Posterior Tongue Tie, Base of Tongue Movement, and Pharyngeal Dysphagia: What is the Connection?

Ankyloglossia, or tongue tie, and its impact on the oral phase of feeding has been studied and debated for decades. However, the impact of posterior tongue ties on the pharyngeal phase of swallowing is not well documented in the literature. A videofluoroscopic swallow study (VFSS) allows for visualization of the oral, pharyngeal, and esophageal phases of the swallow. When decreased base of tongue movement, impaired pharyngeal pressure generation, and presence of pharyngeal residue are noted during a VFSS, a neurologic etiology can be suspected. However, in the setting of a normal MRI with normal motor development, other etiologies need to be explored. If it is not neurologic, could it be anatomic? We present a 21-month-old patient with significant pharyngeal phase dysphagia which was most saliently characterized by impaired base of tongue movement, poor pressure generation, and diffuse residue resulting in aspiration. He was eventually diagnosed with a posterior tongue tie and underwent a frenulectomy. Results via subsequent VFSS revealed significant improvement in base of tongue movement, pharyngeal pressure generation, and pharyngeal constriction, resulting in efficient movement of the bolus through the pharynx into the esophagus, no nasopharyngeal regurgitation, no aspiration, and near resolution of his pharyngeal dysphagia. Patients with impaired base of tongue movement and impaired pressure generation resulting in pharyngeal residue in the setting of a normal neurologic workup could possibly present with a posterior tongue tie which should be examined and included in the differential diagnosis.

Spatial orientation of the adult cochlea: rotation, tilt, and angle theta 3.

OBJECTIVE: Quantitative description in adult crania of (1) angular orientation of the basal turn of the cochlea relative to the sagittal (termed "rotation") and Frankfort horizontal (termed "tilt") planes, and angle theta 3 [angular relationship of the line defined by the cochlea's spiral center and cochlear (round) window, to the cochlear window]; (2) orientation of the cochlea relative to the plane defined by the horizontal and vertical portions of the facial nerve; (3) orientation of the basal turn of the cochlea relative to the plane of the posterior semicircular canal; and (4) the association of these orientations with the extent of mastoid pneumatization. METHODS: Postmortem material analysis. From 41 bequeathed anatomical ear-normal cadaveric cranial, high-resolution CT scans were performed of the five crania with the largest and the five with the smallest mastoids. Eleven points in three-dimensional Cartesian space were appointed and studied with the software program FIJI. RESULTS: The median angle values (and ranges) for right ears were: "rotation" 52° (range 47-61); and, "tilt" 84° (79-89). The planes of the cochlear basal turn and facial nerve approximated superimposition: median 15° (2-19). Angle theta 3 for right ears was median 40° (28-44). Bilateral symmetry was found for the relationships between the planes. However, no association of any planar relationship with mastoid pneumatization was suggested. CONCLUSION: Considering the range of angles found in clinically normal adult specimens, spatial orientation of the cochlea may explain some of the difficulties in implantation.

State of the Art in Treating Velopharyngeal Dysfunction.

Velopharyngeal dysfunction (VPD) is a condition that can greatly impact a child's quality of life. The initial evaluation and workup of patients presenting with VPD is generally straightforward, consisting of history taking and physical examination, perceptual speech analysis, and objective techniques such as nasometry and speech endoscopy. However, there is no standardized treatment option. Multiple surgical and nonsurgical techniques have been described, all with varying approaches to correction of the defect and similarly, with varying risks and outcomes. We aim to provide an overview of this condition and available treatment options, as well as highlight recent updates in management, including the use of cine magnetic resonance imaging, new injectable options for pharyngeal augmentation, and the evolving role of robotic surgery. We also discuss techniques to facilitate teaching during oropharyngeal surgery and our approach to revision surgical planning.

Implanting straight into cochlea risks the facial nerve: a Cartesian coordinate study.

PURPOSE: To describe the straight-into-cochlea line that affords the best access for an electrode array to enter via the round window, and how this line relates to the facial nerve, the incus, and mastoid size. The straight-into-cochlea line is important to minimize the cochlear trauma and maximize the likelihood of placement into the scala tympani. METHODS: High-resolution CT scans were obtained for ten craniums with the extremes of large (N = 5) and small (N = 5) mastoid pneumatization; the specimens were from a series of 41 ear normal craniums. Using FIJI, a publicly available software program, the straight-into-cochlea insertion line was determined by defining the x-y-z coordinates of the middle of the round window and a point 6.0 mm into the cochlea on its centrifugal wall. Then, from the extended straight-into-cochlea insertion line, we determined the shortest perpendicular distance to the middle of the fallopian canal, and from that "fallopian point" to the apex of the posterior process of the incus. RESULTS: We found good repeatability of measurements. We found the extended straight-into-cochlea insertion lines routinely close to or in the midst of the fallopian canal (50 % ≤ 1.0 mm). We found the lines 4.7-7.8 mm from the apex of the posterior process of the incus. Line positions relative to "fallopian point" and incus showed no relation to mastoid pneumatization. For the distance "fallopian point" to incus, bilateral symmetry was suggested. CONCLUSIONS: Using landmarks registered in an x-y-z coordinate system, straight-into-cochlea insertion via the round window puts the facial nerve at risk.

An improved method of surgical pathology testing for onychomycosis.

BACKGROUND: Surgical pathology testing for onychomycosis using periodic acid-Schiff staining is the "gold standard." However, routine histopathological methods of processing nail clippings can be limited by poor section quality, higher costs, and delayed turnaround times for some specimens because of tissue hardness. OBJECTIVE: We investigated the utility of sodium hydroxide (NaOH) pretreatment of nail specimens submitted for the histopathologic evaluation of onychomycosis. METHODS: We report our validation of a sodium hydroxide (NaOH) pretreatment protocol during a 7-month study period from 2009-2010. Nail clippings (n = 45) were divided into NaOH-treated and routine processing halves and submitted in separate tissue blocks for parallel processing, embedding, sectioning, and staining for hematoxylin-eosin and periodic acid-Schiff. Histologic sections were scored for section quality and statistical analysis performed. RESULTS: NaOH pretreatment yielded higher quality sections for both hematoxylin-eosin-stained (P < .001) and periodic acid Schiff-stained (P < .001) slides with reduced tissue folding and fragmentation, improved ease of cutting, and adherence of the tissue to glass slides. LIMITATIONS: Direct comparison of the proposed NaOH pretreatment protocol with other pretreatment techniques was not performed. CONCLUSION: NaOH pretreatment of nails submitted for a clinical suspicion of onychomycosis is a simple, rapid, and easily adopted method that leads to improved tissue section quality for optimal histopathologic evaluation and diagnosis. Improved tissue sections and adherence to glass slides can reduce the need for repeat sections, thereby reducing costs and preventing delays in turnaround time.

Cost of Goods Analysis Facilitates an Integrated Approach to Identifying Alternative Synthesis Methodologies for Lower Cost Manufacturing of the COVID-19 Antiviral Molnupiravir.

Orally delivered drugs offer significant benefits in the fight against viral infections, and cost-effective production is critical to their impact on pandemic response in low- and middle-income countries. One example, molnupiravir, a COVID-19 therapy developed by Emory, Ridgeback, and Merck & Co., had potential to benefit from significant cost of goods (COGs) reductions for its active pharmaceutical ingredient (API), including starting materials. A holistic approach to identifying, developing, and evaluating optimized synthetic routes, which includes detailed COGs modeling, provides a rapid means to increase the availability, uptake and application of molnupiravir and other antivirals in global markets. Identification and development of alternate processes for the synthesis of molnupiravir has been conducted by the Medicines for All Institute at Virginia Commonwealth University (M4ALL) and the Green and Turner Labs at the University of Manchester. Both groups developed innovative processes based on synthetic route design and biocatalysis aimed at lowering costs and improving global access. The authors then performed COGs modeling to assess cost saving opportunities. This included a focus on manufacturing environments and facilities amenable to global public health and the identification of key parameters using sensitivity analyses. While all of the evaluated routes provide efficiency benefits, the best options yielded 3-6 fold API COGs reductions leading to treatment COGs as low as <$3/regimen. Additionally, key starting materials and cost drivers were quantified to evaluate the robustness of the savings. Finally, COGs models can continue to inform the focus of future development efforts on the most promising routes for additional cost savings. While the full price of a treatment course includes other factors, these alternative API synthetic approaches have significant potential to help facilitate broader access in low- and middle-income countries. As other promising therapeutics are developed, a similar process could enable rapid cost reductions while enhancing global access.

The utility of handheld ultrasound as a point-of-care screening tool to assess vocal fold impairment following congenital heart surgery.

INTRODUCTION: Vocal fold motion impairment (VFMI) is a known potential complication of congenital heart surgery (CHS). Flexible nasolaryngoscopy (FNL) is the gold standard for evaluation of vocal fold movement but has risks, including epistaxis, desaturation, and changes in heart rate. Laryngeal ultrasound (LUS) has begun to emerge as a diagnostic tool and has been shown to have high accuracy in the evaluation of VFMI. We sought to assess the utility of hand-held LUS as a point-of-care screening tool to assess VFMI in pediatric patients following congenital heart surgery. METHODS: Using a prospective cohort design, children under 18 years who were undergoing congenital heart surgery at a tertiary care pediatric hospital were enrolled. All patients underwent postoperative LUS and FNL. All studies were reviewed by two otolaryngology reviewers blinded to the clinical diagnosis. Higher quality studies were reviewed by two cardiology reviewers also blinded to the clinical diagnosis. Accuracy and inter-rater reliability were calculated. RESULTS: Sixty-two children were screened. Fourteen children with VFMI were identified via FNL. When comparing LUS and FNL, both individual accuracy (90.3% and 75.8%) and interrater agreement (79% overall, 96% for high quality videos) were high for the otolaryngology reviewers. The cardiology reviewers were able to obtain 100% accuracy for high quality videos. CONCLUSION: Handheld LUS has utility as a point-of-care screening tool to assess VFMI. This may have benefit in low-resource settings, for universal screening in cardiac intensive care units, or in settings where otolaryngology consultation may be difficult to obtain.

Cellular and molecular mechanisms of cleft palate development.

Cleft lip and palate are common craniofacial deformities. The etiology underlying these deformities is complex and multifactorial and they can occur as part of one of many chromosomal syndromes, Mendelian single gene disorders, teratogenic effects, and as yet uncharacterized syndromes. Our paper will provide an overview of the multiple genes and molecular pathways that have been implicated in palatal fusion. We believe that understanding the molecular mechanisms of cleft formation can help clinicians anticipate which patients may have difficulties healing and in the future allow them to make surgical and medical treatment decisions based on genetic information.

Simulation-based education to improve emergency management skills in caregivers of tracheostomy patients.

INTRODUCTION: Children with tracheostomies are medically complex and may be discharged with limited and variably trained home nursing support. When faced with emergencies at home, caregivers must often take the lead role in management, and many lack experience with troubleshooting these emergencies prior to initial discharge. METHODS: A high-fidelity simulation-based tracheostomy education program was designed using a programmable mannequin (Gaumard HAL S3004 one-year-old pediatric simulator). At the conclusion of our standard education program, caregivers completed three simulation scenarios: desaturation, mucus plugging, and dislodgement. A trained simulation facilitator graded performance. A self-assessment tool was used to analyze comfort with emergency management at the beginning of training, before and after simulation. Caregivers rated confidence using a 10 cm visual analog scale. All participants completed a post-simulation debriefing session. RESULTS: 39 caregivers completed all three scenarios and returned pre- and post-simulation self-assessments. Mean scores from the caregiver self-assessments increased for all three scenarios, with mean increases of 9 mm for desaturation, 16 mm for mucus plugging, and 10 mm for decannulation. Two patterns of responses emerged: caregivers with progressive increase in confidence through training, and caregivers who initially rated confidence highly, and had confidence decrease as the complexity of true emergency management became apparent. All participants found the simulations to be realistic and helpful. DISCUSSION: High-fidelity simulation training allows for realistic exposure to trach-related emergencies. Many caregivers overestimate their ability to handle emergencies and gain important insight through simulation. IMPLICATIONS FOR PRACTICE: Identification of skills and knowledge gaps prior to discharge allows for targeted re-education in emergency management.

miRNA profiling of primary lung and head and neck squamous cell carcinomas: Addressing a diagnostic dilemma.

OBJECTIVE: To determine whether microRNA (miRNA) profiling of primary lung and head and neck squamous cell carcinomas could be useful to identify a specific miRNA signature that can be used to further discriminate between primary lung squamous carcinomas and metastatic lesions in patients with a history of head and neck squamous cell cancer. METHODS: Specimens of resected primary head and neck and lung squamous cell carcinomas were obtained from formalin-fixed, paraffin-embedded blocks. Paraffin blocks were sectioned and deparaffinized, and total RNA was isolated and profiled. Quantitative polymerase chain reaction was performed to verify array results. RESULTS: Twelve head and neck and 16 lung squamous cell carcinoma samples met quality control metrics and were included for analysis. Forty-eight miRNAs were differentially expressed (P < .05) between the 2 groups. Of these, 30 were also significantly associated (q < .25) with tumor type in 2 independent sets of primary head and neck and lung squamous carcinomas profiled by The Cancer Genome Atlas consortium, including miR-34a and miR-10a. The ratio of miR-10a and miR-10b was especially predictive of primary cancer site in all 3 data sets, with area under the (receiver operating characteristics) curve values ranging from 0.922 to 0.982. Quantitative polymerase chain reaction confirmed the association of miR-34a expression and the miR-10:miR-10b ratio with tumor type. CONCLUSIONS: MicroRNA expression may be useful for discriminating between head and neck and lung squamous cell carcinomas, including miR-34a and the miR-10a:miR-10b ratio. This differentiation has clinical importance because it could help determine the appropriate therapeutic approach.

South Asian adolescents' experiences of acculturative stress and coping.

Despite the significant growth in the South Asian population in the United States over the past 2 decades, the experiences of South Asian adolescents have remained largely invisible. Guided by a socioecological perspective (American Psychological Association, 2012; García Coll & Marks, 2012), this study examined South Asian adolescents' experiences of acculturative stress and approaches to coping with this stress across home and school contexts. A semistructured interview was completed by 16 participants (9 girls, 7 boys; ages 14-18 years) from different South Asian backgrounds, attending an urban public high school in the Northeastern part of the United States. Conventional content analysis was used to analyze the interview data, and revealed 4 broad categories or domains related to participants' experiences as young South Asians in the U.S. These domains include the following: (a) Connection to family, community, and heritage; (b) Challenges to acculturation; (c) Stress accompanying the navigation across cultural contexts; and (d) Coping and resilience. Participants' narratives reflect acculturative stress experienced in home and school contexts which can inhibit psychological well-being and bicultural identity development. The findings have important implications for culturally informed research, intervention, and policy. (PsycINFO Database Record

Recurrent focal segmental glomerulosclerosis apparently resistant to plasmapheresis improves after surgical repair of arteriovenous fistula aneurysms.

Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease and has a high recurrence rate after kidney transplantation, attributed to a circulating permeability factor. Plasmapheresis is the treatment of choice after recurrence to remove the circulating factor. We present a case of recurrent FSGS 6 years after transplantation. It is instructive because proteinuria did not respond to intensive plasmapheresis-combined with rituximab-until the possibility of ineffective apheresis secondary to multiple aneurysms in the arteriovenous fistula (AVF) was considered. Proteinuria improved soon after alternative access for plasmapheresis was secured and AVF aneurysms were surgically repaired.

The Processing of Surgical Specimens With Forensic Evidence: Lessons Learned From the Boston Marathon Bombings.

CONTEXT: Following the Boston Marathon bombings in April 2013, pathology departments at hospitals across Boston, Massachusetts received numerous amputated limbs, as well as other surgical specimens from trauma surgeries. In the absence of clear guidelines, each department faced uncertainties in performing gross examination of these specimens. OBJECTIVE: To develop a protocol for processing surgical specimens with forensic evidence. DESIGN: We collaborated with representatives who knew the practices at 3 major Boston hospitals, the Office of the Chief Medical Examiner of Massachusetts, and a senior team leader for the evidence response team for the Boston, Massachusetts division of the US Federal Bureau of Investigation to construct a protocol for processing specimens with forensic evidence. RESULTS: A simple and robust protocol approved by experts in forensic evidence collection was developed. Important points in this protocol include (1) assigning the task of processing the specimens to one individual or one team of individuals, (2) photographing all specimens before and after washing, (3) obtaining a radiograph of each specimen, and (4) identifying a secure area to store forensic evidence. CONCLUSIONS: When acts of terror occur, protocols provide order and clarification to the processing of surgical specimens. We propose a protocol that provides guidance for pathology departments across the country to handle trauma-related surgical specimens with forensic evidence in an efficient manner to allow optimal patient care and a secure way of gathering forensic evidence.

Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: an experience of 405 cases.

Just two and a half decades ago adult renal cell neoplasms, i.e., those arising from the renal tubules or collecting duct epithelium, were subdivided into two major subtypes: "clear cell carcinoma" and "granular cell carcinoma." Subsequent detailed morphologic and/or cytogenetic studies have resulted in the recognition of several distinctive subtypes of adult renal epithelial neoplasms, which has led to the promulgation of a refined contemporary histologic classification of these tumors. This study examines the prognostic significance of histologic subtyping in accordance with the new classification in a consecutive series of 405 cases treated at a single institution. Cases were histologically classified into 28 (7%) benign tumors [27 (6.7%) renal oncocytomas, 1 (0.2%) metanephric adenoma] and 377 (93%) malignant tumors [255 (63%) conventional (clear cell) renal cell carcinoma, 75 (18.5%) papillary renal cell carcinoma, 24 (5.9%) chromophobe renal cell carcinoma, and 23 (5.7%) renal cell carcinoma, unclassified]. A total of 25 (6.6%) malignant tumors showed evidence of sarcomatoid change. Kaplan-Meier survival analysis with log-rank test showed histologic type (p = 0.002), Fuhrman's nuclear grade (p = 0.001), TNM stage (p = 0.001), vascular invasion (p = 0.001), and necrosis (p = 0.001) to be significantly associated with disease-specific survival and progression-free survival, based on follow-up of 368 patients (mean 64.5 months, median 56 months). The 5-year disease-specific survival for chromophobe renal cell carcinoma, papillary renal cell carcinoma, conventional (clear cell) renal cell carcinoma, and renal cell carcinoma, unclassified was 100%, 86%, 76%, and 24%, respectively; no patient with a benign tumor diagnosis progressed or died of disease. The 5-year progression-free survival for chromophobe renal cell carcinoma, papillary renal cell carcinoma, conventional (clear cell) renal cell carcinoma, and renal cell carcinoma, unclassified was 94%, 88%, 70%, and 18%, respectively. Malignant tumors with sarcomatoid change had a 35% and 27%, 5-year disease-specific and progression-free survival, respectively. Cox proportional hazards regression analysis showed TNM stage (p = 0.001), nuclear grade (p = 0.01), and necrosis (p = 0.05) to be significant predictors of disease-specific survival. In conclusion, our study shows that the histologic categorization of adult renal epithelial neoplasms performed by routine light microscopic hematoxylin and eosin-based examination in accordance with the contemporary classification scheme has prognostic utility.

Cytokeratin 19 is a powerful predictor of survival in pancreatic endocrine tumors.

The prediction of the behavior of pancreatic endocrine tumors (PETs) is a difficult exercise. CK19, a marker of pancreatic ductal cells, does not stain normal islet cells. Our aim was to evaluate the prognostic value of traditional parameters, including the Capella classification, as well as CK19. We evaluated the clinicopathologic features of 101 curatively resected PETs. The influence on survival of size, functional status of tumor, growth pattern, nuclear grade, mitoses (>2/10 HPF), vascular and perineural invasion, and necrosis was determined. Immunohistochemistry for Ki-67 and CK19 was performed in 45 and 54 cases, respectively. Cases were categorized as per the Capella classification as: benign, borderline, low-grade, and high-grade malignant. The different variables were tested by standard univariate and multivariate analyses. Mitoses (P = 0.03), solid pattern (P = 0.04), necrosis (P = 0.01), vascular invasion (P = 0.003), perineural invasion (P = 0.02), CK19 staining (P = 0.0008), and Ki-67 (P = 0.02) were significant prognostic indicators by univariate analysis while the Capella classification was not significant. By multivariate analysis, only CK19 was significant (P = 0.0008). None of the CK19-negative cases died of disease, while 10 of 28 CK19-positive cases died of disease and 3 are alive with disease. The Capella classification includes malignant tumors in its benign and borderline categories. CK19 is a powerful predictor of survival and can potentially segregate benign and malignant PETs. We suggest that all PETs with any one of the following features be diagnosed as malignant: presence of necrosis, vascular invasion, perineural invasion, or CK19 positivity. We hypothesize that a subgroup of PETs may share a common histogenesis with pancreatic adenocarcinomas.

Leiomyoma of the gastrointestinal tract with interstitial cells of Cajal: a mimic of gastrointestinal stromal tumor.

Leiomyomas (LMs) of the gastrointestinal tract arise within the muscularis mucosae (superficial) and muscularis propria (deep). There are isolated reports of KIT-positive cells, presumed interstitial cells of Cajal (ICCs), within gastrointestinal LMs. We have encountered esophageal LMs with a high proportion of KIT-positive and DOG1-positive spindle-shaped cells, an appearance that mimicked gastrointestinal stromal tumor. Our aim was to explore the prevalence of ICCs in LMs of the gastrointestinal tract and the etiopathogenic significance of these cells in this benign neoplasm. We identified 34 esophageal LMs (28 deep, 6 superficial), 8 gastric LMs, and 5 small-bowel LMs (all lesions in muscularis propria). We performed immunohistochemical staining studies for desmin, DOG1, and KIT on these neoplasms. We also evaluated 12 superficial colonic LMs. ICCs were distinguished from mast cells on the basis of morphology (elongated and occasionally branching spindle-shaped cells) and the presence of DOG1 reactivity. Four cases were screened for mutations in PDGFRA exons 12, 14, and 18 and KIT exons 9, 11, 13, and 17. ICCs were identified in all deep esophageal LMs and constituted an average of 20% of the lesional cells; focally, these cells comprised >50% of cells. The density of these cells was significantly higher than the background muscularis propria, and hyperplasia of ICCs was not identified in the adjacent muscle. ICCs were identified in 6 of 8 gastric LMs and 1 of 5 small-bowel LMs and were entirely absent in all superficial esophageal and colonic/rectal LMs. There were no mutations in KIT or PDGFRA. ICCs are universally present in deep esophageal LMs, and thus these neoplasms could be mistaken for gastrointestinal stromal tumors, particularly on biopsy samples, an error associated with adverse clinical consequences. ICCs are also identified in gastric and intestinal LMs, albeit in a smaller proportion of cases. Colonization and hyperplasia by non-neoplastic ICCs likely account for this phenomenon.

Full clinical recovery after topical acyclovir treatment of Epstein-Barr virus associated cutaneous B-cell lymphoma in patient with mycosis fungoides.

Primary cutaneous T- and B-cell lymphomas are a heterogeneous group of diseases with varied clinical presentations and prognosis. The use of new molecular, histological, and clinical criteria has improved their recognition. Cutaneous B-cell and T-cell lymphomas are seldom found together in the same patient. Here we report a rare case of mycosis fungoides variant of a cutaneous T-cell lymphoma (CTCL) which later developed Epstein-Barr virus (EBV) associated cutaneous B-cell lymphoproliferative disorder. The patient initially presented with generalized erythroderma, extensive plaques, and axillary lymphadenopathy. Histopathology and immunophenotyping of her tumor from the right breast nodule revealed a T-cell lymphoma consistent with mycosis fungoides. She was initially treated with pentostatin, followed by topical mechlorethamine and topical steroids. After progression of her mycosis fungoides with worsening diffuse skin lesions on this regimen, her treatments were changed to oral bexarotene with an initial partial response followed by stable disease. Three years from her initial presentation, she developed ulcerated cauliflower-like nodules on her forehead. Biopsy of these lesions revealed EBV-positive large- and medium-sized pleomorphic B-cells consistent with EBV-driven B-cell lymphoproliferative disorder. She was treated with topical acyclovir cream on the involved skin areas while continuing with oral bexarotene for mycosis fungoides. Skin lesions gradually diminished and totally disappeared after four weeks of topical acyclovir treatment. Bexarotene treatment was continued for another year until the mycosis fungoides progressed and became wide spread causing her death four and a half years after the initial diagnosis. The coexistence of two cutaneous non-Hodgkin lymphomas of different lineage in the same patient and the complete clinical response of EBV-related B-cell cutaneous component to topical acyclovir makes this rare case particularly interesting.