Modeling of Ultrasound Stimulation of Adolescent Pancreas for Insulin Release Therapy.

OBJECTIVES: Our previous published studies have focused on safety and effectiveness of using therapeutic ultrasound (TUS) for treatment of type 2 diabetes mellitus (T2DM) in preclinical models. Here we present a set of simulation studies to explore potential ultrasound application schemes that would be feasible in a clinical setting. METHODS: Using the multiphysics modeling tool OnScale, we created two-dimensional (2D) models of the human abdomen from CT images captured from one normal weight adolescent patient, and one obese adolescent patient. Based on our previous studies, the frequency of our TUS was 1 MHz delivered from a planar unfocused transducer. We tested five different insonation angles, as well as four ultrasound intensities combined with four different duty factors and five durations of application to explore how these variables effect the peak pressure and temperature delivered to the pancreas as well as surrounding tissue in the model. RESULTS: We determined that ultrasound applied directly from the anterior of the patient abdomen at 5 W/cm2 delivered consistent acoustic pressures to the pancreas at the levels which we have previously found to be effective at inducing an insulin release from preclinical models. CONCLUSIONS: Our modeling work indicates that it may be feasible to non-invasively apply TUS in clinical treatment of T2DM.

Dose-Dense Docetaxel versus Weekly Paclitaxel following Dose-Dense Epirubicin and Cyclophosphamide as Adjuvant Chemotherapy in Node-Positive Breast Cancer Patients: A Retrospective Cohort Analysis.

METHODS: This study included patients from two prospective studies conducted in our institute from April 2007 to March 2009. Ninety-one women with axillary lymph node-positive breast cancer who had received four cycles of dose-dense epirubicin and cyclophosphamide were treated with either weekly paclitaxel (80 mg/m2) for 12 doses or biweekly docetaxel (75 mg/m2) for four cycles. RESULTS: After a median follow-up of 88 and 109 months, 11 (23.4%) and 10 (22.7%) patients had experienced disease recurrence (p = 0.16), while 10 (21.3%) and 5 (11.4%) patients had died in the paclitaxel and docetaxel arm, respectively (p = 0.56). No significant difference could be seen in 5-year DFS or OS among groups (HR: 0.58; 95% CI: 0.19-1.81, p = 0.35; HR: 0.58; 95% CI: 0.19-1.81, p = 0.35, respectively). CONCLUSION: In conclusion, both evaluated adjuvant chemotherapy regimens have comparable effectiveness regarding DFS and OS.

Sensorineural Hearing Loss and Tinnitus Characteristics in Patients With Idiopathic Intracranial Hypertension.

OBJECTIVES: To characterize patterns of sensorineural hearing loss (SNHL) and tinnitus in patients with idiopathic intracranial hypertension (IIH). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Adult patients diagnosed with IIH via lumbar puncture (LP) between 2010 and 2020 who had available audiograms. The study included a total of 40 patients; 33 women, and 7 men with a median age of 43. INTERVENTIONS: Diagnostic LP and audiogram. MAIN OUTCOME MEASURES: Otologic symptoms, ophthalmologic signs, hearing thresholds, cerebrospinal fluid opening pressures. RESULTS: The most commonly reported symptoms were tinnitus in 28 (70%, 23 pulsatile and 5 tonal), aural fullness in 11 (28%), and vertigo in 10 (25%). Twenty-nine patients had ophthalmologic examinations and 18 had evidence of papilledema. Twenty-five (63%) patients had hearing loss in at least one ear at one frequency range. Patients presented with both unilateral and bilateral hearing loss across low, middle, and high frequency ranges. No significant association was observed between hearing loss threshold and LP opening pressure except for 250 Hz in the left ear. After stratification by tinnitus group (pulsatile, tonal, and no tinnitus), no significant difference was found between mean hearing loss threshold at different frequencies. In addition, no significant mean age difference was identified in patients within each tinnitus group. CONCLUSIONS: There was no classic pattern or presentation for hearing loss in our IIH patients. They developed sudden, unilateral, or bilateral SNHL in low, middle, or high frequency range. The degree of hearing loss did not correlate with CSF opening pressure.

Characterization of Sensorineural Hearing Loss in Adult Patients With Sickle Cell Disease: A Systematic Review and Meta-analysis.

OBJECTIVES AND MAIN OUTCOME MEASURES: To determine the prevalence of sensorineural hearing loss (SNHL) attributable to sickle cell disease (SCD) in the global adult population and to identify factors contributing to its severity. STUDY DESIGN: Systematic Review and Meta-analysis. METHODS: We performed a comprehensive literature search for scientific articles in PubMed, Scopus, CINAHL, Web of Science, and the Cochrane Library that reported the incidence of hearing loss in populations over 18 years of age with SCD. RESULTS: We identified 138 studies from the initial search, 12 of which met inclusion criteria and were utilized for data analysis. A total of 636 SCD patients and 360 controls were included in the Cochrane Review Manager 5.3 meta-analysis. There was a statistically significant increase in the prevalence of SNHL in adults with SCD compared with the general population with a cumulative risk ratio (RR) of 6.03. CONCLUSIONS: This is the first systematic investigation of the relationship between SCD and SNHL in adult patients across the globe. SNHL is more prevalent in patients with SCD, specifically those of the HbSS genotype, than the general population likely due to the pathophysiology of the disease and its effects on labyrinthine microvasculature. The increased prevalence of SNHL in the adult SCD population warrants future research into the predictors of SNHL severity and merits routine audiometric monitoring of adult SCD patients.

Prevalence of Sensorineural Hearing Loss in Pediatric Patients with Sickle Cell Disease: A Meta-analysis.

OBJECTIVES: To determine the prevalence of Sensorineural Hearing Loss (SNHL) attributable to Sickle Cell Disease (SCD) in the global pediatric population and to identify factors contributing to its severity. STUDY DESIGN: Meta-analysis. METHODS: We performed a comprehensive literature search for scientific articles in PubMed, Scopus, CINAHL, Web of Science, and the Cochrane Library that reported the incidence of hearing loss in populations under 18 years of age with excluding studies analyzing patients on iron chelation therapy, adults, or those without objective audiological analysis. RESULTS: We identified 138 initial studies with 17 selected for analysis after applying the exclusion criteria. A total of 1,282 SCD patients and 553 controls were included in the meta-analysis. There was a statistically significant increase in the prevalence of SNHL in children with SCD compared to the general population with a cumulative risk ratio of 3.33. CONCLUSION: This is the first systematic investigation of the relationship between SCD and SNHL in pediatric patients across the globe. The increased prevalence of SNHL in the pediatric SCD population warrants future research into the predictors of SNHL severity and merits routine audiometric monitoring of SCD patients to reduce the social and developmental morbidity of hearing loss at a young age. PROSPERO Registration #: CRD42019132601. Laryngoscope, 131:1147-1156, 2021.

A Case of Incus Necrosis Following Oral and Intratympanic Steroid Administration for Sensorineural Hearing Loss.

OBJECTIVE: Intratympanic (IT) steroid injections are often used for the treatment of inner ear pathologies, including sudden sensorineural hearing loss. IT steroids are also commonly used in conjunction with or in case of systemic steroid therapy failure. They are viable options for patients who cannot endure side effects or are at high risk of complications from systemic therapy. The duration of treatment, strength, and type of steroid, and number of IT injections are important factors that impact possible treatment complications. Reported complications, though uncommon, include tympanic membrane perforation, otalgia, vertigo, otitis media, and acne. In this report, we explore a novel case of incus necrosis associated with oral and/or IT steroid administration. STUDY DESIGN: Clinical Capsule Report. SETTING: Tertiary Academic Center. PATIENT: We present a case of a 70-year-old male with sudden sensorineural hearing loss who developed incus necrosis and conductive hearing loss following treatment with oral and intratympanic steroids. INTERVENTION: The patient underwent a left tympanoplasty with ossicular chain reconstruction to treat the conductive component of his hearing loss. RESULTS: The left tympanoplasty almost fully-resolved the conductive component of his hearing loss. However, intraoperative and CT assessment of the temporal bone revealed resorption of the long process of the incus, with otherwise normal-appearing ossicles. CONCLUSION: We report the first case of possible steroid-induced necrosis of the long process of the incus. Owing to its tenuous blood supply, the incus may be predisposed to steroid-induced osteonecrosis similar to that of the femoral head.

Absence of Axoglial Paranodal Junctions in a Child With CNTNAP1 Mutations, Hypomyelination, and Arthrogryposis.

Leukodystrophies and genetic leukoencephalopathies are a heterogeneous group of heritable disorders that affect the glial-axonal unit. As more patients with unsolved leukodystrophies and genetic leukoencephalopathies undergo next generation sequencing, causative mutations in genes leading to central hypomyelination are being identified. Two such individuals presented with arthrogryposis multiplex congenita, congenital hypomyelinating neuropathy, and central hypomyelination with early respiratory failure. Whole exome sequencing identified biallelic mutations in the CNTNAP1 gene: homozygous c.1163G>C (p.Arg388Pro) and compound heterozygous c.967T>C (p.Cys323Arg) and c.319C>T (p.Arg107*). Sural nerve and quadriceps muscle biopsies demonstrated progressive, severe onion bulb and axonal pathology. By ultrastructural evaluation, septate axoglial paranodal junctions were absent from nodes of Ranvier. Serial brain magnetic resonance images revealed hypomyelination, progressive atrophy, and reduced diffusion in the globus pallidus in both patients. These 2 families illustrate severe progressive peripheral demyelinating neuropathy due to the absence of septate paranodal junctions and central hypomyelination with neurodegeneration in CNTNAP1-associated arthrogryposis multiplex congenita.