Acute Kidney Injury Associated with Severe SARS-CoV-2 Infection: Risk Factors for Morbidity and Mortality and a Potential Benefit of Combined Therapy with Tocilizumab and Corticosteroids.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients with severe COVID-19. METHODS: We retrospectively reviewed 249 patients admitted to an intensive care unit (ICU) during the first wave of the pandemic to determine risk factors for AKI. Demographics, comorbidities, and clinical and outcome variables were obtained from electronic medical records. RESULTS: Univariate analysis revealed older age, higher admission serum creatinine, elevated Sequential Organ Failure Assessment (SOFA) score, elevated admission D-Dimer, elevated CRP on day 2, mechanical ventilation, vasopressor requirement, and azithromycin usage as significant risk factors for AKI. Multivariate analysis demonstrated that higher admission creatinine (p = 0.0001, OR = 2.41, 95% CI = 1.56-3.70), vasopressor requirement (p = 0.0001, OR = 3.20, 95% CI = 1.69-5.98), elevated admission D-Dimer (p = 0.008, OR = 1.0001, 95% CI = 1.000-1.001), and elevated C-reactive protein (CRP) on day 2 (p = 0.033, OR = 1.0001, 95% CI = 1.004-1.009) were independent risk factors. Conversely, the combined use of Tocilizumab and corticosteroids was independently associated with reduced AKI risk (p = 0.0009, OR = 0.437, 95% CI = 0.23-0.81). CONCLUSION: This study confirms the high rate of AKI and associated mortality among COVID-19 patients admitted to ICUs and suggests a role for inflammation and/or coagulopathy in AKI development. One should consider the possibility that early administration of anti-inflammatory agents, as is now routinely conducted in the management of COVID-19-associated acute respiratory distress syndrome, may improve clinical outcomes in patients with AKI.

Can google glass™ technology improve freezing of gait in parkinsonism? A pilot study.

PURPOSE: Freezing of gait (FOG) is a disabling phenomenon defined by the periodic absence or reduction of forward progression of the feet despite the intention to walk. We sought to understand whether Google Glass (GG), a lightweight wearable device that provides simultaneous visual-auditory cues, might improve FOG in parkinsonism. METHODS: Patients with parkinsonism and FOG utilized GG custom-made auditory-visual cue applications: "Walk With Me" and "Unfreeze Me" in a single session intervention. We recorded ambulation time with and without GG under multiple conditions including 25 feet straight walk, dual task of performing serial 7's while straight walking, 180 degree turn after walking 25 feet, and walking through a doorway. FOG and patient experience questionnaires were administered. RESULTS: Using the GG "Walk With Me" program, improvements were noted in the following: average 25 feet straight walk by 0.32 s (SD 2.12); average dual task of serial 7's and 25 feet straight walk by 1.79 s (SD 2.91); and average walk through doorway by 0.59 s (SD 0.81). Average 180 degree turn after 25 feet walk worsened by 1.89 s (SD 10.66). Using the "Unfreeze Me" program, only the average dual task of serial 7's and 25 feet straight walk improved (better by 0.82 s (SD 3.08 sec). All other tasks had worse performance in terms of speed of completion. CONCLUSION: This feasibility study provides preliminary data suggesting that some walking tasks may improve with GG, which uses various musical dance programs to provide visual and auditory cueing for patients with FOG.IMPLICATIONS FOR REHABILITATIONFreezing of gait in parkinsonian syndromes is a disabling motor block described by patients as having their feet stuck to the floor leading to difficulty in initiation of gait and increased risk for falls.Wearable assistive devices such as Google Glass™ use visual and auditory cueing that may improve gait pattern in patients with freezing of gait.Augmented reality programs using wearable assistive devices are a home-based therapy, with the potential for reinforcing physical therapy techniques; this is especially meaningful during the COVID-19 pandemic when access to both medical and rehabilitative care has been curtailed.

Reliability of Cell-Free DNA and Targeted NGS in Predicting Chromosomal Abnormalities of Patients With Myeloid Neoplasms.

Introduction: Cytogenetic analysis is important for stratifying patients with various neoplasms. We explored the use of targeted next generation sequencing (NGS) in detecting chromosomal structural abnormalities or copy number variations (CNVs) in patients with myeloid neoplasms. Methods: Plasma cell-free DNA (cfDNA) from 2821 myeloid or lymphoid neoplasm patients were collected. cfDNA was sequenced using a 275 gene panel. CNVkit software was used for analyzing and visualizing CNVs. Cytogenetic data from corresponding bone marrow (BM) samples was available on 89 myeloid samples. Results: Of the 2821 samples, 1539 (54.5%) showed evidence of mutations consistent with the presence of neoplastic clones in circulation. Of these 1539 samples, 906 (59%) showed abnormalities associated with myeloid neoplasms and 633 (41%) with lymphoid neoplasms. Chromosomal structural abnormalities in cfDNA were detected in 146 (16%) myeloid samples and 76 (12%) lymphoid samples. Upon comparison of the myeloid samples with 89 BM patients, NGS testing was able to reliably detect chromosomal gain or loss, except for fusion abnormalities. When cytogenetic abnormalities were classified according to prognostic classes, there was a complete (100%) concordance between cfDNA NGS data and cytogenetic data. Conclusions: This data shows that liquid biopsy using targeted NGS is reliable in detecting chromosomal structural abnormalities in myeloid neoplasms. In specific circumstances, targeted NGS may be reliable and efficient to provide adequate information without the need for BM biopsy considering broad mutation profiling can be obtained through adequate sequencing within the same test. Overall, this study supports the use of liquid biopsy for early diagnosis and monitoring of patients with myeloid neoplasms.

Molecular Imaging of Striatal Dopaminergic Neuronal Loss and the Neurovascular Unit in Parkinson Disease.

Parkinson disease (PD) is the second most common neurodegenerative disorder, characterized by loss of nigrostriatal dopaminergic neurons. Impairment of the neurovascular unit (NVU) has been hypothesized to play a critical role in early PD pathophysiology, and to precede neurodegenerative mechanisms. [C-11]-PE2I (N-(3-iodoprop-2E-enyl)-2b-carbomethoxy-3b-(4-methyl-phenyl)nortropane) (PE2I) is a PET radiotracer targeting neuronal dopamine transporters (DaT) with high specificity, allowing for highly accurate and specific DaT quantification. We investigated NVU integrity using arterial spin labeling (ASL) MRI in a prospective cohort of 26 patients with PD, and correlated our findings with analysis of striatal DaT density using PE2I PET in a subcohort of 17 patients. Analysis was performed in FreeSurfer to obtain rCBF and mean standardized regional PET avidity. Pearson correlations and Mann-Whitney tests were performed. Significantly lower mean normalized striatal PE2I SUV values were seen in multiple regions in patients with greater disease duration (p < 0.05). PET uptake in the putamen correlated with disease duration independent of patient age. Stratifying patients based on Montreal Cognitive Assessment (MoCA) scores (stratified into ≥ 27 vs. < 27), there was statistically significantly lower PE2I PET avidity in the higher MoCA score group in both more and less affected sides of the caudate, putamen and pallidum (p < 0.05). A moderate negative correlation between MDS-UPDRS part 3 (motor) "off" and rCBF values was also seen in the L and R cerebellum WM (r = -0.43 and -0.47, p < 0.05). A statistically significant negative correlation was found between dominant hand pegboard test results and rCBF in the less affected pallidum (r = -0.41; p = 0.046). A statistically significant negative correlation of ASL MRI with [11C]-PE2I PET was also found (r = -0.53 to -0.58; p-value 0.017-0.033) between left cerebral WM rCBF and more and less affected striatal PET regions. Our ROI-based analyses suggest that longer disease duration is associated with lower rCBF and lower PE2I mean SUV, implying greater NVU dysfunction and dopaminergic neuronal loss, respectively. Combined ASL MRI and PE2I PET imaging could inform future prospective clinical trials providing an improved mechanistic understanding of the disease, laying the foundation for the development of early disease biomarkers and potential therapeutic targets.