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Abstract Vestibular schwannomas (VS) are the most common tumor of the skull base with available treatment options that carry a risk of iatrogenic injury to the facial nerve, which can significantly impact patients’ quality of life. As facial nerve outcomes remain challenging to prognosticate, we endeavored to utilize machine learning to decipher predictive factors relevant to facial nerve outcomes following microsurgical resection of VS. A database of patient-, tumor- and surgery-specific features was constructed via retrospective chart review of 242 consecutive patients who underwent microsurgical resection of VS over a 7-year study period. This database was then used to train non-linear supervised machine learning classifiers to predict facial nerve preservation, defined as House-Brackmann (HB) I vs. facial nerve injury, defined as HB II–VI, as determined at 6-month outpatient follow-up. A random forest algorithm demonstrated 90.5% accuracy, 90% sensitivity and 90% specificity in facial nerve injury prognostication. A random variable (rv) was generated by randomly sampling a Gaussian distribution and used as a benchmark to compare the predictiveness of other features. This analysis revealed age, body mass index (BMI), case length and the tumor dimension representing tumor growth towards the brainstem as prognosticators of facial nerve injury. When validated via prospective assessment of facial nerve injury risk, this model demonstrated 84% accuracy. Here, we describe the development of a machine learning algorithm to predict the likelihood of facial nerve injury following microsurgical resection of VS. In addition to serving as a clinically applicable tool, this highlights the potential of machine learning to reveal non-linear relationships between variables which may have clinical value in prognostication of outcomes for high-risk surgical procedures.

Objective: This study assessed the prevalence of SARS-CoV-2 positivity in a cohort of pregnant patients served by a single health system. Treatments and outcomes are compared by maternal SARS-CoV-2 status and COVID-19 symptomatology., Methods: This was a retrospective cohort study of patients with delivery outcomes from March 2020-December 2021. SARS-CoV-2 positivity was defined by patients who had a positive test or COVID-19 diagnosis during pregnancy. Descriptive analysis compared demographics, medical management during pregnancy, and both perinatal and non-obstetric outcomes by SARS-CoV-2/COVID-19 status (negative, positive-asymptomatic, and positive-symptomatic)., Results: Of 24,310 pregnancies, 94.6% were negative, 3.9% were positive-asymptomatic, and 1.5% were positive-symptomatic. Non-delivery hospitalizations were highest among positive-symptomatic patients (16.8%), followed by positive-asymptomatic patients (3.9%) and lastly negative patients (2.7%) ( p  < 0.001). Likewise, Intensive Care Unit (ICU) admissions during an antepartum or delivery admission were higher for positive-symptomatic patients (13.0%) compared to positive-asymptomatic patients or negative patients (0.7% and 0.5%, respectively, p  < 0.001). The rate of preterm birth was significantly higher in positive-symptomatic patients compared to positive-asymptomatic and negative patients (15.7% vs. 9.5% and 9.8%, respectively, p  = 0.002). There were no statistically significant differences in rates of miscarriage or intrauterine fetal demise. Maternal readmission, administration of corticosteroids for fetal lung maturity, birthweight, and neonatal intensive care unit (NICU) admission were significantly affected by SARS-CoV-2 status., Conclusion: Pregnant patients testing positive for SARS-CoV-2 were mostly asymptomatic and identified during routine screening. Symptomatic patients were significantly more likely to require hospitalization and ICU admission with some increase in adverse perinatal outcomes.

Gene therapy holds promise for treatment of inherited retinal dystrophies, a group of rare genetic disorders characterized by severe loss of vision. Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene therapy clinical trial in 12 patients with retinal dystrophy caused by biallelic mutations in the retinaldehyde-binding protein 1 (RLBP1) gene of the visual cycle. The primary endpoints were systemic and ocular safety and recovery of dark adaptation. Secondary endpoints included microperimetry, visual field sensitivity, dominant eye test and patient-reported outcomes. Subretinal delivery of an adeno-associated viral vector (AAV8-RLBP1) was well tolerated with dose-dependent intraocular inflammation which responded to corticosteroid treatment, and focal atrophy of the retinal pigment epithelium as the dose limiting toxicity. Dark adaptation kinetics, the primary efficacy endpoint, improved significantly in all dose-cohorts. Treatment with AAV8-RLBP1 resulted in the resolution of disease-related retinal deposits, suggestive of successful restoration of the visual cycle. In conclusion, to date, AAV8-RLBP1 has shown preliminary safety and efficacy in patients with RLBP1-associated retinal dystrophy. Trial number: NCT03374657., (© 2024. The Author(s).)

The purpose of this study was to evaluate the influence of knee joint range of motion (RoM) on the torque-velocity relationship and fatigue in the knee extensor muscles of 7 young (median = 26 y) and 7 older (68 y) adults. Each leg was assigned a RoM (35° or 75°) over which to perform a torque-velocity protocol (maximal isokinetic contractions, 60-300°·s-1) and a fatigue protocol (120 maximal contractions at 120°·s-1, 0.5 Hz). Six older participants were unable to reach 300°·s-1 over 35°. Therefore, the velocity eliciting 75% of peak torque at 60°·s-1 (V75, °·s-1) was calculated for each RoM from a fit of individual torque-velocity curves (60-240°·s-1), and ΔV75 (35°-75°) was determined. Fatigue (final torque/initial torque) was used to calculate Δfatigue (35°-75°). ΔV75 was not different from 0 in young (-28.3°·s-1 [-158.6 to 55.7], median [range], P = .091) or older (-18.5°·s-1 [-95.0 to 23.9], P = .128), with no difference by age (P = .710). In contrast, fatigue was greater for 75° in young (Δfatigue = 25.9% [17.5-30.3], P = .018) and older (17.2% [11.9-52.9], P = .018), with no effect of age (P = .710). These data indicate that, regardless of age, RoM did not alter the torque-velocity relationship between 60 and 240°·s-1, and fatigue was greater with a larger RoM.