Tinnitus to Alpha Burst Transcranial Magnetic Stimulation.

ola Kala shared this article with you from Inoreader A Chart Review to Assess the Response of Veterans Suffering from Tinnitus to Alpha Burst Transcranial Magnetic Stimulation. Μέσω tinnitus Related Articles A Chart Review to Assess the Response of Veterans Suffering from Tinnitus to Alpha Burst Transcranial Magnetic Stimulation. Int Tinnitus J. 2020 Nov 18;24(1):40-48 Authors: Ring A, Crowder C, Wyer SL, Phillips B Abstract OBJECTIVE: The purpose of this chart review was to assess the response of veterans suffering from tinnitus to Magnetic EEG/EKGguided resonance therapy and Alpha Burst Stimulation (ABS), while also investigating the safety profile of this therapy combination. EEG/EKG-guided Repetitive Transcranial Magnetic Stimulation (rTMS) delivers high-energy electromagnetic pulses to induce current flow in the neocortex. ABS provides rTMS pulses in short, high-frequency bursts. MATERIALS AND METHODS: All equipment used to evaluate and treat participants are either FDA-cleared or are exempt from clearance and listed with the United States FDA. Stimulation was delivered with a MagPro R30 and an MCF-B65 butterfly coil. Charts were reviewed from patients who had received a combination of EEG/EKG-guided rTMS and ABS therapy to relieve symptoms of tinnitus. Paired samples t-tests were performed on the Tinnitus Functional Index (TFI) and Neurobehavioral Symptom Inventory (NSI) scales. Treatment logs and therapy notes were reviewed for safety data. Adverse events or side effects were extracted from therapy notes. Linear regression was used to analyze the relationship between number of therapy sessions, and reported patient symptoms. RESULTS: Eighteen of the 23 patients reported significant improvements in tinnitus symptoms. For patients reporting improvements, there was an average 44% reduction in tinnitus symptoms and a 60% reduction in NSI scores following intervention. No patients experienced adverse side effects. The most common side effects were headache and fatigue. CONCLUSION: Based on the results from this study, noninvasive neuromodulation holds promise as a potential treatment for tinnitus. Additional investigation in controlled studies may be warranted. PMID: 33206487 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical and morphological results of xenografts to use in myringoplasty.

ola Kala shared this article with you from Inoreader Clinical and morphological results of xenografts to use in myringoplasty. Μέσω tinnitus Related Articles Clinical and morphological results of xenografts to use in myringoplasty. Int Tinnitus J. 2020 Nov 18;24(1):1-6 Authors: Aj B, Khm M, Us K, Sh K, No A, Ja D, Az S, Se A Abstract The main aim of our study was to study morphological state of the autograft from the fascia of the temporal muscle in myringoplasty. Until now, there is no consensus on issue of which fabrics are more suitable for use in the eardrum. We decided to study of use of an autograft from the fascia of the temporal muscle for myringoplasty in rabbits in the experiment, and in patients with chronic dry mesotympanitis. An electron microscopic examination of the fascia taken immediately, after 10, 20 min and 1 h after sampling. It was found that there are no gross destructive changes in the fascia structure. Minor changes are detected in the form of a light disorganization of the collagen complex, granular dystrophy with an increase in cell. Inflammatory diseases of the middle ear are widespread among population of all age groups. In the experiment, a positive result was obtained in 29 (82.8%) rabbits. In our research we performed morphological features of xenograft engraftment in an ex perimental animal on 3, 7, 14, 21 days and 1-3 months. In period from 3 days to 3 months after operation, the animals were euthanized by an air embolism and subjected to pathological examination. Then recovered xenograft, was examined macro and microscopically. Pieces were fixed in a 10% solution of neutral formalin. After washing with water, dehydration was carried out in alcohol and chloroform, and after, waxed with paraffin. Histological sections were stained with hematoxylin-eosin. Collagen fibers were detected by method of Vann-Gieson. PMID: 33206488 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Influence of Cochlear Implantation on Balance Function in Pediatrics.

ola Kala shared this article with you from Inoreader Influence of Cochlear Implantation on Balance Function in Pediatrics. Μέσω tinnitus Related Articles Influence of Cochlear Implantation on Balance Function in Pediatrics. Int Tinnitus J. 2020 Nov 18;24(1):xxx-xx Authors: Bayat A, Farhadi M, Emamdjomeh H, Nadimi Z, Mirmomeni G, Saki N Abstract BACKGROUND AND OBJECTIVE: Patients with profound Sensorineural Hearing Loss (SNHL) are susceptible to vestibular disturbances following Cochlear Implant (CI) surgery. This study aimed to evaluate vestibular dysfunctions following unilateral CI in the congenitally deaf children. METHODS: This was a cross-sectional study conducted on 24 children (mean age: 10.56 ± 5.49 years old) who underwent unilateral CI and 24 age-matched controls (mean age: 11.13 ± 6.21 years old). Vestibular functions were assessed by Vestibular Evoked Myogenic Potential (VEMP) and Computerized Dynamic Posturography (CDP). The VEMP test was performed for otolith's function (especially saccule) evaluation. Sensory Organization Test (SOT) protocol of CDP was also utilized to differentiate the role of various sensory systems contributing to postural stability. In addition, total equilibrium score was calculated. The variables were comparatively assessed between the two groups. RESULTS: The mean p13-n23 amplitude in the CI users was significantly lower than the controls (p<0.05). However, the two groups showed no significant difference in cVEMP latency values (p>0.05). The SOT analysis revealed that 45.83% (11/24) of the CI subjects had some kind of sensory abnormalities: 7 cases (29.17%) vestibular, 2 cases (8.33%) visual, 2 cases (8.33%) vestibular and somatosensory involvements. Furthermore, total equilibrium score was significantly reduced in implanted group than the controls (p<0.001). At least, 70.59% (12/24) CI patients showed abnormal values in the CDP or cVEMP examinations. CONCLUSION: This study shows functional vestibular impairments in children who underwent CI. These patients showed significantly increased postural instability which was more evident in dynamic conditions. These findings provide the basis for better pre-operative counseling and postoperative vestibular rehabilitation to CI recipients. PMID: 33206489 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Safety and clinical activity of a new anti-PD-L1 antibody as monotherapy or combined with targeted therapy in advanced solid tumors: the PACT phase Ia/Ib trial

Cancer shared this article with you from Inoreader Safety and clinical activity of a new anti-PD-L1 antibody as monotherapy or combined with targeted therapy in advanced solid tumors: the PACT phase Ia/Ib trial Via Clinical Cancer Research Online First Articles Purpose: This phase Ia/Ib PACT study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of a new PD-L1 inhibitor, LY3300054, as monotherapy or in combination with ramucirumab, abemaciclib, or merestinib (a type II MET kinase inhibitor) in patients with advanced, refractory solid tumors (NCT02791334). Patients and methods: Patients were enrolled into cohorts of escalating LY3300054 dose (phase Ia) as monotherapy (N=15) or combined with ramucirumab (N=10), abemaciclib (N=24), or merestinib (N=12). The phase Ib dose expansion enrolled eight patients with melanoma in the monotherapy arm and 12 patients with pancreatic cancer in the merestinib combination arm. Combination treatments were administered concurrently from day 1 of each cycle. A 14-day lead-in abemaciclib arm was also explored. Primary endpoints were dose-limiting toxicity (DLT) and safety. Results: Treatment-related adverse events included fatigue and nausea in the mon otherapy arm (13% for each), hypothyroidism (30%) in the ramucirumab arm, diarrhea (54%) in the abemaciclib arm, and nausea (25%) in the merestinib arm. DLTs associated with hepatoxicity were observed in three of four patients in the abemaciclib lead-in cohorts. No DLTs or grade 3 or 4 hepatoxicity were reported in the concurrent abemaciclib arm. Pharmacokinetic characteristics were comparable to other PD-L1 inhibitors. One patient in each arm experienced a partial response per RECIST v1.1 lasting ≥7 months. Conclusions: LY3300054 was well tolerated without unexpected safety concerns when administered alone or concurrently with ramucirumab, abemaciclib, or merestinib. Lead-in abemaciclib before combining with LY3300054 was not feasible due to hepatotoxicity. Durable clinical benefits were seen in all regimens. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Combined Inhibition of G{alpha}q and MEK Enhances Therapeutic Efficacy in Uveal Melanoma.

Cancer shared this article with you from Inoreader Combined Inhibition of G{alpha}q and MEK Enhances Therapeutic Efficacy in Uveal Melanoma. Via Clinical Cancer Research Online First Articles Purpose: All uveal melanoma and a fraction of other melanoma subtypes are driven by activation of the Gαq pathway. Targeting these melanomas has proven difficult despite advances in the molecular understanding of key driver signaling pathways in the disease pathogenesis. Inhibitors of Gαq have shown promising preclinical results, but their therapeutic activity in distinct Gαq mutational contexts and in vivo have remained elusive. Experimental Design: We used an isogenic melanocytic cellular system to systematically examine hotspot mutations in GNAQ (e.g., G48V, R183Q, Q209L) and CYSLTR2 (L129Q) found in human uveal melanoma. This cellular system and human uveal melanoma cell lines were used in vitro and in vivo xenograft studies to assess the efficacy of Gαq inhibition as a single agent and in combination with MEK inhibition. Results: We demonstrate that the Gαq inhibitor YM-254890 inhibited downstream signaling and in vitro growth in all mutants. In vivo, YM-254890 slowed tumor growth but did not cause regression in human uveal melanoma xenografts. Through comprehensive transcriptome analysis, we observed that YM-254890 caused inhibition of the MAPK signaling with evidence of rebound by 24 hours and combination treatment of YM-254890 and a MEK inhibitor led to sustained MAPK inhibition. We further demonstrate that the combination caused synergistic growth inhibition in vitro and tumor shrinkage in vivo. Conclusions: These data suggest that the combination of Gαq and MEK inhibition provides a promising therapeutic strategy and improved therapeutic window of broadly targeting Gαq in uveal melanoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Therapeutic potential of NTRK3 inhibition in desmoplastic small round cell tumor

Cancer shared this article with you from Inoreader Therapeutic potential of NTRK3 inhibition in desmoplastic small round cell tumor Via Clinical Cancer Research Online First Articles Purpose: Desmoplastic small round cell tumor (DSRCT) is a highly lethal intra-abdominal sarcoma of adolescents and young adults. DSRCT harbors a t(11;22)(p13:q12) that generates the EWSR1-WT1 chimeric transcription factor, the key oncogenic driver of DSRCT. EWSR1-WT1 rewires global gene expression networks and activates aberrant expression of targets that together mediate oncogenesis. EWSR1-WT1 also activates a neural gene expression program. Experimental Design: Among these neural markers, we find prominent expression of neurotrophic tyrosine kinase receptor 3 (NTRK3), a druggable receptor tyrosine kinase. We investigated the regulation of NTRK3 by EWSR1-WT1 and its potential as a therapeutic target in vitro and in vivo, the latter using novel patient-derived models of DSRCT. Results: We find that EWSR1-WT1 binds upstream of NTRK3 and activates its transcription. NTRK3 mRNA is highly expressed in DSRCT compared to other major chimeric t ranscription factor-driven sarcomas and most DSRCT are strongly immunoreactive for NTRK3 protein. Remarkably, expression of NTRK3 kinase domain mRNA in DSRCT is also higher than in cancers with NTRK3 fusions. Abrogation of NTRK3 expression by RNAi silencing reduces growth of DSRCT cells and pharmacologic targeting of NTRK3 with entrectinib is effective in both in vitro and in vivo models of DSRCT. Conclusions: Our results indicate that EWSR1-WT1 directly activates NTRK3 expression in DSRCT cells, which are dependent on its expression and activity for growth. Pharmacologic inhibition of NTRK3 by entrectinib significantly reduces growth of DSRCT cells both in vitro and in vivo, providing a rationale for clinical evaluation of NTRK3 as a therapeutic target in DSRCT. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Recommendation regarding the cranial upper border of level IIb in delineating clinical target volumes (CTV) for nasopharyngeal carcinoma

Cancer shared this article with you from Inoreader Recommendation regarding the cranial upper border of level IIb in delineating clinical target volumes (CTV) for nasopharyngeal carcinoma Via Latest Results for Radiation Oncology Abstract Purpose To recommend a cranial border for level IIb in delineating clinical target volumes (CTV) for nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy and to help reach a consensus on contouring level IIb in CTV. Methods From 2012 to 2016, 331 nonmetastatic NPC patients treated with IMRT were retrospectively enrolled. Based on the AJCC 8th staging system of NPC, there were 15 stage I, 76 stage II, 103 stage III, and 137 stage IV patients. The distribution of cervical lymph nodes in NPC was assessed based on imaging. Comparisons of the safety and parotid dose parameters between patients with and without a reduction in the size of level IIb were conducted using SPSS 25.0 and R 2.14.2 software. Results Metastasis rates in the most commonly involved lymph nodes, the lateral retropharyngeal and IIb nodes, were 82.8% and 64.0%, respectively. Among patients with level IIb involvement, the upper borders of the metastatic nodes were beyond the caudal edge of C1 in 13.7% of cases. The parotid gland D50 and V26 values were significantly reduced after modifying the upper bound of level IIb used to delineate the CTV (P = 0.000). Conclusion In principle, the upper bound of level IIb should reach the lateral skull base during delineation of the cervical CTV for NPC. To protect the parotid glands, however, individualized reduction of the upper bound of level IIb is recommended for patients who meet certain criteria. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.