Histologic Examination of Vocal Fold Mucosal Wave and Vibration.

OBJECTIVES: Despite gross anatomic and histologic differences between human and canine vocal folds, similar wave patterns have been described yet not fully characterized. We reconstructed vocal fold (VF) vibration in a canine hemilarynx and performed histologic examination of the same vocal fold. We demonstrate comparable wave patterns while exploring the importance of certain anatomic architectures. METHODS: An in vivo canine hemilarynx was phonated against a glass prism at low and high muscle activation conditions. Vibration was captured using high-speed video, and trajectories of VF medial surface tattooed landmarks were 3D-reconstructed. The method of empirical eigenfunctions was used to capture the essential dynamics of vibratory movement. Histologic examination of the hemilarynx was performed. RESULTS: Oscillation patterns were highly similar between the in vivo canine and previous reports of ex vivo human models. The two most dominant eigenfunctions comprised over 90% of total variance of movement, representing opening/closing and convergent/divergent movement patterns, respectively. We demonstrate a vertical phase difference during the glottal cycle. The time delay between the inferior and superior VF was greater during opening than closing for both activation conditions. Histological examination of canine VF showed not only a thicker lamina propria layer superiorly but also a distinct pattern of thyroarytenoid muscle fibers and fascicles as described in human studies. CONCLUSIONS: Histologic and vibratory examination of the canine vocal fold demonstrated human vocal fold vibratory patterns despite certain microstructural differences. This study suggests that the multilayered lamina propria may not be fundamental to vibratory patterns necessary for human-like voice production. LEVEL OF EVIDENCE: NA (Basic science study) Laryngoscope, 134:264-271, 2024.

Effects of Thyroarytenoid Activation Induced Vibratory Asymmetry on Voice Acoustics and Perception.

INTRODUCTION: Asymmetry of vocal fold (VF) vibration is common in patients with voice complaints and also observed in 10% of normophonic individuals. Although thyroarytenoid (TA) muscle activation plays a crucial role in regulating VF vibration, how TA activation asymmetry relates to voice acoustics and perception is unclear. We evaluated the relationship between TA activation asymmetry and the resulting acoustics and perception. METHODS: An in vivo canine model of phonation was used to create symmetric and increasingly asymmetric VF vibratory conditions via graded stimulation of bilateral TA muscles. Naïve listeners (n = 89) rated the perceptual quality of 100 unique voice samples using a visual sort-and-rate task. For each phonatory condition, cepstral peak prominence (CPP), harmonic amplitude (H1-H2), and root-mean-square (RMS) energy of the voice were measured. The relationships between these metrics, vibratory asymmetry, and perceptual ratings were evaluated. RESULTS: Increasing levels of TA asymmetry resulted in declining listener preference. Furthermore, only severely asymmetric audio samples were perceptually distinguishable from symmetric and mildly asymmetric conditions. CPP was negatively correlated with TA asymmetry: voices produced with larger degrees of asymmetry were associated with lower CPP values. Listeners preferred audio samples with higher values of CPP, high RMS energy, and lower H1-H2 (less breathy). CONCLUSION: Listeners are sensitive to changes in voice acoustics related to vibratory asymmetry. Although increasing vibratory asymmetry is correlated with decreased perceptual ratings, mild asymmetries are perceptually tolerated. This study contributes to our understanding of voice production and quality by identifying perceptually salient and clinically meaningful asymmetry. LEVEL OF EVIDENCE: N/A (Basic Science Study) Laryngoscope, 134:1327-1332, 2024.

Usefulness of Children's Hospital of Philadelphia ROP (CHOP ROP) model in the prediction of type 1 ROP.

Purpose: Children's Hospital of Philadelphia retinopathy of prematurity (CHOP ROP) model can be used to predict ROP, a leading cause of childhood blindness, using risk factors such as postnatal weight gain, birth weight (BW), and gestation age (GA). The purpose of this study was to determine the usefulness of the CHOP ROP for the prediction of treatable ROP. Methods: This was a prospective observational study. Babies <34 weeks of GA, BW <2000 grams, and GA 34-36 weeks with risk factors such as respiratory distress syndrome (RDS) were included; ROP screening, follow-up, and treatment were performed based on national guidelines. The average daily postnatal weight gain was measured, and the CHOP nomogram was plotted. Babies were categorized as high risk or low risk based on the "CHOP" alarm. The sensitivity and specificity of the CHOP ROP for the detection of treatable ROP were determined. In case of poor sensitivity, a new cutoff alarm level was planned using logistic regression analysis. Results: Of 62 screened infants, 23 infants did not fulfill the criteria of the CHOP algorithm and were excluded. Thus, in the study on 39 infants, the predictive model with an alarm level of 0.014 had 100% specificity and 20% sensitivity. With the "new" alarm level (cutoff) of 0.0003, the CHOP nomogram could detect all the infants who developed treatable ROP, that is, sensitivity increased to 100% but specificity decreased to 10.5%. Conclusion: The CHOP ROP model with a cutoff point (0.014) performed poorly in predicting severe ROP in the study. Thus, there is a need to develop inclusive and more sensitive tailor-made algorithms.

Beyond Tradition: Non-surgical Endodontics and Vital Pulp Therapy as a Dynamic Combination.

Symptomatic irreversible pulpitis and apical periodontitis in mature permanent teeth present challenges in their management. Traditional treatment approaches, such as root canal therapy or tooth extraction, may compromise tooth structure and oral function. This review article explores the combination of non-surgical endodontic treatment and vital pulp therapy as an alternative approach for these conditions. The purpose is to examine this combined approach's effectiveness, benefits, challenges, and limitations. The objectives include reviewing the literature, evaluating clinical outcomes, discussing potential benefits, and providing recommendations for clinical practice. The combination approach aims to preserve tooth structure, promote healing, and reduce postoperative complications. The article discusses the rationale for combining the two techniques, presents evidence supporting their efficacy, and outlines the techniques and protocols involved. Clinical outcomes, case studies, potential challenges, and comparative analysis with traditional approaches are also explored. Future directions and research recommendations highlight areas for further investigation, innovations, and the development of clinical guidelines. In conclusion, the combination of non-surgical endodontic treatment and vital pulp therapy offers a valuable strategy for managing mature permanent mandibular molars with symptomatic irreversible pulpitis and apical periodontitis. Further research and advancements are needed to refine the treatment protocol and expand the evidence base, and clinicians should stay updated to provide optimal care and improve patient outcomes.

Calcium Channel Blockers- Induced Iatrogenic Gingival Hyperplasia: Case Series.

Hypertension rightfully termed as "Silent killer" is associated with increase in morbidity and mortality when left untreated. Calcium channel blockers are the most commonly prescribed first-line anti-hypertensive drugs in India. Calcium channel blockers are known to cause gingival hyperplasia but with lower incidence rates compared to the other two groups causing iatrogenic gingival overgrowth, immunosuppressants, and anticonvulsants. Nifedipine administration, among the calcium channel blockers, has been frequently associated with iatrogenic gingival hyperplasia. Incidence of amlodipine-induced gingival hyperplasia which has similar pharmacodynamic action like nifedipine, had been reported rarely. Here, we present a case series of drug induced gingival overgrowth caused by calcium channel blockers used for the management of hypertension. All the patient's condition improved after withdrawal of the offending drug, oral prophylaxis and intervention, and alternate drug from other first-line drugs were started for managing hypertension.

Validation and enhancement of a vocal fold medial surface 3D reconstruction approach for in-vivo application.

In laryngeal research, studying the vertical vocal fold oscillation component is often disregarded. However, vocal fold oscillation by its nature is a three-dimensional process. In the past, we have developed an in-vivo experimental protocol to reconstruct the full, three-dimensional vocal fold vibration. The goal of this study is to validate this 3D reconstruction method. We present an in-vivo canine hemilarynx setup using high-speed video recording and a right-angle prism for 3D reconstruction of vocal fold medial surface vibrations. The 3D surface is reconstructed from the split image provided by the prism. For validation, reconstruction error was calculated for objects located at a distance of up to 15 mm away from the prism. The influence of camera angle, changing calibrated volume, and calibration errors were determined. Overall average 3D reconstruction error is low and does not exceed 0.12 mm at 5 mm distance from the prism. Influence of a moderate (5°) and large (10°) deviation in camera angle led to a slight increase in error to 0.16 mm and 0.17 mm, respectively. This procedure is robust towards changes in calibration volume and small calibration errors. This makes this 3D reconstruction approach a useful tool for the reconstruction of accessible and moving tissue surfaces.

Guidelines for endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA): Joint Indian Chest Society (ICS)/Indian Association for Bronchology (IAB) recommendations.

Over the past decade, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an indispensable tool in the diagnostic armamentarium of the pulmonologist. As the expertise with EBUS-TBNA has evolved and several innovations have occurred, the indications for its use have expanded. However, several aspects of EBUS-TBNA are still not standardized. Hence, evidence-based guidelines are needed to optimize the diagnostic yield and safety of EBUS-TBNA. For this purpose, a working group of experts from India was constituted. A detailed and systematic search was performed to extract relevant literature pertaining to various aspects of EBUS-TBNA. The modified GRADE system was used for evaluating the level of evidence and assigning the strength of recommendations. The final recommendations were framed with the consensus of the working group after several rounds of online discussions and a two-day in-person meeting. These guidelines provide evidence-based recommendations encompassing indications of EBUS-TBNA, pre-procedure evaluation, sedation and anesthesia, technical and procedural aspects, sample processing, EBUS-TBNA in special situations, and training for EBUS-TBNA.

Anterior Matrix Systems for Composite Restorations: A Review.

In the field of restorative dentistry, composite resins have emerged as the most utilized materials. They revolutionized the cosmetic approach to anterior tooth treatment since their introduction to dental practice. In cases where one or more of the tooth's walls are absent, matrices are employed to assist in the creation of the proper anatomic contour and proximal contacts without the occurrence of gingival overhangs. Matrices come in a variety of designs suitable for various therapeutic conditions. Depending on the level of tooth destruction, they might range from a simple metal or plastic strip to a circumferential ring of metal surrounding the entire crown. Although the handling characteristics of modern composites have significantly improved, dentists still encounter challenges with the development of good interproximal contact and proper anatomical contour. The utilization of an anterior matrix system can be paramount in achieving these objectives.

Histological transformation to gliosarcoma with combined BRAF/MEK inhibition in BRAF V600E mutated glioblastoma.

The identification of BRAF V600 mutation in multiple cancers beyond melanoma and the development of combined BRAF and MEK targeting agents have altered the landscape of tissue-agnostic precision oncology therapies with an impact on survival outcomes. Despite initial efficacy, resistance emerges, and it is pertinent to identify putative resistance mechanisms. We report a case of recurrent glioblastoma (GBM) harboring BRAF V600E alteration who initially responded to combined BRAF + MEK inhibition and subsequently developed treatment resistance by histological transformation to gliosarcoma and acquisition of oncogenic KRAS G12D and an NF1 L1083R mutation. This documented case represents an initial evidence of a developing phenomenon in cancer research as it provides the first evidence of an emergent KRAS G12D/NF1 L1083R aberration with histological transformation occurring concurrently with primary BRAF V600E-altered glioblastoma as a previously unrecognized acquired mechanism of resistance in the setting of combined BRAF and MEK inhibition. This novel finding not only sheds new light on the RAS/MAPK pathway but also highlights the potential for morphological transformation to gliosarcoma, underscoring the critical need for further investigation in this area.

Study to evaluate the relation between weight gain in infants and occurrence of retinopathy of prematurity.

Purpose: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Capturing serial daily postnatal weight gain can act as an innovative, low-cost method of risk stratification. We aim to study the relation between weight gain in infants and occurrence of ROP. Methods: The prospective, observational study was conducted on 62 infants. ROP screening was done based on the Rashtriya Bal Swasthya Karyakram (RBSK) criteria. Infants were classified into no ROP (n = 28), mild ROP (n = 8), and treatable ROP (n = 26) groups. Average daily postnatal weight gain was measured and its relation to development of ROP was studied. All statistical calculations were done using Statistical Package for the Social Sciences (SPSS) 21 version (SPSS Inc., Chicago, IL, USA) statistical program for Microsoft Windows. Results: Mean rate of weight gain in no ROP group, mild ROP group, and treatable ROP group was 33.12, 27.19, and 15.31 g/day, respectively (P = 0.001). Mean gestational age and birth weight in treatable group (n = 26) were 31.38 weeks and 1572.31 g, respectively. Receiver operating curve analysis revealed a cutoff of 29.33 g/day for ROP and 21.91 g/day for severe ROP. Conclusion: We concluded that, babies with poor weight gain of below 29.33 g/day are at high risk for ROP and babies with wight gain of 21.91 g/day are at high risk for severe ROP. These babies should be followed meticulously. So, the rate of weight gain of a preterm can help us to prioritize babies.

Top advances of the year: Precision oncology.

The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered "undruggable" for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.

Videofluoroscopic Measures of Swallowing After Partial Epiglottidectomy for Dysphagia.

OBJECTIVE: Partial epiglottidectomy has a role in improving dysphagia due to epiglottic obstruction. This study evaluates objective parameters of swallow function in patients who underwent partial epiglottidectomy. STUDY DESIGN: Retrospective study design. SETTING: Tertiary Care University Academic Medical Center. METHODS: A review was performed of patients who underwent CO2 laser partial epiglottidectomy for the treatment of dysphagia at a single tertiary care academic center over a 4-year period. Objective swallowing parameters were evaluated from pre- and postoperative modified barium swallow studies using SwallowTail Advanced Measurement software using blinded reviewers. The postswallow pharyngeal residue (bolus clearance ratio or BCR), spatiotemporal swallowing variables (oropharyngeal [OPT], hypopharyngeal [HPT], and total pharyngeal transit times [TPT]), and airway protection (Penetration-Aspiration Scale [PAS]) were analyzed. Student paired t test was used to determine significant changes in outcome parameters pre- and postsurgery. RESULTS: Forty-three patients (age range 45-92 years, median 70) met the inclusion criteria. A majority (69.8%) had a history of external beam radiation therapy for head and neck cancer. BCR decreased significantly from a mean of 31.7% presurgery to 24.2% (p = .01) postsurgery. OPT, HPT, and TPT did not differ significantly postsurgery. The mean Eating Assessment Tool-10 score improved from 25.1 to 20.2 after treatment (p = .03). PAS score improved by 15.4% and remained stable at 66.2% after surgery. CONCLUSION: Partial epiglottidectomy improves pharyngeal bolus clearance in properly selected patients with dysphagia due to epiglottic obstruction. Patients demonstrated stable swallow function with the benefit of reduced postswallow residue following surgical intervention.

Safety of Platelet-Rich Plasma Subepithelial Infusion for Vocal Fold Scar, Sulcus, and Atrophy.

OBJECTIVE: To demonstrate the safety profile of platelet-rich plasma (PRP) as an injectable therapeutic for the treatment of vocal fold scarring and atrophy. METHODS: Preliminary report on a prospective clinical trial of patients with vocal fold scar or atrophy undergoing unilateral vocal fold subepithelial infusion with autologous PRP. Enrolled patients underwent four subepithelial injections spaced 1 month apart. Adverse events were assessed peri and post-injection at each session. Patient-reported outcomes were collected at every visit using the Voice Handicap Index-10 (VHI-10) and Vocal Fatigue Index (VFI) questionnaires. RESULTS: Twelve patients underwent unilateral vocal fold injection with autologous PRP prepared according to Eclipse PRP® system protocol. Forty-three injections were performed using a peroral or percutaneous approach. An average of 1.57 ± 0.4 cc (range 0.6-2.0 cc) injectate was used. All patients tolerated the procedure without difficulty or peri-procedural complications. The average duration of follow-up was 3.6 ± 1.8 months. No significant inflammatory reactions or adverse events were seen to date. There was statistically significant improvement in patient-reported outcomes at the 3 month follow up (n = 9) follow-up (mean ΔVHI-10 = 10.8, p < 0.001, mean ΔVFI = 18.9, p = 0.01, t test, paired two sample for means, two-tail). All nine patients who completed the series of four injections subjectively (yes/no) reported they were satisfied with the results. CONCLUSION: This prospective study cohort demonstrated a favorable safety profile, with no adverse events or peri-procedural complications. Subjective improvements in vocal quality and reduction in vocal fatigue need to be clinically correlated with further study. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:647-653, 2023.

Control of Pre-phonatory Glottal Shape by Intrinsic Laryngeal Muscles.

OBJECTIVES: Surgical manipulations to treat glottic insufficiency aim to restore the physiologic pre-phonatory glottal shape. However, the physiologic pre-phonatory glottal shape as a function of interactions between all intrinsic laryngeal muscles (ILMs) has not been described. Vocal fold posture and medial surface shape were investigated across concurrent activation and interactions of thyroarytenoid (TA), cricothyroid (CT), and lateral cricoarytenoid/interarytenoid (LCA/IA) muscles. STUDY DESIGN: In vivo canine hemilarynx model. METHODS: The ILMs were stimulated across combinations of four graded levels each from low-to-high activation. A total of 64 distinct medial surface postures (4 TA × 4 CT × 4 LCA/IA levels) were captured using high-speed video. Using a custom 3D interpolation algorithm, the medial surface shape was reconstructed. RESULTS: Combined activation of ILMs yielded a range of unique pre-phonatory postures. Both LCA/IA and TA activation adducted the vocal fold but with greater contribution from TA. The transition from a convergent to a rectangular glottal shape was primarily mediated by TA muscle activation but LCA/IA and TA together resulted in a smooth rectangular glottis compared to TA alone, which caused rectangular glottis with inferomedial bulging. CT activation resulted in a lengthened but slightly abducted glottis. CONCLUSIONS: TA was primarily responsible for the rectangular shape of the adducted glottis with synergistic contribution from the LCA/IA. CT contributed minimally to vocal fold medial shape but elongated the glottis. These findings further refine laryngeal posture goals in surgical correction of glottic insufficiency. LEVEL OF EVIDENCE: NA, Basic science Laryngoscope, 133:1690-1697, 2023.

3D Reconstruction of Phonatory Glottal Shape and Volume: Effects of Neuromuscular Activation.

INTRODUCTION: Although phonatory glottal posture and airflow pulse shape affect voice quality, studies to date have been limited by visualization of vocal fold (VF) vibration from a superior view. We performed a 3D reconstruction of VF vibratory motion during phonation from a medial view and assessed the glottal volume waveform and resulting acoustics as a function of neuromuscular stimulation. STUDY DESIGN: In vivo canine hemilarynx phonation. METHODS: Across 121 unique combinations of the superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN) stimulation, the hemilarynx was excited to the oscillation with airflow. VF medial surface reference points were tracked on high-speed video, mapped into 3D space, and surface shape was restored using cubic spline interpolation. Glottal surface shape, reconstruction-based parameters, and glottal volume waveform were calculated. Fundamental frequency (F0), cepstral peak prominence (CPP), and harmonic amplitude (H1-H2) were measured from high-quality audio samples. RESULTS: The glottis was convergent during opening and divergent during closing. Neuromuscular activation changed phonatory glottal shape and reduced glottal volume. Significant reduction in glottal volume and closing quotient were present with SLN stimulation. RLN stimulation significantly increased F0 and CPP and decreased H1-H2 (constricted glottis), while SLN effects were similar and synergistic with concurrent RLN stimulation. CONCLUSION: 3D reconstruction of in vivo medial surface vibration revealed effects of laryngeal nerve stimulation on glottal vibratory pattern and acoustic correlates of voice quality. SLN activation resulted in significantly quicker glottal closure per cycle, decreased glottal volume, and higher-pitched, less breathy, and less noisy voice. RLN had a similar effect on acoustic measures. LEVEL OF EVIDENCE: NA, Basic Science Laryngoscope, 133:357-365, 2023.

Understanding the Complexities of Cast Post Retention: A Comprehensive Review of Influential Factors.

This comprehensive review delves into the intricate landscape of cast post retention in restorative dentistry, encompassing historical perspectives, contemporary techniques, and future directions. Examining factors ranging from tooth-related considerations to prosthesis-related dynamics, the review provides a detailed analysis of clinical techniques, including step-by-step procedures, common challenges, and innovative advancements. Technological breakthroughs, such as digital impressions, computer-aided design and computer-aided manufacturing (CAD/CAM) technology, three-dimensional (3D) printing, and finite element analysis, are explored for their transformative impact on precision and customization. The discussion extends to the promising future of cast post retention, emphasising emerging materials, the integration of artificial intelligence in treatment planning, and patient-specific approaches. Implications for clinical practice underscore the importance of individualised treatment planning and the adoption of advanced technologies. Recommendations for future research advocate for comprehensive long-term clinical studies, investigations into AI-driven treatment planning, and a focus on patient outcomes and satisfaction. This review consolidates existing knowledge and anticipates a future marked by enhanced precision, individualised care, and improved long-term success in cast post-retained restorations.