the patient began palliative gemcitabine and erlotinib chemotherapy. After three months, this treatment strategy resulted in a CR, as determined by imaging studies. Therapy was discontinued after 14 months due to the development of peritoneal metastases and the patient was referred for treatment with the folinic acid, 5-fluorouracil, irinotecan and oxaliplatin regimen. A CR is rarely reported in pancreatic cancer, however, a treatment strategy of gemcitabine and erlotinib may induce rapid regression of advanced-stage disease.

Objective: This study reports the presence of sleep-disordered breathing (SDB) symptoms among first graders. We evaluated the severity of symptoms and parental satisfaction in children who had undergone adenotonsillectomy (T&A) compared to children who never had T&A., Methods: A population-based, cross-sectional study was conducted. Parent-reported questionnaire data including age, weight, height, BMI, history of T&A, and SDB symptoms (snoring intensity, observed dyspneas, mouth breathing during sleep) were analyzed., Results: Of 3580 eligible children, 2504 (69.9 %) returned questionnaires. Two hundred fifty-nine (10.3 %) children had a history of T&A. Within this group, 76 % of parents were still satisfied with their child's outcome after surgery. The satisfaction rate decreased from 88.9 % in those who had surgery within 1 year to 71.3 % in those who had surgery ≥3 years prior. The mean values of intensity for all analyzed SDB symptoms on a five-point scale were significantly higher for children who had ever undergone T&A when compared to those who never underwent surgery [e.g., snoring (2.11 vs 1.87; P = 0.0004), dyspneas (1.64 vs 1.22; P < 0.0001), and mouth breathing during sleep (2.95 vs 2.58; P < 0.0001)]. For those who had undergone T&A, 24 % of caregivers were not satisfied with the surgical outcome and the symptom intensity was highest (snoring = 3.16, dyspneas = 2.20, and mouth breathing = 4.23) for these children., Conclusions: The mean SDB symptom intensity was significantly higher in children who had undergone T&A when compared to those who had not. The elevated symptom intensity in those children whose caregivers were not satisfied after T&A suggests possible SDB recurrence and need for further evaluation.

The cancer stem cell (CSC) model has recently been approached also in renal cell carcinoma (RCC). A few populations of putative renal tumor-initiating cells (TICs) were identified, but they are indifferently understood; however, the first and most thoroughly investigated are CD105-positive CSCs. The article presents a detailed comparison of all renal CSC-like populations identified by now as well as their presumable origin. Hypoxic activation of hypoxia-inducible factors (HIFs) contributes to tumor aggressiveness by multiple molecular pathways, including the governance of immature stem cell-like phenotype and related epithelial-to-mesenchymal transition (EMT)/de-differentiation, and, as a result, poor prognosis. Due to intrinsic von Hippel-Lindau protein (pVHL) loss of function, clear-cell RCC (ccRCC) develops unique pathological intra-cellular pseudo-hypoxic phenotype with a constant HIF activation, regardless of oxygen level. Despite satisfactory evidence concerning pseudo-hypoxia importance in RCC biology, its influence on putative renal CSC-like largely remains unknown. Thus, the article discusses a current knowledge of HIF-1α/2α signaling pathways in the promotion of undifferentiated tumor phenotype in general, including some experimental findings specific for pseudo-hypoxic ccRCC, mostly dependent from HIF-2α oncogenic functions. Existing gaps in understanding both putative renal CSCs and their potential connection with hypoxia need to be filled in order to propose breakthrough strategies for RCC treatment.

Nasopharyngeal chordoma is a rare type of malignant neoplasm that originates in the remnants of the notochord, a primitive tissue of embryonic origin preserved outside the axial skeleton. Approximately one-third of chordomas are located in the base of the skull, in the midline of the body. The slow growth rate of the tumor, which gradually fills the nasopharyngeal cavity, contributes to a delayed oncological diagnosis. Among its isolated and non-specific symptoms, the obstruction of the nasopharynx is dominant, thus, sleep-disordered breathing (SDB) may occur. The current study presents the case of a 32-year-old female patient who was incidentally diagnosed with a nasopharyngeal chordoma during a diagnostic examination for SDB. The diagnostic examination was performed as a part of a research program for pathologically obese patients who qualified for bariatric surgery. Following tumor resection, a significant improvement in various polysomnographic parameters occurred, including a decrease in the apnea hypopnea index from 53.5 to 6.4 and an increase in the mean saturation rate from 92.5 to 95%, confirming that an association exists between tumor obstruction of the nasopharynx and SDB. The incidental diagnosis of this rare type of neoplasm drew attention to diagnostic and therapeutic problems associated with nasopharyngeal chordomas. Furthermore, it indicated the necessity for the accurate laryngological examination of patients with SDB.