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Τετάρτη 15 Δεκεμβρίου 2021

Identification of heterogeneity and prognostic key genes associated with uveal melanoma using single-cell RNA-sequencing technology

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Uveal melanoma (UM) is the most common intraocular malignancy in adults. The prognosis is poor once metastasis has developed. The treatment of metastatic UM remains challenging nowadays due to lacking a deep understanding of the biological characteristics of this disease. Here, we revealed the cell subpopulations w ith distinct functional status and the existence of cells with high invasive potential within heterogeneous primary and metastatic UM. The single-cell sequencing data were retrieved from GSE139829 and GSE138433, through which we identified a new cell cluster related to metastatic UM as a unique type of immune cell. The cell–cell communication was conducted by 'Cellchat' to understand the cell crosstalk between these immune cells and their surrounding cells. The crucial signals contributing most to outgoing or incoming signaling of this cell group were identified to reveal the crucial pathway genes. Furthermore, we judged the prognostic value of these candidates on the basis of the data downloaded from The Cancer Genome Atlas. The results demonstrated that the increased IL10, SELPLG, EPHB and ITGB2 signaling pathways could be promising predicting factors for the patient prognosis in UM. Conclusively, we discover the potential key signals of UM for occurrence and metastasis, and also provide a theoretical basis for judging whether there is a high risk of metastasis or recurrence. * Songlin Sun and Rui Shi contributed equally to the writing of this article. Received 25 May 2021 Accepted 24 August 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 Fengyuan Sun, PhD, MD, Tianjin Medical University Eye Hospital, Xiqing District, No.251 Fukang Road, Tianjin 300384, Tianjin, China, Tel: +086 022 86428810; e-mail: tianjiny2020@163.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Thyroid Cancer Incidence Trends

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Objective

To analyze thyroid cancer incidence trends among Filipinos relative to non-Filipino Asians and non-Hispanic Whites in the US.

Study Design

Population-based analysis of cancer incidence data.

Methods

Population-based analysis of cancer incidence data from Surveillance, Epidemiology, and End Results 9 detailed Asian/Pacific Islander subgroup incidence and population datasets. Adult patients aged 20 and older with thyroid cancer diagnosed in 2004 to 2014 were included. Annual percent change (APC) of the incidence rates were calculated using joinpoint regression analysis.

Results

The incidence rates were 19.57 (95% CI 19.03–20.12) per 100,000 for Filipinos, 10.45 (95% CI 10.22–10.68) per 100,000 for non-Filipino Asians, and 13.94 (95% CI 13.85–14.02) per 100,000 for non-Hispanic Whites. The highest increase was seen among non-Hispanic Whites (average APC 5.04, 95% CI 4.61–5.46). Incidence rates of tumors ≤ 2 cm remained stable among Filipinos but increased in non-Filipino Asians (average APC 5.38, 95% CI 2.51–8.34) and non-Hispanic Whites (average APC 5.81 95% CI 4.52–7.11).

Conclusion

Filipinos have high incidence of thyroid cancer compared with other racial/ethnic groups. However, non-Hispanic Whites have the highest increase in incidence rates, resulting in a significant narrowing of the gap in incidence rates between Filipinos and non-Hispanic Whites. This is most likely due to enhanced detection of small tumors in non-Hispanic Whites. Laryngoscope, 2021

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Association between olfactory dysfunction and COVID-19 severity: A prospective study in a highly complex hospital in Peru

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Ear Nose Throat J. 2021 Dec 15:1455613211066691. doi: 10.1177/01455613211066691. Online ahead of print.

ABSTRACT

INTRODUCTION: Olfactory dysfunction has been included among the early symptoms of coronavirus disease (COVID-19). Evidence suggests that a relationship exists between the duration of olfaction disorders and the probability of developing severe COVID-19. Given the scope of the COVID-19 pandemic, this study aimed to determine the frequency of smell alteration and it s association with the severity of COVID-19 in a referral hospital in Peru, which is one of the most affected countries in the Latin American region.

MATERIALS AND METHODS: This study was an observational, prospective cohort study that included patients with COVID-19 who were treated at the Hospital Nacional Edgardo Rebagliati Martins from August to November 2020. To assess the association, the chi-square test of independence or Fisher's exact test was performed. The outcome variable was COVID-19 severity, and the exposure variable was olfactory dysfunction. The first data collection was in the emergency department and the follow-up was via telephone.

RESULTS: A total of 179 patients were included. The mean age was 61.6 ± 15.5 years, and 129 patients (72.1%) were male. Olfactory dysfunction was observed in 43 patients (24%). An inverse association was found between age and olfactory dysfunction (P = .002). No significant association was found between COVID-19 sev erity level and olfactory alteration (P = .056). However, a direct association was found between COVID-19 severity and age (P = .003), cough (P < .001), and respiratory distress (P = .003).

CONCLUSION: This study did not find any association between the severity of COVID-19 and olfactory dysfunction. It showed a low incidence rate of smell alteration compared with studies from other regions. Moreover, smell alteration was associated with younger age.

PMID:34908507 | DOI:10.1177/01455613211066691

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Concomitant Variants in NF1, LZTR1, and GNAZ Genes Probably Contribute to the Aggressiveness of Plexiform Neurofibroma and Warrant Treatment with MEK Inhibitor

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Abstract

Neurofibromatosis 1 (NF1) is caused by germline mutations in the NF1 gene and manifests as proliferation of various tissues, including plexiform neurofibromas. The plexiform neurofibroma phenotype varies from indolent to locally aggressive, suggesting contributions of other modifiers in addition to somatic loss of NF1. Here, we investigated a life-threatening plexiform neurofibroma in a 9-month-old female infant with NF1. Germline mutations in two Rasopathy-associated genes were identified using whole exome sequencing - a de-novo pathogenic variant in the NF1 gene, and a known pathogenic variant in the LZTR1 gene. Somatic analysis of the plexiform neurofibroma revealed NF1 loss of heterozygosity and a variant in GNAZ, a gene encoding a G Protein Coupled Receptor. Cells expressing mutant GNAZ exhibited increased ERK 1,2 activation compared to those expressing wild type GNAZ. Taken together, we suggest the variants in NF1, LZRT1, and GNAZ act synergistically in our patient, leading to MAPK pathway activation and contributing to the severity of the patient's plexiform neurofibromatosis. After treatment with the MEK inhibitor, trametinib, a prominent clinical improvement was observed in this patient. This case study contributes to the knowledge of germline and somatic non-NF1 variants affecting the NF1 clinical phenotype and supports use of personalized, targeted therapy.

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Τρίτη 14 Δεκεμβρίου 2021

MiR-124-3p attenuates brain microvascular endothelial cell injury in vitro by promoting autophagy

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Histol Histopathol. 2021 Dec 13:18406. doi: 10.14670/HH-18-406. Online ahead of print.

ABSTRACT

Traumatic brain injury (TBI) can cause the pathological disruption of the blood-brain barrier (BBB) and associated neurological injury. Reducing the severity of such barrier disruption following TBI can decrease the degree of brain edema, suppress intracranial inflammation, and thereby protect against neurological damage. The BBB is made up of brain microvascular endothelial cells (BMVECs), neurons, pericytes, astrocytes, and extracellular matrix components. In prior analyses, we have demonstrated that miR-124-3p expression is enhanced in microglia-derived exosomes following TBI, with this miRNA being capable of promoting neural repair after such injury. Based upon these results, the present study was formulated to examine the impact of miR-124-3p on BMVEC function and to evaluatethe mechanistic basis for its activity by overexpressing miR-1 24-3p in these endothelial cells. We utilized a bEnd.3 cell scratch wound in vitro model to simulate TBI-associated brain microvascular endothelial cell injury. Lipofectamine3000 was used to transfect endothelial cells such that they overexpressed miR-124-3p. Fluorescence microscopy was used to observe the effects of miR-124-3p expression on these endothelial cells. TUNEL+CD31 immunofluorescence stainingwas employed to observe endothelial cell apoptosis. Tight junctions were observed via ionconductivity microscopy. Western blotting was used to detect the expression of tight junction proteins (occludin, ZO-1), autophagy-associated proteins (Beclin-1, p62, LC3-II/LC3-I), and mTOR-associated proteins (p-mTOR, PDE4B). Chloroquine was used to treat these injured endothelial cells overexpressing miR-124-3p, and endothelial cell apoptosis was assessed via TUNEL+CD31 immunofluorescence staining. We found that the upregulation of miR-124-3p was sufficient to suppress bEnd.3 cell apoptotic de ath following in vitro scratch injury while promoting the upregulation of the tight junction proteins ZO-1 and occludin in these cells, thereby reducing the degree of leakage across the cerebral microvascular endothelial barrier. These protective effects may be related to the ability of miR-124-3p to suppress mTOR signaling and to induce autophagic activity within BMVECs. These data support a model wherein miR-124-3p can inhibit mTOR signaling and promote autophagic induction in BMVECs, thereby protecting these cells against TBI-induced damage.

PMID:34897628 | DOI:10.14670/HH-18-406

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E‐cigarette use and tobacco harm reduction: A pilot survey study evaluating perspectives of head and neck surgeons

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Abstract

Background

Electronic cigarettes (EC) are popular devices that aerosolize a nicotine and have been controversially considered tool for smoking cessation and tobacco harm reduction (THR). The purpose of this pilot study was to identify head and neck cancer (HNC) surgeons' attitudes/perspectives of EC and smoking cessation counseling.

Methods

Cross-sectional survey administered to American Head and Neck Society (AHNS) members.

Results

Response rate was 136 members (15.1%) with the majority 102 (75.00%) having unfavorable attitude toward EC for smoking cessation. Fifty-eight respondents (42.7%) were familiar with THR. Those familiar with THR 37 (63.79%) routinely inquire about EC use. Compared between THR familiarity, 22 (37.93%) believed the benefits of EC for smoking cessation outweighed the potential risks.

Conclusions

HNC specialists have an unfavorable attitude toward EC. Those familiar with THR were more likely to inquire about EC use. They were also less likely to have a definitive opinion on the benefits of quitting combustible cigarettes.

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Skin Color Match in Head and Neck Reconstructive Surgery

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Objectives/Hypothesis

To quantify the degree of color match achieved during microvascular facial reconstruction, and to describe a novel technique for improving reconstructive skin color match. We hypothesize that split-thickness skin grafts (STSG) placed atop de-epithelialized free tissue produces better facial skin color match than free tissue with intact epithelium.

Study Design

Cross sectional photographic study of reconstructed facial skin color match.

Methods

Sixty-eight adults, who underwent head and neck reconstructive surgery, were divided into six categories based on cutaneous reconstructive technique: cervicofacial flap, radial forearm free flap (RFFF), fibula free flap, anterolateral thigh free flap (ALT), STSG over adiopofascial flap (STAFF), and STSG over myogenous flap (STMF). Averaged color samplings of the reconstructed defect and adjacent normal skin were taken from digital photographs. The color difference was calculated using the delta-E calculation. Blinded expert observers also rated the degree of color match. Nonparametric cohort contrast and correlation statistical analyses were performed.

Results

The mean delta-E's and 10-point Likert ratings for the ALT, fibula, RFFF, STAFF, STMF, and cervicofacial flaps were 11.6, 10.0, 7.7, 6.3, 8.8, and 4.7, and 5.1, 6.4, 2.4, 3.2, 2.7, and 1.1, respectively. Likert scale inter-rater correlation was strong, with coefficient = 0.80.

Conclusions

On average, STSG over de-epithelialized myogenous and adipofascial free tissue transfers produced a better color match than the skin paddles of donor sites, with the exception of the radial forearm donor site. Delta-E values obtained from photos correlated well with expert ratings of color match. This reliable technique for quantifying color match may be used in future studies.

Level of Evidence

3 Laryngoscope, 2021

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A Case Report of a Middle Ear Mass Originated From Cartilage-like Tissue Treated With Transcanal Endoscopic Ear Surgery

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Ear Nose Throat J. 2021 Dec 14:1455613211065510. doi: 10.1177/01455613211065510. Online ahead of print.

ABSTRACT

Middle ear tumors are relatively rare, and among them, the diagnoses of middle ear lesions originating from cartilage-like tissue are even rarer. Use of transcanal endoscopic ear surgery (TEES) has increased in recent years because of its advantages, such as clear visual field and minimally invasive procedure. Here, we report a middle ear mass originating from car tilage-like tissue treated with TEES. A 62-year-old woman presented with progressive right-sided hearing loss. A white mass was revealed through the tympanic membrane, and pure-tone audiometry detected a mean 50.0 dB conductive hearing loss. Computed tomography showed a mass in the tympanic cavity. TEES was performed for diagnosis and treatment. A white translucent tumor was observed intraoperatively, and it was completely resected. Histopathological examination confirmed the diagnosis of a mass originating from degenerated cartilage-like tissue. To the best of our knowledge, this is the first study of a middle ear mass originating from cartilage-like tissue treated with TEES. TEES with its clear visual field and precise techniques was beneficial in treating the middle ear lesions circumscribed in the tympanic cavity.

PMID:34904447 | DOI:10.1177/01455613211065510

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Root Cause Analysis of Na131I Contamination

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J Nucl Med Technol. 2021 Dec;49(4):350-353. doi: 10.2967/jnmt.121.262492.

ABSTRACT

Establishing a cause-and-effect relationship for an adverse event is one of the key steps in preventing them and involves multiple people, resources, and steps, thus requiring a root cause analysis. Here, we describe a root cause analysis performed in the nuclear medicine department for an event involving Na131I contamination. Oral administration of Na131I in a capsule minimizes the risk of contamination and spills. However, the patient must be able to swallow a capsule. Na131I in capsule form is currently in widespread use for treatment of hyperthyroidism and thyroid cancer. Na131I in liquid form is rarely available immediately on demand and must be ordered at least 24-48 h in advance of the planned administration. The events leading to the incident, immediate remedial steps taken, and subsequent root cause analysis are described. The corrective actions taken after the root cause analysis, as well as the subsequent effectiveness of these actions, are mentioned. There may be one or multiple causes for an adverse event. It is important to identify the root cause. Corrective actions derived from the root cause can help prevent similar adverse events in the future. Therapeutic procedures in nuclear medicine involve unsealed radioactive sources, further adding a separate layer of immediate steps and reporting to the root cause analysis it self.

PMID:34862264 | DOI:10.2967/jnmt.121.262492

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Endoscopic Anatomy of the Zygomatic Nerve: Implications for the Endoscopic Transmaxillary Approach

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1739237

Background Understanding the anatomic features of the zygomatic nerve is critical for performing the endoscopic transmaxillary approach properly. Injury to the zygomatic nerve can result in facial numbness and corneal problems. Objective To evaluate the surgical anatomy of the zygomatic nerve and its segments from an endoscopic endonasal perspective for clinical implications of performing the endoscopic transmaxillary approach. Methods The origin, course, length, and segments of the zygomatic nerve were studied in four specimens from an endonasal perspective. Results The zygomatic nerve arises 4.1 ± 1.7 mm from the foramen rotundum of the maxillary nerve in the superolateral pterygopalatine fossa (PPF). According to its anatomic region in endonasal endoscopic surgery, we divided the zygomatic nerve into two segments: the PPF segment, from origin to the point of entry under Muller's muscle, which runs superolaterally to the inferior orbital fissure (IOF) (length, 4.6 ± 1.3 mm), and the IOF segment, starting at the entry point in Muller's muscle and terminating at the exit point in the IOF, which travels between Muller's muscle and the great wing of the sphenoid bone (length, 19.6 ± 3.6 mm). In the transmaxillary approach, the zygomatic nerve is a critical landmark in the superolateral PPF. Conclusion The zygomatic nerve travels in the PPF and the IOF; better visualization and preservation of this nerve during endonasal endoscopic surgery are crucial for successful outcomes.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Δευτέρα 13 Δεκεμβρίου 2021

Prognostic role of neutrophil lymphocyte ratio and mean platelet volume in Bell's palsy: Comparison of diabetic and non-diabetic patients

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Braz J Otorhinolaryngol. 2021 Nov 15:S1808-8694(21)00184-1. doi: 10.1016/j.bjorl.2021.10.003. Online ahead of print.

ABSTRACT

OBJECTIVES: A low Neutrophil Lymphocyte Ratio (NLR) has been shown to be associated with good prognosis in Bell's Palsy (BP). However, the effect of chronic diseases that may affect the NLR, including Diabetes Mellitus (DM), has not been clarified in this context. This study aimed to evaluate the relationship between NLR and Mean Platelet Volume (MPV) in BP according to whether it is accompanied by DM, and their relationship with prognosis.

METHODS: A prospective observational study was conducted from May 2014 to May 2020 in a tertiary referral center, of all 79 consecutive participants diagnosed with BP in department of otolaryngology and 110 consecutive healthy participants admitted to the check-up unit. Patients diagnosed with BP were divided into two groups according to whether they were diagnosed with DM: diabetic BP patients (DM-BP, n = 33) and non-diabetic BP patients without any chronic disease (nonDM-BP, n = 46). Neutrophil (NEUT) and Lymphocyte (LYM) counts, and Mean Platelet Volume (MPV) were assessed from peripheral blood samples, and the NLR was calculated. Prognosis was evaluated using the House-Brackmann Score (HBS) six months after diagnosis.

RESULTS: The mean NLR was 2.85 ± 1.85 in BP patients and 1.69 ± 0.65 in the control group. The mean NLR was significantly higher in BP patients than healthy controls (p < 0.001). The mean NLR was 2.58 ± 1.83 in the nonDM-BP group, 3.23 ± 1.83 in the DM-BP group, and 1.69 ± 0.65 in the control group. The NLR was significantly higher in the nonDM-BP and DM-BP groups than in the control group (p < 0.05). The recovery was 90% according to the HBS. The optimal cut-off value was 2.41 (p = 0.5).

CONCLUSION: The NLR was increased in both diabetic and non-diabetic BP and had similar prognostic value in predicting th e HBS before treatment in diabetic and non-diabetic patients with BP. MPV wasn't significantly different in diabetic and non-diabetic BP patients compared with the normal population.

PMID:34895869 | DOI:10.1016/j.bjorl.2021.10.003

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