MEK Inhibitors for Neurofibromatosis Type 1 Manifestations: Clinical Evidence and Consensus

alexandrossfakianakis shared this article with you from Inoreader MEK Inhibitors for Neurofibromatosis Type 1 Manifestations: Clinical Evidence and Consensus via Neuro-Oncology Advance Access Abstract The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 has made it the first medical therapy approved for this indication in the United States, the European Union and elsewhere. Several recently published and ongoing clinical trials have demonstrated that MEKi may have potential benefit for a variety of other NF1 manifestations, and there is broad interest in the field regarding the appropriate clinical use of these agents. In this review, we present the current evidence regarding the use of existing MEKi for a variety of NF1-related manifestations, including tumor (neurofibromas, malignant peripheral nerve sheath tumors, low grade glioma, and juvenile myelomonocytic leukemia) and non-tumor (bone, pain, and neurocognitive) manifestations. We discuss the potential utility of MEKi in related genetic conditions characterized by overactivation of the RAS pathway (RASopathies). In addition, we review practical treatment considerations for the use of MEKi as well as provide consensus recommendations regarding their clinical use from a panel of experts. View on Web

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Sound Induced Vibrations Deform the Organ of Corti Complex in the Low-Frequency Apical Region of the Gerbil Cochlea for Normal Hearing

alexandrossfakianakis shared this article with you from Inoreader Sound Induced Vibrations Deform the Organ of Corti Complex in the Low-Frequency Apical Region of the Gerbil Cochlea for Normal Hearing via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com AbstractHuman speech primarily contains low frequencies. It is well established that such frequencies maximally excite the cochlea near its apex. But, the micromechanics that precede and are involved in this transduction are not well understood. We measured vibrations from the low-frequency, second turn in intact gerbil cochleae using optical coherence tomography (OCT). The data were used to create spatial maps that detail the sound-evoked motions across the sensory organ of Corti complex (OCC). These maps were remarkably similar across animals and showed little variation with frequency or level. We identify four, anatomically distinct, response regions within the OCC: the basilar membrane (BM), the outer hair cells (OHC), the lateral compartment (lc), and the tectorial membrane (TM). Resu... View on Web

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Performance of the Neck Imaging Reporting and Data System as applied by general neuroradiologists to predict recurrence of head and neck cancers

alexandrossfakianakis shared this article with you from Inoreader Performance of the Neck Imaging Reporting and Data System as applied by general neuroradiologists to predict recurrence of head and neck cancers via Head & Neck Abstract Background The Neck Imaging Reporting and Data System (NI-RADS) is used to assess imaging after head and neck cancer treatment. We evaluated NI-RADS with general neuroradiologists rather than with head and neck subspecialists. Methods Computed tomography and magnetic resonance imaging examinations with/without positron emission tomography from May 2018 to September 2020 were retrospectively identified. NI-RADS scores at the primary site and lymph nodes were provided by 21 neuroradiologists. Recurrence status was based on clinical and imaging findings. Area under the curve (AUC) was used to assess accuracy. Results We assessed 608 scans from 464 patients. For NI-RADS categories 1, 2, and 3, primary site recurrence rates were 5%, 29%, and 65% with AUC of 0.765, while lymph node recurrence rates were 3%, 10%, and 80% with AUC of 0.820. Conclusions NI-RADS as used by general neuroradiologists is effective in separating head and neck cancers into discrete categories for predicting recurrent disease. View on Web

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Deriving prognostic significance from a molecular subtype model of laryngeal carcinoma

alexandrossfakianakis shared this article with you from Inoreader Deriving prognostic significance from a molecular subtype model of laryngeal carcinoma via Head & Neck Abstract Background This study explored whether laryngeal carcinoma could be divided into different subtypes based on molecular differences using a molecular subtype-prediction model. Methods We extracted data from the Cancer Genome Atlas and Gene Expression Omnibus databases and then performed unsupervised cluster analysis to identify discrete molecular subtypes of laryngeal carcinoma. Significance analysis of microarrays was performed to detect differentially expressed genes for each subtype, and gene set enrichment analysis and the GenCliP3 software were used to label gene functions and identify key pathways. Results We categorized 126 patients into C1 and C2 molecular subtypes associated with pathologic grade. The C2 subtype appeared more aggressive, with a worse prognosis. The most significant enrichment pathway of the C2 subtype was the Hedgehog pathway, and GLI1 was a core gene. Conclusions Laryngeal carcinoma can be divided into two subtypes based on differences in molecular expression, which could identify key molecules associated with prognosis. View on Web

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Influence of supplement administration of omega‐3 on the subcutaneous tissue response of endodontic sealers in Wistar Rats

alexandrossfakianakis shared this article with you from Inoreader Influence of supplement administration of omega‐3 on the subcutaneous tissue response of endodontic sealers in Wistar Rats via International Endodontic Journal Abstract Aim Natural substances such as omega-3 have been used in the medical field due to their numerous properties and, in particular, modulating effect on the systemic and local inflammatory processes. Thus, this study evaluated the influence of omega-3 supplementation on the subcutaneous tissue response of endodontic sealers in Wistar Rats. Methodology Polyethylene tubes were implanted in the subcutaneous tissue of 48 animals (one empty for control and three filled with Sealapex, AH Plus or Endofill). The animals were treated with omega-3 (TO) or water (TW). Treatments started 15 days before implantation until euthanasia. After 5, 15 and 30 days (n=8), animals were euthanized and polyethylene tubes and surrounding tissue were removed and processed for histological analysis. The inflammatory reaction was analysed by Haematoxylin and Eosin stain and immunolabeling for IL-6 and TNF-α. The collagen maturity was analysed by picrosirius red stain and calcium deposition by von Kossa stain and polarized light. Results were statistically analysed (p<0.05). Results Among TW sealers groups, Endofill evoked a more intense inflammatory infiltrate compared with AH Plus and control in the 30-day period (p=0.009). However, in TO sealers groups, there was no difference among the sealers and control in all periods (p>0.05). Comparing each sealer as a function of the supplementation with water or omega-3, there are differences for Endofill (p=0.001) and Sealapex (p=0.005) in the 30-day period, presenting lower inflammatory infiltrate in the animals treated with omega 3. A higher percentage of immature fibres was observed at 15 and 30 days in the TO group, compared with TW group (p<0.05). The deposition of calcium particles was observed only by Sealapex in all periods, despite the supplementation procedure. Conclusions Omega-3 supplementation influence the tissue reactions of endodontic sealers, modulating inflammation, the immunolabeling of IL-6 and TNF-α, the repair process and it does not interfere with calcium deposition. View on Web

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Immediate curative effects of exercise therapy in patients with myalgia of the masticatory muscles

alexandrossfakianakis shared this article with you from Inoreader Immediate curative effects of exercise therapy in patients with myalgia of the masticatory muscles via Journal of Oral Rehabilitation Abstract Background Exercise therapy is occasionally considered as an initial treatment for temporomandibular disorders. However, pain can be exacerbated during exercise therapy. Objective To investigate the immediate curative effects of exercise therapy in patients with masticatory muscle myalgia. Methods Fifty-nine patients with masticatory muscle myalgia were included. Therapists performed exercise therapy (stretched the painful masseter and/or cervical muscles along the direction of muscle contraction) in 10 rounds of traction, each lasting 10 seconds. The patient's pain-free maximum mouth opening distance and degree of pain (VAS value) before and immediately after exercise therapy were compared using the Wilcoxon signed rank test. Mann-Whitney U test was used for the subgroup comparisons. Results Mouth opening increased from 41 (IQR 38–43) to 46 (IQR 43–48) mm, and pain alleviation from 48 (IQR 31–56) to 21 (IQR 10–56) immediately following exercise therapy (p < 0.001 for both). None of the patients experienced pain exacerbation or reduction in mouth opening post exercise. No difference in mouth opening distance changes according to sex, painful side, painful site, and therapist were observed (p > 0.05 for all). Pain reduction was greater in patients with unilateral pain (26, IQR 12–39) than those with bilateral (13, IQR 5–25) (p = 0.019). There were no differences in the change in the degree of pain according to sex, painful site, and therapist (p > 0.05 for all). Conclusion Exercise therapy immediately enlarged the mouth opening distance and reduced myalgia; therefore, it could be helpful in managing masticatory muscle myalgia. View on Web

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