Genetic Testing in Head and Neck Paraganglioma: Who,What, and Why?

Background Genetic testing in head and neck paragangliomas (HNPG) can have profound implications in patient and family counseling.Methods Retrospective review was performed of patients with HNPG at a cancer care center from 1970 to present. Patient demographics, disease patterns, outcomes, and genetic mutations were analyzed.Results We identified 26 patients with available genetic testing results. Sixteen had mutations. Succinate dehydrogenase gene, sub unit D (SDHD) accounted for 75% of mutations, of which P81L accounted for 75%. The remainder had SDHB mutations. Patients with mutations were younger (average age 39.5 years versus 48.4 years), 63% (versus 40%) had multiple tumors, 94% (60%) had at least one carotid body tumor, and family history was positive in 38% (20%).Conclusion Patients suspected of heritable HNPG should undergo testing first at the SDHD and SDHB loci, and those with younger age, multiple tumors, carotid body tumors, and positive family history are more likely to have mutations.     

Effect of varying bulb height on articulation and nasalance in maxillectomy patients with hollow bulb obturator

PurposeTo evaluate the effect of bulb height of hollow bulb obturator prosthesis on articulation and nasalance.MethodA total of 10 patients, who were to undergo maxillectomy falling under Aramany class-I and II, with normal speech and hearing pattern were selected for the study. They were provided 2 maxillary obturators, one extending full height of the defect and other with bulb height approximately up to inferior nasal concha. The patients were asked to wear each obturator for 6 weeks and the speech analysis was done to measure changes in articulation and nasalance at 6 different stages of treatment i.e. preoperative, postoperative (after complete healing), 24 h and 6 weeks after providing full bulb height obturator and reduced bulb height obturator. Articulation was measured objectively for distortion, addition, substitution and omission by speech pathologist and nasalance was measured by Dr. SPEECH software.ResultComparison between full and reduced bulb height for nasalance and articulation, showed that there was no statistical significant difference (P > 0.05) between the two for both the parametres.ConclusionArticulation and nasality improves after providing obturator. Articulation and nasalance both are independent of bulb height.     

Mitochondrial function in human brains is affected by pre‐ and post mortem factors

G. Harish, C. Venkateshappa, A. Mahadevan, N. Pruthi, M. M. S. Bharath and S. K. Shankar (2013) Neuropathology and Applied Neurobiology 39, 298–315 Mitochondrial function in human brains is affected by pre‐ and post mortem factors Aim: Mitochondrial function and the ensuing ATP synthesis are central to the functioning of the brain and contribute to neuronal physiology. Most studies on neurodegenerative diseases have highlighted that mitochondrial dysfunction is an important event contributing to pathology. However, studies on the human brain mitochondria in various neurodegenerative disorders heavily rely on post mortem samples. As post mortem tissues are influenced by pre‐ and post mortem factors, we investigated the effect of these variables on mitochondrial function. Methods: We examined whether the mitochondrial function (represented by mitochondrial enzymes and antioxidant activities) in post mortem human brains (n = 45) was affected by increased storage time (11.8–104.1 months), age of the donor (2 days to 80 years), post mortem interval (2.5–26 h), gender difference and agonal state [based on Glasgow Coma Scale: range = 3–15] in the frontal cortex, as a prototype. Results: We observed that the activities of citrate synthase, succinate dehydrogenase and mitochondrial reductase (MTT) were significantly affected only by gender difference (citrate synthase: P = 0.005; succinate dehydrogenase: P = 0.01; mitochondrial reductase: P = 0.006), being higher in females, but not by any other factor. Mitochondrial complex I activity was significantly inhibited by increasing age (r = ?0.40; P = 0.05). On the other hand, the mitochondrial antioxidant enzyme glutathione reductase decreased with severe agonal state (P = 0.003), while the activity of glutathione‐S‐transferase declined with increased storage time (P = 0.005) and severe agonal state (P = 0.02). Conclusion: Our data highlight the influence of pre‐ and post mortem factors on preservation of mitochondrial function with implications for studies on brain pathology employing stored human samples.     

Temporary Health Impact of Prostate MRI and Transrectal Prostate Biopsy in Active Surveillance Prostate Cancer Patients

PurposeTo assess the temporary health impact of prostate multiparametric MRI (mpMRI) and transrectal prostate biopsy in an active surveillance prostate cancer population.MethodsA two-arm institutional review board–approved HIPAA-compliant prospective observational patient-reported outcomes study was performed from November 2017 to July 2018. Inclusion criteria were men with Gleason 6 prostate cancer in active surveillance undergoing either prostate mpMRI or transrectal prostate biopsy. A survey instrument was constructed using validated metrics in consultation with the local patient- and family-centered care organization. Study subjects were recruited at the time of diagnostic testing and completed the instrument by phone 24 to 72 hours after testing. The primary outcome measure was summary testing-related quality of life (summary utility score), derived from the testing morbidities index (TMI) (scale: 0 = death and 1 = perfect health). TMI is stratified into seven domains, with each domain scored from 1 (no health impact) to 5 (extreme health impact). Testing-related quality-of-life measures in the two cohorts were compared with Mann-Whitney U test.ResultsIn all, 122 subjects were recruited, and 90% (110 of 122 [MRI 55 of 60, biopsy 55 of 62]) successfully completed the survey instrument. The temporary quality-of-life impact of transrectal biopsy was significantly greater than that of prostate mpMRI (0.82, 95% confidence interval [CI] 0.79-0.85, versus 0.95, 95% CI 0.94-0.97; P < .001). The largest mean domain-level difference was for intraprocedural pain (transrectal biopsy 2.6, 95% CI 2.4-2.8, versus mpMRI 1.3, 95% CI 1.1-1.5; P < .001).ConclusionTransrectal prostate biopsy has greater temporary health impact (lower testing-related quality-of-life measure) than prostate mpMRI.     

Correction to: Epilepsy related multimorbidity,polypharmacy and risks in adults with intellectual disabilities: a national study

Journal of Neurology -