Inpatient rehabilitation outcomes in patients with the new diagnosis of COVID-19 tractopathy: a case series.

STUDY DESIGN: Retrospective Case Series. OBJECTIVES: Describe the inpatient rehabilitation outcomes of four patients with COVID-19 tractopathy. SETTING: Olmsted County, Minnesota, United States of America. METHODS: Retrospective review of medical records was performed to collect patient data. RESULTS: Four individuals (n = 4, 3 men and 1 woman, mean age 58.25 years [range 56-61]) completed inpatient rehabilitation during the COVID-19 pandemic. All presented after COVID-19 infection and were admitted to acute care with progressive paraparesis. None were able to ambulate on admission to acute care. All received extensive evaluations which were largely negative except for mildly elevated CSF protein and MRI findings of longitudinally extensive T2 hyperintensity signal changes in the lateral (n = 3) and dorsal (n = 1) columns. All patients experienced incomplete spastic paraparesis. All patients experienced neurogenic bowel dysfunction; a majority experienced neuropathic pain (n = 3); half experienced impaired proprioception (n = 2); and a minority experienced neurogenic bladder dysfunction (n = 1). Between rehabilitation admission and discharge, the median improvement in lower extremity motor score was 5 (0-28). All patients were discharged home, but only one was a functional ambulator at time of discharge. CONCLUSION: While the underlying mechanism is yet to be elucidated, in rare cases a COVID-19 infection can lead to a tractopathy, presenting as weakness, sensory deficits, spasticity, neuropathic pain, and neurogenic bladder/bowel. Patients with COVID-19 tractopathy would benefit from inpatient rehabilitation to enhance their functional mobility and independence.

The International Standards for Neurological Classification of Spinal Cord Injury: Classification Accuracy and Challenges.

Background: Successful utilization of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) requires a comprehensive understanding of its rules, terminology, and several complex concepts. There have been no studies investigating classification accuracy since the newest ISNCSCI revision (2019). Objectives: To evaluate classification accuracy of SCI professionals using the 2019 ISNCSCI edition, identify common mistakes and areas of confusion, and assess associations between experience in ISNCSCI classification and performance. Methods: Members of the International Spinal Cord Society (ISCoS) and attendees of the ISCoS Annual Scientific Meeting 2021 were invited to complete an online survey that included six ISNCSCI cases to classify. Results: A total of 107 persons completed the survey, with overall classification accuracy of 74.6%. Accuracy was highest for injury completeness (95.3%) and sensory level (91.1%) and lowest for motor zone of partial preservation (ZPP; 54.7%) and ASIA Impairment Scale (AIS) grade (57.3%). Newer concepts, including the appropriate documentation of non-SCI conditions and classification of ZPP in incomplete injuries, contributed to several common errors. There was a significant association between overall classification accuracy and self-rated experience in the ISNCSCI classification (p = .017). Experience with the ISNCSCI examination, experience in SCI medicine, and occupation were not found to be significantly associated with overall classification accuracy. Conclusion: Classification accuracy of an international cohort of SCI professionals was modest but greater than previous reports. Knowledge deficits about the 2019 ISNCSCI updates are prevalent and contribute to common classification errors. Further training in the utilization of the ISNCSCI is needed.

Going Virtual: A Virtual Summer Physical Medicine and Rehabilitation Externship Experience for Medical Students.

ABSTRACT: Opportunities for early medical student exposure to the field of physical medicine and rehabilitation (PM&R) are desirable for promoting the field as a career choice and are useful for introducing students to the care of people with disabilities. The COVID-19 pandemic disrupted medical education and caused the cancellation of many in-person clinical programs, including the Medical Student Summer Clinical Externship in PM&R supported by the Association of Academic Physiatrists. This article describes the process by which an in-person summer clinical externship program was effectively converted into a Virtual PM&R Experience using a combination of independent assignments and small-group sessions. A total of 87 medical students completed the Virtual PM&R Experience over two summers. The participants of the program met the program learning objectives, including enhancing their understanding of physiatry as a career and recognizing the medical and social issues that affect persons with disability.

Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lung adenocarcinoma tumors in Kras(G12D-LSL) mice.

The role of PI3K and MAPK pathways in tumor initiation and progression is well established; hence, several inhibitors of these pathways are currently in different stages of clinical trials. Recent studies identified a PI3K/mTOR (PF-04691502) and a MEK inhibitor (PD-0325901) with strong potency and efficacy in different cell lines and tumor models. PD-0325901, however, showed adverse effects when administered at or above MTD (maximum tolerated dose) in the clinic. Here, we show in preclinical models that PD-0325901 at doses well below MTD (sub-MTD 1.5 mg/kg SID) is still a potent compound as single agent or in combination with PF-04691502. We first observed that PD-0325901 at 1.5 mg/kg SID and in combination with PF-04691502 (7.5 mg/kg; SID) significantly inhibited growth of H460 (carry Kras and PIK3CA mutations) orthotopic lung tumors. Additionally, we tested efficacy of PD-0325901 in Kras(G12D-LSL) conditional GEMMs (genetically engineered mouse models) which are a valuable tool in translational research to study tumor progression. Intranasal delivery of adenoviruses expressing Cre recombinase (Adeno-Cre) resulted in expression of mutant Kras leading to development of tumor lesions in lungs including adenomatous hyperplasia, large adenoma, and adenocarcinoma. Similar to H460 tumors, PD-0325901 as single agent or in combination with PF-04691502 significantly inhibited growth of tumor lesions in lungs in Kras(G12D-LSL) mice when treatment started at adenocarcinoma stage (at 14 weeks post-Adeno-Cre inhalation). In addition, immunohistochemistry showed inhibition of pS6 (phosphorylated ribosomal S6) in the treated animals particularly in the combination group providing a proof of mechanism for tumor growth inhibition. Finally, m-CT imaging in live Kras(G12D-LSL) mice showed reduction of tumor burdens in PD-0325901-treated animals at sub-MTD dose. In conclusion, our data suggest that PD-0325901 at doses below MTD is still a potent compound capable of tumor growth inhibition where Kras and/or PI3K are drivers of tumor growth and progression.