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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Abutment mechanical complications of a Morse taper connection implant system: A 1‐ to 9‐year retrospective study

alexandrossfakianakis shared this article with you from Inoreader Abutment mechanical complications of a Morse taper connection implant system: A 1‐ to 9‐year retrospective study via Clinical Implant Dentistry and Related Research Abstract Background The fracture of a Morse tapered abutment connection in an osseointegrated implant is one of the most serious mechanical complications, and it is extremely hard to deal with this complication in clinical practice. Purpose The aim of this study was to explore the cumulative mechanical complications focus on abutment of a platform switching Morse taper connection implant system after loading, and to perform a retrospective, approximately 1- to 9-year follow-up study to identify the predisposing factors. Materials and Methods A total of 495 patients with 945 fitted implants were enrolled in this study with a follow-up from January 2012 to January 2020. The data of mechanical complications of the abutment, including abutment fracture (AF) and abutment screw loosening (ASL), and possible causative factors were extracted and evaluated statistically. Results A total of 25 out of 945 (2.65%) cumulative abutment mechanical complications occurred. AF was the most common complication (n = 13, 1.38%), followed by ASL (n = 12, 1.27%). For AF, gender, type of prosthesis, abutment design, and implant diameter were identified as the causative factors. AF was mostly observed in the single crown of males in molar areas, while ASL was more likely to occur on an angled abutment than on a non-angled abutment. Moreover, the abutment with the positioning index (/X) had a higher incidence of fracture than the abutment without the positioning index (C/). Conclusions This study shows that the Morse taper connection is a safe abutment connection. AF occurs more frequently within single crowns in molar area of males, especially with the positioning index (/X), while ASL is more likely to occur in an angled abutment. 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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Characterizing the Relationship Between Reflection and Distortion Otoacoustic Emissions in Normal-Hearing Adults

alexandrossfakianakis shared this article with you from Inoreader Characterizing the Relationship Between Reflection and Distortion Otoacoustic Emissions in Normal-Hearing Adults via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com AbstractOtoacoustic emissions (OAEs) arise from one (or a combination) of two basic generation mechanisms in the cochlea: nonlinear distortion and linear reflection. As a result of having distinct generation processes, these two classes of emissions may provide non-redundant information about hair-cell integrity and show distinct sensitivities to cochlear pathology. Here, we characterize the relationship between reflection and distortion emissions in normal hearers across a broad frequency and stimulus-level space using novel analysis techniques. Furthermore, we illustrate the promise of this approach in a small group of individuals with mild-moderate hearing loss. A "joint-OAE profile" was created by measuring interleaved swept-tone stimulus-frequency OAEs (SFOAEs) and 2f1-f2 distorti... View on Web

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Real‐life impact of tenofovir disoproxil fumarate and entecavir therapy on lipid profile, glucose and uric acid in chronic hepatitis B patients

alexandrossfakianakis shared this article with you from Inoreader Real‐life impact of tenofovir disoproxil fumarate and entecavir therapy on lipid profile, glucose and uric acid in chronic hepatitis B patients via Journal of Medical Virology Abstract Background & Aims The impact of long-term nucleos(t)ide analogs treatment on host metabolism is a concern. Hence, we conducted this study to compare the effect of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on metabolic parameters among CHB patients. Methods In this real-life retrospective study, 2,030 CHB outpatients treated with ETV or TDF at Nanfang Hospital, China, were included. For treatment-naïve patients, pretreatment and semiannual metabolic parameters were collected. For treatment-experienced patients, metabolic parameters were collected at the first visit. Propensity score matching (PSM) was used to balance the effects of potential confounding factors. Results Among 122 treatment-naïve patients and 1908 treatment-experienced patients, ETV-treated patients were older with a higher percentage of metabolic syndrome. After PSM, the characteristics were comparable between the two groups. For treatment-naïve patients, fou r lipid parameters, including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein and triglyceride levels showed a decreasing trend during the 42-month TDF treatment, while they remained relatively stable or increased during ETV treatment. At month 30, the levels of TC and LDL among TDF-treated patients were significantly lower than those among ETV-treated patients (TC: 4.7 vs. 3.9 mmol/L, p=0.004; LDL: 3.0 vs. 2.4 mmol/L, p=0.009). For treatment-experienced patients, we also observed lower levels of lipid parameters in patients with different durations of TDF treatment. The levels of glucose and uric acid were similar among ETV- and TDF-treated patients. Conclusion TDF has a lipid-lowering effect in CHB patients, which provides a basis for the selection of antiviral drugs for aging CHB patients. This article is protected by copyright. All rights reserved. View on Web

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A seroepidemiological study across age groups before and after the 2010–2011 mumps epidemic in Japan

alexandrossfakianakis shared this article with you from Inoreader A seroepidemiological study across age groups before and after the 2010–2011 mumps epidemic in Japan via Journal of Medical Virology Abstract In Japan, large-scale mumps epidemics recur every 4–6 years because of low vaccination coverage. This study aimed to describe the seroprevalence of mumps in the Japanese population and identify the age groups most affected. The prevalence of anti-mumps antibodies was evaluated based on 1000 serum samples obtained from the Japanese National Serum Reference Bank. These samples consisted of 50 sera for each of 10 different age groups, collected during 2007–2008 (pre-epidemic period) and 2012–2013 (post-epidemic period). Seropositivity was lowest in the 6–11 months subgroup (3% and 0% in pre- and post-epidemic periods, respectively) and highest in the 10–14 years group (66% and 72% in pre- and post-epidemic periods, respectively). A comparison of anti-mumps antibody prevalence throughout the two periods considered revealed a large rise seropositivity among the 2004–2008 birth cohort, using that of the 1–4 years group as representative in the pre-ep idemic period (from 22% in pre- to 58% in post-epidemic periods) (P=0.0002). These results indicate that most people likely gain antibodies to the mumps virus during their childhood, especially during the first epidemic that they experience after their second year of life. Therefore, children should be vaccinated against mumps soon after their first birthday for effective prevention. This article is protected by copyright. All rights reserved. View on Web

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Longitudinal follow‐up of HPV16 sequence after cervical infection: low intra‐host variation and no correlation with clinical evolution

alexandrossfakianakis shared this article with you from Inoreader Longitudinal follow‐up of HPV16 sequence after cervical infection: low intra‐host variation and no correlation with clinical evolution via Journal of Medical Virology ABSTRACT Human papillomavirus (HPV) 16 exhibits different variants that may differ in their carcinogenic risk. In order to identify some high-risk variants, we sequenced and compared HPV16 whole genomes obtained from a longitudinal cohort of 34 HPV16-infected women who had either spontaneously cleared their infection (clearance group or "C"), or developed cervical high-grade lesions following a viral persistence (group persistence or "P"). Phylogenetic analysis of paired samples obtained at the beginning (C0 or P0) and at the end (C2 or P2) of the follow-up (median intervals between C0-C2 and between P0-P2 were 16 and 36.5 months, respectively) revealed a low genetic variability within the host compared to the genetic inter-host diversity. By comparing our HPV16 sequences to a reference sequence, we observed 301 different substitutions, more often transitions (60.9%) than transversions (39.1%), that occurred throughout the viral genome, but with a low frequen cy in E6 and E7 oncogenes (10 and 9 substitutions), suggesting a high conservation of these genes. Deletions and insertions were mostly observed in intergenic regions of the virus. The only significant substitution found between the subgroups C2 and P2 was observed in the L2 gene (L330F), with an unclear biological relevance. Our results suggest a low longitudinal intra-host evolution of HPV16 sequences and no correlation between genetic variations and clinical evolution. This article is protected by copyright. All rights reserved. View on Web

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Voice and communication after open partial horizontal laryngectomies: A cross‐sectional outcome study

alexandrossfakianakis shared this article with you from Inoreader Voice and communication after open partial horizontal laryngectomies: A cross‐sectional outcome study via Head & Neck Abstract Objective The present study evaluates voice and communication after open partial horizontal laryngectomies (OPHLs), according to surgery and patient-related variables. Methods Fifty-eight patients were included: 18 type I OPHL, 20 type II OPHL and 20 type III OPHL. Acoustic, aerodynamic, endoscopic, perceptual and self-assessment analyses were carried out. Surgery-related variables and patient-related variables were considered for the analysis. Results Type I OPHL revealed the best phonatory outcomes. Type II and type III OPHL showed similar and poor results, with a highly deteriorated voice quality. A significant difference in MTP was found for patients who had both arytenoids/cricoarytenoid units preserved. Age and time from surgery showed significant correlations with voice quality after OPHLs. Conclusions Voice and communication outcomes after OPHLs are heterogeneous and might be influenced by several factors. Knowing variables with a substantial impact on phonatory outcomes may help clinicians in the preoperative decision-making process and the postoperative rehabilitative program. 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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