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Τετάρτη 18 Αυγούστου 2021

Phenotypic changes on central nervous system (CNS) tumor cell lines cultured in vitro 2D and 3D models and treated with cisplatin

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Via histochem

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Acta Histochem. 2021 Aug 14;123(6):151768. doi: 10.1016/j.acthis.2021.151768. Online ahead of print.

ABSTRACT

Despite aggressive therapy, most patients with brain tumors present disease relapse due to the cellular and molecular nature of these tumors. One of the models that best explains the heterogeneity observed in CNS tumors is the presence of cancer stem cells (CSCs). In this paper, we evaluated platinum-based response in brain tumor U-87 MG, LN-18, and KELLY cell lines cultured in monolayer (2D) and neurosphere (CSC enrichment- 3D) models. We evaluated mRNA expression of heat shock proteins (HSPA1A, HSPB1, HSPA1AL, TRAP1, and HSPD1), and DNA repair gene ERCC1. Changes in cell cycle and glycosylation profile were assessed by flow cytometry. After treatment with cisplatin, we found that the mRNA expression of HSPs markedly increased in the U-87 MG and LN-18 neurosphere cells. In KELLY monolayer cells, cisplatin induced upregulation of all genes. In KELLY neurosphere cells, only the HSPA1A, HSPB1, TRAP1, and HSPD1 genes were upregulated. The proportion of cells in the G0/G1 phase was significantly higher in U-87 MG neurosphere cisplatin-treated cells. A trend towards a greater proportion of cells in the S phase of U-87 MG monolayer cisplatin-treated cells was also observed. On the other hand, a significant decrease in the number of cells in the S phase and an increase in G2/M was observed in LN-18 monolayer cisplatin- treated cells. Glycosylation analysis using lectins showed a higher surface binding for PNA in the U-87 MG treated monolayer and a lower binding for Concanavalin A in the treated neurospheres. The binding of Isolectin GS-IB4, GSII, and SBA in KELLY monolayer cisplatin-treated cells was lower whereas the proportion of cells labeled with Concanavalin A was higher. In the KELLY neurosphere cisplatin-treated cells, the binding of Concanavalin A was lower than nontreated cells. Thus, our findings strongly supported the idea that definitions of phenotypic characteristics may help to establish better therapeutic strategies for brain tumors.

PMID:34403847 | DOI:10.1016/j.acthis.2021.151768

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Utility of Telemedicine for Diagnosis and Management of Laryngology‐Related Complaints during COVID‐19

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Abstract

Objective

To investigate the concordance in diagnosis and management between initial telemedicine visits and subsequent in-person visits with laryngoscopy for laryngology-related complaints during COVID-19.

Study Design

Retrospective cohort study

Methods

Patients who presented to a tertiary care center with laryngology-related complaints (voice, swallowing, airway, general throat complaints and others) and completed initial telemedicine visits and subsequent in-person visits with laryngoscopy between March and October 2020 were included (n=250). Preliminary diagnoses and managements provided during initial telemedicine visits were compared to the diagnoses and managements during subsequent in-person visits with laryngoscopy. Multivariable logistic regression analysis was performed to compare concordance rates in diagnosis and management by chief complaint categories after adjusting for relevant demographic and clinical factors.

Results

Overall concordance rates in diagnosis and management between the initial telemedicine visit and subsequent laryngoscopy exam were 86.1% and 93.7%, respectively. Mean (SD) days until laryngoscopy from the initial visit were 21.2 (23.0). Concordance rates were not associated with patient's age, gender, preferred language, provider, telemedicine visit duration or days until laryngoscopy. Management concordance rate was relatively lower among patients with general throat complaints in comparison to voice-related complaints (OR:0.27, 95% CI: 0.08-0.90). Management changes after laryngoscopy included need for further imaging, procedures, voice therapy and referral to other specialists.

Conclusion

Concordance rates in diagnosis and management remained high between the initial telemedicine visit and subsequent in-person visit with laryngoscopy for new patients presenting with laryngology-related complaints during the COVID-19 pandemic. While laryngoscopy is still essential to confirm diagnosis and provide appropriate management, telemedicine may be a feasible alternative to provide suitable empiric therapy until laryngoscopy can be safely performed.

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Development of recognized position‐guided navigation system

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Abstract:

Background

Previously, we developed an image-guided navigation system (IG-NS) incorporating augmented reality (AR) technology. Nevertheless, the system could still only aid the operator by presenting imagery and was short of achieving the goal of developing a real navigation system. Therefore, we developed a recognized position-guided navigation system (RP-NS) and herein reported the functionality and usefulness of this system in a phantom model for clinical applications.

Methods

We developed RP-NS which was reconstructed by adding the positional recognition and instruction functions with the cautions by displaying the images on the monitor with a voice to the IG-NS. We evaluated accuracy of positional recognition and instruction functions using phantom model. By utilizing the chronological recording of the tip position of the surgical apparatus, the surgical precision of the operators was assessed. Finally, the feasibility of improvements in surgical precision using this system was evaluated.

Results

The RP-NS indicated an accuracy of the position recognition functions with an error of 2.7 mm. The surgeons could perform partial hepatectomies within mean value of 7.5% error as compared with calculated volume according to the instruction. Improvements in surgical precision using this system were obtained on the surgeons with different levels.

Conclusions

The RP-NS was highly effective as a navigation system owing to precise positional recognition and adequate instruction functions. Therefore, these results indicate that the use of this system may complement differences in proficiency, and numerically evaluate surgical skills and analyze tendencies of surgeons.

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Dynamic effect of 3 locking plates fixated to humeral fracture based on multibody musculoskeletal model

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Abstract

This study attempts to analyze the biomechanical effect of internal fixation (plated in parallel or plated vertically) on the basis of distal humeral fractures on musculoskeletal multibody dynamics using AnyBody in Finite Element Method. Humeral 3D models were reconstructed by MIMICS after volunteers' CT image input in *.dicom format, and processed by Geomagic Studio for surfaces, while locking plates and screws were then designed by Pro-E. A humeral model of T-type fracture was created and assembled in Hypermesh, to integrate fixtures (e.g., MPL/ PML/ ML), to grid the mesh and then assign materials. A musculoskeletal model of the upper limb was established by AnyBody to simulate elbow flexion and extension. They were finally imported to Abaqus for boundary conditions and dynamic analysis. In terms of Von Mises stress, its maximum increased and then decreased gradually during the joint motion, but P >0.05 in SPSS suggests no significant difference for all 3 fixtures. In terms o f displacement, when the elbow was at 90°, each motional pattern reached its peak as follows: ML180°=0.28mm, MPL90°=0.49mm & PML90°=0.54mm during flexion;ML180°=0.073mm, MPL90°=0.10mm & PML90°=0.12mm during extension. P < 0.05 suggests a significant difference for the displacements of all 3 fixations. P=0.007<0.01667 suggests the significant difference between the 2 fixations, e.g., PML90° and ML180°, indicating that the peak displacement of ML180° is less than that of PML90°. After generally analyzed in musculoskeletal dynamics, the biomechanical property of the fixtures was presented as: the displacement of the parallel plate was less than that of the vertical, and the parallel plate may optimize the clinical reduction anatomically.

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Segmentation of Brain Tumor in 3D Intraoperative Ultrasound Imaging

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Abstract

Background

Intraoperative Ultrasound (iUS), using a navigation system and preoperative magnetic resonance imaging (pMRI), supports the surgeon intraoperatively in identifying tumor margins. Therefore, visual tumor enhancement can be supported by efficient segmentation methods.

Methods

A semi-automatic and two registration-based segmentation methods are evaluated to extract brain tumors from 3D-iUS data. The registration-based methods estimated the brain deformation after craniotomy based on pMRI and 3D-iUS data. Both approaches use the Normalized Gradient Field (NGF) and Linear Correlation of Linear Combinations (LC2) metrics. Proposed methods were evaluated on 66 B-mode and contrast-mode 3D-iUS data with metastasis and glioblastoma.

Results

The semi-automatic segmentation achieved superior results with Dice Similarity Index (DSI) values between [85.34, 86.79] % and Contour Mean Distance (CMD) values between [1.05, 1.11] mm for both modalities and tumor classes.

Conclusions

Better segmentation results were obtained for metastasis detection than glioblastoma, preferring 3D-intraoperative B-mode over 3D-intraoperative contrast-mode.

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Decreased Facial Emotion Recognition in Elderly Patients With Hearing Loss Reflects Diminished Social Cognition

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Ann Otol Rhinol Laryngol. 2021 Aug 17:34894211040057. doi: 10.1177/00034894211040057. Online ahead of print.

ABSTRACT

OBJECTIVE: The main objective of this research was to evaluate the correlation between the severity of hearing loss and the facial emotional recognition as a critical part of social cognition in elderly patients.

METHODS: The prospective study was comprised of 85 individuals. The participants were divided into 3 groups. The first group consisted of 30 s ubjects older than 65 years with a bilateral pure-tone average mean >30 dB HL. The second group consisted of 30 subjects older than 65 years with a PTA mean ≤30 dB HL. The third group consisted of 25 healthy subjects with ages ranging between 18 and 45 years and a PTA mean ≤25 dB HL. A Facial Emotion Identification Test and a Facial Emotion Discrimination Test were administered to all groups.

RESULTS: Elderly subjects with hearing loss performed significantly worse than the other 2 groups on the facial emotion identification and discrimination tests (P < .05). Appealingly, they identified a positive emotion, "happiness," more accurately in comparison to the other negative emotions.

CONCLUSIONS: Our results suggest that increased age might be associated with decreased facial emotion identification and discrimination scores, which could be deteriorated in the presence of significant hearing loss.

PMID:34404263 | DOI:10.1177/00034894211040057

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Successful management of spontaneous intracranial hypotension with epidural blood patch

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BMJ Case Rep. 2021 Aug 17;14(8):e240936. doi: 10.1136/bcr-2020-240936.

ABSTRACT

Spontaneous intracranial hypotension (SIH) is characterised by postural headache and a cerebrospinal fluid (CSF) pressure of ≤6 cmH20 measured with the patient in the lateral decubitus position. Other symptoms include tinnitus, altered hearing, diplopia, photophobia, nausea and neck stiffness, and must not have occurred within a month of dural puncture. Symptoms typically remit after normalisation of CSF pressure or successful sealing of the CSF leak. An epidural blood patch (EBP) is a treatment option in those who have not responded to bed rest, fluids, non-steroidal anti-inflammatories or caffeine. We present a case of SIH successfully treated with both conservative measures and EBP. We compare our case with similar cases in the literature and summarise what is known about EBP for SIH to help clinicians take a more informed approach to managing such patients.

PMID:34404644 | DOI:10.1136/bcr-2020-240936

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Update on 'Treatment of orthostatic headache without intracranial hypotension: A case report' - nine years later

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Cephalalgia. 2021 Aug 18:3331024211038656. doi: 10.1177/03331024211038656. Online ahead of print.

ABSTRACT

BACKGROUND: In 2013, one of the authors described a 36-year-old female with orthostatic headache without documented intracranial hypotension or evidence of cerebrospinal fluid leak, despite extensive workup. Headache was unresponsive to conservative treatment since 2010, showed only transient benefit after repeated epidural blood patches while vitamin A supplementation resulted in progressive improvement.

CASE: Since 2013, the patient followed a relapsing and remitting course yet relapse control became difficult after a drug induced liver injury required vitamin A discontinuation in 2017, when her headache became chronic. Greater occipital nerve blocks provided pain relief as alternative but were stopped due to the pandemic and her latest severe relapse, in late 2020, required not only restarting anaesthetic blocks and aggressive m edication management, but also reassessing and treating comorbidities (obstructive sleep apnoea and major depressive disorder) with modest benefit.

CONCLUSION: Orthostatic headache without intracranial hypotension is rare, with only 28 cases reported so far, all treated empirically and all treatment options revealing to be mostly ineffective. Vitamin A anecdotally appeared to be useful in our case but had to be stopped for severe side effects, so unfavourable long-term prognosis, in ours and 2/3 of the reported cases, seems to be the rule in this intriguing entity.

PMID:34404249 | DOI:10.1177/03331024211038656

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Mucoepidermoid carcinoma of the head and neck: CRTC1/3 MAML 2 translocation and its prognosticators

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Eur Arch Otorhinolaryngol. 2021 Aug 17. doi: 10.1007/s00405-021-07039-2. Online ahead of print.

ABSTRACT

PURPOSE: Mucoepidermoid carcinoma (MEC) of the head and neck is a prevalent malignant salivary gland tumour with a reported good outcome. The aim of this study was to report the outcome in our centre.

METHODS: A retrospective chart analysis with survival analyses was performed combined with fluorescence in situ hybridization (FISH) analysis to assess CRTC1/3 MAML 2 fusion gene presence.

RESULTS: Sixty-four cases of MEC were identified. Median age at presentation was 51.4 years with a predominance for parotid gland involvement. Five, 10- and 20- year disease-free survival was 98%, 90% and 68%, respectively. Overall survival was 94%, 90% and 64%, respectively. Local recurrence was seen up to 14 years after primary diagnosis; distant metastases were diagnosed up to 17 years later. The overall recurrence rate was less than 2 0 per cent. CRTC1/3 MAML 2 fusion gene presence showed no survival benefit.

CONCLUSION: MEC of the head and neck has a favorable outcome with the exception of high-grade MEC. PNI and nodal involvement are not rare. CRTC1/3 MAML 2 fusion gene presence showed no survival benefit. The tendency for late onset of loco-regional and distant recurrence should not be underestimated.

PMID:34405264 | DOI:10.1007/s00405-021-07039-2

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Selpercatinib-Enhanced Radioiodine Uptake in RET-Rearranged Thyroid Cancer

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Thyroid. 2021 Aug 18. doi: 10.1089/thy.2021.0144. Online ahead of print.

ABSTRACT

BACKGROUND: Metastatic thyroid cancers may dedifferentiate and become radioactive iodine refractory. The redifferentiating effect of pharmacological drugs was reported with inhibitors of the MAPK pathway in cancer with point mutation in oncogenes. The potential redifferentiating effect of inhibitors targeting oncogenic fusion genes is only suggested by a recent and unique publication using larotrectin ib in a NTRK rearranged tumor. Patients finding. Selpercatinib a highly selective RET inhibitor, was recently approved by the FDA for the treatment of RET fusion-positive lung and thyroid cancers. We had the unprecedented opportunity to observe restoration of iodine-131 uptake after selpercatinib treatment for a non-radioiodine avid metastatic thyroid cancer with a RET/PTC3 fusion gene.

CONCLUSION: This finding of a redifferentiation effect with selpercatinib targeting a RET fusion gene, reinforces the proof of concept of this new therapeutic opportunity. Therefore, future clinical trials and treatment strategies must not forget to evaluate the redifferentiating effect of drugs targeting gene rearrangements. Furthermore, the combined approach with a targeted therapy and radioactive iodine may increase anti-tumor efficacy and minimize acquired resistance to RET inhibitors.

PMID:34405703 | DOI:10.1089/thy.2021.0144

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Histone Deacetylase 4 Controls Extracellular Matrix Production in Orbital Fibroblasts from Graves' Ophthalmopathy Patients

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Thyroid, Ahead of Print.
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