Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Τετάρτη 8 Δεκεμβρίου 2021

Cortical Atrophy, White Matter Lesions, and Bulb Configuration in Patients with Idiopathic Olfactory Loss and Other Causes of Olfactory Loss

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Introduction: While magnetic resonance imaging (MRI) is not included in the current guidelines for diagnosing olfactory disorders in the most recent position paper on olfactory dysfunction, both 1.5T and 3T MRI are commonly used in the diagnostic workup of many patients with olfactory loss. Often, MRI is used to rule out intracranial tumours, but other useful information may be obtained from MRI scans in these patients. The potential of MRI in olfactory loss depends on sufficient knowledge of structural changes in different aetiologies of olfactor y loss. We present common clinical MRI findings in olfactory loss and evaluate the usefulness of structural integrity scores in differentiating between aetiologies. Methods: In this study, we investigated if white matter hyperintensities (WMHs, measured by Fazekas score), global cortical atrophy (GCA), and medial temporal lobe atrophy (MTA) are more common in patients with idiopathic olfactory loss than in patients with acquired olfactory loss due to other aetiologies. Furthermore, we compared olfactory bulb (OB) configurations in different olfactory loss aetiologies. Results: In 88 patients with olfactory loss, WMHs, GCA, and MTA were not more significant findings on MRI in idiopathic olfactory loss (n = 51) compared with other causes of acquired olfactory loss (Fazekas score p = 0.2977; GCA score p = 0.6748; MTA score p = 0.7851). Bulb configurations differed in patients suffering from post-traumatic olfactory loss and may ai d in identifying the underlying aetiology in patients where trauma is among the suspected causes of olfactory loss. Conclusion: We recommend that structural MRI with an OB sequence is included in the diagnostic evaluation of olfactory loss with suspected congenital and post-traumatic aetiology and should be considered in idiopathic olfactory loss with suspected central aetiology (e.g., tumour).
ORL
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Changes in olfaction and taste in patients hospitalized for COVID-19 and their relationship to patient evolution during hospitalization

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Braz J Otorhinolaryngol. 2021 Nov 24:S1808-8694(21)00193-2. doi: 10.1016/j.bjorl.2021.11.002. Online ahead of print.

ABSTRACT

OBJECTIVES: During the COVID-19 pandemic, several cases of changes in olfaction and taste associated with the infection have been reported. Therefore, otolaryngologists are frequently the first medical professionals sought by patients. The aim of this study was to evaluate the frequency of olfaction and taste disorders in patients hospitalized with COVID-19, and their association with other clinical manifestations and patient evolution during hospitalization.

METHODS: 248 patients, admitted to three public hospitals in Belo Horizonte, Minas Gerais, Brazil, were prospectively included: Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG), Hospital Júlia Kubitschek (HJK) and Hospital Eduardo de Menezes (HEM), who, upon admission to hospital, presented with Severe Acute Respiratory Syndro me due to COVID-19. Clinical and laboratory variables and outcomes during hospitalization were prospectively collected from the electronic medical records. The collection of sociodemographic and symptomatology data during the acute phase was carried out prospectively in electronic medical records and confirmed with the patients at a subsequent outpatient visit.

RESULTS: The most frequently reported symptoms were dyspnea (77.4%), cough (69.8%) and fever (55.2%). During the acute phase of the disease, 95 (38.3%) and 87 (35.1%) patients reported taste and olfaction disorders, respectively. There was a lower prevalence of dysosmia among patients with previous comorbidities (p < 0.05). Both symptoms were associated with less need for intensive care admission (p = 0.001 for dysgeusia and p = 0.021 for dysosmia) and a negative correlation with length of hospital stay (dysosmia: r = -0.175, p < 0.05; dysgeusia: r = -0.29, p < 0.001) and length of stay in the ICU (dysosmia: r = -0.136, p < 0.05; dysgeusia: r = -0.215, p < 0.05). The absence of taste disorders was also associated with a greater need for mechanical ventilation (p < 0.001).

CONCLUSION: Changes in taste and olfaction were reported by a large number of patients in the acute phase of COVID-19. In this study, both were markers of better clinical patient evolution.

LEVEL OF EVIDENCE: 1B.

PMID:34876382 | DOI:10.1016/j.bjorl.2021.11.002

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Combined underwater endoscopic and microscopic surgery for external auditory canal cholesteatoma: A case report

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Ear Nose Throat J. 2021 Dec 7:1455613211064011. doi: 10.1177/01455613211064011. Online ahead of print.

ABSTRACT

Transcanal endoscopic ear surgery is a minimally invasive procedure that allows a clear visualization of the middle ear. Recently, indications for endoscopic surgery have been expanding. We performed combined underwater endoscopic and microscopic surgery for external auditory canal cholesteatoma, the computer tomography of which indicates the possibility of cholest eatoma not only in the canal wall but also in the mastoid. The 30° endoscope and underwater technique makes the surgical view clear, and we could remove the cholesteatoma without canalplasty. To the best of our knowledge, no case of external auditory canal cholesteatoma treated with underwater endoscopic and microscopic surgery has been previously reported. This case indicates that the procedure could be a good indication for external auditory canal cholesteatoma.

PMID:34875889 | DOI:10.1177/01455613211064011

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Cerebrospinal fluid leak as a driving factor in chronic subdural hematoma formation: A histological study

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Surg Neurol Int. 2021 Nov 23;12:578. doi: 10.25259/SNI_950_2021. eCollection 2021.

ABSTRACT

BACKGROUND: Chronic subdural hematoma (CSDH) represents the most common neurosurgical disease. Given the demographic shift toward an aging population, the overall incidence of this condition is increasing. Nevertheless, clarity in the pathophysiological process is yet to be made. Several etiological mechanisms have been proposed to initiate and consequently promote fluid collection in the subdural space. Traumatic injury of the bridging veins has long been considered the primum movens of the pathology but increasing evidence shows that trauma is not the only factor involved. Along with recent advances we sought to understand the role of the cerebrospinal fluid (CSF) in the buildup of the intense inflammatory reaction that characterizes CSDH.

METHODS: In the present study, we examined histological features of reactive membranes secondary to extrac ranial CSF leakage with CSDH-related membranes. Similarity and differences between the specimens were examined by means of light microscopy.

RESULTS: Histological similarities were consistently found between CSDH membranes and reactive membranes secondary to CSF leakage in the extracranial space. Activated histiocytes were highlighted in all specimens along with an intense inflammatory reaction.

CONCLUSION: CSDH is most likely the result of a complex interaction among different pathophysiological events resulting from both traumatic and inflammatory etiologies. In the present work, we highlight how CSF leakage could be an early factor that leads to a cascade of events that culminates in CSDH formation.

PMID:34877064 | PMC:PMC8645496 | DOI:10.25259/SNI_950_2021

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Τρίτη 7 Δεκεμβρίου 2021

YYFZBJS inhibits colorectal tumorigenesis by remodeling gut microbiota and influence on M2 macrophage polarization in vivo and in vitro

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Am J Cancer Res. 2021 Nov 15;11(11):5338-5357. eCollection 2021.

ABSTRACT

Our previous studies indicated that the extract of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) had potent anticancer activities by significantly inhibiting intestinal tumor development in ApcMin/+ mice. However, knowledge regarding the mechanism and effect of YYFZBJS in the prevention of colorectal cancer is limited. In this study, we aim to investigate the preventive effects of YYFZBJS in enterotoxigenic Bacteroides fragilis (ETBF)-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. First, the colonic tissues of the AOM/DSS mouse models were collected for biomedical analysis, and gut microbiota profiling was detected post YYFZBJS treatment using a 16S rRNA gene sequencing. Then, antibiotic solution (Abx) mice were acclimated with AOM/DSS treatment and then fed with ETBF with or without YYFZBJS for three cyc les. As expected, the intragastric administration of YYFZBJS in the AOM/DSS mouse model significantly decreased the tumor load, the severity of disease activity index (DAI) scores, and the level of M2 macrophage markers such as CD206, Arg-1 and IL-10. Notably, the reverse of polarized macrophages induced by YYFZBJS could suppress CRC cell proliferation and infiltration, as demonstrated by the decrease of some tumor proliferation-related proteins in a dose-dependent manner. Importantly, ETBF dysbiosis can contribute to colon tumor development by stimulating p-STAT3 mediated M2 macrophages polarization to promote chronic inflammation and adenoma malignant transformation, which YYFZBJS can effectively limit. Altogether, we demonstrate that ETBF dysbiosis may contribute to M2 macrophages-promoted colon carcinogenesis and progression of CRC cells, while YYFZBJS could be a promising protective agent against ETBF-mediated colorectal cancer.

PMID:34873464 | PMC:PMC8640793

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Highly potent dopamine receptor D2 antagonist ONC206 demonstrates anti-tumorigenic activity in endometrial cancer

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Am J Cancer Res. 2021 Nov 15;11(11):5374-5387. eCollection 2021.

ABSTRACT

Endometrial cancer (EC) is a highly obesity-driven cancer, with limited treatment options. ONC201 is an imipridone that selectively antagonizes the G protein-coupled receptors dopamine receptor D2 and D3 (DRD2/3) and activates human mitochondrial caseinolytic protease P (ClpP). It is a promising first-in-class small molecule that has been reported to have anti-neoplastic activity in various types of cancer through induction of the integrated stress response (ISR) as well as through stimulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and subsequent induction of apoptosis. ONC201 is being evaluated in Phase II clinical trials for solid tumors and hematological malignancies, including EC. ONC206 is an analog of ONC201 with nanomolar potency in Phase I clinical trials. This study evaluated the anti-tumor efficacy of ONC206 in EC cell lines and the Lkb1fl/flp53fl/fl genetically engineered mouse model of endometrioid EC. ONC206 revealed greater potency than ONC201 in the inhibition of proliferation in EC cell lines, with IC50 concentration ranges of 0.21-0.32 µM for ONC026 versus 2.14-3.53 µM for ONC201. ONC206 induced cellular stress, apoptosis and cell cycle G1 arrest, accompanied by inhibition of the AKT/mTOR/S6 pathways in EC cells. Diet-induced obesity accelerated tumor growth in Lkb1fl/flp53fl/fl mice. ONC206 inhibited EC tumor size and weight in both obese and lean mice after 4 weeks of treatment. Treatment with ONC206 led to a decrease in expression of Ki67, BCL-XL and phosphorylation of S6, as well as an increase in ClpP in endometrial tumors under both obese and lean conditions. Overall, the pre-clinical efficacy of ONC206 is promising and worthy of further exploration in clinical trials for endometrioid EC.

PMID:34873466 | PMC:PMC8640798

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Genome-wide identification of m6A-associated functional SNPs as potential functional variants for thyroid cancer

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Am J Cancer Res. 2021 Nov 15;11(11):5402-5414. eCollection 2021.

ABSTRACT

m6A methylation has been demonstrated to be one of the most important epigenetic regulation mechanisms in cell differentiation and cancer development especially m6A derived diagnostic and prognostic biomarkers have been identified in the past several years. However, systemic investigation to the interaction between germline single-nucleotide polymorphisms (SNPs) and m6A has not been conducted yet. In this study, we collected previous identified significant thyroid cancer associated SNPs from UKB cohort (358 cases and 407,399 controls) and ICR cohort (3,001 patients and 287,550 controls) and thyroid eQTL (sample size = 574 from GTEx project) and m6A-SNP (N = 1,678,126) were applied to prioritize the candidate SNPs. Finally, five candidate genes (PLEKHA8, SMUG1, CDC123, RMI2, ACSM5) were identified to be thyroid cancer associated m6A-related genetic suscepti bility. Loss and gain function studies of m6A writer proteins confirm that ACSM5 is regulated by m6A methylation of mRNA. Moreover, ACSM5 is downregulated in thyroid cancer and inversely correlated with PTC malignancy and patient survival. Together, our study highlight mRNA-seq and m6A-seq double analysis provided a novel approach to identify cancer biomarkers and understanding the heterogeneity of human cancers.

PMID:34873468 | PMC:PMC8640822

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