Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms

Influence of motor complete spinal cord injury on visceral and subcutaneous adipose tissue measured by multi-axial magnetic resonance imaging

Objective: Abdominal obesity conveys substantial health risks, in association with high levels of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and an increased proportion of VAT to SAT. The purposes were to determine the influence of spinal cord injury (SCI) on the associations between single axial cross-sectional area (CSA) slices and the average CSA or volumes of VAT and SAT across multi-axial slices of magnetic resonance imaging (MRI); and the relationships relative to the whole body composition and anthropometrics. Methods: Thirteen healthy male participants with traumatic motor complete SCI underwent fast spin-echo MRI to measure VAT and SAT across multi-axial slices, followed by dual-energy X-ray absorptiometry to measure whole body fat-free mass (FFM) and fat mass (FM). Waist circumference (WC) was also measured in the seated position. Results: The trunk CSAs of VAT and SAT were 99 ± 51 and 164 ± 69 cm 2 , respectively, and the ratio of VAT to SAT was 0.68 ± 0.33. The CSAs of VAT and SAT at a single slice strongly predicted the average CSA and modestly predicted the volumes across multi-axial slices. VAT and SAT represented 5.7 ± 1.8% and 9.7 ± 3.2% of the total body FM, respectively. Percent body FFM was negatively related to VAT and SAT volumes, but not to a single axial CSA. Conclusion: A single slice CSA can modestly predict the volume of multi-axial slices in individuals with SCI, yet it is not related to any of the body composition variables. Increased percent FFM is associated with a reduction in VAT and SAT volumes measured across multi-axial slices. The ratio of VAT to SAT is greater than 0.4, suggesting that individuals with SCI are at high risk of developing metabolic sequelae

Locomotor and resistance training restore walking in an elderly person with a chronic incomplete spinal cord injury

To determine the effects of 10~weeks of locomotor training (LT) using body weight supported (BWS) treadmill training and resistance training (RT) programs on over-ground walking recovery, walking speed and distance, functional independent measure (FIM), walking index for spinal cord injury (WISCI) and Berg Balance Score in an elderly person with an incomplete spinal cord injury (SCI). A 66 year-old-male with a chronic incomplete SCI at C5/C6 ASIA Impairment Scale (AIS) D was admitted for rehabilitation following posterior laminectomy at L3-L5. The participant was a short distance ambulator relying primarily on his power wheelchair for mobility. He completed 10~weeks of LT using manual BWS treadmill twice weekly and RT for knee extensor muscle groups twice a week. A weekly test of the over-ground distance and speed were recoded over the course of the 10~weeks. Additionally, the participant underwent a three month evaluation after discharge. The 10-week program resulted in independent use of bilateral Canadian crutches to ambulate for 200 feet and increased over-ground walking speed. The FIM score increased from 3 to 6 and Berg balance score increased from 11 to 41. The WISCI score increased from 1 to 10. Three months post-discharge, the participant maintained his functional independency in sit to stand activity and over-ground walking. A combined program of LT and RT could enhance walking recovery in a person with a long-term SCI. The findings suggest that twice a week of LT can promote motor recovery if it is accompanied with an approach that effectively loads the paralyzed lower extremities

Femoral Bone Marrow Adiposity and Cortical Bone Cross-Sectional Areas in Men With Motor Complete Spinal Cord Injury

To (1) quantify yellow and red bone marrow (BM) and cortical bone cross-sectional areas (CSAs) of the femur in persons with motor complete spinal cord injury (SCI) compared with healthy able-bodied control subjects and (2) determine the relationships between yellow and red BM, cortical CSAs, and thigh composition and measurements from dual-energy x-ray absorptiometry in men with complete SCI. Cross-sectional. Clinical hospital and academic settings. Eight persons with motor complete SCI and 6 age-matched healthy control subjects underwent magnetic resonance imaging of both thighs to measure BM adiposity (BMA) and cortical CSA followed by whole-body dual-energy x-ray absorptiometry to measure bone mineral density and body composition for the SCI group. Cortical bone CSA adjusted to total subperiosteal bone CSA was 1.5-2 times lower in men with SCI compared with able-bodied control subjects across the femoral length (P =.003). Yellow BMA CSA was 2-3 times greater in men with SCI compared with able-bodied control subjects (P < .0001). Opposite relationships were found between the yellow BMA CSA and cortical bone CSAs in men with SCI (negative association) and able-bodied control subjects (positive association). Yellow BMA was negatively associated with bone mineral density and bone mineral content and with skeletal muscle CSA and fat-free mass (P <.05) in men with SCI. Finally, yellow BMA was positively related to thigh subcutaneous adipose tissue. After SCI, cortical bone CSA becomes thinner and is associated with greater accumulation of yellow BMA. Yellow BMA is associated with changes in bone CSA and bone mass, as well as increased fat mass, after SCI

Acute effects of locomotor training on neuromuscular and metabolic profile after incomplete spinal cord injury

Locomotor training (LT) enhances walking in individuals with spinal cord injuries (SCIs). We tested the acute effects of 4 days of LT using BWSTT combined with Robotic Locomotor therapy compared to BWSTT twice weekly. Two non-ambulatory participants with an American Spinal Injury Association Impairment Scale (AIS) D. Both received LT for 2 weeks as a portion of their clinical inpatient rehabilitation program and both used wheelchairs as their primary method of mobility. Over a 2 week period, one participant received a total of 8 visits consisting of manual BWSTT (twice weekly) combined with Robotic locomotor therapy (twice weekly). The other participant preformed manual BWSTT (twice weekly) for a total of 4 visits. Resting energy expenditure, body composition, muscle strength, submaximal oxygen consumption (VO2) and blood lactate during LT were measured pre and post-training. The average maximum voluntary contraction of both knee extensor muscle groups increased by 28-34% with associated reduction in spasticity to the BWSTT participant. Two week interventions resulted in a downward shift of the lactate concentrations for both participants, increase in resting energy expenditure and shift in substrate utilization. A clinical paradigm of incorporating BWSTT with robotic locomotor therapy for 4 days/ week did not provide additional physiological benefits to skeletal muscle strength, spasticity or metabolic profile compared to twice weekly of LT using BWSTT