The presence of TIM‐3 positive cells in WHO grade III and IV astrocytic gliomas correlates with isocitrate dehydrogenase mutation status

pa.ythelady61 shared this article with you from Inoreader The presence of TIM‐3 positive cells in WHO grade III and IV astrocytic gliomas correlates with isocitrate dehydrogenase mutation status Via Brain Pathology Abstract Diffuse gliomas are aggressive brain tumors that respond poorly to immunotherapy including immune checkpoint inhibition. This resistance may arise from an immunocompromised microenvironment and deficient immune recognition of tumor cells due to low mutational burden. The most prominent genetic alterations in diffuse glioma are mutations in the isocitrate dehydrogenase (IDH) genes that generate the immunosuppressive oncometabolite D‐2‐hydroxyglutarate. Our objective was to explore the association between IDH mutation and presence of cells expressing the immune checkpoint proteins galectin‐9 and/or T‐cell immunoglobulin and mucin‐domain containing‐3 (TIM‐3). Astrocytic gliomas of World Health Organization (WHO) grades III or IV (36 IDH‐mutant and 36 IDH‐wildtype) from 72 patients were included in this study. A novel multiplex chromogenic immunohistochemistry panel was applied using antibodies against galectin‐9, TIM‐3, and the oligodendrocyte transcription fact or 2 (OLIG2). Validation studies were performed using data from The Cancer Genome Atlas (TCGA) project. IDH mutation was associated with decreased levels of TIM‐3+ cells (P < 0.05). No significant association was found between galectin‐9 and IDH status (P = 0.10). Most TIM‐3+ and galectin‐9+ cells resembled microglia/macrophages, and very few TIM‐3+ and/or galectin‐9+ cells co‐expressed OLIG2. The percentage of TIM‐3+ T cells was generally low, however, IDH‐mutant tumors contained significantly fewer TIM‐3+ T cells (P < 0.01) and had a lower interaction rate between TIM‐3+ T cells and galectin‐9+ microglia/macrophages (P < 0.05). TCGA data confirmed lower TIM‐3 mRNA expression in IDH‐mutant compared to IDH‐wildtype astrocytic gliomas (P = 0.013). Our results show that IDH mutation is associated with diminished levels of TIM‐3+ cells and fewer interactions between TIM‐3+ T cells and galectin‐9+ microglia/macrophages, suggesting reduced activity of the galectin‐9/TIM‐3 immune checkpoint pathway in IDH‐mutant astrocytic gliomas. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Distinct circular RNA expression profiles in pediatric ependymomas

pa.ythelady61 shared this article with you from Inoreader Distinct circular RNA expression profiles in pediatric ependymomas Via Brain Pathology Abstract Pediatric ependymomas frequently develop in the cerebellum and are currently treated using non‐specific therapies, in part, because few somatically mutated driver genes are present, and the underlying pathobiology is poorly described. Circular RNAs (circRNAs) constitute as a large class of primarily non‐coding RNAs with important roles in tumorigenesis, but they have not been described in pediatric ependymomas. To advance our molecular understanding of ependymomas, we performed Next Generation Sequencing (NGS) of rRNA‐depleted total RNA of 10 primary ependymoma and 3 control samples. CircRNA expression patterns were correlated to disease stage, outcome, age and gender. We found a profound global downregulation of circRNAs in ependymoma relative to control samples. Many differentially expressed circRNAs were discovered and circSMARCA5 and circ‐FBXW7, which are described as tumor suppressors in glioma and glioblastomas in adults, were among the most downregulated. Moreover, patients with a dismal outcome clustered separately from patients with a good prognosis in unsupervised hierarchical cluster analyses. Next, NanoString nCounter experiments were performed, using a custom‐designed panel targeting 66 selected circRNAs, on a larger cohort that also included medulloblastomas and pilocytic astrocytomas. These experiments indicated that circRNA expression profiles are different among distinct pediatric brain tumor subtypes. In particular, circRNAs derived from RMST, LRBA, WDR78, DRC1 and BBS9 genes were specifically upregulated in ependymomas. In conclusion, circRNAs have different expression profiles in ependymomas relative to controls and between survivors and patients with a dismal outcome, suggesting that circRNAs could be exerted as diagnostic and prognostic biomarkers in the future if further validated in larger cohorts. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Limitations of preoperative cytology for medullary thyroid cancer: Proposal for improved preoperative diagnosis for optimal initial medullary thyroid carcinoma specific surgery

pa.ythelady61 shared this article with you from Inoreader Limitations of preoperative cytology for medullary thyroid cancer: Proposal for improved preoperative diagnosis for optimal initial medullary thyroid carcinoma specific surgery Via Head & Neck Abstract Background Preoperative diagnosis of medullary thyroid carcinoma (MTC) is often difficult, given the poor sensitivity of fine‐needle aspiration (FNA) cytology for MTC. This study investigates this issue and presents recommendations for improving preoperative diagnostic paradigms in MTC cases. Design/Method Histopathologically confirmed MTC patients with preoperative cytologic assessment of index nodules were enrolled. FNA diagnosis, final pathology, and surgery details were collected. Results Out of 71 patients, 49 (69%) were diagnosed by FNA as either definitive MTC (35, 49%) or suspected MTC (14, 20%) and 22 (31%) patients had no indication of MTC on FNA. Conclusion In a tertiary‐care setting, one‐third of subjects had an FNA interpretation that did not suggest the possibility of MTC. The limitations of preoperative diagnosis are especially problematic for MTC as they can cause delayed or incomplete treatment. Additional testing is proposed to improve preoperative diagnosis and surgical care of MTC patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Preliminary development and validation of a measure of fear of swallowing and swallowing‐related movement injury in head and neck cancer: Swallowing Kinesiophobia Scale

pa.ythelady61 shared this article with you from Inoreader Preliminary development and validation of a measure of fear of swallowing and swallowing‐related movement injury in head and neck cancer: Swallowing Kinesiophobia Scale Via Head & Neck Abstract Background Fear is an under‐recognized issue in intervention adherence in head and neck cancer (HNC). We developed and validated a patient reported outcome for swallowing fear in HNC patients. Methods Items were adapted from the Tampa Scale for Kinesiophobia to swallowing function. A beta version was completed by 51 HNC patients undergoing chemo +/− radiotherapy at baseline and post‐treatment. Psychometric and factor structure analyses were applied. Results Swallowing Kinesiophobia Scale (SWKS) demonstrated strong face and content validity, internal consistency, and test‐retest reliability. Factor analysis revealed three‐factors: somatic factor, swallow avoidance, and fear of harm. Factors correlated positively with depression score, worry scale, and anxiety and pain scales. Score differences between patient subgroups (dysphagic vs nondysphagic) confirmed discriminative validity. Conclusion The SWKS is a psychometrically valid tool to identify patients with fear of swallowing and swallowing‐related movement. It can help identify patients early in treatment who may need additional support. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Treatment choice in single‐sided deafness and asymmetric hearing loss. A prospective, multi‐center cohort study on 155 patients

pa.ythelady61 shared this article with you from Inoreader Treatment choice in single‐sided deafness and asymmetric hearing loss. A prospective, multi‐center cohort study on 155 patients Via Clinical Otolaryngology Abstract Objectives To describe the treatment choice in a cohort of subjects with single‐sided deafness (SSD) and asymmetric hearing loss (AHL). To assess the reliability of the treatment trials. Design In this national, multi‐centre, prospective study, the choice of subjects was made after two consecutive trials of Contralateral Routing Of the Signal (CROS) hearing aids and a Bone Conduction Device (BCD) on a headband. Subjects could proceed with one of these two options, opt for cochlear implantation or decline all treatments. Setting Seven tertiary university hospitals. Participants 155 subjects with SSD or AHL fulfilling the candidacy criteria for cochlear implantation, with or without associated tinnitus. Main outcome measures After the two trials, the number of subjects choosing each option was described. Repeated assessments of both generic and auditory‐specific quality of life were conducted, as well as hearing assessments (speech recognition in noise and horizontal localization). Results CROS was chosen by 75 subjects, followed by cochlear implantation (n=51), BCD (n=18) and abstention (n=11). Patients who opted for cochlear implantation had a poorer quality of life (p=0.03). The improvement of quality of life indices after each trial was significantly associated with the final treatment choice (p=0.008 for generic indices, p=0.002 for auditory specific indices). The follow‐up showed that this improvement had been overestimated in the CROS group, with a long‐term retention rate of 52.5%. Conclusions More than one third of SSD/AHL subjects are unsatisfied after CROS and BCD trials. Repeated quality of life assessments help counselling the patient for his/her treatment choice. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Singing voice range profile: new objective evaluation methods for voice change after thyroidectomy

pa.ythelady61 shared this article with you from Inoreader Singing voice range profile: new objective evaluation methods for voice change after thyroidectomy Via Clinical Otolaryngology Abstract Background After surgery in the thyroid region, patients may present with phonation or singing difficulty, even within their vocal range. We designed a novel voice evaluation method that reflects subjective and objective voice complications of the surgery. Methods This tool recorded patients' voice ranges while singing, which was named the singing voice range profile (singing VRP). Patients were asked to sing "Happy Birthday", which has a one‐octave scale, at a comfortable tone and intensity. The singing VRP, standard VRP, and voice handicap index‐10 (VHI‐10) results were recorded before thyroidectomy and 1 and 3 months after thyroidectomy for 128 patients. For subgroup analysis, a group where the maximum F0 of standard VRP in 1 month postoperatively was lower than the highest singing F0 of the preoperative singing VRP was defined as "Collapsed group" and the other group was "Preserved group". Results The changes in the highest, lowest, and range of singing fundamental frequency (F0) had decreased at 1 month postoperatively. Subsequently, they had improved significantly at 3 months postoperatively but were lower than those preoperatively (all p < .05, except for the change in the lowest singing F0 between 1 and 3 months postoperatively, p = .274). In the subgroup analysis, the singing range of the collapsed group (n = 65) showed significantly lower VHI‐10 scores, range of vocal F0, and singing F0 than those of the preserved group (n = 63) at 1 and 3 months postoperatively (all p < .001). At 3 months postoperatively, the singing F0 range in the preserved group had recovered to the range before surgery (13.0 ± 1.3 vs. 13.1 ± 1.4, p = .746 for the preserved group, and 13.0 ± 1.3 vs. 11.5 ± 2.4, p < .001 for the collapsed group). Conclusions Parameters measured by singing VRP showed a trend similar to the change in VHI‐10 and the maximum F0 of standard VRP. In addition, singing VRP allowed a qualitative classification of the postoperative voice function when combined with standard VRP. Therefore, it can be used as a supplementary voice evaluation tool to reflect the physiologic and functional aspects of voice. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Facial and hearing outcomes in transmastoid nerve decompression for Bell’s palsy, with preservation of the ossicular chain

pa.ythelady61 shared this article with you from Inoreader Facial and hearing outcomes in transmastoid nerve decompression for Bell's palsy, with preservation of the ossicular chain Via Clinical Otolaryngology Abstract Introduction Facial nerve decompression is a salvage treatment for Bell's palsy patients for whom a poor prognosis is anticipated with standard medical treatment. The transmastoid approach is a frequently performed approach, but it remains unknown if this surgery is effective when the ossicular chain is preserved. This study aimed to determine the efficacy of facial nerve decompression using the transmastoid approach in Bell's palsy. Methods This retrospective study included patients who had undergone transmastoid facial nerve decompression with ossicular chain preservation and patients who met the criteria for surgery, but received only medical treatment between January 2007 to May 2019, at a single centre. Results The recovery rate to House‐Brackmann grade I in the decompression group in the early phase (≤18 days after onset) was higher than that of the medical treatment group, although the difference was not significant (70% vs. 47%, P=0.160). However, within this early surgery group, a subgroup of cases with ≥95% facial nerve degeneration demonstrated a significant improvement in recovery rate (73% vs. 30%, P=0.018). Among surgeries performed in the late phase (≥19 days), only a subgroup with ≥95% facial nerve degeneration was available for analysis, and the difference in recovery rate was not significant compared with medical treatment alone (26% vs. 30%, P=1.00). Post‐surgical hearing evaluation demonstrated that average hearing deterioration was 1.3dB which was non‐significant, suggesting this procedure does not cause hearing loss. Conclusions Transmastoid facial nerve decompression with ossicular chain preservation in the early phase after symptom‐onset is an effective salvage treatment for severe Bell's palsy with ≥95% facial neve degeneration. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Long‐term Swallowing Outcomes of Radiotherapy and Transoral Laser Microsurgery for T1 Glottic Cancer Treatment

pa.ythelady61 shared this article with you from Inoreader Long‐term Swallowing Outcomes of Radiotherapy and Transoral Laser Microsurgery for T1 Glottic Cancer Treatment Via Clinical Otolaryngology Abstract Both CO2 transoral laser microsurgery (CO2 TOLMS) and radiotherapy (RT) are standard of care in early glottic carcinoma. However, previous studies focus on voice outcomes rather than swallowing outcomes. This study aimed to compare the late post‐treatment effects of CO2 TOLMS and RT treatment on swallowing function in T1 glottic carcinoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Changes in healthcare utilization for pediatric tonsillectomy and adenoidectomy in the Netherlands: a population‐based study

pa.ythelady61 shared this article with you from Inoreader Changes in healthcare utilization for pediatric tonsillectomy and adenoidectomy in the Netherlands: a population‐based study Via Clinical Otolaryngology Abstract Objectives Tonsillectomy and adenoidectomy in children are controversial subjects with large regional variation in treatment, partly explained by cultural differences and lack of high‐quality evidence on indications. A quality of care cycle was executed on this topic in the Netherlands. The objective of this study was to estimate changes in healthcare utilization for pediatric tonsil surgery during and after the quality of care cycle. Methods Population‐based data on tonsillectomies and adenoidectomies in children up to age 10 was retrieved retrospectively from Dutch administrative databases between 2005 and 2018. A change point analysis was performed to find the most pivotal change point in surgical rates. Surgical patients' characteristics before and after this point were compared descriptively. Impact on healthcare budget and societal costs were estimated using current prices and cost‐effectiveness analyses. Results The annual number of adenotonsillectomies reduced by 10952 procedures (‐39%; from 12.9 per 1000 children to 8.7 per 1000 children) between 2005 and 2018, and the number of adenoidectomies by 14757 procedures (‐49%; from 13.8 per 1000 children to 7.8 per 1000 children). The most pivotal change point was observed around 2012, accompanied by small changes in patient selection for surgery before and after 2012. An estimated €5.3 million per year was saved on the healthcare budget and €10.4 million per year on societal costs. Conclusion The quality of care cycle resulted in fewer operations, with a concomitant reduction of costs. We suggest that part of these savings be invested in new research to maintain the quality of care cycle. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Factors influencing long‐term treatment response to botulinum toxin injection for spasmodic dysphonia

pa.ythelady61 shared this article with you from Inoreader Factors influencing long‐term treatment response to botulinum toxin injection for spasmodic dysphonia Via Clinical Otolaryngology Abstract Objective The purpose of this study was to evaluate the outcomes of long‐term botulinum toxin type A (BoNTA) treatment for adductor spasmodic dysphonia (AdSD) and to determine the factors predictive of treatment response by investigating dose stability and average intervals. Design Retrospective cohort study. Setting Academic tertiary medical center. Exposures A total of 470 patients with adductor spasmodic dysphonia, who received electromyography‐guided BoNTA injections over 12 years, were retrospectively enrolled in this study. Main Outcomes and Measures The patients' demographic data, baseline voice dynamics, and treatment profiles (dose, frequency, and intervals) were evaluated. Factors correlating with the dose adjustment ratio (number of increasing dosing/total number of BoNTA toxin injections) and changes in intervals between injections were statistically analyzed. Results A total of 122 patients, who received ≥ 4 injections and whose average treatment interval was < 240 days, were finally evaluated. Of them, 115 (94.3 %) were female and seven (5.7 %) were male, and the mean age at initial treatment was 34.89 ± 13.07 and 41.14 ± 12.71 years, respectively. On average, patients received 18.00 ± 13.33 injections (1.67 ± 0.60 U/injection) to alternating unilateral vocal folds. The treatment period was 65.07 ± 43.28 months and the mean interval between injections was 4.16 ± 1.28 months. The mean dose adjustment ratio among patients who received ≥ 4 injections was 0.15 ± 0.13, and dose changes occurred 4.36 times/patient. The patients' age and gender significantly affected the treatment response, where younger or female patients showed greater dosing variability and shorter intervals between injections. However, the baseline voice dynamics (voice handicap index, fundamental frequency, jitter, shimmer, noise‐to‐harmonic ratio, maximum p honation time, and degree of voice breaks) did not predict the dose adjustment ratio or interval changes. In addition, patients with fluctuating doses showed lower age and higher VHI subscale scores, and patients with long treatment interval (≥ 100 days and < 240 days) showed higher SDF0. Conclusions Almost all patients received stable low doses of BoNTA over time, irrespective of the baseline results. Patients' age, gender, and VHI scores were correlated with poor treatment responses, such as frequent dose changes and shorter intervals between injections. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Factors related to a non‐localising technetium 99m sestamibi scan result during parathyroid adenoma imaging in primary hyperparathyroidism

pa.ythelady61 shared this article with you from Inoreader Factors related to a non‐localising technetium 99m sestamibi scan result during parathyroid adenoma imaging in primary hyperparathyroidism Via Clinical Otolaryngology Abstract Objectives The aim of this study is to investigate factors that are associated with having a non‐localising 99mTc‐sestamibi scan. Design A retrospective study was performed on patients that underwent parathyroid surgery performed within a single institution between 2001 and 2018. Setting Single tertiary centre for parathyroid surgery. Participants 230 patients underwent surgery for primary hyperparathyroidism due to a solitary parathyroid adenoma and had pre‐operative 99mTc‐sestamibi imaging. Main outcome measures Variables including age, gender, intra‐operative location of parathyroid adenoma, adenoma weight and pre‐ & post‐operative calcium and parathyroid hormone levels were investigated through univariate and multivariate analysis to identify any association with having a non‐localising (negative) 99mTc‐sestamibi scan result. Results Multivariate analysis identified that right‐sided adenomas (p=0.038), superior adenomas (p=0.042) and a lower pre‐operative PTH level (p=0.034) were all individual factors associated with having a negative 99mTc‐sestamibi scan result. Although the weight of the adenoma was significant on univariate analysis (p=0.029), this was not demonstrated on multivariate analysis (p=0.422). Conclusion Factors that were associated with having non‐localising 99mTc‐sestamibi scan were right‐sided adenomas, superior adenomas, and lower pre‐operative PTH level. Further large prospective multicentre studies are needed to further evaluate these initial findings. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Epstein‐Barr virus may contribute to the pathogenesis of adult‐onset recurrent respiratory papillomatosis: A preliminary study.

pa.ythelady61 shared this article with you from Inoreader Epstein‐Barr virus may contribute to the pathogenesis of adult‐onset recurrent respiratory papillomatosis: A preliminary study. Via Clinical Otolaryngology Abstract Objective Human papillomavirus (HPV) causes adult onset recurrent respiratory papillomatosis (AORRP), but AORPP prevalence is much lower than HPV prevalence. Thus, HPV infection is necessary, but not sufficient, to cause AORRP and other factors likely contribute to its pathogenesis. The present study aimed to investigate whether co‐infection with herpetic viruses may contribute to the pathogenesis of AORRP. Design Prospective case‐control study conducted from January 2018 to November 2019. Settings Tertiary referral center. Participants Eighteen consecutive patients with AORRP and 18 adults with healthy laryngeal mucosa (control group) undergoing surgery. Main outcome measures Cytomegalovirus, Epstein‐Barr virus (EBV), herpes simplex viruses 1 and 2, human herpesvirus 6, varicella zoster virus, and HPV (including genotyping) were detected in biopsies of papilloma or healthy mucosa using real‐time polymerase chain reaction and reverse line blot. Dysplasia and Ki67 levels were determined in papilloma specimens. Results EBV was present in 6 (33.3%) AORRP patients and no control patients (P=0.019). Presence was not dependent on tobacco exposure (P=0.413) or HPV genotype or concentration (P>0.999). EBV presence was strongly related to increased cell proliferation (P=0.005) and number of previous surgeries (P=0.039), but not dysplasia (P>0.999). Human herpesvirus 6 was found in 3 (16.7%) AORRP biopsies, with one false positive. No other herpetic virus was found. Conclusions Unlike other herpetic viruses, EBV seems to interact with HPV, enhancing cell proliferation and contributing to the pathogenesis and progression of AORRP. Further research is required to elucidate specific interactions and their role in the pathogenesis of AORRP. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.