Cardiometabolic risk factor clustering in persons with spinal cord injury: A principal component analysis approach.

CONTEXT/OBJECTIVE: To identify cardiometabolic (CM) measurements that cluster to confer increased cardiovascular disease (CVD) risk using principal component analysis (PCA) in a cohort of chronic spinal cord injury (SCI) and healthy non-SCI individuals. APPROACH: A cross-sectional study was performed in ninety-eight non-ambulatory men with chronic SCI and fifty-one healthy non-SCI individuals (ambulatory comparison group). Fasting blood samples were obtained for the following CM biomarkers: lipid, lipoprotein particle, fasting glucose and insulin concentrations, leptin, adiponectin, and markers of inflammation. Total and central adiposity [total body fat (TBF) percent and visceral adipose tissue (VAT) percent, respectively] were obtained by dual x-ray absorptiometry (DXA). A PCA was used to identify the CM outcome measurements that cluster to confer CVD risk in SCI and non-SCI cohorts. RESULTS: Using PCA, six factor-components (FC) were extracted, explaining 77% and 82% of the total variance in the SCI and non-SCI cohorts, respectively. In both groups, FC-1 was primarily composed of lipoprotein particle concentration variables. TBF and VAT were included in FC-2 in the SCI group, but not the non-SCI group. In the SCI cohort, logistic regression analysis results revealed that for every unit increase in the FC-1 standardized score generated from the statistical software during the PCA, there is a 216% increased risk of MetS (P = 0.001), a 209% increased risk of a 10-yr. FRS ≥ 10% (P = 0.001), and a 92% increase in the risk of HOMA2-IR ≥ 2.05 (P = 0.01). CONCLUSION: Application of PCA identified 6-FC models for the SCI and non-SCI groups. The clustering of variables into the respective models varied considerably between the cohorts, indicating that CM outcomes may play a differential role on their conferring CVD-risk in individuals with chronic SCI.

Preliminary observations on the administration of a glucagon-like peptide-1 receptor agonist on body weight and select carbohydrate endpoints in persons with spinal cord injury: A controlled case series.

CONTEXT/OBJECTIVE: To describe the effect of semaglutide, a glucagon-like peptide-1 (GLP-1) agonist, to reduce body weight and improve glycemic control in overweight or obese individuals with spinal cord injury (SCI). DESIGN: Open-label, randomized drug intervention case series. SETTING: This study was performed at James J. Peters VA Medical Center (JJP VAMC) and Kessler Institute for Rehabilitation (KIR). PARTICIPANTS: Five individuals with chronic SCI meeting criteria for obesity and abnormal carbohydrate metabolism. INTERVENTION: Administration of semaglutide (subcutaneously once per week) versus no treatment (control) for 26 weeks. OUTCOME MEASURES: Change in total body weight (TBW), fat tissue mass (FTM), total body fat percent (TBF%), and visceral adipose tissue volume (VATvol) was determined at baseline and after 26 weeks using Dual energy X-ray absorptiometry; fasting plasma glucose (FPG) concentration and serum glycated hemoglobin (HbA1C) values were obtained at the same two time points. RESULTS: In 3 participants, after 26 weeks of semaglutide administration, TBW, FTM, TBF%, and VATvol decreased, on average, by 6, 4.4 kg, 1.7%, and 674 cm3, respectively. In addition, values for FPG and HbA1c decreased by 17 mg/dl and 0.2%, respectively. After 26 weeks of observation in the 2 control participants, TBW, FTM, TBF% and VATvol increased on average by 3.3 , 4.5 kg, 2.5%, and 991 cm3, respectively. The average values for FPG and HbA1c also increased by 11 mg/dl and 0.3%, respectively. CONCLUSIONS: Administration of semaglutide for 26 weeks resulted in favorable changes in body composition and glycemic control, suggesting a reduced risk for the development of cardiometabolic disease in obese individuals with SCI.Trial registration: ClinicalTrials.gov identifier: NCT03292315.

Self-reported effects of warm seasonal temperatures in persons with spinal cord injury.

OBJECTIVE: Spinal cord injury (SCI) interrupts motor, sensory, and autonomic pathways, impairing mobility and increasing heat storage during warm seasonal temperatures due to compromised autonomic control of vasodilation and sweating and recognition of body temperature. Thus, persons with SCI are more vulnerable to hyperthermia and its adverse effects. However, information regarding how persons with SCI perceive warmer seasons and whether thermal discomfort during warmer seasons restricts routine activities remains anecdotal. DESIGN: Cross-sectional, self-report surveys. SETTING: VA Medical Center and Kessler Institute for Rehabilitation. PARTICIPANTS: Three groups of 50 participants each: tetraplegia, paraplegia, and matched non-SCI controls. OUTCOME MEASURES: Tetraplegia, paraplegia, and control groups responded "yes" or "no" when asked whether warm seasonal temperatures adversely affected comfort or participation in routine activities. RESULTS: The percentage of responses differed among tetraplegia, paraplegia, and control groups when asked if they required ≥20 min to cool down once overheated (44 vs. 20 vs. 12%; X2 = 14.7, P < 0.001), whether heat-related discomfort limited their ability to go outside (62 vs. 34 vs. 32%; X2 = 11.5, P = 0.003), if they needed to use a water-mister because of the heat (70 vs. 44 vs. 42%; X2 = 9.8, P = 0.008), and if heat-related discomfort limited participation in social activities (40 vs. 20 vs. 16%; X2 = 8.7, P = 0.01). CONCLUSION: Warmer seasonal temperatures had a greater negative impact on reported comfort and daily activities of persons with SCI than non-SCI controls. Those with tetraplegia were most adversely affected. Our findings warrant increasing awareness and identifying interventions to address the vulnerability of persons with SCI to hyperthermia.

Clinical trial of home blood pressure monitoring following midodrine administration in hypotensive individuals with spinal cord injury.

BACKGROUND: Individuals with spinal cord injury (SCI) above thoracic level-6 (T6) experience impaired descending cortical control of the autonomic nervous system which predisposes them to blood pressure (BP) instability, including includes hypotension, orthostatic hypotension (OH), and autonomic dysreflexia (AD). However, many individuals do not report symptoms of these BP disorders, and because there are few treatment options that have been proven safe and effective for use in the SCI population, most individuals remain untreated. OBJECTIVE: The primary aim of this investigation was to determine the effects of midodrine (10 mg) prescribed TID or BID in the home environment, compared to placebo, on 30-day BP, study withdrawals, and symptom reporting associated with OH and AD in hypotensive individuals with SCI. DESIGN/METHODS: Participants were randomly assigned to received midodrine/placebo or placebo/midodrine, with a 2-weeks washout period in between, and both the participants and investigators were blinded to randomization order. Study medication was taken 2 or 3 times/day, depending on their sleep/wake schedule, BP, and any related symptoms were recorded before and 1 h after each dosage and periodically throughout the day. RESULTS: Nineteen individuals with SCI were recruited; however, 9 withdrew prior to completion of the full protocol. A total of 1892 BP recordings (75 ± 48 recordings/participant/30-day period) were collected in the 19 participants over the two 30-day monitoring periods. Average 30-day systolic BP was significantly increased with midodrine compared to placebo (114 ± 14 vs. 96 ± 11 mmHg, respectively; P = 0.004), and midodrine significantly reduced the number of hypotensive BP recordings compared to placebo (38.7 ± 41.9 vs. 73.3 ± 40.6, respectively; P = 0.01). However, compared to placebo, midodrine increased fluctuations in BP, did not improve symptoms of OH, but did significantly worsen the intensity of symptoms associated with AD (P = 0.03). CONCLUSION: Midodrine (10 mg) administered in the home environment effectively increases BP and reduces the incidence of hypotension; however these beneficial effects come at the expense of worsened BP instability and AD symptom intensity.

Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury.

Twelve months following discontinuation of denosumab, the percent decrease in mean bone mineral density (BMD) values at the hip and knee regions were similar between both the denosumab and placebo groups. These findings emphasize the need for additional trials to understand the effect of continued administration of denosumab after subacute spinal cord injury (SCI) to avoid this demineralization. OBJECTIVE: To determine changes in BMD 1 year after denosumab was discontinued in participants with subacute SCI who had drug treatment initiated within 90 days post SCI and continued for 1 year. METHODS: Fourteen participants who completed a randomized, double-blinded, placebo-controlled drug trial (parent study: denosumab 60 mg (Prolia, Amgen Inc., n = 8) or placebo (n = 6); administered at baseline, 6, and 12 months) were followed 12 months after the 18 months from baseline primary end point was completed. The BMD of skeletal regions below the SCI at higher risk of fracture was measured [total hip, distal femur epiphysis (DFE), distal femur metaphysis (DFM), and proximal tibia epiphysis (PTE)] by dual energy X-ray absorptiometry. RESULTS: The percent decreases in mean BMD values at all regions of the hip and knee from 18 to 30 months were similar in both the denosumab and placebo groups. However, at 30 months, the absolute values for mean BMD remained significantly higher in the drug treatment than that of the placebo group at the DFM (p = 0.03), DFE (p = 0.04), and PTE (p = 0.05). CONCLUSIONS: In persons with SCI who initiated denosumab treatment during the subacute injury phase and maintained treatment for 1 year, the discontinuation of drug resulted in percent loss of mean BMD similar to that of the placebo group, with absolute mean BMD values at the knee regions at the 12-month follow-up visit significantly higher in the drug treatment than those in the placebo group. These data underscore the need to study continued administration of denosumab after subacute SCI to avoid marked demineralization in the sublesional skeleton upon discontinuation of this agent.

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.

Generation of a Reference Dataset to Permit the Calculation of T-scores at the Distal Femur and Proximal Tibia in Persons with Spinal Cord Injury.

Persons with traumatic spinal cord injury (SCI) have severe bone loss below the level of lesion with the distal femur (DF) and proximal tibia (PT) being the skeletal regions having the highest risk of fracture. While a reference areal bone mineral density (aBMD) database is available at the total hip (TH) using the combined National Health and Nutrition Examination Survey (NHANES) III study and General Electric (GE) combined (GE/NHANES) to calculate T-score (T-scoreGE/NHANES), no such reference database exists for aBMD of the DF, and PT. The primary objectives of this study were (1) to create a reference dataset of young-healthy able-bodied (YHAB) persons to calculate T-score (T-scoreYHAB) values at the DF and PT, (2) to explore the impact of time since injury (TSI) on relative bone loss in the DF and PT regions using the two computation models to determine T-score values, and (3) to determine agreement between T-score values for a cohort of persons with SCI using the (T-scoreYHAB) and (T-scoreGE/NHANES) reference datasets. A cross-sectional prospective data collection study. A Department of Veterans Affairs Medical Center and a Private Rehabilitation Hospital. A normative reference aBMD database at the DF and PT was collected in 32 male and 32 female Caucasian YHAB participants (n=64) and then applied to calculate T-score values at the DF and PT in 105 SCI participants from a historical cohort. The SCI participants were then grouped based on TSI epochs (E-I: TSI < 1y, E-II: TSI 1-5y, E-III: TSI 6-10y, E-IV: TSI 11-20y, E-V: TSI > 20y). N/A. The knee and hip aBMD values were obtained by dual energy X-ray absorptiometry (GE Lunar iDXA) using standard clinical software for proximal femur orthopedic knee software applications. There were no significant differences in mean aBMD values across the four YHAB age subgroups (21-25, 26-30, 31-35, and 36-40 yr of age) at the TH, DF, and PT; mean aBMD values were higher in men compared to the women at all skeletal regions of interest. Using the mean YHAB aBMD values to calculate T-score values at each TSI epoch for persons with SCI, T-score values decreased as a function of TSI, and they continued to decline for 11-20 yr. Moderate kappa agreement was noted between the YHAB and the GE/NHANES reference datasets for the T-score cutoff criteria accepted to diagnose osteoporosis (i.e., SD <-2.5). A homogeneous reference dataset of YHAB aBMD values at the DF and PT was applied to calculate T-score values in persons with chronic SCI. There was a moderate level of agreement at the TH between the YHAB and GE/NHANES reference datasets when applying the conventional T-score cutoff value for the diagnosis of osteoporosis.

Surveillance for Pressure Injuries on Admission to Inpatient Rehabilitation Hospitals During the COVID-19 Pandemic.

OBJECTIVE: To determine if the incidence of pressure injuries (PIs) on admission to an inpatient rehabilitation hospital (IRH) system of care was increased during the early coronavirus disease 2019 (COVID-19) pandemic period. DESIGN: Retrospective survey chart review of consecutive cohorts. Admissions to 4 acute IRHs within 1 system of care over the first consecutive 6-week period of admitting patients positive for COVID-19 during the initial peak of the COVID-19 pandemic, April 1-May 9, 2020. A comparison was made with the pre-COVID-19 period, January 1-February 19, 2020. SETTING: Four acute IRHs with admissions on a referral basis from acute care hospitals. PARTICIPANTS: A consecutive sample (N=1125) of pre-COVID-19 admissions (n=768) and COVID-19 period admissions (n=357), including persons who were COVID-19-positive (n=161) and COVID-19-negative (n=196). MAIN OUTCOME MEASURES: Incidence of PIs on admission to IRH. RESULTS: Prevalence of PIs on admission during the COVID-19 pandemic was increased when compared with the pre-COVID-19 period by 14.9% (P<.001). There was no difference in the prevalence of PIs in the COVID-19 period between patients who were COVID-19-positive and COVID-19-negative (35.4% vs 35.7%). The severity of PIs, measured by the wound stage of the most severe PI the patient presented with, worsened during the COVID-19 period compared with pre-COVID-19 (χ2 32.04%, P<.001). The length of stay in the acute care hospital before transfer to the IRH during COVID-19 was greater than pre-COVID-19 by 10.9% (P<.001). CONCLUSIONS: During the early part of the COVID-19 pandemic time frame, there was an increase in the prevalence and severity of PIs noted on admission to our IRHs. This may represent the significant burden placed on the health care system by the pandemic, affecting all patients regardless of COVID-19 status. This information is important to help all facilities remain vigilant to prevent PIs as the pandemic continues and potential future pandemics that place strain on medical resources.

Predicting Cardiometabolic Risk From Visceral Abdominal Adiposity in Persons With Chronic Spinal Cord Injury.

Persons with spinal cord injury (SCI) have increased adiposity that may predispose to cardiovascular disease compared to those who are able-bodied (AB). The purpose of this study was to determine the relationships between dual energy X-ray absorptiometry (DXA)-derived visceral adipose tissue (VAT) and biomarkers of lipid metabolism and insulin resistance in persons with chronic SCI. A prospective observational study in participants with chronic SCI and age- and gender-matched AB controls. The study was conducted at a Department of Veterans Affairs Medical Center and Private Rehabilitation Hospital. The quantification of DXA-derived VAT volume (VATvol) and blood-derived markers of lipid and carbohydrate metabolism were determined in 100 SCI and 51 AB men. The VATvol was acquired from a total body DXA scan and analyzed using iDXA enCore CoreScan software (GE Lunar). Blood samples were collected for the serum lipid profile and plasma and glucose concentrations, with the latter two values used to calculate a measure of insulin resistance. In the SCI and AB groups, VAT% was significantly correlated with most cardiometabolic biomarkers. The results of the binary logistic regression analysis revealed that participants who had a VATvol above the cutoff value of 1630 cm3 were 3.1-, 4.8-, 5.6-, 19.2-, and 16.7-times more likely to have high serum triglycerides (R2N= 0.09, p = 0.014), low serum high density lipoprotein cholesterol (R2N = 0.16, p < 0.001), HOMA2-IR (R2N = 0.18, p < 0.001), metabolic syndrome (R2N = 0.25, p < 0.001), and a 10-yr Framingham Risk Score ≥ 10% (R2N = 0.16, p = 0.001), respectively, when compared to participants below this VATvol cutoff value. Our findings reveal that persons with chronic SCI have a higher VATvol than that of AB controls, and VATvol correlates directly with biomarkers of lipid and carbohydrate metabolism that are strong predictors of cardiometabolic disorders.

Screening for Deep Vein Thrombosis in Persons With COVID-19 Upon Admission to an Inpatient Rehabilitation Hospital.

OBJECTIVE: The aim of the study was to determine the prevalence of deep venous thrombosis detected by duplex screening and risk factors associated with deep venous thrombosis in patients with COVID-19 upon admission to an inpatient rehabilitation hospital. DESIGN: This is a retrospective review. SETTING: The setting is three freestanding inpatient rehabilitation hospitals operating as one system. PARTICIPANTS: The participants are consecutive patients with a diagnosis of COVID-19 admitted to an inpatient rehabilitation hospital without a diagnosis of deep venous thrombosis or screening duplex ultrasound prior to transfer. INTERVENTIONS: A duplex ultrasound of lower limbs was performed upon admission to inpatient rehabilitation hospital. OUTCOME MEASURES: Primary outcome was the percentage of admission patients with a lower limb deep venous thrombosis. Secondary factors included potential risk factors for a positive screen for deep venous thrombosis. RESULTS: A lower limb deep venous thrombosis was diagnosed in 22% (25/113) of the patients tested, with eight patients (7.1%) having a proximal deep venous thrombosis. Risk factors for screening positive for a deep venous thrombosis included being male, younger, and having been on a ventilator during the acute illness. CONCLUSIONS: The high rate of deep venous thrombosis observed in these patients suggests that the risk of venous thromboembolic disorders after severe COVID-19 illness is considerable and surveillance measures of such patients should be undertaken.

The PITCH study: pitcher injuries during the first 30 days of the coronavirus disease 2019 halted Major League Baseball season.

Background: Major League Baseball (MLB) was among the first professional team sports leagues to resume play in the United States after public health measures related to the appearance of coronavirus disease 2019 caused interruptions to preseason training and major alterations to regular season play. There was a high level of concern that these athletes were ill-prepared for competition and would experience an increased risk of injury under the restricted play rules. Methods: The data in our study were compiled using publicly accessible records of players placed on injured lists from 2015 to 2020. These records came from 4 open access websites: rotoworld.com, fangraphs.com, foxsports.com, and spotrac.com. All injuries were confirmed using the transaction database found on the official MLB website (mlb.com). Results: A greater proportion of pitchers were injured during the first 30 days of the 2020 season compared to the first 30 days of any of the 5 prior seasons (29.74% vs. 11.72%, n=2190, P<.001). There was a demonstrated increase in injury risk in 2020 for the following anatomic locations: back and trunk, shoulder, upper arm and elbow, forearm and wrist, and hand and finger (P=.02; confidence interval [0.497-5.783]). When dividing the first month of play in 2020 into equal halves (15 days each), the number of relief pitcher injuries increased with time (60% vs. 78%, P=.04). Lastly, there was no proportional difference in placement on the short-term vs. long-term injured list. Conclusion: A significantly large increase in soft tissue injuries in 2020 compared to the prior 5 seasons predominantly affected the trunk and the upper extremity of pitchers in the first 30 days of play. Alterations to preseason training and regular season play in the 2020 MLB season due to coronavirus disease 2019 may have been particularly disadvantageous to professional pitchers who are positioned at baseline, the most injury prone position.

Administration of Denosumab Preserves Bone Mineral Density at the Knee in Persons With Subacute Spinal Cord Injury: Findings From a Randomized Clinical Trial.

Persons with neurologically motor-complete spinal cord injury (SCI) have a marked loss of bone mineral density (BMD) of the long bones of the lower extremities, predisposing them to fragility fractures, especially at the knee. Denosumab, a commercially available human monoclonal IgG antibody to receptor activator of nuclear factor-κB ligand (RANKL), may provide an immunopharmacological solution to the rapid progressive deterioration of sublesional bone after SCI. Twenty-six SCI participants with subacute motor-complete SCI were randomized to receive either denosumab (60 mg) or placebo at baseline (BL), 6, and 12 months. Areal bone mineral density (aBMD) by dual energy x-ray absorptiometry (DXA) at 18 months at the distal femur was the primary outcome and aBMD of the proximal tibia and hip were the secondary outcomes analyzed in 18 of the 26 participants (denosumab, n = 10 and placebo, n = 8). The metrics of peripheral QCT (pQCT) were the exploratory outcomes analyzed in a subsample of the cohort (denosumab, n = 7 and placebo n = 7). The mean aBMD (±95% CI) for the denosumab versus the placebo groups demonstrated a significant group × time interactions for the following regions of interest at BL and 18 months: distal femoral metaphysis = mean aBMD 1.187; 95% CI, 1.074 to 1.300 and mean aBMD 1.202; 95% CI, 1.074 to 1.329 versus mean aBMD 1.162; 95% CI, 0.962 to 1.362 and mean aBMD 0.961; 95% CI, 0.763 to 1.159, respectively (p < 0.001); distal femoral epiphysis = mean aBMD 1.557; 95% CI, 1.437 to 1.675 and mean aBMD 1.570; 95% CI, 1.440 to 1.700 versus mean aBMD 1.565; 95% CI, 1.434 to 1.696 and mean aBMD 1.103; 95% CI, 0.898 to 1.309, respectively (p = 0.002); and proximal tibial epiphysis = mean aBMD 1.071; 95% CI, 0.957 to 1.186 and mean aBMD 1.050; 95% CI, 0.932 to 1.168 versus mean aBMD 0.994; 95% CI, 0.879 to 1.109 and mean aBMD 0.760; 95% CI, 0.601 to 0.919, respectively (p < 0.001). Analysis of pQCT imaging revealed a continued trend toward significantly greater loss in total volumetric BMD (vBMD) and trabecular vBMD at the 4% distal tibia region, with a significant percent loss for total bone mineral content. Thus, at 18 months after acute SCI, our findings show that denosumab maintained aBMD at the knee region, the site of greatest clinical relevance in the SCI population. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Cardiovascular Autonomic Dysfunction in Spinal Cord Injury: Epidemiology, Diagnosis, and Management.

Spinal cord injury (SCI) disrupts autonomic circuits and impairs synchronistic functioning of the autonomic nervous system, leading to inadequate cardiovascular regulation. Individuals with SCI, particularly at or above the sixth thoracic vertebral level (T6), often have impaired regulation of sympathetic vasoconstriction of the peripheral vasculature and the splanchnic circulation, and diminished control of heart rate and cardiac output. In addition, impaired descending sympathetic control results in changes in circulating levels of plasma catecholamines, which can have a profound effect on cardiovascular function. Although individuals with lesions below T6 often have normal resting blood pressures, there is evidence of increases in resting heart rate and inadequate cardiovascular response to autonomic provocations such as the head-up tilt and cold face tests. This manuscript reviews the prevalence of cardiovascular disorders given the level, duration and severity of SCI, the clinical presentation, diagnostic workup, short- and long-term consequences, and empirical evidence supporting management strategies to treat cardiovascular dysfunction following a SCI.

Screening Testing for SARS-CoV-2 upon Admission to Rehabilitation Hospitals in a High COVID-19 Prevalence Community.

BACKGROUND: While planning for the care of coronavirus disease 2019 (COVID-19) patients during the pandemic crisis has dominated the focus of leaders of inpatient rehabilitation facilities (IRFs), patients with injuries/illnesses unrelated to COVID-19 continue to need inpatient rehabilitation admission. To maintain a safe environment for all patients and staff, we established an admission screening plan of testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to determine the presence of asymptomatic patients who were infected with the virus upon admission. OBJECTIVE: To determine the prevalence of patients who test positive for SARS-CoV-2 but were presumed to be COVID-19 negative at the time of admission to IRF in New Jersey. DESIGN: Retrospective analysis of SARS-CoV-2 testing results. SETTING: Four freestanding IRFs in New Jersey operated as one system. PATIENTS: All (N = 103) patients sequentially admitted from 4 to 27 April 2020 with no symptoms or evidence of COVID-19 disease at the time of transfer from the acute hospital. INTERVENTIONS: Specimens were collected for SARS-CoV-2 analysis at the time of admission to the IRF and patients were monitored for subsequent symptom development over the next 14 days. MAIN OUTCOME MEASURES: Results of SARS-CoV-2 testing upon admission and evidence of development of clinical signs or symptoms of COVID-19. RESULTS: Seven asymptomatic persons (6.8% of admissions) without clinical signs/symptoms of COVID-19 tested positive on admission. Of these, five developed symptoms of COVID-19, with a mean onset of 3.2 (range of 2-5) days. Five additional patients became symptomatic and tested positive within the next 3 to 10 days (mean of 5.2 days). Overall, 11.6% of admissions (12/103) had a positive test within 14 days of admission. CONCLUSIONS: Admission testing to postacute centers for SARS-CoV-2 can help identify presymptomatic or asymptomatic individuals, especially in areas where COVID-19 is prevalent. Negative results, however, do not preclude COVID-19 and should not be used as the sole basis for patient management decisions.

Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI.

STUDY DESIGN: Clinical trial. OBJECTIVES: Individuals with spinal cord injury (SCI) above T6 experience impaired descending cortical control of the autonomic nervous system, which predisposes them to hypotension. However, treatment of hypotension is uncommon in the SCI population because there are few safe and effective pharmacological options available. The primary aim of this investigation was to test the efficacy of a single dose of midodrine (10 mg), compared with placebo, to increase and normalize systolic blood pressure (SBP) between 110 and 120 mmHg during cognitive testing in hypotensive individuals with SCI. Secondary aims were to determine the effects of midodrine on cerebral blood flow velocity (CBFv) and global cognitive function. SETTING: United States clinical research laboratory. METHODS: Forty-one healthy hypotensive individuals with chronic (≥1-year post injury) SCI participated in this 2-day study. Seated SBP, CBFv, and cognitive performance were monitored before and after administration of identical encapsulated tablets, containing either midodrine or placebo. RESULTS: Compared with placebo, midodrine increased SBP (4 ± 13 vs. 18 ± 24 mmHg, respectively; p < 0.05); however, responses varied widely with midodrine (-15.7 to +68.6 mmHg). Further, the proportion of SBP recordings within the normotensive range did not improve during cognitive testing with midodrine compared with placebo. Although higher SBP was associated with higher CBFv (p = 0.02), global cognitive function was not improved with midodrine. CONCLUSIONS: The findings indicate that midodrine increases SBP and may be beneficial in some hypotensive patients with SCI; however, large heterogeneity of responses to midodrine suggests careful monitoring of patients following administration. CLINICAL TRIALS REGISTRATION: NCT02307565.

Measurement of Visceral Adipose Tissue in Persons With Spinal Cord Injury by Magnetic Resonance Imaging and Dual X-Ray Absorptiometry: Generation and Application of a Predictive Equation.

PURPOSE: Dual energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) permits quantification of visceral adipose tissue (VAT). However, DXA has not been validated against MRI in persons with chronic spinal cord injury (SCI). A predictive equation was generated from the measurement of VAT by MRI, a "gold" standard to quantitate VAT, compared to that of DXA, a method with several practical advantages. METHOD: DXA and MRI scans were performed in 27 participants with SCI. MRI multiaxial images were captured for VAT analysis. DXA-VAT was quantified at the android region (DXA-VATANDROID-VOL) using enCore software. Android regions of DXA and MRI were matched using android height. Volumes of multiaxial MRI-VAT and subcutaneous adipose tissue (SAT) were quantified for the android region (MRI-VATANDROID-VOL, MRI-SATANDROID-VOL) and total trunk (MRI-VATANDROID-VOL). Linear regression analysis was used to establish the proposed predication equations. The prediction equations were then applied to an independent sample that consisted of 98 participants with SCI. Bland-Altman analysis was used to determine the limits of agreement. RESULTS: DXA-VATANDROID-VOL predicted 92% of the variance in MRI-VATANDROID-VOL (SEE = 252.5, p < 0.0005) and 85% of the variance in MRI-VATTRUNK-VOL (SEE = 1526.9, p < 0.0005). DXA-SATANDROID-VOL predicted 81.5% of the variance in MRI-SATANDROID-VOL (SEE = 458.2, p < 0.0005). Bland-Altman analysis revealed a high level of agreement between MRI-VATANDROID-VOL and DXA-VATANDROID-VOL (mean bias = 58.45 cm3). A predicted mean DXA-VATANDROID-VOL of 995.2 cm3 was estimated as the population-specific cut-off point for high levels of VAT. CONCLUSION: DXA-VATANDROID-VOL may accurately predict MRI-VATANDROID-VOL in persons with SCI. The ability of DXA to detect VAT changes in longitudinal studies in persons with SCI should be performed.

Reliability of S3 pressure sensation and voluntary hip adduction/toe flexion and agreement with deep anal pressure and voluntary anal contraction in classifying persons with traumatic spinal cord injury.

Context/Objective: The sacral examination components of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), namely deep anal pressure (DAP) and voluntary anal sphincter contraction (VAC), are often difficult to perform. We evaluated whether pressure sensation at the S3 dermatome (S3P), and voluntary hip adductor or toe flexor contraction (VHTC) are tenable alternatives. Here we report test-retest reliability and agreement of these components at 1 month after spinal cord injury (SCI), and impact of disagreement on American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades. Design: Longitudinal cohort. ISNCSCI examination, S3P and VHTC conducted at 1-month post-injury; retest of the sacral exam, S3P and VHTC within 3 days. Follow-up examinations performed at 3, 6, and 12 months. Setting: Five Spinal Cord Injury Model System Centers. Participants: Subjects with acute traumatic SCI, neurological levels T12 and above, AIS grades A-C. Interventions: None. Outcome Measures: ISNCSCI exam, AIS grades. Results: Fifty-one subjects had 1-month data, and 39 had at least one follow-up examination. Test-retest reliability indicated perfect agreement (kappa = 1.0) for all data except S3P (kappa = 0.96). The agreement was almost perfect between S3P and DAP (kappa = 0.84) and between VHTC and VAC (kappa = 0.81). VHTC and VAC differed more often with neurologic levels below T10, possibly due to root escape in conus medullaris injuries. Conclusion: S3P and VHTC show promise as alternatives to DAP and VAC for determining sacral sparing in persons with neurologic levels T10 and above. Reliability and agreement should be evaluated at earlier timepoints and in children with SCI.

Relationships between T-scores at the hip and bone mineral density at the distal femur and proximal tibia in persons with spinal cord injury.

Objective: To identify T-score values at the total hip (TH) and femoral neck (FN) that correspond to the cutoff value of <0.60 g/cm2 for heightened risk of fracture at the distal femur (DF) and proximal tibia (PT).Design: Retrospective analysis of data in a research center's database. Setting: Community-based individuals with spinal cord injury (SCI). Participants: 105 unique individuals with SCI. Outcome Measurements: DXA derived areal BMD (aBMD) and T-score of the DF, PT, TH, and FN. Results: The aBMD at the DF and PT regions were predictors of T-scores at the TH (R2 = 0.63, P < 0.001 and R2 = 0.65, P < 0.001) and FN (R2 = 0.55, P < 0.001 and R2 = 0.58, P < 0.001). Using the DF and PT aBMD of 0.60 g/cm2 as a value below which fractures were more likely to occur, the predicted T-score was -3.1 and -3.5 at the TH and -2.6 and -2.9 at the FN, respectively. However, when the predicted and observed T-score values disagree outside the 95% limit of agreement, the predicted T-score values are lower than the measured T-score values, overestimating the measured values between -2.0 and -4.0 SD. Conclusion: The DF and PT cutoff value for aBMD of 0.60 g/cm2 was a moderate predictor of T-score values at the TH and FN, with considerable inaccuracies outside the clinically acceptable limits of agreement. As such, the direct measurement of knee aBMD in persons with SCI should be performed, whenever possible, prior to prescribing weight bearing upright activities, such as robotic exoskeletal-assisted walking.

A Four Month Randomized Controlled Trial on the Efficacy of Once-daily Fenofibrate Monotherapy in Persons with Spinal Cord Injury.

An open-label, randomized clinical trial of once-daily fenofibrate monotherapy administered for 2- (Mo2) and 4- (Mo4) months using modified intervention thresholds for triglyceride (TG) was performed in persons with chronic spinal cord injury (SCI). Fenofibrate (145 mg tablet) was self-administered daily in 10 persons with SCI for 4 months with monthly blood testing to quantify the lipoprotein profile (e.g., serum TG, LDL-C, and HDL-C concentrations). Eight SCI participants were control subjects. In comparison to the control group, the treatment group at Mo2 had a 40% (±12%; p < 0.05) reduction in serum TG concentration, a 28% (±21%; p < 0.05) increase in HDL-C and 14% (±20%; p < 0.05) decline in LDL-C. In the same comparison at Mo4, the treatment group maintained a 40% (±20%; p < 0.05) reduction in serum TG concentration, had an 18% in reduction in LDL-C (±12%; p < 0.05) and a 23% (±23%; p < 0.05) increase in HDL-C. Fenofibrate monotherapy for Mo2 and Mo4 initiated in persons with SCI resulted in a robust and favorable change in the serum lipoprotein profile and ratios, suggesting reduced risk for cardiovascular disease.

Blood Pressure Instability in Persons With SCI: Evidence From a 30-Day Home Monitoring Observation.

BACKGROUND: To determine the degree of blood pressure instability over a 30-day home observation in participants with spinal cord injury grouped by level of injury pertaining to cardiovascular autonomic regulation. METHODS: This is an observational study completed at the Kessler Foundation and James J. Peters Veterans Medical Center. Seventy-two participants with tetraplegia (C1-T1), 13 with high thoracic (T2-T4), and 28 with low thoracic (T5-T12) injury participated in this study. Participants were asked to record their blood pressure using an ambulatory blood pressure monitor three times a day for 30 days. RESULTS: The number of blood pressure fluctuations was significantly increased in the tetraplegia group compared with the paraplegia groups. Age and duration of injury contributed to an increase in the observation of 30-day blood pressure instability; however, completeness of injury did not. CONCLUSION: The data indicate significant blood pressure instability that may not be exclusive to persons with tetraplegia; in fact, individuals with low thoracic injuries demonstrated severe blood pressure fluctuations. The use of a monitor at home for an extended period may help document dangerous and extreme fluctuations in blood pressure and should be considered an important adjunctive clinical practice for tracking of the secondary consequences in the spinal cord injury population.