Medicare Restriction of Telehealth Speech Services Negatively Impacts Patient Care.

OBJECTIVE: Ample literature shows voice and swallowing therapy, in-person or virtual, to be essential for Otolaryngology and Speech-Language Pathology care. In March 2023, Medicare announced discontinuing teletherapy reimbursement in hospital-based outpatient departments, effective May 2023. This decision was subsequently reversed; however, the uncertain interval period provided the opportunity to study the impact of eliminating teletherapy. STUDY DESIGN: Prospective cohort. SETTING: Tertiary laryngology center. METHODS: Affected Medicare patients were contacted via mailed letter, phone, and secure patient portal and offered to change appointments to in-person, teletherapy with cash self-payment ($165-282/session) or cancellation. Demographics and responses were collected. Statistical analyses conducted using Student's t test. RESULTS: Fifty-three patients (28 female; mean age 66.8 ± 14.2 years) were impacted. 64% (n = 34) changed to in-person appointment, 28% (n = 15) canceled, 8% (n = 4) did not respond. No patients opted to self-pay. 67% of patients that canceled telehealth care cited distance from in-person care location. The mean distance for canceled versus rescheduled patients was 92.3 ± 93.0 versus 32.8 ± 57.4 miles, P = .034. Mean age, gender, and number of sessions were not different between groups. Mean time to third next available therapy appointment was 96 ± 46 versus 46 ± 12 days before and after rule change, P = .007. Upon Medicare's reversal, this trend rebounded to nearly baseline (mean 77 ± 12 days, P = .12). CONCLUSION: Medicare's discontinuation of reimbursement for teletherapy services caused nearly 30% of patients to cancel voice and swallowing therapy, primarily due to distance. These cancellations led to decreased access to care for Medicare patients with voice/swallowing diagnoses, which affect function, quality of life, and potentially even mortality risk.

STAT6-targeting antisense oligonucleotides against solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare, non-hereditary soft tissue sarcoma thought to originate from fibroblastic mesenchymal stem cells. The etiology of SFT is thought to be due to an environmental intrachromosomal gene fusion between NGFI-A-binding protein 2 (NAB2) and signal transducer and activator protein 6 (STAT6) genes on chromosome 12, wherein the activation domain of STAT6 is fused with the DNA-binding domain of NAB2 resulting in the oncogenesis of SFT. All NAB2-STAT6 fusion variations discovered in SFTs contain the C-terminal of STAT6 transcript, and thus can serve as target site for antisense oligonucleotides (ASOs)-based therapies. Indeed, our in vitro studies show the STAT6 3' untranslated region (UTR)-targeting ASO (ASO 993523) was able to reduce expression of NAB2-STAT6 fusion transcripts in multiple SFT cell models with high efficiency (half-maximal inhibitory concentration: 116-300 nM). Encouragingly, in vivo treatment of SFT patient-derived xenograft mouse models with ASO 993523 resulted in acceptable tolerability profiles, reduced expression of NAB2-STAT6 fusion transcripts in xenograft tissues (21.9%), and, importantly, reduced tumor growth (32.4% decrease in tumor volume compared with the untreated control). Taken together, our study established ASO 993523 as a potential agent for the treatment of SFTs.

Burden of Illness in People with Alzheimer's Disease: A Systematic Review of Epidemiology, Comorbidities and Mortality.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide, and an updated quantification of its impact on morbidity, disability, and mortality is warranted. We conducted a systematic literature review, focusing on the past decade, to characterize AD and assess its impact on affected individuals. METHODS: Searches of Embase, MEDLINE, and the Cochrane Library were conducted on August 7, 2020 and updated on November 10, 2021. Observational studies from any country reporting incidence, prevalence, comorbidities, and/or outcomes related to disability and mortality/life expectancy, in people with mild cognitive impairment (MCI) due to AD, or mild, moderate, or severe AD dementia, were considered relevant. RESULTS: Data were extracted from 88 studies (46 incidence/prevalence; 44 comorbidities; 25 mortality-/disability-related outcomes), mostly from Europe, the USA, and Asia. AD dementia diagnosis was confirmed using biomarkers in only 6 studies. Estimated 5-year mortality in AD was 35%, and comorbidity prevalence estimates varied widely (hypertension: 30.2-73.9%; diabetes: 6.0-24.3%; stroke: 2.7-13.7%). Overall, people with AD dementia were more likely to have cardiovascular disease or diabetes than controls, and 5-year mortality in people with AD dementia was double that in the age- and year-matched general population (115.0 vs 60.6 per 1,000 person-years). CONCLUSIONS: AD is associated with excess morbidity and mortality. Future longitudinal studies of population aging, incorporating biomarker assessment to confirm AD diagnoses, are needed to better characterize the course of MCI due to AD and AD dementia.

Surgical Outcomes in Zenker Diverticula: A Multicenter, Prospective, Longitudinal Study.

OBJECTIVE: To compare improvement in patient-reported outcomes (PROM) in persons undergoing endoscopic and open surgical management of Zenker diverticula (ZD). METHODOLOGY: Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgery for ZD. Patient survey, radiography reports, and the 10-item Eating Assessment Tool (EAT-10) pre- and post-procedure were abstracted from a REDCap database, which summarized means, medians, percentages, and frequencies of. Outcome based on operative intervention (endoscopic vs. open) was compared using t-test, Wilcoxon rank sum test or chi-square test, as appropriate. RESULTS: One hundred and forty-seven persons were prospectively followed. The mean age (SD) of the cohort was 68.7 (11.0). Overall, 66% of patients reported 100% improvement in EAT-10; 81% of patients had greater than 75% improvement; and 88% had greater than 50% improvement. Endoscopic was used for n = 109 patients, and open surgical intervention was used for n = 38. The median [interquartile range, IQR] EAT-10 percent improvement for endoscopic treatment was 93.3% [72, 100], and open was 100% [92.3, 100] (p = 0.05). The incidence of intraoperative complications was 3.7% for endoscopic and 7.9% for open surgical management. The median [IQR] in follow-up was 86 and 97.5 days, respectively. CONCLUSION: Both endoscopic and open surgical management of ZD provide significant improvement in patient-reported outcomes. The data suggest that open diverticulectomy may provide a modest advantage in symptomatic improvement compared to endoscopic management. The data suggest that the postoperative complication rate is higher in the open surgical group. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:97-102, 2024.

Technical Challenges for Laryngeal Electromyography.

BACKGROUND/OBJECTIVE: Laryngeal electromyography (LEMG) is a useful diagnostic test in the evaluation of vocal fold paralysis (VFP). This study investigates factors that can make LEMG challenging to perform. METHODS: Patients with subacute unilateral VFP presented for LEMG were prospectively enrolled. Demographic data including BMI, previous neck surgery, and anatomic factors were collected. Patient-reported pain related to the procedure was recorded on a visual analogue scale (VAS). Electromyographer and otolaryngologist recorded a consensus rating of the perceived difficulty in performing the test and confidence in using the results for clinical decision-making. RESULTS: A total of 111 patients (56.8% female) were enrolled between August 2015 and August 2018. The mean age was 55 ± 14 years, and the average body mass index (BMI) was 28.5 ± 6.4. The mean patient-reported VAS score for pain was 35 ± 24. Notably, 31.2% of the tests were considered "very easy," 32.1% were considered "mildly challenging" and 23.9% and 12.8% were considered "moderately challenging" and "extremely challenging," respectively, by the clinicians. Common factors affecting LEMG difficulty included poorly palpable surface anatomy (50.5%) and patient intolerance (15.6%). Clinicians felt confident in 76.1% of the test findings. Bivariate analyses showed that prior neck surgery is associated with elevated VAS (p = 0.02), but clinician-perceived difficulty of performing the test is not associated with elevated VAS scores (p = 0.55). CONCLUSIONS: Majority of LEMG tests are well tolerated by patients. Physicians reported more confidence using LEMG for clinical decision-making when the test was easier to perform. Difficult surface anatomy and patient intolerance affects clinician confidence in integrating the test results with clinical care. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:831-834, 2024.

Postoperative Care of Zenker Diverticula: Contemporary Perspective from the Prospective OUtcomes Cricopharyngeaus Hypertonicity (POUCH) Collaborative.

OBJECTIVES: The aim of the study was to identify trends in postoperative management of persons undergoing surgery for Zenker diverticula (ZD) by evaluating length of stay (LOS), diet on discharge, and imaging with or without surgical complication. METHODS: Prospectively enrolled adult patients with cricopharyngeal muscle dysfunction with diverticula undergoing surgery from August 1, 2017 to February 1, 2023 were included. Data were extracted from a multi-institutional REDCap database, summarizing means, medians, percentages, and frequencies. Fisher's exact or chi squared analyses were utilized, as appropriate, to compare subsets of data. Descriptive analysis assessed differences in clinical course and the relationship to postoperative management. RESULTS: There were 298 patients with a mean (standard deviation) age of 71.8 (11.2) years and 60% male. Endoscopic surgery was performed in 79.5% (237/298) of patients versus 20.5% (61/298) open surgery. Sixty patients (20.1%) received postoperative imaging, with four leaks identified. Complications were identified in 9.4% of cases (n = 29 complications in 28 patients), more commonly in open surgery. Most (81.2%) patients were discharged within 23 h. About half of patients (49%) were discharged from the hospital on a pureed/liquid diet; 36% had been advanced to a soft diet. In patients without complications, LOS was significantly longer following open cases (p = 0.002); postoperative diet was not different between open and endoscopic (p = 0.26). CONCLUSIONS: Overall, most patients are discharged within 23 h without imaging. However, LOS was affected by surgical approach. Postoperative complications are different in endoscopic versus open surgery. Complications with either approach were associated with prolonged LOS, need for imaging, and diet restriction. LEVEL OF EVIDENCE: Level III Laryngoscope, 134:2678-2683, 2024.

Reduced Plasma-Membrane Calcium ATPase Activity and Extracellular Acidification Trigger Presynaptic Homeostatic Potentiation at the Mouse Neuromuscular Junction.

At the vertebrate neuromuscular junction (NMJ), presynaptic homeostatic potentiation (PHP) refers to an increase in neurotransmitter release that restores the strength of synaptic transmission following a blockade of nicotinic acetylcholine receptors (nAChRs). Mechanisms informing the presynaptic terminal of the loss of postsynaptic receptivity remain poorly understood. Previous research at the mouse NMJ suggests that extracellular protons may function as a retrograde signal that triggers an upregulation of neurotransmitter output (measured by quantal content, QC) through the activation of acid-sensing ion channels (ASICs). We further investigated the pH-dependency of PHP in an ex-vivo mouse muscle preparation. We observed that increasing the buffering capacity of the perfusion saline with HEPES abolishes PHP and that acidifying the saline from pH 7.4 to pH 7.2-7.1 increases QC, demonstrating the necessity and sufficiency of extracellular acidification for PHP. We then sought to uncover how the blockade of nAChRs leads to the pH decrease. Plasma-membrane calcium ATPase (PMCA), a calcium-proton antiporter, is known to alkalize the synaptic cleft following neurotransmission in a calcium-dependent manner. We hypothesize that since nAChR blockade reduces postsynaptic calcium entry, it also reduces the alkalizing activity of the PMCA, thereby causing acidosis, ASIC activation, and QC upregulation. In line with this hypothesis, we found that pharmacological inhibition of the PMCA with carboxyeosin induces QC upregulation and that this effect requires functional ASICs. We also demonstrated that muscles pre-treated with carboxyeosin fail to generate PHP. These findings suggest that reduced PMCA activity causes presynaptic homeostatic potentiation by activating ASICs at the mouse NMJ.

Clinician accuracy in identifying essential laryngeal landmarks on swallowing fluoroscopy.

Objective: Identification of anatomical landmarks is essential for interpretation of video fluoroscopic swallow studies (VFSS). This investigation sought to confirm the location of essential laryngeal landmarks and determine clinician accuracy in structure identification on VFSS. Methods: A single human cadaver was used to generate unmarked standard lateral and anterior-posterior (AP) fluoroscopic images. Essential laryngeal structures (e.g., true vocal fold, arytenoid) were directly identified using a guidewire placed through an endoscope while obtaining corresponding marked fluoroscopic images. Licensed clinicians (speech-language pathologists [SLP], laryngologists) and trainees (otolaryngology residents, SLP clinical fellows [CF]) identified 18 structures (9 lateral, 9 AP) on unmarked images. Answers were compared to corresponding marked images. The percentage of accurate identification was calculated for each clinician and then compared between groups using t-tests. Results: Twenty-four individuals (10 SLPs, 1 CF, 9 residents, 4 laryngologists) from six institutions completed structure identification. Mean overall accuracy was 41.7 ± 13.0% (range 18.8-68.8%). There were no significant differences in mean overall accuracy between trainees (41.9 ± 12.9%) and clinicians (42.0 ± 13.1%), p = .97, or between SLPs (45.5 ± 12.8%) and physicians (38.9 ± 12.3%), p = .22. On average, participants were significantly more accurate identifying structures on lateral view (53.1 ± 16.1%) than AP (27.3 ± 22.8%), p < .001. Less than half of participants accurately identified the laryngeal ventricle, cricoid, epiglottic petiole, and the anterior commissure on lateral view. Conclusions: The ability of certified clinicians and trainees to correctly identify essential anatomic landmarks on swallowing fluoroscopy may be poor. Future work is needed to identify how we can train clinicians on more accurate identification of essential anatomic structures on swallowing fluoroscopy.Level of Evidence: NA.

Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells.

Adult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells (OPCs). We examined the capacity of rat cortical OPCs to be re-specified to a neuronal lineage both in vitro and in vivo. Expressing the developmental transcription factor Neurogenin2 (Ngn2) in OPCs isolated from adult rat cortex resulted in their expression of early neuronal lineage markers and genes while downregulating expression of OPC markers and genes. Ngn2 induced progression through a neuronal lineage to express mature neuronal markers and functional activity as glutamatergic neurons. In vivo retroviral gene delivery of Ngn2 to naive adult rat cortex ensured restricted targeting to proliferating OPCs. Ngn2 expression in OPCs resulted in their lineage re-specification and transition through an immature neuronal morphology into mature pyramidal cortical neurons with spiny dendrites, axons, synaptic contacts, and subtype specification matching local cytoarchitecture. Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry.

Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.

Small animals do not replicate the severity of the human foreign-body response (FBR) to implants. Here we show that the FBR can be driven by forces generated at the implant surface that, owing to allometric scaling, increase exponentially with body size. We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant. FBRs to such elevated extrinsic forces in the mice were also mediated by the activation of Rac2 signalling in a subpopulation of mechanoresponsive myeloid cells, which could be substantially reduced via the pharmacological or genetic inhibition of Rac2. Our findings provide an explanation for the stark differences in FBRs observed in small animals and humans, and have implications for the design and safety of implantable devices.

Effectiveness of out-patient based acute heart failure care: a pilot randomised controlled trial.

OBJECTIVES: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). METHODS: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. RESULTS: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient. CONCLUSIONS: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.

A British Society for Haematology Guideline: Diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies.

The objective of this guideline is to provide healthcare professionals with clear, up-to-date and practical guidance on the management of thrombotic thrombocytopenic purpura (TTP) and related thrombotic microangiopathies (TMAs), including complement-mediated haemolytic uraemic syndrome (CM HUS); these are defined by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and small vessel thrombosis. Within England, all TTP cases should be managed within designated regional centres as per NHSE commissioning for highly specialised services.

Synergistic regulation of uterine radial artery adaptation to pregnancy by paracrine and hemodynamic factors.

Fetal growth throughout pregnancy relies on delivery of an increasing volume of maternal blood to the placenta. To facilitate this, the uterine vascular network adapts structurally and functionally, resulting in wider blood vessels with decreased flow-mediated reactivity. Impaired remodeling of the rate-limiting uterine radial arteries has been associated with fetal growth restriction. However, the mechanisms underlying normal or pathological radial artery remodeling are poorly understood. Here, we used pressure myography to determine the roles of hemodynamic (resistance, flow rate, shear stress) and paracrine [ß-estradiol, progesterone, placental growth factor (PlGF), vascular endothelial growth factor] factors on rat radial artery reactivity. We show that ß-estradiol, progesterone, and PlGF attenuate flow-mediated constriction of radial arteries from nonpregnant rats, allowing them to withstand higher flow rates in a similar manner to pregnant vessels. This effect was partly mediated by nitric oxide (NO) production. To better understand how the combination of paracrine factors and shear stress may impact human radial artery remodeling in the first half of gestation, computational models of uterine hemodynamics, incorporating physiological parameters for trophoblast plugging and spiral artery remodeling, were used to predict shear stress in the upstream radial arteries across the first half of pregnancy. Human microvascular endothelial cells subjected to these predicted shear stresses demonstrated higher NO production when paracrine factors were added. This suggests that synergistic effects of paracrine and hemodynamic factors induce uterine vascular remodeling and that alterations in this balance could impair radial artery adaptation, limiting blood flow to the placenta and negatively impacting fetal growth.NEW & NOTEWORTHY Placenta-specific paracrine factors ß-estradiol, progesterone, and placental growth factor attenuate flow-mediated constriction of the rate-limiting uterine radial arteries, enabling higher flow rates in pregnancy. These paracrine factors induce their actions in part via nitric oxide mediated mechanisms. A synergistic combination of paracrine factors and shear stress is likely necessary to produce sufficient levels of nitric oxide during early human pregnancy to trigger adequate uterine vascular adaptation.

Validating the Perceived Active School Travel Enablers and Barriers - Child (PASTEB-C) questionnaire.

OBJECTIVES: Presently, child-specific tools and instruments related to active school travel (AST) are lacking. This methodological shortcoming often contributes to suboptimal AST behaviour evaluations and intervention programming. The aim of this paper was to develop and validate a theoretically informed child-specific scale regarding multiple perceived barriers and enablers known to impact children's participation in AST. STUDY DESIGN: Mixed methods. METHODS: A mixed-methods and multistudy scale development approach featuring the application of social-ecological theory, a validation pilot study (n = 80), and test-retest study (n = 96) was conducted in collaboration with children in Ontario, Canada. In tandem with completing cognitive interviews and online surveys, multiple analyses, including a qualitative thematic analysis, along with weighted Cohen's kappa, Cronbach's alpha, and confirmatory factor analysis were undertaken. RESULTS: Qualitative analyses of the developed tool addressed face validity concerns related to the response options and definitions of terms used. Following the reliability analyses of 40 items, two confirmatory factor analyses were run to assess the construct validation of perceived AST barriers and enablers, and resulted in the development of the 24-item Perceived Active School Travel Enablers and Barriers - Child (PASTEB-C) questionnaire. CONCLUSION: The developed PASTEB-C questionnaire may be used to inform the programming and development of AST interventions, as well as conduct child-specific AST research.

A British Society for haematology guideline: diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies

The objective of this guideline is to provide healthcare professionals with clear, up-to-date and practical guidance on the management of thrombotic thrombocytopenic purpura (TTP) and related thrombotic microangiopathies (TMAs), including complement-mediated haemolytic uraemic syndrome (CM HUS); these are defined by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and small vessel thrombosis. Within England, all TTP cases should be managed within designated regional centres as per NHSE commissioning for highly specialised services.

Sequential Unfolding Mechanisms of Monomeric Caspases.

Caspases are evolutionarily conserved cysteinyl proteases that are integral in cell development and apoptosis. All apoptotic caspases evolved from a common ancestor into two distinct subfamilies with either monomeric (initiators) or dimeric (effectors) oligomeric states. The regulation of apoptosis is influenced by the activation mechanism of the two subfamilies, but the evolution of the well-conserved caspase-hemoglobinase fold into the two subfamilies is not well understood. We examined the folding landscape of monomeric caspases from two coral species over a broad pH range of 3-10.5. On an evolutionary timescale, the two coral caspases diverged from each other approximately 300 million years ago, and they diverged from human caspases about 600 million years ago. Our results indicate that both proteins have overall high stability, ∼15 kcal mol-1, near the physiological pH range (pH 6-8) and unfold via two partially folded intermediates, I1 and I2*, that are in equilibrium with the native and the unfolded state. Like the dimeric caspases, the monomeric coral caspases undergo a pH-dependent conformational change resulting from the titration of an evolutionarily conserved site. Data from molecular dynamics simulations paired with limited proteolysis and MALDI-TOF mass spectrometry show that the small subunit of the monomeric caspases is unstable and unfolds prior to the large subunit. Overall, the data suggest that all caspases share a conserved folding landscape, that a conserved allosteric site can be fine-tuned for species-specific regulation, and that the subfamily of stable dimers may have evolved to stabilize the small subunit.

Reduction of Tumor Growth with RNA-Targeting Treatment of the NAB2-STAT6 Fusion Transcript in Solitary Fibrous Tumor Models.

Solitary fibrous tumor (SFT) is a rare soft-tissue sarcoma. This nonhereditary cancer is the result of an environmental intrachromosomal gene fusion between NAB2 and STAT6 on chromosome 12, which fuses the activation domain of STAT6 with the repression domain of NAB2. Currently there is not an approved chemotherapy regimen for SFTs. The best response on available pharmaceuticals is a partial response or stable disease for several months. The purpose of this study is to investigate the potential of RNA-based therapies for the treatment of SFTs. Specifically, in vitro SFT cell models were engineered to harbor the characteristic NAB2-STAT6 fusion using the CRISPR/SpCas9 system. Cell migration as well as multiple cancer-related signaling pathways were increased in the engineered cells as compared to the fusion-absent parent cells. The SFT cell models were then used for evaluating the targeting efficacies of NAB2-STAT6 fusion-specific antisense oligonucleotides (ASOs) and CRISPR/CasRx systems. Our results showed that fusion specific ASO treatments caused a 58% reduction in expression of fusion transcripts and a 22% reduction in cell proliferation after 72 h in vitro. Similarly, the AAV2-mediated CRISPR/CasRx system led to a 59% reduction in fusion transcript expressions in vitro, and a 55% reduction in xenograft growth after 29 days ex vivo.

Assessment of Patients Receiving Short-Interval Botulinum Toxin Chemodenervation Treatment for Laryngeal Dystonia and Essential Tremor of the Vocal Tract.

Importance: The gold-standard treatment for laryngeal dystonia (LD) and essential tremor of the vocal tract (ETVT) is botulinum toxin (BoNT) chemodenervation. Although safe and effective, it is not curative, and periodic injections are required. Some medical insurance companies only cover injections at a 3-month interval, though some patients benefit from injections more frequently. Objective: To determine the proportion and characteristics of patients who receive BoNT chemodenervation treatment in intervals shorter than 90 days. Design, Setting, and Participants: This retrospective cohort study across 3 quaternary care neurolaryngology specialty practices in Washington and California recruited patients who underwent at least 4 consecutive laryngeal BoNT injections for LD and/or ETVT in the past 5 years. Data were collected from March through June 2022 and analyzed from June through December 2022. Exposure: Laryngeal BoNT treatment. Main Outcomes and Measures: Biodemographic and clinical variables, injection characteristics, evolution during the 3 interinjection intervals, and lifetime laryngeal BoNT treatment data were collected from patient medical records. Logistic regression was used to assess association to the short-interval outcome, defined as an average injection interval shorter than 90 days. Results: Of 255 patients included from the 3 institutions, 189 (74.1%) were female, and the mean (SD) age was 62.7 (14.3) years. The predominant diagnosis was adductor LD (n = 199 [78.0%]), followed by adductor dystonic voice tremor (n = 26 [10.2%]) and ETVT (n = 13 [5.1%]). Seventy patients (27.5%) received short-interval injections (<90 days). The short-interval group was younger than the long-interval group (≥90 days), with a mean (SD) age of 58.6 (15.5) years and 64.2 (13.5) years, respectively, and a mean difference of -5.7 years (95% CI, -9.6 to -1.8 years). There were no patient-related differences between the short- and long-interval groups in terms of sex, employment status, or diagnosis. Conclusions and Relevance: This cohort study demonstrated that while insurance companies often mandate a 3-month or greater interval for BoNT chemodenervation financial coverage, there is a considerable subset of patients with LD and ETVT who receive short-interval treatment to optimize their vocal function. Short-interval chemodenervation injections demonstrate a similar adverse effect profile and do not appear to predispose to resistance through antibody formation.

Presumptive Diagnosis in Tele-Health Laryngology: A Multi-Center Observational Study.

OBJECTIVES: Early in the COVID-19 pandemic, outpatient visits were adapted for the virtual setting, forcing laryngologists to presume certain diagnoses without the aid of laryngoscopy, solely based on history and the limited physical exam available via video visit. This study aims to examine the accuracy of presumptive diagnoses made via telemedicine, compared to subsequent in-person follow up, where endoscopic examination could confirm or refute suspected diagnoses. METHODS: A retrospective chart review was conducted of 38 patients evaluated for voice-related issues at NYU Langone Health and the University of California-San Francisco. Presumptive diagnoses at the initial telemedicine encounter were noted, along with diagnostic cues used for clinical reasoning and recommended treatment plans. These presumptive diagnoses were compared to diagnoses and plans established following laryngoscopy at follow-up in-person visits. RESULTS: After laryngoscopy at the first in-person visit, 38% of presumptive diagnoses changed, as did 37% of treatment plans. The accuracy varied among conditions. Muscle tension dysphonia and Reinke's edema were accurately diagnosed without laryngoscopy, but other conditions, including vocal fold paralysis and subglottic stenosis, were not initially suspected, relying on laryngoscopy for diagnosis. CONCLUSIONS: While some laryngologic conditions may be reasonably identified without in-person examination, laryngoscopy remains central to definitive diagnosis and treatment. Telemedicine can increase access to care, but it may provide more utility as a screening tool, triaging which patients should present more urgently for in-person laryngoscopy. LEVEL OF EVIDENCE: 4.

Variations in Practices and Preferences of Vocal Fold Injection Materials: A National Survey.

BACKGROUND: Vocal fold injection augmentation (VFI) is a common procedure for the treatment of glottic insufficiency. Material options for VFI and decisions regarding material selection are not standardized and often based on clinician preference. OBJECTIVE: This study aims to understand the variations in provider preference and utilization of injectable materials for VFI. METHODS: A 40-question survey was sent to 158 academic laryngologists. Questions pertained to the type of injectable materials used including brand preferences and rationale for preferences. RESULTS: Ninety-seven of the 158 laryngologists contacted participated in the survey (61.4%). The most frequently used injectable materials were Hyaluronic Acid (HA)-based products. Carboxymethylcellulose (CMC)-based products were preferred for trial augmentation (57.2%), HA-based products were preferred for acute/subacute vocal fold paralysis, presbyphonia, and sulcus/scar (54.2%, 61.5%, 44.7%, 41.7% respectively), and Calcium Hydroxyapatite (CaHA)-based products were preferred for long-term paralysis (28.1%). CMC-based products were discontinued by 21.8% of participants, largely due to quick material resorption. 17.8% of participants discontinued HA-based products largely due to adverse events and 26.0% abandoned CaHA-based products mostly due to inflammatory properties causing vocal fold stiffness and material unpredictability. Over 30% of respondents reported wanting to reinitiate micronized alloderm Cymetra® as an available injectable. CONCLUSION: Our survey demonstrated that there are significant variations in practice and preferences in regard to injectable material selection for VFI. As there is limited data on the direct material comparison, understanding the rationale behind these variations is crucial to guide new providers in material selection and provide information to patients undergoing these procedures. LEVEL OF EVIDENCE: 5 Laryngoscope, 133:1176-1183, 2023.