Introduction and expression of PIK3CAE545K in a papillary thyroid cancer BRAFV600E cell line leads to a dedifferentiated aggressive phenotype

xlomafota13 shared this article with you from Inoreader Introduction and expression of PIK3CAE545K in a papillary thyroid cancer BRAFV600E cell line leads to a dedifferentiated aggressive phenotype Via Journal of Otolaryngology - Head & Neck Surgery Anaplastic thyroid cancer (ATC) is a rare, aggressive form of undifferentiated thyroid cancer, which exhibits rapid progression and is almost universally fatal. At least a subset of ATC is thought to arise fro... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA)

xlomafota13 shared this article with you from Inoreader Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA) Via radioactive iodine J Clin Oncol. 2022 Feb 22:JCO2100714. doi: 10.1200/JCO.21.00714. Online ahead of print. ABSTRACT PURPOSE: Selumetinib can increase radioactive iodine (RAI) avidity in RAI-refractory tumors. We investigated whether selumetinib plus adjuvant RAI improves complete remission (CR) rates in patients with differentiated thyroid cancer (DTC) at high risk of primary treatment failure versus RAI alone. METHODS: ASTRA (NCT01843062) is an international, phase III, randomized, placebo-con trolled, double-blind trial. Patients with DTC at high risk of primary treatment failure (primary tumor > 4 cm; gross extrathyroidal extension outside the thyroid gland [T4 disease]; or N1a/N1b disease with ≥ 1 metastatic lymph node(s) ≥ 1 cm or ≥ 5 lymph nodes [any size]) were randomly assigned 2:1 to selumetinib 75 mg orally twice daily or placebo for approximately 5 weeks (no stratification). On treatment days 29-31, recombinant human thyroid-stimulating hormone (0.9 mg)-stimulated RAI (131I; 100 mCi/3.7 GBq) was administered, followed by 5 days of selumetinib/placebo. The primary end point (CR rate 18 months after RAI) was assessed in the intention-to-treat population. RESULTS: Four hundred patients were enrolled (August 27, 2013-March 23, 2016) and 233 randomly assigned (selumetinib, n = 155 [67%]; placebo, n = 78 [33%]). No statistically significant difference in CR rate 18 months after RAI was observed (selumetinib n = 62 [40%]; placebo n = 30 [38%]; odds ratio 1.07 [95% CI, 0.61 to 1.87]; P = .8205). Treatment-related grade ≥ 3 adverse events were reported in 25/154 patients (16%) with selumetinib and none with placebo. The most common adverse event with selumetinib was dermatitis acneiform (n = 11 [7%]). No treatment-related deaths were reported. CONCLUSION: Postoperative pathologic risk stratification identified patients with DTC at high risk of primary treatment failure, although the addition of selumetinib to adjuvant RAI failed to improve the CR rate for these patients. Future strategies should focus on tumor genotype-tailored drug selection and maintaining drug dosing to optimize RAI efficacy. PMID:35192411 | DOI:10.1200/JCO.21.00714 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cochlear Fluid Spaces and Structures of the Gerbil High-Frequency Region Measured Using Optical Coherence Tomography (OCT)

xlomafota13 shared this article with you from Inoreader Cochlear Fluid Spaces and Structures of the Gerbil High-Frequency Region Measured Using Optical Coherence Tomography (OCT) Via Journal of the Association for Research in Otolaryngology Abstract Since it has been difficult to directly observe the morphology of the living cochlea, our ability to infer the mechanical functioning of the living ear has been limited. Nearly all our knowledge about cochlear morphology comes from postmortem tissue that was fixed and processed using procedures that possibly distort the structures and fluid spaces of the organ of Corti. In this study, optical coherence tomography was employed to obtain volumetric images of the high-frequency hook region of the gerbil cochlea, as viewed through the round window, with far better resolution capability than had been possible before. The anatomical structures and fluid spaces of the organ of Corti were segmented and quantified in vivo and over a 90-min postmortem period. We find that the arcuate-zone and pectinate-zone widths change very little postmortem. The volume of the scala tympani between the round-window membrane and basilar membrane and the volume of the inner spiral sulcus d ecrease in the first 60-min postmortem. While textbook drawings of the mammalian organ of Corti and cortilymph prominently depict the tunnel of Corti, the outer tunnel is typically missing. This is likely because textbook drawings are typically made from images obtained by histological methods. Here, we show that the outer tunnel is nearly twice as big as the tunnel of Corti or the space of Nuel. This larger outer tunnel fluid space could have a substantial, little-appreciated effect on cochlear micromechanics. We speculate that the outer tunnel forms a resonant structure that may affect reticular-lamina motion. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Evaluation of reconstructed auricles by convolutional neural networks

xlomafota13 shared this article with you from Inoreader Evaluation of reconstructed auricles by convolutional neural networks Via Journal of plastic, reconstructive & aesthetic surgery : JPRAS J Plast Reconstr Aesthet Surg. 2022 Jan 31:S1748-6815(22)00050-X. doi: 10.1016/j.bjps.2022.01.037. Online ahead of print. ABSTRACT The difficulty in determining which structures are crucial to ensure a natural-looking ear has been plaguing surgeons for many years. This preliminary study explores the feasibility of training convolutional neural network (CNN) models to evaluate a reconstructed auricle as accurate as a human would. By visualizing the attention of trained models, the criteria for the design of a natural-looking auricle can be established. A total of 400 pictures were evaluated by 20 volunteers, and 20 labeled datasets were generated, which were then used to train ResNet models that had been pre-trained on ImageNet. The saliency maps and occlusion maps of each trained model were calculated to capture the attention of models. The average accuracy of the 20 models was 0.8245 ± 0.0356 (>0.80), and the evaluation results of the trained model and the medical student showed a significant correlation (P < 0.05). For the attention visualization of auricles labeled as normal, distribution of the highlighted portions corresponded to a linear contour of the helix, the inferior crura of the antihelix, and the contour of the concha. A CNN can provide an evaluation of a reconstructed auricle in a manner similar to that of a medical student. Saliency maps generated by the CNN demonstrate the subjective view, which was consistent with professional opinion. PMID:35183463 | DOI:10.1016/j.bjps.2022.01.037 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bmal1 promotes cementoblast differentiation and cementum mineralization via Wnt/β-catenin signaling

xlomafota13 shared this article with you from Inoreader Bmal1 promotes cementoblast differentiation and cementum mineralization via Wnt/β-catenin signaling Via histochem Acta Histochem. 2022 Feb 17;124(3):151868. doi: 10.1016/j.acthis.2022.151868. Online ahead of print. ABSTRACT Remodeling of the cementum plays a crucial role in periodontal regenerative therapy, while the precise mechanism of cementogenesis has yet been adequately understood. Recent studies have indicated the connection between osteogenic differentiation and Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (Bmal1). Besides, Wnt/β-catenin signal ing is proven to be an essential regulator in cementogenesis. In this study, we found a robust expression of Bmal1 in cementoblasts in the mandibular first molar of mice by immunohistochemical staining. To further explore the role of Bmal1 in cementogenesis, we examined the expression pattern of Bmal1 in OCCM-30, an immortalized murine cementoblast cell line by qRT-PCR and western blot. Our data demonstrated the upregulation of Bmal1 at both mRNA and protein levels during differentiation. Additionally, stable knockdown of Bmal1 in OCCM-30 cells resulted in downregulation of osteogenic markers such as alkaline phosphatase (Alp), osteopontin (Opn), and osteocalcin (Ocn), and reduced formation of mineralized nodules. Moreover, qRT-PCR and western blot results exhibited that the expression of β-catenin was attenuated by Bmal1 deficiency. We also found that the mRNA levels of Tcf1 and Lef1, the target transcription factors of β-catenin, were reduced by Bmal1 deficiency. In conclusion, this study preliminarily confirms that Bmal1 promotes cementoblast differentiation and cementum mineralization via Wnt/β-catenin signaling, which contributes to a potential strategy in periodontal regenerative therapy. PMID:35183881 | DOI:10.1016/j.acthis.2022.151868 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Locoregional Control and Survival in Children, Adolescents, and Young Adults With Localized Head and Neck Alveolar Rhabdomyosarcoma-The French Experience

xlomafota13 shared this article with you from Inoreader Locoregional Control and Survival in Children, Adolescents, and Young Adults With Localized Head and Neck Alveolar Rhabdomyosarcoma-The French Experience Via oto-rhino-laryngologie Front Pediatr. 2022 Feb 4;9:783754. doi: 10.3389/fped.2021.783754. eCollection 2021. ABSTRACT INTRODUCTION: The head and neck (HN) are the most frequent sites of pediatric rhabdomyosarcoma (RMS). Alveolar RMS (ARMS) represents ~20% of all RMS cases and frequently spread to lymph nodes (LNs). The aim was to report locoregional control, event-free survival (EFS), and overall survival (OS), according to clinical and pathological features, LN staging, and treatment modalities. METHODS: The study included all patients prospectively enrolled in EpSSG RMS 2005 study under 21 years of age with localized HN ARMS and diagnosed between 2005 and 2016 in France. Medical data including imaging, surgical report, and radiation therapy planes were analyzed. RESULTS: Forty-eight patients (median age 6 years; range 4 months-21 years), corresponding to 30 parameningeal and 18 non-parameningeal ARMS, were included. There were 33 boys (69%). Tumor loca tions included the following: orbit (n = 7) among which four cases had bone erosion, paranasal sinuses and nasal cavity (n = 16), deep facial spaces (n = 10), nasolabial fold (n = 8), and other non-parameningeal HN sites (n = 7). A fusion transcript of PAX3-FOXO1 or PAX7-FOXO1 was expressed in 33 of the 45 cases (73%) with molecular analysis. At diagnosis, 10 patients had primary resection of the primary tumor (PRPT) (none with microscopic complete resection) and 9 had LN staging. After induction chemotherapy, 26 patients (54%) had secondary resection of the primary tumor (SRPT) and 13 patients (27%) had cervical LN dissection. A total of 43 patients (90%) were treated with radiation therapy.With a median follow-up of 7 years (range 2-13 years), 5-year OS and EFS were 78% (95% CI, 63-88%) and 66% (95% CI, 51-78%), respectively. We observed 16 events (10 deaths): 4 local, 4 regional, 1 local and regional, and 7 metastatic. In univariate analysis, OS was only superior for patients under 10 years of age (p = 0.002), while FOXO1-negative ARMS, SRPT for parameningeal ARMS, and LN surgery were associated with significantly better EFS. CONCLUSION: Our study confirms a better outcome for fusion-negative ARMS and ARMS in children under 10 years. Moreover, LN surgery and SRPT of parameningeal tumor may improve EFS of ARMS. Larger studies are needed to confirm our findings. PMID:35186818 | PMC:PMC8855824 | DOI:10.3389/fped.2021.783754 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer

xlomafota13 shared this article with you from Inoreader Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer Via Head & Neck Abstract Background Numerous studies of head and neck squamous cell carcinoma (HNSCC) have demonstrated disparate outcomes by race and ethnicity. Beyond known associations with socioeconomic variables, whether these are also associated with differences in tumor molecular composition has thus far been poorly explored. Methods We downloaded clinical and multiplatform molecular data from The Cancer Genome Atlas and other published studies. These were compared between non-Hispanic Black (n = 43) and White (n = 354) patients with non-HPV-related tumors, using multivariable models. Publicly available validation cohorts were used. Results Black patients had poorer progression-free survival than White patients. Tumors of Black patients had greater copy number aberrations, and increased SFRP1 methylation and miRNA-mediated PRG4 silencing associated with poor survival. PI3K/AkT/mTOR pathway proteins were differentially expressed. Conclusions There are molecular differences between tumors of Black and White patients that may partially account for differences in survival. These may inform targeted treatment decisions to achieve equitable outcomes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Impact of Component Dorsal Hump Reduction on Patient‐Perceived Nasal Aesthetics and Obstruction in Rhinoplasty

xlomafota13 shared this article with you from Inoreader The Impact of Component Dorsal Hump Reduction on Patient‐Perceived Nasal Aesthetics and Obstruction in Rhinoplasty Via The Laryngoscope Objective This study aimed to evaluate functional and aesthetic patient-reported outcomes using validated metrics after component dorsal hump reduction (DHR) with spreader graft placement, which have not been previously reported. Study Design Prospective cohort study. Methods This prospective cohort study was conducted in a tertiary care medical center. Participants underwent septorhinoplasty (SRP) with spreader graft placement with cosmetic, component DHR (cosmetic DHR), or SRP with spreader graft placement without dorsal hump reduction (noncosmetic, non-DHR). The Nasal Obstruction Symptom Evaluation (NOSE) scale and the FACE-Q Satisfaction with Nose, Nostrils, and Social Functioning scales were administered to patients preoperatively and postoperatively (at 2, 4, 6, and/or 12 months). Pre- and postoperative NOSE and FACE-Q scores were compared. Results A total of 226 patients underwent SRP with spreader graft placement; 113 (50.0%) with cosmetic DHR and 113 (50.0%) noncosmetic, non-DHR (control). Patients who completed the NOSE and FACE-Q surveys preoperatively and at least at one postoperative time point were included. Both cohorts had a statistically and clinically significant improvement in NOSE and FACE-Q scores. There were similar improvements in NOSE scores in both cohorts. Postoperative FACE-Q scores were higher in the cosmetic DHR cohort despite lower preoperative FACE-Q scores when compared to the control cohort. Conclusions Although there are multiple techniques for DHR, component DHR with spreader graft placement has long been considered the standard. Therefore, it is important to note the significant postoperative cosmetic and functional improvements reported by patients who have undergone this procedure to compare to newer techniques as they evolve. Level of Evidence 3 Laryngoscope, 2022 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Gustatory Function in Acute COVID‐19 ‐ Results from Home‐Based Psychophysical Testing

xlomafota13 shared this article with you from Inoreader Gustatory Function in Acute COVID‐19 ‐ Results from Home‐Based Psychophysical Testing Via The Laryngoscope Abstract Objective Gustatory function during COVID-19 is self-reported by around 50% of patients. However, only few studies assessed gustation using psychophysical testing during the acute infection. The objective of this study is to test gustatory function on threshold tests in the very first days of COVID-19. Methods Psychophysical testing consisted of validated and blinded tests for olfaction (NHANES Pocket Smell Test) and gustation (Taste Strips Test). These test kits were sent to home-quarantined patients and self-administered using a detailed instruction sheet. Results A total of 51 patients were included in this study. Testing was performed 6.5±2.7 days after sampling of respiratory swabs. At this time 37% of patients stated to currently experience a gustatory impairment. The mean Taste Strips score was 10.0±3.4 with 28% scoring in the range of hypogeusia. Interestingly, no significant difference in the results of gustatory testing could be observed between the group with subjectively preserved gustation and the group with self-rated taste impairment. Conclusion During the very first days COVID-19, psychophysical gustatory testing revealed hypogeusia in 28%. This is far lower than patients' self-reports. Different to previous studies, we did not find clear evidence for an impairment of only certain taste qualities. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Robotic right colectomy with complete mesocolic excision: Senior versus junior surgeons, a case‐matched retrospective analysis. Short term outcomes between expert and novice surgeon after robotic right colectomy with complete mesocolic excision

xlomafota13 shared this article with you from Inoreader Robotic right colectomy with complete mesocolic excision: Senior versus junior surgeons, a case‐matched retrospective analysis. Short term outcomes between expert and novice surgeon after robotic right colectomy with complete mesocolic excision Via The International Journal of Medical Robotics and Computer Assisted Surgery Abstract Background Robotic surgery may facilitate complex procedures such as right colectomy with complete mesocolic excision (CME) and shorten the learning curve. This study aimed to compare senior and junior surgeons' results in performing robotic right colectomy (RRC) with CME and intracorporeal anastomosis (IA) for right colon cancer. Materials and methods Between January 2015 and April 2020, a total of 161 patients underwent RRC with CME. After propensity score matching, two groups of 31 patients for each surgeon were formed. Intraoperative, postoperative and pathological outcomes were the variables assessed. Results No statistically significant difference was recorded between the two groups. The senior surgeon experienced 16.1% minor complications (Clavien-Dindo I-II) and 3.2% major complications (Clavien-Dindo III-IV), while the novice surgeon reported 19.3% and 3.2% rates of minor and major adverse events, respectively. Conclusions After a structured training protocol, a novice may obtain comparable results to an expert in performing RRC with CME. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cricotracheostomy in a patient with severe kyphosis: A case report

xlomafota13 shared this article with you from Inoreader Cricotracheostomy in a patient with severe kyphosis: A case report Via ear nose throat Ear Nose Throat J. 2022 Feb 21:1455613221077596. doi: 10.1177/01455613221077596. Online ahead of print. ABSTRACT Cricotracheostomy is a useful surgical procedure for opening the airway in cases where conventional tracheotomy is difficult. This is a safe and easy technique involving removal of the anterior portion of the cricoid cartilage. Herein, we report the case of a patient with difficulty in neck extension due to severe kyphosis, who underwent cricotracheostomy. A 65-ye ar-old woman developed dyspnea and was transported to our hospital. SpO2 was 60% (room air) and endotracheal intubation was performed. She was managed on ventilator. However, weaning off the ventilator was difficult, and endotracheal intubation was prolonged. Subsequently, the patient was referred to us for a tracheostomy. The patient was unable to maintain the supine position due to severe kyphosis, and computed tomography revealed that the brachiocephalic artery was running just below the thyroid gland. Therefore, conventional tracheostomy was difficult to perform, and we performed cricotracheostomy instead. After the cricotracheostomy, there were no tracheal problems, such as tracheal stenosis and stomal hemorrhage. Cricotracheostomy can be performed in cases where multiple anatomical difficulties may be faced in the tracheostomy site, as in this case. Furthermore, cricotracheostomy is beneficial for long-term airway management because it causes fewer complications com pared to conventional tracheotomy. PMID:35188407 | DOI:10.1177/01455613221077596 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.