Neurological Applications of Belzutifan in von Hippel Lindau Disease

alexandrossfakianakis shared this article with you from Inoreader Neurological Applications of Belzutifan in von Hippel Lindau Disease via Neuro-Oncology Advance Access Abstract Von Hippel Lindau (VHL) disease is a tumor predisposition syndrome caused by mutations in the VHL gene that presents with visceral neoplasms and growths, including clear cell renal cell carcinoma, and central nervous system manifestations, such as hemangioblastomas of the brain and spine. The pathophysiology involves a dysregulation of oxygen sensing caused by inability to degrade HIFα, leading to overactivation of hypoxic pathways. Hemangioblastomas are the most common tumors in patients with VHL and cause significant morbidity. Until recently, there were no systemic therapies available for patients that could effectively reduce the size of these lesions. Belzutifan, the first approved HIF-2α inhibitor, has demonstrated benefit in VHL-associated tumors, with a 30% response rate in hemangioblastomas and ~30-50% reduction in their sizes over the course of treatment. Anemia is the most prominent adverse eff ect, affecting 76-90% of participants and sometimes requiring dose reduction or transfusion. Other significant adverse events include hypoxia and fatigue. Overall, belzutifan is well tolerated; however, long term data on dosing regimens, safety, and fertility are not yet available. Belzutifan holds promise for treatment of neurological manifestations of VHL and its utility may influence the clinical management paradigms for this patient population. View on Web

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Global survival trends for brain tumours, by histology: analysis

alexandrossfakianakis shared this article with you from Inoreader Global survival trends for brain tumours, by histology: analysis of individual records for 67,776 children diagnosed in 61 countries during 2000-2014 (CONCORD-3) via Neuro-Oncology Advance Access Abstract Introduction Tumours of the central nervous system are among the leading causes of cancer-related death in children. Population-based cancer survival reflects the overall effectiveness of a health care system in managing cancer. Inequity in access to care world-wide may result in survival disparities. Methods We considered children (0-14 years) diagnosed with a brain tumour during 2000-2014, regardless of tumour behaviour. Data underwent a rigorous, three-phase quality control as part of CONCORD-3. We implemented a revised version of the International Classification of Childhood Cancer (3 rd edition) to control for under-registration of non-malignant astrocytic tumours. We estimated net survival using the unbiased non-parametric Pohar Perme estimator. Results The study included 67,776 children. We estimated survival for 12 histology groups, each based on relevant ICD-O-3 codes. Age-standardised five-year net survival for low-grade astrocytoma ranged between 84% and 100% world-wide during 2000-2014. In most countries, five-year survival was 90% or more during 2000-2004, 2005-2009 and 2010-2014. Global variation in survival for medulloblastoma was much wider, with age-standardised five-year net survival between 47% and 86% for children diagnosed during 2010-2014. Conclusions To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumours in children, by histology. We devised an enhanced version of ICCC-3 to account for differences in cancer registration practices world-wide. Our findings may have public health implications, because low-grade glioma is one of the six index childhood cancers included by WHO in the Global Initiative for Childhood Cancer. View on Web

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Fourteen years old as the best age cutoff to differentiate prepubertal from pubertal papillary thyroid carcinoma

alexandrossfakianakis shared this article with you from Inoreader Fourteen years old as the best age cutoff to differentiate prepubertal from pubertal papillary thyroid carcinoma via Head & Neck Abstract Background It is unclear whether differences in clinical presentation and/or prognosis exist between prepubertal papillary thyroid cancer (PTC) and pubertal PTC. At present, there is a lack of definition for the appropriate cutoff age to define prepubertal PTC. Methods This study retrospectively reviewed 227 pediatric PTC patients (aged ≤18 years) who underwent initial surgery from March 2000 to December 2018. The median duration of follow-up was 85 months (range, 8–258). Results The age range was basically linearly related to multiple risk factors, such as T3–T4 disease, distant metastasis. Age (p = 0.032) was an independent risk factor for recurrence and persistent disease. Patients aged <14 years had obviously higher rates of extensive disease. The 10-year disease-free survival (DFS) rate of patients aged <14 years was 59.5% and that of patients aged ≥14 years was 82.6% (p = 0.004). Conclusions Fourteen years of age may be an appropriate cutoff to differentiate prepubertal PTC from pubertal PTC. View on Web

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Association of Genre of Singing and Phonotraumatic Vocal Fold Lesions in Singers

alexandrossfakianakis shared this article with you from Inoreader Association of Genre of Singing and Phonotraumatic Vocal Fold Lesions in Singers via The Laryngoscope This study revealed previously unrecognized associations between singing genre and specific types of vocal fold injury. These findings help to inform mechanistic inferences surrounding the pathophysiology of specific phonotrauma. A combination of factors most likely account for these findings, including vocal technique, acoustic environment and performance schedules. Objectives/Hypothesis To determine if (1) the likelihood of presenting with phonotraumatic lesions differs by singing genre in treatment-seeking singers and (2) if the distribution of phonotraumatic lesion types differs by singing genre. Study Type Retrospective. Methods Records of singers who presented with a voice complaint over the course of 2.5 years (June 2017–December 2019) were reviewed to determine the proportion of those with phonotraumatic lesions as a function of genre (Study 1). Separately, the lesion types and genres of singers diagnosed with phonotraumatic lesions over a 9-year period (July 2011–March 2020) were determined (Study 2). Results In Study 1, 191 of 712 (26.8%) dysphonic singers were diagnosed with phonotraumatic lesions. Country/folk, gospel/jazz, and musical theater singers were more likely to present with phonotraumatic lesions. In Study 2, in 443 singers with phonotraumatic lesions, polyps and pseudocysts, but not nodules, were found to be distributed unequally across genres (χ 2 p = 0.006, p < 0.0001, p = 0.064, respectively). Praise/worship singers had significantly higher proportions of polyps compared to choral singers (OR 4.8 [95% CI 1.9–12.5]) or compared to musical theater singers (OR 7.2 [95% CI 2.5–20.8]). Opera singers had significantly higher proportions of pseudocysts than choral singers (OR 3.1 [95% CI 1.5–6.1]) or musical theater singers (OR 3.7 [95% CI 1.8–7.6]). Conclusions The higher incidence of polyps in praise/worship singers likely reflects the more emphatic nature of singing and the tendency for acute injury. The higher incidence of pseudocysts in opera singers may reflect a more chronic nature of injury. Level of Evidence 4 Laryngoscope, 2022 View on Web

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Outcomes of Non‐Mucosa Sparing Endoscopic Sinus Surgery (Partial Reboot) in Refractory Chronic Rhinosinusitis with Nasal Polyposis: An Academic Hospital Experience

alexandrossfakianakis shared this article with you from Inoreader Outcomes of Non‐Mucosa Sparing Endoscopic Sinus Surgery (Partial Reboot) in Refractory Chronic Rhinosinusitis with Nasal Polyposis: An Academic Hospital Experience via The Laryngoscope We investigated the role of non-mucosa sparing endoscopic sinus surgery (partial reboot) in pluri-operated patients affected by chronic rhinosinusitis with nasal polyps. According to our results, partial reboot should be considered as a therapeutic option in those patients, allowing lower recurrence rate, longer clinical remission, improved quality of life and zeroing oral corticosteroids uptake, as compared to standard endoscopic sinus surgery. Objective The reboot approach could be an effective treatment option to lower recurrence rates (RRs) in recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). The purpose of this study was to investigate RR, recurrence-free survival (RFS), quality of life (QoL) improvement, and oral corticosteroid (OCS) intake in pluri-operated CRSwNP patients treated with partial reboot surgery. Methods A consecutive sample of patients with recalcitrant CRSwNP, ineligible for monoclonal antibodies, underwent partial reboot surgery. The 22-item SinoNasal Outcome Test (SNOT-22), Visual Analogue Scales (VAS) scores, OCS intake, and endoscopic Nasal Polyp Score (NPS) were collected pre and postoperatively. The main outcomes were RR and RFS, and comparison of disease-free time with previous endoscopic surgeries. Results Thirty pluri-operated patients were enrolled. Before the reboot, all had experienced disease recurrence at a mean recurrence time of 8.08 ± 2.83 months after surgery. After reboot, 7 (23.3%) had recurrence at a mean time of 16.67 ± 3.07 months (p = 0.02); none needed additional revision surgery till time of data collection. RR at 12, 18, and 24 months follow-up resulted significantly lower for reboot than other previous surgeries (p = 0.010, p = 0.002, p = 0.016, respectively); RFS difference resulted significant (log-rank test = 4.16; p = 0.04). Differences between pre-and post-operative total and single-items scores of SNOT-22 were significant (p = 0.001), as well as VAS scores (p = 0.001). Before the reboot, 21 patients (70%) took ≥2 OCS courses per year; at the latest follow-up visit, none had taken any course of OCS after reboot. Conclusions The reboot approach showed lower RR, longer RFS, improved QoL, and zeroing of OCS uptake. Larger samples and longer follow-up studies are needed to assess long-term efficacy and safety of this procedure. Level of Evidence Level 4. According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 2022. Laryngoscope, 2022 View on Web

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Perioperative Hypercoagulability in Free Flap Reconstructions Performed for Intracranial Tumors

alexandrossfakianakis shared this article with you from Inoreader Perioperative Hypercoagulability in Free Flap Reconstructions Performed for Intracranial Tumors via The Laryngoscope Patients with intracranial tumors have a higher risk of thromboembolic events. A multi-institutional retrospective chart review was performed of patients who underwent free tissue transfer for scalp/cranial reconstruction. There is an increase in perioperative flap thrombosis in patients with intracranial tumors undergoing free tissue scalp reconstruction, and anticoagulation appears to mitigate this risk. Objective(s) Patients with intracranial tumors have a higher risk of thromboembolic events. This risk increases at the time of surgical intervention. We have noted an anecdotal increase in perioperative flap thrombosis in patients undergoing free tissue transfer for intracranial tumor resection. This study aims to formally evaluate this risk. Methods A multi-institutional retrospective chart review was performed of patients who underwent free tissue transfer for scalp/cranial reconstruction. Perioperative thrombosis and free flap outcomes were evaluated. Results The 209 patients who underwent 246 free tissue transfers were included in the study. The 28 free flap scalp reconstructions were associated with intracranial tumors, 19 were performed following composite cranial resections with associated dural resection/reconstruction, and 199 were performed in the absence of intracranial tumors (control group). There was a significantly higher incidence of perioperative flap thrombosis in the intracranial tumor group (11/28, 39%) when compared to controls (38/199, 19%) (p = 0.0287). This was not seen when scalp tumors extended to the dura alone (4/19, 21%, p = 0.83). Therapeutic anticoagulation used for perioperative thrombosis (defined as intraoperative or in the immediate postoperative phase up to 5 days) was associated with a lower risk of flap failure, although this was not statistically significant (p = 0.148). Flap survival rates were equivalent between flaps performed for intracranial pathology (93.3%) and controls (95%). Conclusion There is an increase in perioperative flap thrombosis in patients with intracranial tumors undergoing free tissue scalp reconstruction. Anticoagulation appears to mitigate this risk. Level of Evidence This recommendation is based on level 3 evidence (retrospective case–control studies, systematic review of retrospective studies, and case reports) Laryngoscope, 2022 View on Web

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Effect of sacubitril/valsartan on cognitive impairment in colchicine‐induced Alzheimer’s model in rats

alexandrossfakianakis shared this article with you from Inoreader Effect of sacubitril/valsartan on cognitive impairment in colchicine‐induced Alzheimer's model in rats via Fundamental & Clinical Pharmacology Abstract Background Alzheimer's disease (AD) is a complex neurodegenerative disease. There is epidemiological evidence that heart failure (HF) patients are at higher risk of developing AD and the impact of sacubitril/valsartan, the first angiotensin receptor-neprilysin inhibitor (ARNI) approved for HF, on cognitive functions is still controversial. Objective To investigate the effect of sacubitril/valsartan on cognitive functions in colchicine-induced AD rat model. Methods Forty adult male Wistar rats were equally allocated into four groups (each of 10 rats). Group I: normal control, Group II: intracerebroventricular injection of colchicine (15μg/5μl/bilaterally), Group III: colchicine (15μg/5μl/bilaterally, icv) + oral sacubitril/valsartan (100 mg/kg/day) for 25 days and Group IV: colchicine (15μg/5μl/bilaterally, icv) + oral valsartan (50 mg/kg/day) for 25 days. Behavioral assessment was done using Morris water maze and passive avoidance tasks. Biochemically, β-amyloid (1-40 and 1-42) peptides, oxidative stress (malondialdehyde and superoxide dismutase) and inflammatory (tumor necrosis factor-alpha) parameters were measured in hippocampus and prefrontal cortex. Results Sacubitril/valsartan exaggerated colchicine-induced cognitive impairment in both Morris water maze and passive avoidance tasks, and was associated with significant increase in β-amyloid accumulation, oxidative stress and inflammation versus valsartan. Conclusion Sacubitril/valsartan caused deleterious effect on cognitive impairment and biochemical alterations in colchicine-induced AD rat model. Hence, special caution should be taken following long-term intake of ARNI on cognitive functions. View on Web

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