Auditory feedback control mechanisms do not contribute to cortical hyperactivity within the voice production network in adductor spasmodic dysphonia

Adductor spasmodic dysphonia (ADSD), the most common form of spasmodic dysphonia, is a debilitating voice disorder characterized by hyperactivity and muscle spasms in the vocal folds during speech. Prior neuroimaging studies have noted excessive brain activity during speech in ADSD participants compared to controls. Speech involves an auditory feedback control mechanism that generates motor commands aimed at eliminating disparities between desired and actual auditory signals. Thus, excessive neural activity in ADSD during speech may reflect, at least in part, increased engagement of the auditory feedback control mechanism as it attempts to correct vocal production errors detected through audition. To test this possibility, functional magnetic resonance imaging was used to identify differences between ADSD participants and age-matched controls in (i) brain activity when producing speech under different auditory feedback conditions, and (ii) resting state functional connectivity within the cortical network responsible for vocalization. The ADSD group had significantly higher activity than the control group during speech (compared to a silent baseline task) in three left-hemisphere cortical regions: ventral Rolandic (sensorimotor) cortex, anterior planum temporale, and posterior superior temporal gyrus/planum temporale. This was true for speech while auditory feedback was masked with noise as well as for speech with normal auditory feedback, indicating that the excess activity was not the result of auditory feedback control mechanisms attempting to correct for perceived voicing errors in ADSD. Furthermore, the ADSD group had significantly higher resting state functional connectivity between sensorimotor and auditory cortical regions within the left hemisphere as well as between the left and right hemispheres, consistent with the view that excessive motor activity frequently co-occurs with increased auditory cortical activity in individuals with ADSD.First author draf

18F-BMS986192 PET imaging of PD-L1 in metastatic melanoma patients with brain metastases treated with immune checkpoint inhibitors:A pilot study

Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 frequently induces tumor response in metastatic melanoma patients. However, tumor response often takes months and may be heterogeneous. Consequently, additional local treatment for non-responsive metastases may be needed, especially in the case of brain metastases. Non-invasive imaging may allow the characterization of (brain) metastases to predict response. This pilot study uses 18F-BMS986192 PET for PD-L1 expression to explore the variability in metastatic tracer uptake and its relation to tumor response, with a special focus on brain metastases. Methods: Metastatic melanoma patients underwent whole-body 18F-BMS986192 PET/CT scanning before and 6 weeks after starting ICI therapy. 18F-BMS986192 uptake was measured in healthy tissues, organs, and tumor lesions. Tumor response was evaluated at 12 weeks using CT thorax/abdomen and MRI brain. RECIST v 1.1 was used to define therapy response per patient. Response per lesion was measured by the percentage change in lesion diameter. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.0. Results: Baseline 18F-BMS986192 PET/CT was performed in 8 patients, with follow-up scans in 4 patients. The highest tracer uptake was observed in the spleen, bone marrow, kidneys, and liver. Tracer uptake in tumor lesions was heterogeneous. In total, 42 tumor lesions were identified at baseline with most lesions in the lungs (n = 21) and brain (n = 14). Tracer uptake was similar between tumor locations. 18F-BMS986192 uptake in lesions at baseline, corrected for blood pool activity, was negatively correlated with the change lesion diameter at response evaluation (r=-0.49, P = 0.005), both in intra- and extracerebral lesions. Receiver operating characteristic (ROC) analysis demonstrated that 18F-BMS986192 uptake can discriminate between responding and nonresponding lesions with an area under the curve of 0.82. At the follow-up scan an increased 18F-BMS986192 uptake compared to baseline scan was correlated with an increased lesion diameter at response evaluation. In the follow-up 18F-BMS986192-PET scan of two patients, ICI-related toxicity (thyroiditis and colitis) was detected. Conclusion: In this pilot study, 18F-BMS986192 PET showed heterogeneous uptake in intra and extracerebral metastatic lesions in melanoma patients. Baseline 18F-BMS986192 uptake was able to predict an ICI treatment-induced reduction in lesion volume, whereas the follow-up PET scan allowed the detection of treatment-induced toxicity

Summarising and validating test accuracy results across multiple studies for use in clinical practice

Following a meta-analysis of test accuracy studies, the translation of summary results into clinical practice is potentially problematic. The sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of a test may differ substantially from the average meta-analysis findings, because of heterogeneity. Clinicians thus need more guidance: given the meta-analysis, is a test likely to be useful in new populations, and if so, how should test results inform the probability of existing disease (for a diagnostic test) or future adverse outcome (for a prognostic test)? We propose ways to address this. Firstly, following a meta-analysis, we suggest deriving prediction intervals and probability statements about the potential accuracy of a test in a new population. Secondly, we suggest strategies on how clinicians should derive post-test probabilities (PPV and NPV) in a new population based on existing meta-analysis results and propose a cross-validation approach for examining and comparing their calibration performance. Application is made to two clinical examples. In the first example, the joint probability that both sensitivity and specificity will be >80% in a new population is just 0.19, because of a low sensitivity. However, the summary PPV of 0.97 is high and calibrates well in new populations, with a probability of 0.78 that the true PPV will be at least 0.95. In the second example, post-test probabilities calibrate better when tailored to the prevalence in the new population, with cross-validation revealing a probability of 0.97 that the observed NPV will be within 10% of the predicted NPV

COVID-19 vaccination in patients with immune thrombocytopenia

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by low platelet count and increased bleeding risk. COVID-19 vaccination has been described as risk factor for de novo ITP, but the effects of COVID-19 vaccination in patients with ITP are unknown. Our aims were to investigate the effects of COVID-19 vaccination in ITP patients on platelet count, bleeding complications and ITP exacerbation (any of: ≥50% decline in platelet count; or nadir platelet count 20% decrease from baseline; or use of rescue therapy). Platelet counts of ITP patients and healthy controls were collected immediately before, 1 and 4 weeks after first and second vaccination. Linear mixed-effects modelling was applied to analyze platelet counts over time. We included 218 ITP patients (50.9% female, mean age 55 years and median platelet count of 106x109/L) and 200 healthy controls (60.0% female, mean age 58 years and median platelet count of 256x109/L). Platelet counts decreased by 6.3% after vaccination. We observed no difference in decrease between the groups. Thirty ITP patients (13.8%, 95%CI 9.5%-19.1%) had an exacerbation and 5 (2.2%, 95%CI 0.7%-5.3%) suffered from a bleeding event. Risk factors for ITP exacerbation were platelet count <50x109/L (OR 5.3, 95%CI 2.1-13.7), ITP treatment at time of vaccination (OR 3.4, 95%CI 1.5-8.0) and age (OR 0.96 per year, 95%CI 0.94-0.99). Our study highlights safety of COVID-19 vaccination in ITP patients and importance of close monitoring platelet counts in a subgroup of ITP patients. ITP patients with exacerbation responded well on therapy

Can predicting COVID-19 mortality in a European cohort using only demographic and comorbidity data surpass age-based prediction: An externally validated study.

peer reviewedOBJECTIVE: To establish whether one can build a mortality prediction model for COVID-19 patients based solely on demographics and comorbidity data that outperforms age alone. Such a model could be a precursor to implementing smart lockdowns and vaccine distribution strategies. METHODS: The training cohort comprised 2337 COVID-19 inpatients from nine hospitals in The Netherlands. The clinical outcome was death within 21 days of being discharged. The features were derived from electronic health records collected during admission. Three feature selection methods were used: LASSO, univariate using a novel metric, and pairwise (age being half of each pair). 478 patients from Belgium were used to test the model. All modeling attempts were compared against an age-only model. RESULTS: In the training cohort, the mortality group's median age was 77 years (interquartile range = 70-83), higher than the non-mortality group (median = 65, IQR = 55-75). The incidence of former/active smokers, male gender, hypertension, diabetes, dementia, cancer, chronic obstructive pulmonary disease, chronic cardiac disease, chronic neurological disease, and chronic kidney disease was higher in the mortality group. All stated differences were statistically significant after Bonferroni correction. LASSO selected eight features, novel univariate chose five, and pairwise chose none. No model was able to surpass an age-only model in the external validation set, where age had an AUC of 0.85 and a balanced accuracy of 0.77. CONCLUSION: When applied to an external validation set, we found that an age-only mortality model outperformed all modeling attempts (curated on www.covid19risk.ai) using three feature selection methods on 22 demographic and comorbid features

Use of Parathyroid Hormone Assay after Thyroidectomy: A Survey of US and European Surgeons

Introduction Hypocalcemia after thyroidectomy results in prolongation of hospitalization and patient discomfort but can be predicted by PTH assays. However, there is considerable variation in their use. Methods This study was undertaken to document current US and European practice patterns regarding the use of this assay. Anonymous surveys were collected in 2009–2011 from members of the American Academies of Otolaryngology-Head and Neck Surgery and Endocrine Surgery and the European, Italian, French, Spanish and British Societies of Endocrine Surgery. Results There were 356 American (3% response) and 61 European (10% response) respondents. 105 (29.8%) American and 25 (41%) European respondents reported routine PTH assay use. Fellowship trained surgeons reported increased use of the PTH assay (P = 0.004). Shorter reported average post-operative hospital stay was associated with American physicians (P = 0.0001), community practice location (P = 0.0002) and routine calcium supplementation ( P = 0.0015). Conclusions Surgical training was associated with routine use of the PTH assay. Average reported hospital stay was lower for American and community practice physicians and correlated with post-operative oral calcium use

Management of Chronic Laryngopharyngeal Neuropathy in the United States and Europe

Objective: This study aimed to analyze differences in the evaluation of laryngopharyngeal neuropathy by laryngologists in the United States and Europe. Methods: Members of the American Laryngological Association (ALA) and the European Laryngological Society (ELS) were surveyed. Questionnaires were ennailed to all 179 members of the ALA and all 324 members of the ELS. Results: Of the ALA members surveyed, 40 (23.3%) responded, compared to 72 members (22.2%) of the ELS group. Of the ALA respondents, 79.5% identified laryngology as their primary area of practice, whereas 56.9% of ELS respondents identified devoting more than 50% of their practice to laryngology. Of ELS laryngologists, 81.1% received training in laryngology or associated subspecialties. For diagnosing laryngopharyngeal neuropathy, the average comfort level on the Likert scale was significantly greater for ALA members than ELS members (P <.01). Furthermore, ALA laryngologists were less likely to consider laryngopharyngeal reflux as an overdiagnosed condition compared to ELS laryngologists (P <.05). Conclusion: Laryngologists in the United States and Europe vary significantly in their familiarity with laryngopharyngeal neuropathy. This could reflect either differences in awareness concerning this condition or a more critical perspective of European providers regarding the chronic laryngopharyngeal neuropathy (CLPN) diagnosis. As CLPN is still lacking definitive proof, the addition of European researchers could aid in validating CLPN and determining its overall effect on the chronic cough population

Management of Chronic Laryngopharyngeal Neuropathy in the United States and Europe

Objective: This study aimed to analyze differences in the evaluation of laryngopharyngeal neuropathy by laryngologists in the United States and Europe. Methods: Members of the American Laryngological Association (ALA) and the European Laryngological Society (ELS) were surveyed. Questionnaires were ennailed to all 179 members of the ALA and all 324 members of the ELS. Results: Of the ALA members surveyed, 40 (23.3%) responded, compared to 72 members (22.2%) of the ELS group. Of the ALA respondents, 79.5% identified laryngology as their primary area of practice, whereas 56.9% of ELS respondents identified devoting more than 50% of their practice to laryngology. Of ELS laryngologists, 81.1% received training in laryngology or associated subspecialties. For diagnosing laryngopharyngeal neuropathy, the average comfort level on the Likert scale was significantly greater for ALA members than ELS members (P <.01). Furthermore, ALA laryngologists were less likely to consider laryngopharyngeal reflux as an overdiagnosed condition compared to ELS laryngologists (P <.05). Conclusion: Laryngologists in the United States and Europe vary significantly in their familiarity with laryngopharyngeal neuropathy. This could reflect either differences in awareness concerning this condition or a more critical perspective of European providers regarding the chronic laryngopharyngeal neuropathy (CLPN) diagnosis. As CLPN is still lacking definitive proof, the addition of European researchers could aid in validating CLPN and determining its overall effect on the chronic cough population

Summarising and validating test accuracy results across multiple studies for use in clinical practice

Following a meta-analysis of test accuracy studies, the translation of summary results into clinical practice is potentially problematic. The sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of a test may differ substantially from the average meta-analysis findings, because of heterogeneity. Clinicians thus need more guidance: given the meta-analysis, is a test likely to be useful in new populations, and if so, how should test results inform the probability of existing disease (for a diagnostic test) or future adverse outcome (for a prognostic test)? We propose ways to address this. Firstly, following a meta-analysis, we suggest deriving prediction intervals and probability statements about the potential accuracy of a test in a new population. Secondly, we suggest strategies on how clinicians should derive post-test probabilities (PPV and NPV) in a new population based on existing meta-analysis results and propose a cross-validation approach for examining and comparing their calibration performance. Application is made to two clinical examples. In the first example, the joint probability that both sensitivity and specificity will be >80% in a new population is just 0.19, because of a low sensitivity. However, the summary PPV of 0.97 is high and calibrates well in new populations, with a probability of 0.78 that the true PPV will be at least 0.95. In the second example, post-test probabilities calibrate better when tailored to the prevalence in the new population, with cross-validation revealing a probability of 0.97 that the observed NPV will be within 10% of the predicted NPV

Acoustic Identification of the Voicing Boundary during Intervocalic Offsets and Onsets Based on Vocal Fold Vibratory Measures

Methods for automating relative fundamental frequency (RFF)—an acoustic estimate of laryngeal tension—rely on manual identification of voiced/unvoiced boundaries from acoustic signals. This study determined the effect of incorporating features derived from vocal fold vibratory transitions for acoustic boundary detection. Simultaneous microphone and flexible nasendoscope recordings were collected from adults with typical voices (N = 69) and with voices characterized by excessive laryngeal tension (N = 53) producing voiced–unvoiced–voiced utterances. Acoustic features that coincided with vocal fold vibratory transitions were identified and incorporated into an automated RFF algorithm (“aRFF-APH”). Voiced/unvoiced boundary detection accuracy was compared between the aRFF-APH algorithm, a recently published version of the automated RFF algorithm (“aRFF-AP”), and gold-standard, manual RFF estimation. Chi-square tests were performed to characterize differences in boundary cycle identification accuracy among the three RFF estimation methods. Voiced/unvoiced boundary detection accuracy significantly differed by RFF estimation method for voicing offsets and onsets. Of 7721 productions, 76.0% of boundaries were accurately identified via the aRFF-APH algorithm, compared to 70.3% with the aRFF-AP algorithm and 20.4% with manual estimation. Incorporating acoustic features that corresponded with voiced/unvoiced boundaries led to improvements in boundary detection accuracy that surpassed the gold-standard method for calculating RFF