ABSTRACT:With the rapid growth and rising interest in the subspecialty of cancer rehabilitation medicine, establishing a structured training and educational curriculum in cancer rehabilitation medicine has become more crucial than ever. For those who are responsible for the educational experiences of students, residents, fellows, or other healthcare professionals, this article provides a systematic approach for establishing a curriculum template relevant for cancer rehabilitation medicine training. This included the assessment of general and targeted needs for learners and educators, rotation goals and objectives, educational strategies, implementation, and evaluation and feedback.

Long-term recovery of limb function is a significant unmet need in people with paralysis. Targeted neuromodulation through epidural stimulation of the spinal cord, when paired with intense physical therapy, has shown promising results towards restoring volitional control of the upper limb in people with tetraplegia. Non-invasive neuromodulation of the cervical spinal cord using transcutaneous spinal cord stimulation (tSCS) has shown similar improvements in upper-limb motor control rehabilitation. However, the potential rehabilitative effects of activating specific cervical spinal segments in a targeted fashion using tSCS has largely remained unexplored. We show in two individuals with SCI that tSCS of the cervical spinal cord resulted in up to 1136% increase in exerted force, with minimal physical therapy. We also show, for the first time, the effectiveness of targeted tSCS in restoring strength (407% increase) and dexterity to the digits in an individual with paralysis of the hand due to a peripheral nerve injury. Furthermore, we believe this is the first study to document a 3-point improvement in sensation in people with SCI or peripheral injury after receiving tSCS. Lastly, participant gains persisted after a one-month period void of stimulation, suggesting tSCS may lead to lasting benefits. Non-invasive targeted spinal cord stimulation shows tremendous promise as a safe and effective therapeutic approach with broad applications.### Competing Interest StatementCEB has financial interests in Sanguistat, LLC and Neuvotion, Inc. and multiple patents in the neurostimulation field. SE has financial interests in Neuvotion, Inc. The remaining authors have no conflicting financial interests.### Clinical TrialNCT04755699### Funding StatementThis study was funded through support provided by Feinstein Institutes for Medical Research at Northwell Health.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:All procedures were approved by the Northwell Health Institutional Review Board.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors.

BackgroundStudents in half of US medical schools do not receive formal instruction in providing medical care for people with disabilities. To address this gap in training, our medical school developed several strategies, including a session for second year medical students to address communication skills, knowledge, and attitudes relevant to delivering healthcare for people with disabilities. Here, our objective was to explore perceptions of people with spinal cord injury (SCI) who participated in the session on its content and structure.MethodsQualitative research using a focus group of people with SCI who participated in an educational session for medical students in an LCME accredited allopathic US medical school. A purposive sample of adults with SCI (N = 8) participated in a focus group. Data were analyzed using a six-phase thematic analysis.ResultsParticipants favorably viewed the educational session, felt their participation was valuable, and had suggestions for its improvement. Four major themes were identified: (1) session format, content; (2) addressing student discomfort and avoidance behaviors; (3) increasing student knowledge and preparation; and (4): important lessons from discussions of past and role-played doctor-patient interactions.ConclusionsFirst-person input from people with SCI is critical to improve medical education and healthcare provision to the SCI community. To our knowledge, this is the first study to report feedback from stakeholders providing specific recommendations for teaching disabilities awareness to undergraduate medical students. We expect these recommendations to be relevant to the SCI and medical education communities in improving healthcare for people with SCI and other disabilities.

Long-term recovery of limb function is a significant unmet need in people with paralysis. Neuromodulation of the spinal cord through epidural stimulation, when paired with intense activity-based training, has shown promising results toward restoring volitional limb control in people with spinal cord injury. Non-invasive neuromodulation of the cervical spinal cord using transcutaneous spinal cord stimulation (tSCS) has shown similar improvements in upper-limb motor control rehabilitation. However, the motor and sensory rehabilitative effects of activating specific cervical spinal segments using tSCS have largely remained unexplored. We show in two individuals with motor-complete SCI that targeted stimulation of the cervical spinal cord resulted in up to a 1,136% increase in exerted force, with weekly activity-based training. Furthermore, this is the first study to document up to a 2-point improvement in clinical assessment of tactile sensation in SCI after receiving tSCS. Lastly, participant gains persisted after a one-month period void of stimulation, suggesting that targeted tSCS may lead to persistent recovery of motor and sensory function.

Individuals with SCI are severely affected by immune system changes, resulting in increased risk of infections and persistent systemic inflammation. While recent data support that immunological changes after SCI differ in the acute and chronic phases of living with SCI, only limited immunological phenotyping in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR <0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, verifying a persistent ‘neurogenic’ imprint. Overall, 2876 DE genes emerge when comparing motor complete to motor incomplete SCI (ANOVA, FDR <0.05), including those related to neutrophils, inflammation, and infection. In summary, we identify a dynamic immunological phenotype in humans, including molecular and cellular changes which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.

Peripheral nerve injury can lead to chronic pain, paralysis, and loss of sensation, severely affecting quality of life. Spinal cord stimulation has been used in the clinic to provide pain relief arising from peripheral nerve injuries, however, its ability to restore function after peripheral nerve injury have not been explored. Neuromodulation of the spinal cord through transcutaneous spinal cord stimulation (tSCS), when paired with activity-based training, has shown promising results towards restoring volitional limb control in people with spinal cord injury. We show, for the first time, the effectiveness of targeted tSCS in restoring strength (407% increase from 1.79 ± 1.24 N to up to 7.3 ± 0.93 N) and significantly increasing hand dexterity in an individual with paralysis due to a peripheral nerve injury (PNI). Furthermore, this is the first study to document a persisting 3-point improvement during clinical assessment of tactile sensation in peripheral injury after receiving 6 weeks of tSCS. Lastly, the motor and sensory gains persisted for several months after stimulation was received, suggesting tSCS may lead to long-lasting benefits, even in PNI. Non-invasive spinal cord stimulation shows tremendous promise as a safe and effective therapeutic approach with broad applications in functional recovery after debilitating injuries.

OBJECTIVES:To determine circulating levels of antibodies (IgA, IgM, IgG1-4) in individuals with SCI as compared to uninjured individuals.STUDY DESIGN:Prospective, observational study.SETTING:Outpatient clinic of a Department of Physical Medicine and Rehabilitation and research institute in an academic medical center.PARTICIPANTS:Individuals with chronic (≥ 1 year from injury) SCI and uninjured individuals.OUTCOME MEASURES:Serum antibody titers were determined by commercial multiplex ELISA.RESULTS:Blood samples were collected from individuals with chronic SCI (N = 29, 83% males) and uninjured individuals (N = 25, 64% males). Among participants with SCI, the distribution of American Spinal Injury Association Impairment Scale (AIS) grades was: A (n = 15), B (n = 2), C (n = 4), D (n = 8). Neurological levels of injury were: cervical (n = 17), thoracic (n = 10), and lumbar (n = 2). IgA levels were significantly elevated in participants with SCI compared to uninjured participants (median: 1.98 vs. 1.21 mg/ml, P < 0.0001), with levels most elevated in individuals with motor complete injuries compared to uninjured participants (P < 0.0003). IgG2 antibodies were also significantly elevated in participants with SCI compared to uninjured participants (median: 5.98 vs. 4.37 mg/ml, P < 0.018).CONCLUSIONS:To our knowledge, this study provides the first evidence of elevated IgA, the antibody type most prevalent at respiratory, genitourinary and gastrointestinal tracts, common sites of infections in individuals with SCI. IgG2 levels were also elevated in individuals with SCI. These data support further investigations of IgA and other antibody types in individuals with chronic SCI, which may be increasingly important in the context of emerging novel infectious diseases such as SARS-CoV-2.

OBJECTIVE:The aim of the study was to present: (1) physiatric care delivery amid the SARS-CoV-2 pandemic, (2) challenges, (3) data from the first cohort of post-COVID-19 inpatient rehabilitation facility patients, and (4) lessons learned by a research consortium of New York and New Jersey rehabilitation institutions.DESIGN:For this clinical descriptive retrospective study, data were extracted from post-COVID-19 patient records treated at a research consortium of New York and New Jersey rehabilitation inpatient rehabilitation facilities (May 1-June 30, 2020) to characterize admission criteria, physical space, precautions, bed numbers, staffing, employee wellness, leadership, and family communication. For comparison, data from the Uniform Data System and eRehabData databases were analyzed. The research consortium of New York and New Jersey rehabilitation members discussed experiences and lessons learned.RESULTS:The COVID-19 patients (N = 320) were treated during the study period. Most patients were male, average age of 61.9 yrs, and 40.9% were White. The average acute care length of stay before inpatient rehabilitation facility admission was 24.5 days; mean length of stay at inpatient rehabilitation facilities was 15.2 days. The rehabilitation research consortium of New York and New Jersey rehabilitation institutions reported a greater proportion of COVID-19 patients discharged to home compared with prepandemic data. Some institutions reported higher changes in functional scores during rehabilitation admission, compared with prepandemic data.CONCLUSIONS:The COVID-19 pandemic acutely affected patient care and overall institutional operations. The research consortium of New York and New Jersey rehabilitation institutions responded dynamically to bed expansions/contractions, staff deployment, and innovations that facilitated safe and effective patient care.

Heart failure (HF) is defined as an inability of the heart to pump blood sufficiently to meet the metabolic demands of the body. HF with systolic dysfunction is caused by a progressive decline in contractile function and chronic hemodynamic overload, and characterized by ventricular hypertrophy and remodeling, neurohormonal compensation mechanisms, and myocardial damage. Transverse aortic constriction (TAC) is a well-established model for inducing hypertrophy and HF in rodents. Mice globally deficient in sirtuin 5 (SIRT5), a NAD + -dependent deacylase, are hypersensitive to cardiac stress and display increased mortality after TAC. Prior studies assessing SIRT5 functions in the heart have all employed loss-of-function approaches. In this study, we generated SIRT5 overexpressing (SIRT5OE) mice, and evaluated their response to chronic pressure overload using TAC. Compared to littermate controls, elevated SIRT5 levels promoted maintenance of cardiac contractile function after 4 weeks of pressure overload, at which point control mice had developed systolic dysfunction, characterized by decreased EF, coupled with ventricular dilation, remodeling and fibrosis. Transcriptomic analysis revealed that SIRT5 suppresses key HF sequelae, including metabolic switch from fatty acid oxidation to glycolysis and immune activation ( i.e., TGFβ, IL6, Renin-Angiotensin, and NFAT, and fibrotic signaling pathways). We conclude that SIRT5 is a limiting factor in the preservation of cardiac function in response to experimental pressure overload.

Objective The aim of the study was to present: (1) physiatric care delivery amid the SARS-CoV-2 pandemic, (2) challenges, (3) data from the first cohort of post–COVID-19 inpatient rehabilitation facility patients, and (4) lessons learned by a research consortium of New York and New Jersey rehabilitation institutions. Design For this clinical descriptive retrospective study, data were extracted from post–COVID-19 patient records treated at a research consortium of New York and New Jersey rehabilitation inpatient rehabilitation facilities (May 1–June 30, 2020) to characterize admission criteria, physical space, precautions, bed numbers, staffing, employee wellness, leadership, and family communication. For comparison, data from the Uniform Data System and eRehabData databases were analyzed. The research consortium of New York and New Jersey rehabilitation members discussed experiences and lessons learned. Results The COVID-19 patients (N = 320) were treated during the study period. Most patients were male, average age of 61.9 yrs, and 40.9% were White. The average acute care length of stay before inpatient rehabilitation facility admission was 24.5 days; mean length of stay at inpatient rehabilitation facilities was 15.2 days. The rehabilitation research consortium of New York and New Jersey rehabilitation institutions reported a greater proportion of COVID-19 patients discharged to home compared with prepandemic data. Some institutions reported higher changes in functional scores during rehabilitation admission, compared with prepandemic data. Conclusions The COVID-19 pandemic acutely affected patient care and overall institutional operations. The research consortium of New York and New Jersey rehabilitation institutions responded dynamically to bed expansions/contractions, staff deployment, and innovations that facilitated safe and effective patient care.

Pain affects most individuals with traumatic spinal cord injury (SCI). Major pain types after SCI are neuropathic or nociceptive, often experienced concurrently. Pain after SCI may be refractory to treatments and negatively affects quality of life. Previously, we analyzed whole blood gene expression in individuals with chronic SCI compared to able-bodied (AB) individuals. Most participants with SCI reported pain (N = 19/28). Here, we examined gene expression of participants with SCI by pain status. Compared to AB, participants with SCI with pain had 468 differentially expressed (DE) genes; participants without pain had 564 DE genes (FDR < 0.05). Among DE genes distinct to participants with SCI with pain, Gene Ontology Biological Process (GOBP) analysis showed upregulated genes were enriched in categories related to T cell activation or inflammation; downregulated genes were enriched in categories related to protein proteolysis and catabolism. Although most participants with pain reported multiple pain types concurrently, we performed a preliminary comparison of gene expression by worst pain problem type. Compared to AB, participants with SCI who ranked neuropathic (N = 9) as worst had one distinct DE gene (TMEM156); participants who ranked nociceptive (N = 10) as worst had 61 distinct DE genes (FDR < 0.05). In the nociceptive group, the GOBP category with the lowest P-value identified among upregulated genes was "positive regulation of T cell activation"; among downregulated genes it was "receptor tyrosine kinase binding". An exploratory comparison of pain groups by principal components analysis also showed that the nociceptive group was enriched in T-cell related genes. A correlation analysis identified genes significantly correlated with pain intensity in the neuropathic or nociceptive groups (N = 145, 65, respectively, Pearson's correlation r > 0.8). While this pilot study highlights challenges of identifying gene expression profiles that correlate with specific types of pain in individuals with SCI, it suggests that T-cell signaling should be further investigated in this context.

A) Photograph of an endoscope within the abdominal cavity with access to the intra-abdominal organs during transmural endoscopy. B) Photograph of a peripheral branch of the posterior Vagus nerve in a patient undergoing the POEM procedure

Background Cervical spinal cord injury severely affects grasping ability of its survivors. Fortunately, many individuals with tetraplegia retain residual arm movements that allow them to reach for objects. We propose a wearable technology that utilizes arm movement trajectory information and deep learning methods to determine grasp selection. Furthermore, we combined this approach with neuromuscular stimulation to determine if self-driven functional hand movement could be enabled in spinal cord injury participants. Methods Two cervical SCI participants performed arbitrary and natural reaching movements toward target objects in three-dimensional space, which were recorded using an inertial sensor worn on their wrist. Time series classifiers were trained to recognize the trajectories using either a Dynamic Time Warping (DTW) algorithm or a Long Short-Term Memory (LSTM) recurrent neural network . As an initial proof-of-concept, we demonstrate real-time classification of the arbitrary movements using DTW only (due to its implementation simplicity), which when used in combination with a high density neuromuscular stimulation sleeve with textile electrodes, enabled participants to perform functional grasping. Results Participants were able to consistently perform arbitrary two-dimensional and three-dimensional arm movements which could be classified with high accuracy. Furthermore, it was found that natural reaching trajectories for two different target objects (requiring two different grasp types) were distinct and also discriminable with high accuracy. In offline comparisons, LSTM (mean accuracies 99%) performed significantly better than DTW (mean accuracies 86 and 83%) for both arbitrary and natural reaching movements, respectively. Type I and II errors occurred more frequently for DTW (up to 60 and 15%, respectively), whereas it stayed under 5% for LSTM. Also, DTW achieved online accuracy of 79%. Conclusions We demonstrate the feasibility of utilizing arm trajectory information to determine grasp selection using a wearable inertial sensor along with DTW and deep learning methods. Importantly, this technology can be successfully used to control neuromuscular stimulation and restore functional independence to individuals living with paralysis. Trial registration NCT, NCT03385005 . Registered September 26, 2017

Abstract Background: Cervical spinal cord injury severely affects grasping ability of its survivors. Fortunately, many individuals with tetraplegia retain residual arm movements that allow them to reach for objects. We propose a wearable technology that utilizes arm movement trajectory information and deep learning methods to determine grasp selection. Furthermore, we combined this approach with neuromuscular stimulation to determine if self-driven functional hand movement could be enabled in spinal cord injury participants.Methods: Two cervical SCI participants performed arbitrary and natural reaching movements toward target objects in three-dimensional space, which were recorded using an inertial sensor worn on their wrist. Time series classifiers were trained to recognize the trajectories using either a Dynamic Time Warping (DTW) algorithm or a Long Short-Term Memory (LSTM) recurrent neural network. As an initial proof-of-concept, we demonstrate real-time classification of the arbitrary movements using DTW only (due to its implementation simplicity), which when used in combination with a high density neuromuscular stimulation sleeve with textile electrodes, enabled participants to perform functional grasping.Results: Participants were able to consistently perform arbitrary two-dimensional and three-dimensional arm movements which could be classified with high accuracy. Furthermore, it was found that natural reaching trajectories for two different target objects (requiring two different grasp types) were distinct and also discriminable with high accuracy. In offline comparisons, LSTM (mean accuracies 99%) performed significantly better than DTW (mean accuracies 86% and 83%) for both arbitrary and natural reaching movements, respectively. Type I and II errors occurred more frequently for DTW (up to 60% and 15%, respectively), whereas it stayed under 5% for LSTM. Also, DTW achieved online accuracy of 79%. Conclusions: We demonstrate the feasibility of utilizing arm trajectory information to determine grasp selection using a wearable inertial sensor along with DTW and deep learning methods. Importantly, this technology can be successfully used to control neuromuscular stimulation and restore functional independence to individuals living with paralysis.

Introduction Traumatic spinal cord injury (SCI) triggers complex changes that can negatively impact health and quality of life. The International SCI Data Sets were developed to enable more comparable data collection on the complex sequelae of SCI across studies. This should facilitate progress in mechanistic understanding and improving treatments of SCI. Study design Prospective observational pilot study. Objectives To collect data on pain symptoms and quality of life (QoL) in adults living with chronic SCI. Setting Academic medical center, New York, USA. Methods The International SCI Basic Pain and Qol Data Sets were used to collect data from participants with chronic SCI (N = 31) at 2 study visits held 6 months apart. The QoL Data Set was also used to collect data from able-bodied persons of similar age and gender distribution (N = 28). Results Most participants with SCI had multiple types and locations of pain problems at both study visits, despite reported being treated for pain. At both visits, the worst pain problem type was nociceptive, followed by neuropathic, which was typically rated of higher intensity. QoL scores were significantly lower across all domains of the data set in persons with SCI than able-bodied persons. Persons with pain tended to have lower QoL scores, although this trend was not significant. Conclusions This study demonstrates the presence, complexity and stability of pain symptoms refractory to treatment and lower quality of life ratings in persons with chronic SCI. Sponsorship Grants from the Craig H. Neilsen Foundation, New York Empire Clinical Research Program, New York State Spinal Cord Injury Research Board.

Abstract Infections are the leading cause of death for individuals with traumatic spinal cord injury (SCI). Along with increased infection rates, inflammation is often also observed in persons with chronic SCI. Together, immunological changes post-SCI are also poised to impede neurological recovery and mediate common medical consequences of SCI, including atherogenesis and neuropathic pain. The molecular mechanisms contributing to increased infection susceptibility and inflammation in persons living with SCI are poorly understood. Here, we used tools of functional genomics to perform a pilot study to compare whole-blood gene expression in individuals with chronic SCI (≥1 year from initial injury; N = 31) and uninjured individuals (N = 26). We identified 1815 differentially expressed genes in all SCI participants and 2226 differentially expressed genes in persons with SCI rostral to thoracic level 5, compared to uninjured participants. This included marked downregulation of natural killer cell genes and upregulation of the proinflammatory Toll-like receptor signaling pathway. These data provide novel mechanistic insights into the causes underlying the symptoms of immune dysfunction in individuals living with SCI.

OBJECTIVE:To identify clinical or demographic variables that influence long-term mortality, as well as in-hospital mortality, with a particular focus on the effects of age.SUMMARY AND BACKGROUND DATA:Cervical spine fractures with or without spinal cord injury (SCI) disproportionately impact the elderly who constitute an increasing percentage of the US population.METHODS:We analyzed data collected for 10 years at a state-designated level I trauma center to identify variables that influenced in-hospital and long-term mortality among elderly patients with traumatic cervical spine fracture with or without SCI. Acute in-hospital mortality was determined from hospital records and long-term mortality within the study period (2003-2013) was determined from the National Death Index. Univariate and multivariate regression analyses were used to identify factors influencing survival.RESULTS:Data from patients (N = 632) with cervical spine fractures were analyzed, the majority (66%) of whom were geriatric (older than age 64). Most patients (62%) had a mild/moderate injury severity score (ISS; median, interquartile range: 6, 5). Patients with SCI had significantly longer lengths of stay (14.1 days), days on a ventilator (3.5 days), and higher ISS (14.9) than patients without SCI (P < .0001 for all). Falls were the leading mechanism of injury for patients older than age 64. Univariate analysis identified that long-term survival decreased significantly for all patients older than age 65 (hazard ratio [HR]: 1.07; P < .0001). Multivariate analysis demonstrated age (HR: 1.08; P < .0001), gender (HR: 1.60; P < .0007), and SCI status (HR: 1.45, P < .02) significantly influenced survival during the study period.CONCLUSION:This study identified age, gender, and SCI status as significant variables for this study population influencing long-term survival among patients with cervical spine fractures. Our results support the growing notion that cervical spine injuries in geriatric patients with trauma may warrant additional research.