Designing a Prolonged Method of Therapeutic Delivery to Support Rehabilitation From Ototoxic Damage in a Schwann Cell Model.

HYPOTHESIS: The ototoxicity of gentamicin and cisplatin can be evaluated with a Schwann cell model to screen for otoprotective agents that can be encapsulated into poly (lactic-co-glycolic acid) (PLGA) microparticles for drug delivery to the inner ear. BACKGROUND: Aminoglycosides and cisplatin are widely prescribed but known to cause ototoxicity. There is strong evidence that compromise to Schwann cells ensheathing inner ear afferent neurons results in inner ear dysfunction mimicking drug-induced ototoxicity. There is a need for a model for ototoxic demyelination to screen medications for protective potential and to subsequently target and tune the delivery of any promising agents. METHODS: RT4-D6P2T rat schwannoma cells were used as a Schwann cell model to assess gentamicin and cisplatin toxicity and to screen for protective agents. Cell viability was evaluated with the MTT cell proliferation assay. N -acetylcysteine (NAC) was encapsulated into a PLGA microparticle, and its elution profile was determined. RESULTS: The estimated 50% lethal concentration dose for gentamicin was 805.6 µM, which was 46-fold higher than that for cisplatin (17.5 µM). In several trials, cells dosed with NAC and cisplatin demonstrated a 22.6% ( p < 0.001) increase in cell viability when compared with cisplatin alone. However, this protective effect was not consistent across all trials. NAC was encapsulated into a PLGA microparticle and elution plateaued at 5 days. CONCLUSION: When dosed at their respective therapeutic ranges, cisplatin is more likely than gentamicin to induce damage to the Schwann cell model. Although NAC demonstrates an uncertain role in protecting against cisplatin-induced Schwann cell cytotoxicity, this study establishes a method to screen for other otoprotective medications to encapsulate into a tunable microparticle for localized drug delivery.

A Rare Case of Laryngeal Non-IgM Lymphoplasmacytic Lymphoma.

Laryngeal lymphoplasmacytic lymphoma has been previously reported only a handful of times in the literature. It can be difficult to diagnose without significant histologic workup and proper methodology. Here, we demonstrate the first known case of laryngeal lymphoplasmacytic lymphoma with non-immunoglobulin M (IgM) features. In this case report, a 79-year-old female with seropositive rheumatoid arthritis presented with five months of dysphonia and dyspnea on exertion. Lab studies revealed high levels of serum IgA and IgG. Flexible laryngoscopy and computed tomography of the neck showed a left supraglottic submucosal mass, which was surgically excised with a carbon dioxide laser. The histology of the mass confirmed the diagnosis of lymphoplasmacytic lymphoma. The patient was treated with 30.6 Gy of radiation therapy and eight cycles of rituximab with successful remission of her lymphoma and no evidence of disease recurrence six months after treatment completion. Lymphoplasmacytic lymphoma without corresponding IgM gammopathy is unusual and has been shown to have a higher frequency of extramedullary involvement. This is the first known manifestation of non-IgM lymphoplasmacytic lymphoma in the larynx.

A Risk Calculator for the Prediction of C5 Nerve Root Palsy After Instrumented Cervical Fusion.

BACKGROUND: C5 palsy is a common postoperative complication after cervical fusion and is associated with increased health care costs and diminished quality of life. Accurate prediction of C5 palsy may allow for appropriate preoperative counseling and risk stratification. We primarily aim to develop an algorithm for the prediction of C5 palsy after instrumented cervical fusion and identify novel features for risk prediction. Additionally, we aim to build a risk calculator to provide the risk of C5 palsy. METHODS: We identified adult patients who underwent instrumented cervical fusion at a tertiary care medical center between 2013 and 2020. The primary outcome was postoperative C5 palsy. We developed ensemble machine learning, standard machine learning, and logistic regression models predicting the risk of C5 palsy-assessing discrimination and calibration. Additionally, a web-based risk calculator was built with the best-performing model. RESULTS: A total of 1024 patients were included, with 52 cases of C5 palsy. The ensemble model was well-calibrated and demonstrated excellent discrimination with an area under the receiver-operating characteristic curve of 0.773. The following features were the most important for ensemble model performance: diabetes mellitus, bipolar disorder, C5 or C4 level, surgical approach, preoperative non-motor neurologic symptoms, degenerative disease, number of fused levels, and age. CONCLUSIONS: We report a risk calculator that generates patient-specific C5 palsy risk after instrumented cervical fusion. Individualized risk prediction for patients may facilitate improved preoperative patient counseling and risk stratification as well as potential intraoperative mitigating measures. This tool may also aid in addressing potentially modifiable risk factors such as diabetes and obesity.

Intractable Hiccups Caused by Diaphragmatic Eventration.

Intractable hiccups are a rare yet debilitating pathology with a broad differential and often indicate a more serious underlying pathology, which can range from neoplasms to structural abnormalities. In this case report, we present a 64-year-old male with seven months of intractable hiccups determined to be caused by eventration of the right hemidiaphragm. The patient was treated with baclofen to treat the hiccups pharmacologically. He was also prescribed voice therapy to establish rescue breathing techniques and reduce laryngospasm. Finally, he was referred to thoracic surgery for further evaluation and potential surgical intervention should his diaphragmatic eventration worsen or cause hypoxemia. To our knowledge, this is the first reported case of an association between diaphragmatic eventration and intractable hiccups. It is important to highlight this addition to the broad differential of intractable hiccups and to emphasize an interdisciplinary approach to workup and treatment of intractable hiccups.