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The following are available online at https://www.mdpi.com/article/ 10.3390/genes14040831/s1, A.A.M.S. received a scholarship from the Philippine Council for Health and Research Development of the Department of Science and Technology (PCHRD-DOST) under the Research Enrichment (Sandwich) Grant of the Accelerated Science and Technology Human Resource Devel- opment Program. O.A.K. was supported by the US National Institutes of Health (NIH)—National Institute on Deafness and Other Communication Disorders (NIDCD) grant T32 DC012280 (to Sue C. Kinnamon and Herman A. Jenkins). This work was supported by the NIH through the NIDCD grants R01 DC019642 (to R.L.P.S.-C. and Ivana V. Yang) and R01 DC013912 (to S.P.G.); and the National Insti- tute of Arthritis and Musculoskeletal and Skin Diseases grant R01 AR068292 (to N.H.-M.). Funding was also provided by Junta de Andalucia, grant Retos en Investigacion PY20_00303 (to J.A.L.-E.)., Vertigo due to vestibular dysfunction is rare in children. The elucidation of its etiology will improve clinical management and the quality of life of patients. Genes for vestibular dysfunction were previously identified in patients with both hearing loss and vertigo. This study aimed to identify rare, coding variants in children with peripheral vertigo but no hearing loss, and in patients with potentially overlapping phenotypes, namely, Meniere’s disease or idiopathic scoliosis. Rare variants were selected from the exome sequence data of 5 American children with vertigo, 226 Spanish patients with Meniere’s disease, and 38 European–American probands with scoliosis. In children with vertigo, 17 variants were found in 15 genes involved in migraine, musculoskeletal phenotypes, and vestibular development. Three genes, OTOP1, HMX3, and LAMA2, have knockout mouse models for vestibular dysfunction. Moreover, HMX3 and LAMA2 were expressed in human vestibular tissues. Rare variants within ECM1, OTOP1, and OTOP2 were each identified in three adult patients with Meniere’s disease. Additionally, an OTOP1 variant was identified in 11 adolescents with lateral semicircular canal asymmetry, 10 of whom have scoliosis. We hypothesize that peripheral vestibular dysfunction in children may be due to multiple rare variants within genes that are involved in the inner ear structure, migraine, and musculoskeletal disease., Philippine Council for Health and Research Development of the Department of Science and Technology (PCHRD-DOST) under the Research Enrichment (Sandwich) Grant of the Accelerated Science and Technology Human Resource Development Program, US National Institutes of Health (NIH)-National Institute on Deafness and Other Communication Disorders (NIDCD) T32 DC012280, NIH through the NIDCD R01 DC019642, R01 DC013912, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) R01 AR068292, Junta de Andalucia PY20_00303

Introduction: Aminoglycoside antibiotics such as gentamicin are bactericidal and effective against gram negative organisms and act synergistically against gram positive organisms, including S taphylococcus aureus. However, they have serious adverse effects such as nephrotoxicity and ototoxicity. Gentamicin ototoxicity may occur after a single dose and results in decreased vestibular function, which is frequently debilitating and often permanent. Objective: To emphasize the risk of gentamicin ototoxicity and suggest alternative antibiotics in penicillin-allergic patients undergoing surgery. Case Summary: We present a case of a woman with preexisting Meniere’s Disease who received gentamicin 400 mg perioperatively for a sigmoidectomy due to a penicillin allergy listed in the patient’s medical record. The patient developed severe ototoxicity preventing her from working or driving. Physical examination was remarkable for a broad-based gait requiring assistance to walk and bilateral corrective saccades. Vestibular testing revealed high-grade bilateral vestibular loss associated with all semicircular canals, a considerable decline compared to her function 3 years prior. Discussion: Gentamicin is indicated for surgical prophylaxis when a patient has a true allergy to penicillins and cannot receive cephalosporins, though alternatives exist. True allergies include IgE-mediated illness (anaphylaxis, bronchospasm, or urticaria 30-60 minutes after administration) or exfoliative reactions (Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis). The authors encourage more prudent use of gentamicin, especially in patients susceptible for debilitating otologic insults, and offer recommendations for alternative agents prior to using gentamicin.

Objective To compare rates of successful tympanic membrane (TM) closure in primary pediatric tympanoplasty between various autologous and non-autologous tissues. Methods A retrospective chart review was performed examining all primary pediatric tympanoplasties over a 20-year period at a single institution. Results In 564 pediatric tympanoplasties, no statistically significant difference existed between success rates of autologous and non-autologous grafts (p = 0.083). Compared with fascia, the hazard ratios (and 95% confidence intervals [CI]) for failure for each graft were as follows: human pericardial collagen (HR 0.90, CI 0.54-1.50, p = 0.680), porcine submucosal collagen (HR 1.07, CI 0.56-2.05, p = 0.830), human acellular dermal collagen (HR 1.66, CI 0.95-2.87, p = 0.073), and "multiple grafts" (HR 0.72, CI 0.26-1.98, p = 0.520). Survival curves demonstrated that 75% of graft failures occurred by 6 months after surgery, the rest occurring between 6 and 12 months postoperatively. Larger perforations encompassing more than or equal to 50% of the TM had lower success rates (HR 1.50, CI 1.02-2.21, p = 0.041) than smaller perforations encompassing less than 50% of the TM. Age was not correlated with success (HR 0.98, CI 0.93-1.03, p = 0.390). Conclusion This study found that non-autologous collagen grafts provide equivalent rates of healing when compared with autologous tissue in primary pediatric tympanoplasty. In addition to the potential for reduced operative time and donor site morbidity, these materials provide a viable graft alternative in fascia-depleted ears.Level of Evidence: Level 4.

Objectives Routine pediatric tonsillectomy ± adenoidectomy (T ± A) is one of the most common procedures for children worldwide, accounting for approximately 2000 procedures per year at our institution. To determine the utility of pathologic analysis of routine, nonsuspicious pediatric tonsil specimens, we investigated the incidence of hematologic and lymphoid malignancy diagnosed at the time of or following T ± A. Methods Retrospective review of patients 0–18 years undergoing T ± A between 2012 and 2020 with or without pathologic analysis. Results Included were 14,141 patients who underwent routine T ± A (mean age 11 ± 4.6 years, 48% female). Of these, tonsils of 2464 patients were sent to pathology, where zero were found to harbor malignancy. Seven patients (0.050%) developed malignancy after T ± A. Of these, 4 had unremarkable tonsils per pathology, and 3 did not have tonsils analyzed. There were 5 cases of Acute Lymphocytic Leukemia (ALL, 0.035%), 1 case of Acute Myeloid Leukemia (0.007%), and 1 case of Lymphoma (0.007%). The average length of time from T ± A to diagnosis was 2.4 ± 1.8 years. Conclusion No cases of occult malignancy were identified in specimens from routine T ± A with pathologic analysis, even among patients who later developed malignancy. This study suggests that sending routine pediatric T ± A specimens for formal pathologic analysis is an inefficient use of resources without appreciably improving the quality and safety of patient care.

Objective: To describe a case of benign paroxysmal positional vertigo (BPPV) resulting in reversible horizontal semicircular canalith jam successfully treated with horizontal canal occlusion. A brief literature review of similar cases was performed. Methods: Case report and literature review. Results: A 68-year-old female presented with apogeotropic positional nystagmus, attributed to reversible horizontal canalith jam mimicking cupulolithiasis that was refractory to tailored repositioning maneuvers across months. She was unable to work due to the severity of her symptoms. She underwent surgical occlusion of the affected canal with immediate resolution of her symptoms. A literature review revealed similar cases of canalith jam mimicking cupulolithiasis. Conclusions: Reversible canalith jam, in which particles moving with horizontal head position alternate between obstructing the semicircular canal and resting on the cupula, can mimic signs of cupulolithiasis. This variant of BPPV can be effectively managed with surgical canal occlusion should symptoms fail to resolve after tailored repositioning maneuvers.

Chronic Forward Head Posture is associated with headaches, neck pain, and disability, though few studies have investigated the effects it has on the suboccipital triangle. The objective of this study was to quantitatively assess whether the biomechanical changes in the suboccipital triangle help explain the clinical manifestations of Forward Head Posture. Specifically, this study aimed to identify whether the Greater Occipital Nerve or C2 nerve root may be compressed in Forward Head Posture. Three-dimensional, specimen-specific computer models were rendered from thirteen cadaveric cervical spine specimens. The spines transitioned from neutral to Forward head posture while motion data was collected. This data was synced with the computer models to make precise measurements. In Forward Head Posture, occiput-C1, C1-C2, and occiput-C2 segments extended by 10.7 ± 4.6 deg, 4.6 ± 4.3 deg, and 15.3 ± 2.3 deg, respectively. The Rectus Capitis Posterior Major and Minor and Obliquus Capitis Superior muscles shortened by 20.0 ± 4.6%, 15.0 ± 7.6%, and 6.6 ± 3.3%, respectively. The Obliquus Capitis muscle inferior length did not change. The suboccipital triangle area decreased by 18.7 ± 6.4%, but the protective gaps surrounding the C2 nerve root and the Greater Occipital Nerve did not reveal clinically significant impingement. The C2 nerve root gap decreased by 1.0 ± 1.3 mm and the Greater Occipital Nerve gap by 0.2 ± 0.18 mm. These results demonstrate that the C2 nerve root and the Greater Occipital Nerve are protected by the bony landscape of the cervical spine. However, there is likely persistent contraction of the rectus muscles in Forward Head Posture, which suggests a secondary tension-type etiology of the associated headache.

Background. Forward head posture (FHP) may be associated with neck pain and poor health-related quality of life. Literature describes only qualitative muscle length changes associated with FHP. Objective. The purpose of this study was to quantify how muscle-tendon unit lengths are altered when human cadaveric specimens are placed in alignments representing different severities of FHP. Design. This biomechanical study used 13 fresh-frozen cadaveric cervical spine specimens (Occiput-T1, 54±15 y). Methods. Specimens’ postural changes simulating increasing FHP severity while maintaining horizontal gaze were assessed. Specimen-specific anatomic models derived from computed tomography–based anatomic data were combined with postural data and specimen-specific anatomy of muscle attachment points to estimate the muscle length changes associated with FHP. Results. Forward head posture was associated with flexion of the mid-lower cervical spine and extension of the upper cervical (sub-occipital) spine. Muscles that insert on the cervical spine and function as flexors (termed “cervical flexors”) as well as muscles that insert on the cranium and function as extensors (“occipital extensors”) shortened in FHP when compared to neutral posture. In contrast, muscles that insert on the cervical spine and function as extensors (“cervical extensors”) as well as muscles that insert on the cranium and function as flexors (“occipital flexors”) lengthened. The greatest shortening was seen in the major and minor rectus capitis posterior muscles. These muscles cross the Occiput-C2 segments, which exhibited extension to maintain horizontal gaze. The greatest lengthening was seen in posterior muscles crossing the C4-C6 segments, which exhibited the most flexion. Limitations. This cadaver study did not incorporate the biomechanical influence of active musculature. Conclusions. This study offers a novel way to quantify postural alignment and muscle length changes associated with FHP. Model predictions are consistent with qualitative descriptions in the literature.