Otology and Audiology: Complications, Challenges, and Concerns in the Patient With Cleft Lip and/or Palate.

Cleft lip and/or palate, a treatable congenital condition, affects around 1 in 700 births, placing a large burden of care on those affected. A multidisciplinary approach to treating the patient involves not only cleft surgery but also a wide array of treatments and preventative therapies to prevent further disease. In this review, the otolaryngology subspecialties, otology and audiology, are discussed in relation to orofacial clefts. As patients with clefts carry a higher risk of permanent hearing loss and speech complications caused by the pathology of their cleft, management of additional diseases such as otitis media with effusion, conductive hearing loss, or infections requires timely evaluation, treatment, and follow-up. The current practice in otology and audiology is discussed with the challenges faced in delivering timely care-in any setting, low or higher income. Lack of consensus and controversies surrounding the use and timing of tympanostomy tubes are reviewed, as well as the palatoplasty types that show significant benefit for otitis media with effusion, audiometry, and speech outcomes. Lastly, a call for further research in clefts and otology and the urgency for its awareness and advocacy in low and middle-income countries is imperative.

Vascular Surgery Training Positions and Applicant 10-Year Trends with Consideration for Further Expansion.

BACKGROUND: There is a significant shortage of vascular surgeons in the United States and projections for these practicing surgical specialists continue to worsen. Annual appraisal of our workforce recruitment and growth is imperative. MATERIALS AND METHODS: Retrospective data were analyzed using the National Resident Matching Program from 2012-2022 applicant appointment years (specialty code for vascular surgery 450). Simple linear trend analysis was performed for the number of positions available and the number of applicants, stratified by fellowship or residency. RESULTS: Over the 10-year study period, the total vascular surgery trainee positions expanded from 161 to 202. Integrated residency positions increased (41 positions in 2012 vs. 84 in 2022) while available fellowship positions remained stagnant (120 in 2012 vs. 118 in 2022). Total applicants rose as well, from 213 to 311. In 2022, unmatched applicants have increased for both paradigms (25 fellowship and 84 residency applicants) and 100% of programs filled. On average, the number of residency positions offered increased by 4 each year (P < 0.0001) and the number of fellowship positions increased by 0.5 each year (P = 0.1617). The number of integrated residency applicants increased by approximately 9 per year (P = 0.001), while the number of fellowships applicants increased by approximately 1.5 per year (P = 0.121). CONCLUSIONS: Applicants for both vascular tracks have increased since 2012 indicating successful recruitment; however, all 2022 programs filled, leaving many applicants unmatched. Residency positions have continued to expand while fellowship positions have not. With the demonstrated surge among applicants, the disproportionate lack of increasing training positions, and the existing shortage of vascular surgeons, there is an urgency to meet the increasing demand. A concerted effort should be made toward adding additional residency and fellowship positions where feasible.

Syngnathia and obstructive apnea in a case of popliteal pterygium syndrome.

UNLABELLED: We describe an infant with popliteal pterygia, syngnathia, cleft lip and palate, and retrognathia diagnosed with popliteal pterygium syndrome (PPS). The neonatal course was complicated by severe obstructive apnea necessitating tracheostomy. CONCLUSION: This report illustrates the potential for airway compromise in PPS patients and the need for thorough neonatal airway assessment.

NAPRT silencing in FH-deficient renal cell carcinoma confers therapeutic vulnerabilities via NAD+ depletion.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts multiple cellular processes and drives tumor progression. High levels of fumarate inhibit alpha ketoglutarate-dependent dioxygenases, including the ten eleven translocation (TET) enzymes and can lead to global DNA hypermethylation. Here, we report patterns of hypermethylation in FH-mutant cell lines and tumor samples are associated with silencing of nicotinate phosphoribosyl transferase (NAPRT), a rate-limiting enzyme in the Preiss-Handler pathway of NAD+ biosynthesis in a subset of HLRCC cases. NAPRT is hypermethylated at a CpG island in the promoter in cell line models and patient samples, resulting in loss of NAPRT expression. We find that FH-deficient RCC models with loss of NAPRT expression, as well as other oncometabolite-producing cancer models that silence NAPRT, are extremely sensitive to nicotinamide phosphoribosyl transferase inhibitors (NAMPTis). NAPRT silencing was also associated with synergistic tumor cell killing with poly(ADP)-ribose polymerase inhibitors (PARPis) and NAMPTis, which was associated with effects on PAR-mediated DNA repair. Overall, our findings indicate that NAPRT-silencing can be targeted in oncometabolite-producing cancers and elucidates how oncometabolite associated hypermethylation can impact diverse cellular processes and leads to therapeutically relevant vulnerabilities in cancer cells. Implications: NAPRT is a novel biomarker for targeting NAD+ metabolism in FH-deficient HLRCCs with NAMPTis alone and targeting DNA repair processes with the combination of NAMPTis and PARPis.

Vascular tumors have increased p70 S6-kinase activation and are inhibited by topical rapamycin.

Vascular tumors are endothelial cell neoplasms whose cellular and molecular mechanisms, leading to tumor formation, are poorly understood, and current therapies have limited efficacy with significant side effects. We have investigated mechanistic (mammalian) target of rapamycin (mTOR) signaling in benign and malignant vascular tumors, and the effects of mTOR kinase inhibitor as a potential therapy for these lesions. Human vascular tumors (infantile hemangioma and angiosarcoma) were analyzed by immunohistochemical stains and western blot for the phosphorylation of p70 S6-kinase (S6K) and S6 ribosomal protein (S6), which are activated downstream of mTOR complex-1 (mTORC1). To assess the function of S6K, tumor cells with genetic knockdown of S6K were analyzed for cell proliferation and migration. The effects of topical rapamycin, an mTOR inhibitor, on mTORC1 and mTOR complex-2 (mTORC2) activities, as well as on tumor growth and migration, were determined. Vascular tumors showed increased activation of S6K and S6. Genetic knockdown of S6K resulted in reduced tumor cell proliferation and migration. Rapamycin fully inhibited mTORC1 and partially inhibited mTORC2 activities, including the phosphorylation of Akt (serine 473) and PKCα, in vascular tumor cells. Rapamycin significantly reduced vascular tumor growth in vitro and in vivo. As a potential localized therapy for cutaneous vascular tumors, topically applied rapamycin effectively reduced tumor growth with limited systemic drug absorption. These findings reveal the importance of mTOR signaling pathways in benign and malignant vascular tumors. The mTOR pathway is an important therapeutic target in vascular tumors, and topical mTOR inhibitors may provide an alternative and well-tolerated therapy for the treatment of cutaneous vascular lesions.

Cultural Trauma Scale: Psychometric evaluation of Black men's beliefs, emotions, and coping.

Racism and gender-based prejudice produce a synergistic and toxic effect that necessitates analysis. There is a need to conduct more research with Black men as their experiences with race-based trauma may differ, given their concurrent disproportionate exposure to other forms of violence. OBJECTIVE: The study's purpose was to develop items for and evaluate the factor structure and internal consistency of the Cultural Trauma Scale (CuTS) in an exclusive sample of Black men. METHOD: Using the Yale Center for Clinical Investigation, Community Alliance for Research Engagement principles, the study was conducted in a context of community-engaged research. Data were collected from individual interviews and focus groups, subject matter experts, and a sample of 150 adult Black men. Principal axis factoring (PAF) was used to determine the factor structure of the scale items. RESULTS: Via PAF the final factor structure included five constructs addressing: American and its justice system: cognitive-emotional responses (Cronbach's α = .88), cognitive-behavioral coping (Cronbach's α = .77), willingness to seek cultural trauma treatment (Cronbach's α = .88), tripartite police fear (Cronbach's α = .81), and resilience (Cronbach's α = .61). CONCLUSIONS: The CuTS represents psychometric advancement in the measurement of Black male social justice and healing from cultural trauma. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The racial pandemic experienced by Black American men: Cognitive-behavioral and structural implications.

Issues of systemic racism, mass incarceration, and cultural trauma (CT) are linked to emotional sequelae sufficient for treatment. However, attempts to explain the psychosocial reactions of Black American (BA) men to racial injustice and treat CT must be considered in the context of the current and past structural environments in which they live. The purpose of the present study was to obtain in-depth, thick description of two related factors: BA males' perceptions of injustice during the racial pandemic and the consequent psychosocial implications for theory and treatment. An interview guide addressing racial injustice, CT, and coping was used to conduct individual and focus groups' interviews with 20 BA men. The data were analyzed using thematic analysis. The qualitative analysis found five themes that collectively fulfilled the study's aims: (1) A violation of the social contract for Black American men, (2) Black American male distrust for police, (3) tripartite Black American male, police fear and heterogeneous emotions, (4) spiritual, technological, appraisal, and relational Black American male coping for racial injustice, and (5) Black American male resilience despite permanence of the racial status quo. As it pertains to BA male racial injustice and the residual CT, the qualitative data suggested multidimensional interventions that are cognitive-behavioral and structural in nature may be worthy of further empirical investigation. From a CT intervention perspective, the five emerging themes can be directly translated into cognitive-behavioral principles regarding therapeutic rapport, cultural adaptation, emphasis on positivity, and collaborative empiricism when working with BA men. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial.

OBJECTIVE: Vagus Nerve Stimulation (VNS) paired with rehabilitation delivered by the Vivistim® Paired VNS™ System was approved by the FDA in 2021 to improve motor deficits in chronic ischemic stroke survivors with moderate to severe arm and hand impairment. Vagus nerve stimulators have previously been implanted in over 125,000 patients for treatment-resistant epilepsy and the surgical procedure is generally well-tolerated and safe. In this report, we describe the Vivistim implantation procedure, perioperative management, and complications for chronic stroke survivors enrolled in the pivotal trial. METHODS: The pivotal, multisite, randomized, triple-blind, sham-controlled trial (VNS-REHAB) enrolled 108 participants. All participants were implanted with the VNS device in an outpatient procedure. Thrombolytic agents were temporarily discontinued during the perioperative period. Participants were discharged within 48 hrs and started rehabilitation therapy approximately 10 days after the Procedure. RESULTS: The rate of surgery-related adverse events was lower than previously reported for VNS implantation for epilepsy and depression. One participant had vocal cord paresis that eventually resolved. There were no serious adverse events related to device stimulation. Over 90% of participants were taking antiplatelet drugs (APD) or anticoagulants and no adverse events or serious adverse events were reported as a result of withholding these medications during the perioperative period. CONCLUSIONS: This study is the largest, randomized, controlled trial in which a VNS device was implanted in chronic stroke survivors. Results support the use of the Vivistim System in chronic stroke survivors, with a safety profile similar to VNS implantations for epilepsy and depression.

Vagus nerve stimulation for drop attacks in a pediatric population.

A retrospective analysis of 43 patients with drop attack seizures who were treated with vagus nerve stimulation (VNS) was undertaken to determine the efficacy of VNS and to determine pre-implantation characteristics associated with VNS success. It was found that on last follow-up, 46% of patients had at least a 75% reduction in drops per day. Forty-six percent of patients had less than a 50% reduction in drops per day and were considered nonresponders. Univariate analysis failed to uncover significant associations between pre-implantation characteristics and VNS success. It was found that atonic head nods were more amenable to VNS treatment as compared with atonic or tonic drop attacks. In addition, patients with focal or lateralized epileptiform abnormalities responded better to VNS compared with those with more diffuse or poorly localized findings on ictal and/or interictal recordings. Our data suggest that VNS offers significant palliative benefit to many children with medically intractable drop attack seizures.

Intra-capsular complete tonsillectomy, a modification of surgical technique to eliminate delayed post-operative bleeding.

Pediatric tonsillectomy is a frequently performed procedure using a variety of surgical techniques. Despite decades of modern surgical experience and advances in tools and techniques, a consensus on which technique is superior for minimizing complications has not been established. In a 2014 study, the authors examined differing surgical techniques and devices to determine if there was a significant difference in the bleed rates based on technique and device [1]. In that study 7024 children were evaluated, of which a total of 1.4% (n = 99) of children experienced a postoperative hemorrhage that required a second surgery. There was no significant difference found between the four different techniques that were evaluated. Although the combined rates of post-operative hemorrhage requiring a second surgery was lower compared to many other published reports, we hypothesized that continued improvement in surgical techniques could eliminate post-operative hemorrhage completely. As follow up to that study, we decided on a collective change in technique, and subsequent analysis of our post-operative results with respect to only one outcome, post-operative hemorrhage requiring a second surgery. With a new standardized technique in place, we retrospectively evaluated one year of surgical outcomes. These procedures were performed using the technique of a modified and complete, intra-capsular Coblator tonsillectomy. Of the 783 tonsillectomies done in 12 months, we found there were 0 patients that had experienced a postoperative hemorrhage requiring a second surgery. Based on our previous study with a rate of 1.4% post-operative hemorrhage we would have expected to have 11 episodes of post-operative hemorrhage requiring a second surgery.

Post-tonsillectomy hemorrhage rates in children compared by surgical technique.

Despite the sheer number of pediatric tonsillectomies performed in the United States annually, there is no clear consensus as to which surgical technique is superior. One way to compare surgical techniques is to study the morbidity associated with each. We report postoperative hemorrhage rates, one of the frequently encountered major adverse events, as part of a retrospective chart review across four different surgical techniques. These surgeries involved either (1) Coblation, (2) Co-blation with partial suture closure of the tonsillar fossa, (3) diathermy, or (4) partial intracapsular tonsillectomy (PIT). Of the 7,024 children we evaluated, 99 (1.4%) experienced a postoperative hemorrhage that required a second surgery; hemorrhage occurred after 33 of the 3,177 Coblation-alone procedures (1.04%), 28 of the 1,633 Coblation with partial suture closure procedures (1.71%), 29 of the 1,850 diathermies (1.57%), and 9 of the 364 PIT procedures (2.47%). Statistical analysis of hemorrhage rates with each surgical technique yielded p values >0.05 in each case (Coblation alone and Coblation with partial suture closure: p = 0.29; diathermy: p = 0.47; PIT, p = 0.20). Based on these data, we conclude that none of these techniques is significantly superior in terms of decreasing the risk of post-tonsillectomy hemorrhage in children. Therefore, surgeons should continue to use the surgical procedure they are most familiar with to optimize recovery in the postoperative period.

Anesthetic management of a young adult with complex congenital heart disease and bronchopleural fistula for rigid bronchoscopy.

The number of adults with congenital heart disease and those who require anesthetic care are increasing. We describe the anesthetic management of a young adult with palliated complex congenital heart disease and a chronic postsurgical bronchopleural fistula for rigid bronchoscopy. Perioperative considerations in the care of patients with single ventricle physiology for noncardiac procedures are reviewed. Specific requirements for rigid bronchoscopy are discussed in addition to the anesthetic implications of a bronchopleural fistula and particular concerns in the patient with single ventricle physiology.

The bacteriostatic properties of ear tubes made of absorbable polylactic acid.

OBJECTIVE: Tympanostomy tube placement remains the most common reason children are brought to the operating room. Of the known complications, transient, recurrent, and chronic otorrhea represent the most common and challenging sequelae of tube insertion. This study was performed to determine if the acidic nature of the polymer of lactic acid (PLA), a possible material for the construction of ear tubes, would have bacteriostatic properties. MATERIAL AND METHODS: Experimental PLA tubes and control fluoroplastic tubes were inoculated with a broth of Pseudomonas aeruginosa or Staphylococcus aureus and incubated. Fluid recovered from the tubes was plated and incubated again. Colony counts were recorded at 24 and 48 h. Two separate trials were conducted for each organism. Repeated measures analysis of variance (ANOVA) models were used to assess the effects of the type of tube, the experimental run, and the tube by run interaction on colony counts. RESULTS: In the Pseudomonas experiments, the mean colony count of the PLA tube group (Run 1: 1.0; Run 2: 26.6) was significantly lower than the mean colony count in the fluoroplastic tube group (Run 1: 132.6; Run 2: 122.2; p=0.0150). Similarly, in the S. aureus experiments, the mean colony count of the PLA tube group (Run 1: 88.2; Run 2: 92.6) was significantly lower than the mean colony count in the fluoroplastic tube group (Run 1: 335.0; Run 2: 325.8; p<0.0001). CONCLUSION: PLA has many properties including an apparent bacteriostatic quality, which may make it an attractive material for the construction of tympanostomy tubes.

Novel Association of Odontogenic Myxoma with Constitutional Chromosomal 1q21 Microduplication: Case Report and Review of the Literature.

Odontogenic myxoma (OM) is a rare, benign, and locally aggressive tumor. It tends to occur in the posterior maxilla and mandible and is often associated with root resorption and perforation of cortex. Histopathologically, there is a proliferation of spindle, bipolar, and stellate cells, with bland nuclei within a myxoid to infrequently fibromyxoid extracellular matrix. Long, thin residual bony trabeculae are often seen floating within the spindle cell proliferation because of the infiltrating nature of this tumor, and these trabeculae impart a "soap bubble" or "tennis-racket" radiologic appearance. No syndromic association of OM has been reported. Although similar histopathologic features are shared with cardiac myxoma and soft tissue myxoma, mutations in the GNAS gene have not been identified in OM to date, and only 2 of 17 OMs showed mutations in the PRKAR1A gene. In this report, we describe a case of OM in a patient with constitutional 1q21 microduplication, a locus that harbors genes encoding certain proteins in the cAMP-dependent protein kinase A (PKA) signaling pathway, including G-protein-coupled receptors and 1 phosphodiesterase interacting protein. Review of the literature describes the key clinical features and molecular pathogenesis of 1q21 microduplication, as well as highlighting the role of PKA signaling pathway in the pathogenesis of myxomas in general.

Case series: A novel technique for the treatment of external auditory canal stenosis.

External auditory canal (EAC) stenosis can exist as an isolated problem, as a component of craniofacial disorders, or in association with genetic syndromes. We present five cases and demonstrate the efficacy of a minimally invasive way of opening the EAC, facilitating better hearing, easier office examination, and allowing for other necessary treatments such as ear tube placement or use of a hearing aid. Follow-up ranged from 1 to 19 months, with all patients demonstrating significant improvement. We believe this is a novel surgical approach which is easy to perform, cost effective, and may be applicable to a wide range of patients.

Sildenafil for microcystic lymphatic malformations of the head and neck: A prospective study.

BACKGROUND: Microcystic lymphatic malformations (LM) are congenital birth defects that can cause severe functional or esthetic deformity. At this time, several treatment interventions are possible, but there is no ideal therapy. A recently published article noted a coincidental improvement in microcystic LMs with the use of sildenafil for pulmonary hypertension, but conclusive and reproducible data is lacking regarding its efficacy. METHODS AND RESULTS: A prospective study was conducted to examine the subjective and objective results associated with sildenafil use in the treatment of microcystic LMs. Patients under the age of 18 were enrolled, and after evaluation with pre-intervention magnetic resonance imaging (MRI) studies, each was given a 6-week course of sildenafil. Subjective outcomes were obtained, and postoperative MRIs were used to objectively quantify changes. Five patients between the ages of 4 and 11 were enrolled in the study. All patients had microcystic LMs of the head and neck. All patients had undergone previous treatment interventions utilizing various modalities, and each was now seeking treatment for functional and cosmetic purposes. All patients had minimal to no response from a subjective standpoint. Comparison of pre- and post-treatment MRIs also demonstrated minimal to no response. CONCLUSIONS: The use of sildenafil for the treatment of microcystic lymphatic malformations did not have any appreciable effect on our selected population of pediatric patients who had been resistant to previous therapies. Further studies would be necessary to determine if other cohorts may benefit.