Worsening physical functioning in patients with neuroinflammatory disease during the COVID-19 pandemic.

OBJECTIVE: To quantify changes in psychological wellbeing and physical function as reported by people with neurological inflammatory disease (PwNID) during the COVID-19 pandemic. METHODS: 1134 PwNID and 868 control participants were recruited through five major academic medical centers in the Northeast/Mid-Atlantic U.S. beginning in April 2020. Participants completed serial surveys throughout the COVID-19 pandemic that aimed to quantify mood symptoms and physical function, analyzed cross-sectionally with a smaller cohort analyzed longitudinally. RESULTS: Throughout the pandemic, depression scores were not significantly different between PwNID and controls, although a higher proportion of PwNID reported clinically significant depression at study entry. Depression scores did not worsen over time for either group. Loneliness was the strongest predictor of worse depression, along with older age, male gender in both PwNID and controls, as well as lack of disease modifying therapy use, and disease duration in PwNID only. In contrast, physical disability worsened significantly over time for both PwNID and controls. Age, DMT status and comorbid health conditions emerged as significant predictors of physical function. CONCLUSIONS: Depressive symptoms remained consistent for both PwNID and controls throughout the COVID-19 pandemic, but physical function worsened significantly over time for both groups. This is particularly impactful for PwNID, who have higher baseline levels of physical disability, and underscores the importance of reinstituting services and interventions that facilitate exercise and reconditioning for this population.

Vaccination Against SARS-CoV-2 in Neuroinflammatory Disease: Early Safety/Tolerability Data.

BACKGROUND: Patients with autoimmune disease and on immunotherapy were largely excluded from seminal anti-SARS-CoV-2 vaccine trials. This has led to significant vaccine hesitancy in patients with neuroinflammatory diseases (NID); including, but not limited to: multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), neurosarcoidosis and myelin oligodendrocyte antibody-mediated disease (MOG-AD). Data is urgently needed to help guide clinical care in the NID population. METHODS: This was a cross-sectional observational study evaluating adults with a neurologist-confirmed diagnosis of a neuroinflammatory disease (NID) and a neurologically asymptomatic control population. Participants were recruited from multiple academic centers participating in the MS Resilience to COVID-19 Collaborative study. We analyzed participant responses from a vaccine-specific questionnaire collected between February and May 2021. RESULTS: 1164 participants with NID and 595 controls completed the vaccine survey. Hesitancy rates were similar between NID and control groups (n = 134, 32.7% NID vs. n = 56, 30.6% control; p = 0.82). The most common reasons for hesitancy in NID participants were lack of testing in the autoimmune population and fear of demyelinating/neurologic events. Unvaccinated patients who had discussed vaccination with their doctor were less likely to be hesitant (n=184, 73.6% vs. n=83, 59.7%; p = 0.007). 634 NID patients and 332 controls had received at least one dose of a vaccine against SARS-CoV-2 at the time of survey completion. After adjusting for age, BMI, and comorbidities, there was no difference in self-reported side effects (SE) between groups with the first dose (n = 256, 42.2% NID vs. 141, 45.3% control; p = 0.20) or second dose (n = 246, 67.0% NID vs. n = 114, 64.8% control, p = 0.85) of the mRNA vaccines nor with the viral-vector vaccines (n = 6, 46% NID vs. n = 8, 66% control; p = 0.39). All reported SEs fell into the expected SE profile. There was no difference in report of new/recurrent neurologic symptoms (n = 110, 16.2% vaccinated vs. 71, 18.2% unvaccinated; p = 0.44) nor radiologic disease activity (n = 40, 5.9% vaccinated vs. n = 30, 7.6% unvaccinated) between vaccinated and unvaccinated NID participants. CONCLUSIONS: We found no difference in patient-reported vaccine side effects and no evidence of NID worsening after vaccination. Large-scale real-world evidence is needed for further validation.

Applying Deep Learning to Accelerated Clinical Brain Magnetic Resonance Imaging for Multiple Sclerosis.

Background: Magnetic resonance (MR) scans are routine clinical procedures for monitoring people with multiple sclerosis (PwMS). Patient discomfort, timely scheduling, and financial burden motivate the need to accelerate MR scan time. We examined the clinical application of a deep learning (DL) model in restoring the image quality of accelerated routine clinical brain MR scans for PwMS. Methods: We acquired fast 3D T1w BRAVO and fast 3D T2w FLAIR MRI sequences (half the phase encodes and half the number of slices) in parallel to conventional parameters. Using a subset of the scans, we trained a DL model to generate images from fast scans with quality similar to the conventional scans and then applied the model to the remaining scans. We calculated clinically relevant T1w volumetrics (normalized whole brain, thalamic, gray matter, and white matter volume) for all scans and T2 lesion volume in a sub-analysis. We performed paired t-tests comparing conventional, fast, and fast with DL for these volumetrics, and fit repeated measures mixed-effects models to test for differences in correlations between volumetrics and clinically relevant patient-reported outcomes (PRO). Results: We found statistically significant but small differences between conventional and fast scans with DL for all T1w volumetrics. There was no difference in the extent to which the key T1w volumetrics correlated with clinically relevant PROs of MS symptom burden and neurological disability. Conclusion: A deep learning model that improves the image quality of the accelerated routine clinical brain MR scans has the potential to inform clinically relevant outcomes in MS.

Characterization of outcomes in patients with advanced genitourinary malignancies treated with immune checkpoint inhibitors.

PURPOSE: Several immune checkpoint inhibitors (ICIs) are FDA approved for treatment of genitourinary (GU) malignancies. We aim to determine demographic and clinicopathologic characteristics that significantly affect clinical outcomes in patients with advanced stage GU malignancies treated with ICIs. MATERIALS AND METHODS: We performed a single-center, consecutive, retrospective cohort analysis on patients with metastatic or unresectable GU malignancies who were treated with ICIs at the University of Michigan. Immune-related adverse events (irAEs), putative immune-mediated allergies, and overall response rates (ORR) were assessed. Comorbidity index scores were calculated. Survival analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS), stratifying and controlling for a variety of clinicopathologic baseline factors including site of metastases. RESULTS: A total of 160 patients were identified with advanced renal cell carcinoma (RCC) or urothelial carcinoma. Median PFS and OS were 5.0 and 23.6 months for RCC, and 2.8 and 9.6 months for urothelial carcinoma, respectively. Patients who experienced increased frequency and higher grade irAEs had better ICI treatment response (P < 0.0001). Presence of liver metastases was associated with poor response to ICI therapy (P = 0.001). Multivariable modeling demonstrates that patients with urothelial carcinoma and liver metastases had statistically worse PFS and OS compared to patients with RCC or other sites of metastases, respectively. CONCLUSION: Greater frequency and higher grades of irAEs are associated with better treatment response in patients with RCC and urothelial malignancy receiving ICI therapy. The presence of liver metastases denotes a negative predictive marker for immunotherapy efficacy. SUMMARY: Immune checkpoint inhibitors (ICI) are increasingly used to treat genitourinary (GU) malignancies. However, clinical data regarding patients with advanced-stage GU malignancies treated with ICI is lacking. Thus, we performed a single-center, retrospective cohort study on patients with metastatic and unresectable renal cell carcinoma (RCC) and urothelial carcinoma who were treated with ICIs at the University of Michigan to provide demographic and clinicopathologic data regarding this population. We specifically focused on immune-related adverse events (irAEs), immune-mediated allergies, and the associated overall response rates (ORR). To better assess performance status, we calculated comorbidity scores for all patients. Finally, survival analyses for progression-free survival (PFS) and overall survival (OS) were performed using Kaplan-Meier analysis and Cox proportional hazards modeling, stratifying and controlling for clinicopathologic baseline factors, including sites of metastases, in our multivariable analysis. A total of 160 patients were identified with advanced RCC or urothelial carcinoma. We found decreased PFS (2.8 vs. 5.0 months) and decreased OS (9.8 vs. 23.6 months) for urothelial carcinoma compared to RCC patients. We noted that patients who experienced increased frequency and higher grades of irAEs had better treatment ORR with ICI therapy (P ≤ 0.0001). The presence of liver metastases was associated with worse ORR (P = 0.001), PFS (P = 0.0014), and OS (P = 0.0028) compared to other sites of metastases including lymph node, lung, and CNS/bone. The poor PFS and OS associated with urothelial carcinoma and liver metastases were preserved in our multivariable modeling after controlling for pertinent clinical factors. We conclude that greater frequency and higher grades of irAEs are associated with better treatment response in GU malignancy patients receiving ICI, a finding that is consistent with published studies in other cancers. The presence of liver metastases represents a significantly poor predictive marker in GU malignancy treated with ICI. Our findings contribute to the growing body of literature that seeks to understand the clinicopathologic variables and outcomes associated with ICI therapy.