Mark S. Nash

Study Design: Prospective case series with body mass index (BMI)-matched case-controls. Objectives: To compare resting and postprandial inflammasome biomarkers and metabolic measurements in people with and without chronic spinal cord injury (SCI). Setting: A tertiary academic rehabilitation center in an urban, metropolitan setting in the southeastern United States. Methods: Blood samples were collected from 5 individuals with chronic SCI and 5 BMI-matched controls without chronic SCI at baseline and at 80 and 400 min following the consumption of a 600-kcal liquid meal comprised of 35% fat, 50% carbohydrate, and 15% protein. Inflammasome biomarkers included apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin-18 (IL-18), caspase-1 (CASP-1), and triggering receptor expressed on myeloid cells-2 (TREM-2). Metabolic biomarkers included glucose, insulin, triglyceride (TG), non-esterified fatty acid (NEFA), and glycerol. Results: Individuals with chronic SCI showed higher mean baseline concentrations of all inflammatory markers. There were greater mean postprandial decreases of ASC and CASP-1, with values remaining below baseline at 400 min. IL-18 remained near baseline. TREM-2 declined modestly in both groups. There were relative differences in glycemic and lipemic postprandial responses between groups at 80 min. Conclusions: In this case series, individuals with chronic SCI exhibited higher mean baseline inflammasome biomarker levels and different postprandial trajectories compared to controls. These preliminary hypothesis-generating observations warrant adequately powered studies to clarify the role of inflammasome-related mechanisms in inflammatory and metabolic dysregulation of chronic SCI.

Background: Chronic spinal cord injury (SCI) significantly accelerates morbidity and mortality, partly due to the increased risk of cardiometabolic diseases (CMD), including neurogenic obesity, dyslipidemia, and impaired glucose metabolism. While exercise and dietary interventions have shown some transient benefits in reducing CMD risk, they often fail to improve clinically relevant disease markers and cardiovascular events. Moreover, SCI also places caregiving demands on their caregivers, who themselves experience health and functional decline. This underscores the need for more substantial interventions that incorporate appropriate physical activity, heart-healthy nutrition, and behavioral support tailored to the SCI population. Objectives: This randomized clinical trial (RCT) protocol will (1) assess the health and functional effects, user acceptance, and satisfaction of a 6-month comprehensive therapeutic lifestyle intervention (TLI) adapted from the National Diabetes Prevention Program (DPP) for individuals with chronic SCI and (2) examine the impact of a complementary caregiver program on the health and function of SCI caregivers and evaluate user acceptance and satisfaction. Caregivers (linked with their partners) will be randomized to ‘behavioral support’ or ‘control condition’. Methods: Dyadic couples comprise individuals with SCI (18–65 years, >1-year post-injury, ASIA Impairment Scale A-C, injury levels C5-L1) and non-disabled SCI caregivers (18–65 years). Both groups undergo lock-step circuit resistance training, a calorie-restricted Mediterranean-style diet, and 16 educational sessions focused on diet/exercise goals, self-monitoring, psychological and social challenges, cognitive behavioral therapy, and motivational interviewing. The outcome measures encompass the cardiometabolic risks, cardiorespiratory fitness, inflammatory stress, multidimensional function, pain, life quality, independence, self-efficacy, program acceptance, and life satisfaction for SCI participants. The caregiver outcomes include multidimensional function, pain, quality of life, independence, and perceived caregiver burden. Discussion/Conclusions: This study evaluates the effects and durability of a structured, multi-modal intervention on health and function. The results and intervention material will be disseminated to professionals and consumers for broader implementation. Trial Registration: ClinicalTrials.gov, ID: NCT02853149 Registered 2 August 2016.

More than 16 000 Americans experience spinal cord injury (SCI), resulting in chronic disability and other secondary sequelae, each year. Improvements in acute medical management have increased life expectancy. Cardiovascular disease is a leading cause of death in this population, and seems to occur earlier in individuals with SCI compared with the general population. People with SCI experience a high burden of traditional cardiovascular disease risk factors, including dyslipidemia and diabetes, and demonstrate anatomic, metabolic, and physiologic changes alongside stark reductions in physical activity after injury. They also experience multiple, complex barriers to care relating to disability and, in many cases, compounding effects of intersecting racial and socioeconomic health inequities. Given this combination of risk factors, some investigators have proposed that people with SCI are at increased risk for cardiovascular disease, beyond that associated with traditional risk factors, and SCI could be considered a risk-enhancing factor, analogous to other risk-enhancing factors defined by the 2019 American Heart Association/American College of Cardiology Primary Prevention Guidelines. However, more research is needed in this population to clarify the role of traditional risk factors, novel risk factors, health care access, social determinants of health, and intersectionality of disability, race, and socioeconomic status. There is an urgent need for primary care physicians and cardiologists to have awareness of the importance of timely diagnosis and management of cardiac risk factors for people with SCI.

Study design: The pilot study was completed in 5 phases (Control and 4 phases of IMT) incorporating assessments at Baseline 1 (BL1), BL2, Follow-up 1 (F1), F2, F3, and F4. Objective: To assess the adherence and impact of a daily high-intensity (80% of max) inspiratory muscle training (IMT) home program with once weekly supervision for people with spinal cord injury (SCI). Setting: Assessments: research institution or zoom. IMT: participant’s home. Methods: Participants completed daily IMT in IMT Phase 1 and 2, once weekly in IMT Phase 3, self-selected frequency in IMT Phase 4. All phases had one weekly supervised session except IMT Phase 4. Primary outcomes included adherence and a difficulty score [DS (0- not difficult to 10- the most difficult)]. Secondary outcomes included respiratory function and seated balance. Results: Data from 10 people with chronic SCI (>1 year) (Cervical level of injury: 6, AIS: A-B, injury duration: 10.9 years 95% CI [3.9, 18.1]) were used in the analysis. Participants completed 69% of their training days in IMT Phase 1 and 65% overall reporting an average DS of 7.4 ± 1.4. Only one participant completed training during IMT Phase 4. One participant’s training load was reduced due to suspected overtraining. Maximal inspiratory pressure (MIP), sustained MIP (SMIP), and total power (TP), improved significantly (p < 0.05) from BL2 to F1. Conclusion: Our data suggest that people with SCI can perform high-intensity IMT at home to improve inspiratory performance. It is strongly recommended that participants be intermittently monitored for adherence and safety. ClinicalTrials.gov Registration number: NCT04210063.

Introduction Whole body energy expenditure and lipid oxidation (Lox) are upregulated during and after exercise. Persons with spinal cord injury (SCI) generally have a blunted ability to utilize fat during exercise, but it is unknown if their substrate partitioning is affected during recovery from exercise. Purpose To determine the effect of a single session of upper body circuit resistance exercise (CRE) on energy expenditure and Lox during exercise recovery in persons with and without SCI. Methods Twenty four persons (3 groups; 7 male and 1 female per group) without paralysis (neurologically intact; N) or with chronic (≥ 1 yr) paraplegia (P) or tetraplegia (T) participated. Energy expenditure and substrate partitioning were assessed via indirect calorimetry before, during, and three times after (up to 120 min after) a single session of CRE, or time-matched seated control (CON). Results During CRE, all groups experienced a similar relative increase in oxygen consumption (49 ± 13, 55 ± 11, and 48 ± 15% VO_2peak for N, P, and T, respectively). The Post_0-120 energy expenditure was greater following CRE vs. CON (P < 0.01) and independent of injury characteristics (10.6, 22.6, and 14.3% higher than CON for N, P, and T; P = 0.21). The absolute increase in Lox above CON during recovery was similar for N, P, and T (5.74 ± 2.81, 6.62 ± 3.10, and 4.50 ± 3.91 g, respectively; P = 0.45). Conclusions Energy expenditure and lipid utilization was increased similarly following circuit exercise in persons without and with spinal cord injury in a manner independent of level of injury.

Objective: To test in mice with a double mutation of the ApoE gene (ApoE^-/-) whether spinal cord injury (SCI) hastens the native trajectory of, and established component risks for, atherosclerotic disease (AD), and whether Salsalate anti-inflammatory pharmacotherapy attenuates the impact of SCI. Methods: ApoE^-/- mice were anesthetized and underwent a T9 laminectomy. Exposed spinal cords were given a contusion injury (70 k-dynes). Sham animals underwent all surgical procedures, excluding injury. Injured animals were randomized to 2 groups: SCI or SCI_+Salsalate [120 mg/Kg/day i.p.]. Mice were serially sacrificed at 20-, 24-, and 28-weeks post-SCI, and body mass was recorded. At sacrifice, heart and aorta were harvested intact, fixed in 10% buffered formalin, cleaned and cut longitudinally for en face preparation. The aortic tree was stained with oil-red-O (ORO). AD lesion histomorphometry was calculated from the proportional area of ORO. Plasma total cholesterol, triglycerides and proatherogenic inflammatory cytokines (PAIC’s) were analyzed. Results: AD lesion in the aortic arch progressively increased in ApoE^-/-, significant at 24- and 28-weeks. AD in SCI is significantly greater at 24- and 28-weeks compared to time-controlled ApoE^-/-. Salsalate treatment attenuates the SCI-induced increase at these time points. Body mass in all SCI groups are significantly reduced compared to time-controlled ApoE^-/-. Cholesterol and triglycerides are significantly higher with SCI by 24- and 28-weeks, compared to ApoE^-/-, and Salsalate reduces the SCI-induced effect on cholesterol. PAIC’s interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL-5) are significantly greater with SCI compared to ApoE^-/- at varying timepoints. Salsalate confers a marginal reducing effect on PAIC’s by 28-weeks compared to SCI. Regression models determine that each PAIC is a significant and positive predictor of lesion. (p’s <0.05). Conclusions: SCI accelerates aortic AD and associated risk factors, and anti-inflammatory treatment may attenuate the impact of SCI on AD outcomes. PAIC’s IL-1β, IL-6, TNFα, MCP-1, and CCL-5 may be effective predictors of AD.

Spinal cord injury (SCI) results in an array of cardiometabolic complications, with obesity being the most common component risk of cardiometabolic disease (CMD) in this population. Recent Consortium for Spinal Cord Medicine Clinical Practice Guidelines for CMD in SCI recommend physical exercise as a primary treatment strategy for the management of CMD in SCI. However, the high prevalence of obesity in SCI and the pleiotropic nature of this body habitus warrant strategies for tailoring exercise to specifically target obesity. In general, exercise for obesity management should aim primarily to induce a negative energy balance and secondarily to increase the use of fat as a fuel source. In persons with SCI, reductions in the muscle mass that can be recruited during activity limit the capacity for exercise to induce a calorie deficit. Furthermore, the available musculature exhibits a decreased oxidative capacity, limiting the utilization of fat during exercise. These constraints must be considered when designing exercise interventions for obesity management in SCI. Certain forms of exercise have a greater therapeutic potential in this population partly due to impacts on metabolism during recovery from exercise and at rest. In this article, we propose that exercise for obesity in SCI should target large muscle groups and aim to induce hypertrophy to increase total energy expenditure response to training. Furthermore, although carbohydrate reliance will be high during activity, certain forms of exercise might induce meaningful postexercise shifts in the use of fat as a fuel. General activity in this population is important for many components of health, but low energy cost of daily activities and limitations in upper body volitional exercise mean that exercise interventions targeting utilization and hypertrophy of large muscle groups will likely be required for obesity management.